SlideShare ist ein Scribd-Unternehmen logo
1 von 11
Downloaden Sie, um offline zu lesen
Epidemiology, Treatment, and Outcomes of
                   Nosocomial Bacteremic Staphylococcus
                   aureus Pneumonia*
                   C. Andrew DeRyke, Thomas P. Lodise, Jr., Michael J. Rybak and Peggy
                   S. McKinnon

                   Chest 2005;128;1414-1422
                   DOI 10.1378/chest.128.3.1414
                   The online version of this article, along with updated information and
                   services can be found online on the World Wide Web at:
                   http://chestjournal.chestpubs.org/content/128/3/1414.full.html




                    Chest is the official journal of the American College of Chest
                    Physicians. It has been published monthly since 1935.
                    Copyright2005by the American College of Chest Physicians, 3300
                    Dundee Road, Northbrook, IL 60062. All rights reserved. No part of
                    this article or PDF may be reproduced or distributed without the prior
                    written permission of the copyright holder.
                    (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml)
                    ISSN:0012-3692




Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                     © 2005 American College of Chest Physicians
Epidemiology, Treatment, and
Outcomes of Nosocomial Bacteremic
Staphylococcus aureus Pneumonia*
C. Andrew DeRyke, PharmD; Thomas P. Lodise, Jr., PharmD;
Michael J. Rybak, PharmD, MS; and Peggy S. McKinnon, PharmD


       Objective: To describe outcomes associated with nosocomial bacteremic Staphylococcus aureus
       pneumonia (NBSAP) and to determine whether delay in adequate antimicrobial treatment is a
       risk factor for negative clinical and microbiological outcomes.
       Design: Retrospective cohort analysis.
       Setting: This study was conducted at Detroit Receiving Hospital and University Health Center,
       which is a 279-bed, level 1 trauma center in Detroit, MI.
       Patients: All episodes of NBSAP identified from January 1, 1999, to April 30, 2004.
       Results: Of 206 patients identified over a 5-year period with positive blood and respiratory
       cultures for S aureus, 60 patients met strict clinical, radiographic, and microbiological criteria for
       NBSAP. The overall mean ( SD) characteristics include the following: age, 55.5 15.0 years;
       acute physiology and chronic health evaluation II score, 20 (range, 3 to 41); ICU at onset, 93.3%;
       mechanical ventilation, 83.3%; length of stay (LOS) prior to NBSAP, 9 days (range, 2 to 81 days);
       methicillin-resistant S aureus (MRSA) rate, 70%; and all-cause hospital and infection-related
       mortality (IRM), 55.5% and 40.0%, respectively. Overall, S aureus pneumonia developed late in
       the patient’s hospital stay in ICU patients previously receiving mechanical ventilation and was
       associated with high crude mortality and IRM rates. No significant difference existed with respect
       to mortality or infection-related LOS between patients who had received early appropriate
       antibiotic therapy vs those who had received delayed appropriate antibiotic therapy at the onset
       of pneumonia or in patients with methicillin-sensitive S aureus pneumonia vs those with MRSA
       pneumonia.
       Conclusion: IRM from NBSAP is high, and standard therapies evaluated at the time of this study
       resulted in poor clinical outcomes. Delayed therapy was not found to be a predictor of adverse
       outcomes; however, this lack of ability to detect a difference may be a product of small sample
       size. These findings suggest that newer agents with enhanced clinical activity in NBSAP are
       needed and that these should be evaluated in a real-world setting, where outcomes of the most
       ill patients can be assessed.                                        (CHEST 2005; 128:1414 –1422)

       Key words: bacteremia; clinical outcomes; critical care; cross-infection; hospital mortality; ICU; infection; staphylo-
       coccal infections; staphylococcal pneumonia; ventilator-associated pneumonia

       Abbreviations: APACHE acute physiology and chronic health evaluation; CART classification and regression tree
       analysis; IR-LOS infection-related length of stay; IRM infection-related mortality; NBSAP nosocomial bactere-
       mic Staphylococcus aureus pneumonia; MRSA methicillin-resistant Staphylococcus aureus; MSSA methicillin-
       sensitive Staphylococcus aureus; VAP ventilator-associated pneumonia




N osocomial pneumonia is infection and second
  most common hospital
                         currently the
                                        is the
                                                                     monia ranges from 7.8 to 68.0%, and is influenced by
                                                                     the duration of hospital and ICU stay, the specific
leading cause of death from hospital-acquired infec-                 diagnostic method used for pathogen detection, and
tions.1 The incidence of acquiring nosocomial pneu-                  the patient population studied.1 The rate of nosoco-
                                                                     mial pneumonia secondary to Staphylococcus aureus
*From the Anti-Infective Research Laboratory, Wayne State
                                                                     has increased steadily over the past 2 decades.2 In
University, Detroit, MI (Drs. Rybak and McKinnon); the De-
partment of Pharmacy, Barnes Jewish Hospital, St. Louis, MO          Reproduction of this article is prohibited without written permission
(Dr. McKinnon); the Center for Anti-Infective Research and           from the American College of Chest Physicians (www.chestjournal.
Development, Hartford Hospital, Hartford, CT (Dr. DeRyke);           org/misc/reprints.shtml).
and Albany College of Pharmacy, Albany, NY (Dr. Lodise).             Correspondence to: Peggy S. McKinnon, PharmD, Barnes-Jewish
Manuscript received December 23, 2004; revision accepted             Hospital, Mailstop 90 –52-411, 216 South Kings Hwy, St. Louis,
January 26, 2005.                                                    MO 63110; e-mail: psm9154@bjc.org

1414                                                                                                                 Clinical Investigations

             Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                                  © 2005 American College of Chest Physicians
one review3 of three major studies examining the               University Human Investigation Committee. This investigation
etiology of ventilator-associated pneumonia (VAP), S           included all of the episodes of NBSAP identified from January 1,
                                                               1999, to April 30, 2004. Nosocomial pneumonia, or hospital-
aureus was the most frequently isolated Gram-posi-
                                                               acquired pneumonia, was defined as pneumonia occurring 48
tive organism and the second-most isolated organism            h after hospital admission and excluding any infection that was
only behind Pseudomonas aeruginosa. Most studies               incubating at the time of hospital admission.17
estimate that S aureus accounts for 15 to 35% of all              For the purposes of this investigation, the diagnosis of NBSAP
nosocomial pneumonia cases; however, the true in-              was defined based on clinical, radiographic, and microbiological
cidence depends on many factors, such as patient               criteria.18 –21 Within 72 h of the first positive culture, a chest
demographics, local susceptibility patterns, and               radiograph must also have been abnormal, and the patient must
                                                               have had signs and symptoms consistent with nosocomial pneu-
methods of diagnosis.3
                                                               monia. In order to fulfill the requirement for bacteremic pneu-
                                                               monia, at least one S aureus-positive blood culture not related to
      For editorial comment see page 1093                      another source of infection and one S aureus-positive respiratory
                                                               culture must have been obtained within 72 h of each other as
   Although there is increased recognition of S au-            well. Possible respiratory cultures included positive growth in the
reus as a major pathogen causing nosocomial pneu-              culture of pleural fluid, positive sputum culture/tracheal aspirate
monia, there are few studies4 –7 with descriptive data         (defined as secretions from the lungs, bronchi, or trachea that
specifically evaluating patient outcomes of S aureus           contain numerous or a moderate number of neutrophils and rare
pneumonia. In addition, in the last decade, evidence           or few squamous epithelial cells) findings, and a positive quanti-
                                                               tative culture result from minimally contaminated lower respira-
has accumulated demonstrating that initial inappro-            tory tract specimens (eg, BAL fluid with          10,000 cfu/mL).
priate antibiotic treatment is an important indepen-           Radiographic criteria for pneumonia were met if the chest
dent predictor of excess mortality in patients with            radiograph yielded a new or progressive and persistent infiltrate,
nosocomial pneumonia.8 –11 To our knowledge, no                consolidation, or cavitation. Persistence of an infiltrate was
data exist examining the impact of delayed appropri-           defined as having the infiltrate present radiographically for at
ate antibiotic treatment specifically for bacteremic S         least 72 h. Patients were defined as symptomatic if one of the
aureus pneumonia. In a retrospective study12 evalu-            following were present: fever (ie, temperature            38°C or
                                                               100.4°F) or hypothermia (ie, temperature 35°C or 95°F) with
ating S aureus bacteremia, a delay in treatment with           no other recognized cause; leukopenia (ie, WBC count, 4,000
antibiotics for 44.75 h was found to be an inde-               cells/ L) or leukocytosis (ie, WBC count, 10,000 cells/ L); or,
pendent predictor of infection-related mortality               for adults      70 years old, altered mental status with no other
(IRM) [adjusted odds ratio, 3.8; 95% confidence                recognized cause. Patients also had to exhibit one of the following
interval, 1.3 to 11.0; p 0.01]. It is unknown if this          signs: new onset of purulent sputum, change in the character of
44.75-h breakpoint is applicable to patients with              the sputum, increased respiratory secretions, or increased suc-
bacteremic S aureus pneumonia. Although the im-                tioning requirements; new onset or worsening of cough, dyspnea,
                                                               or tachypnea (respiratory rate, 25 breaths/min); or worsening
pact of methicillin resistance on the outcomes of              gas exchange (eg, O2 desaturation [Pao2/fraction of inspired
patients with S aureus bacteremia has been exten-              oxygen ratio of      240], increased oxygen requirements, or in-
sively evaluated, little information exists on the im-         creased ventilation demand).
pact of the methicillin resistance of patients with               Medical charts were screened to exclude the following possible
nosocomial bacteremic S aureus pneumonia (NBSAP).              alternative causes for fever and radiographic chest densities. The
Furthermore, less information exists on the impact of          presence of atelectasis was defined by the complete disappear-
empirical antibiotic selection on NBSAP. Over the past         ance of radiographic densities within 48 h of evaluation. Conges-
                                                               tive heart failure with pulmonary edema was defined as a
few years, studies13–16 have suggested that vancomycin         resolution of pulmonary infiltrates following diuresis. A pulmo-
may not be optimal for the treatment of S aureus               nary embolism was defined by the presence of at least two
pneumonia, especially in the subset of patients who            segmental or larger mismatched perfusion abnormalities on a
have been infected with methicillin-resistant S aureus         ventilation-perfusion scan or suggestive radiographic findings on
(MRSA). To evaluate the epidemiology, treatment, and           pulmonary angiography and spiral CT scan.
outcomes of NBSAP, a retrospective cohort analysis                Patients with endovascular infections, including endocarditis,
was performed. Specifically, we examined the impact of         were excluded because of the potential for hematogenous spread
                                                               of S aureus to the lungs, thus complicating our retrospective
methicillin resistance, empirical therapy, and delayed         diagnosis of S aureus pneumonia. Patients with endocarditis were
treatment on the outcomes of patients with NBSAP.              identified by transthoracic or transesophageal echocardiography
                                                               and/or documentation of the diagnosis in the medical record.

               Materials and Methods                           Study Design

Study Population                                                 To evaluate the epidemiology, treatment, and outcomes of
                                                               NBSAP, a retrospective cohort analysis was performed. Specifi-
  This study was conducted at Detroit Receiving Hospital and   cally, we examined the impact of methicillin resistance, empirical
University Health Center, which is a 279-bed, level 1 trauma   therapy, and delayed treatment on the outcomes of patients with
center in Detroit, MI, and was approved by the Wayne State     NBSAP.

www.chestjournal.org                                                                  CHEST / 128 / 3 / SEPTEMBER, 2005     1415

               Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                                    © 2005 American College of Chest Physicians
Data Collection                                                        antimicrobial therapy. To prevent bias, investigators involved in
                                                                       the outcome assessments were blinded to both susceptibility data
   Clinical Data: Data extracted from the patient medical records      and treatment data, including the time to receipt of treatment.
and pharmacy database included the following: age; sex; comor-
bidities present; prior antibiotic use (within 30 days prior to
NBSAP); length of hospitalization before the onset of nosocomial       Definitions
pneumonia (total hospitalization and hospitalization in the ICU);
mechanical ventilation at the onset of nosocomial pneumonia;              Clinical outcomes were evaluated as successes or failures.
Charlson comorbidity index score22; and severity of illness based      Clinical success included clinical resolution, which was defined as
on APACHE (acute physiology and chronic health evaluation) II          the complete resolution of all signs and symptoms of pneumonia
scores at the time of admission to the ICU.23 If the patients were     (return to preinfection baseline) along with improvement, or lack
not admitted to the ICU, the APACHE II score was determined            of progression, of all abnormalities on the chest radiograph, and
at hospital admission.                                                 clinical improvement, which was defined in patients if a partial
   The following comorbid conditions were documented: diabe-           resolution of clinical signs and symptoms occurred such that no
tes mellitus; heart failure; COPD; asthma; hepatic dysfunction;        additional antimicrobial therapy was required, along with the
renal failure (as indicated by the necessity for dialysis); malig-     improvement or stabilization of chest radiographic findings.
nancy; HIV infection; alcoholism; presence of decubitus ulcers         Patients who died or whose conditions did not improve were
(stage II to IV); administration of immunosuppressive drugs (ie,       deemed as having clinical failure. Clinical failure was defined as
receipt of 20 mg prednisone or an equivalent corticosteroid            the persistence of clinical signs and symptoms, the persistence of
per day for 14 days before the onset of nosocomial pneumonia           positive culture findings, and/or a lack of resolution of infiltrates
or the receipt of any neoplastic chemotherapy in the 3 months          on the chest radiograph.
before the onset of nosocomial pneumonia); surgery requiring              Microbiological outcomes were categorized as eradication or
   48 h of hospitalization in the 30 days before the onset of          persistence. Microbiological eradication included documented
nosocomial pneumonia; and the presence of burns on 30% of              eradication, defined as the elimination of baseline pathogens
the body surface area.                                                 based on subsequent negative blood and respiratory culture
   Microbiological Data: Collected microbiological data included       findings, and presumed eradication, which was denoted in pa-
all of the positive blood or respiratory culture findings, irrespec-   tients in whom presumed eradication occurred based on clinical
tive of the pathogen identified. Susceptibility testing was per-       resolution, but no subsequent cultures were obtained. Microbi-
formed using the microtiter-well method, and the results were          ological persistence included documented persistence, which was
interpreted according to National Committee for Clinical Labo-         defined as the persistence of bacteria despite the appropriate use
ratory Standards guidelines24 by the clinical microbiological          of antibiotic therapy based on in vitro susceptibility results, and
laboratory.                                                            presumed persistence, which was denoted in patients in whom
   Treatment Data: All of the antimicrobial agents administered        presumed microbiological failure occurred based on clinical
to provide activity against S aureus isolates were noted. Empiric      failure, but no subsequent cultures were obtained.
treatment was the first antibiotic regimen provided following the         Death was considered to be related to NBSAP (ie, IRM) if one
onset of infection. Treatment was considered to be appropriate         or more of the following criteria were present: (1) blood and/or
on the basis of the following two factors: the timing of treatment     respiratory cultures were positive for S aureus at the time of
relative to the first positive blood or respiratory culture finding;   death; (2) death occurred before the resolution of signs and
and the in vitro susceptibility of the blood or respiratory isolate.   symptoms of the nosocomial pneumonia; (3) death occurred
Timing was evaluated based on a previously described breakpoint           14 days after the onset of nosocomial pneumonia without
of 44.75 h, which was determined by classification and regression      another explanation; (4) autopsy findings indicated pneumonia as
tree analysis (CART) as an independent predictor of mortality in       a cause of death; and (5) pneumonia was indicated as a cause of
S aureus bactermia.12 If a patient had received at least one IV        death on the death certificate.
antibiotic to which the S aureus blood or respiratory isolate was         The calculation of IR-LOS was measured from the time when
susceptible and the antibiotic had been administered within            the first positive blood or respiratory culture finding was col-
44.75 h, it was considered to be appropriate early treatment. For      lected until the end of antimicrobial treatment, death, or hospital
example, an individual with MRSA bacteremia receiving vanco-           discharge. The calculation of IR-LOS excluded patients who died
mycin within 44.75 h would be classified as having received early      secondary to nosocomial pneumonia.
appropriate treatment. A patient with MRSA initially treated with         An infection-related cost of hospitalization was determined for
a -lactam but not receiving vancomycin within 44.75 h would be         each patient. The Detroit Receiving Hospital accounting depart-
considered as having received delayed treatment. In addition, we       ment supplied the cost figures. For patients who lived or did not
utilized CART analysis to determine whether there was a differ-        die secondary to NBSAP, the cost was calculated from the onset
ent breakpoint to better describe the critical time to appropriate     of infection until the last day that antimicrobial therapy active
antibiotic treatment for this cohort of NBSAP patients.                against S aureus was administered (ie, the IR-LOS). For those
                                                                       patients who died because of NBSAP, the cost was calculated
                                                                       from the onset of infection until the day of the patient’s death.
Outcome Assessment

  The following primary end points were assessed: (1) IRM; (2)         Statistical Analysis
hospital (crude) mortality; and (3) infection-related length of stay
length (IR-LOS) after the onset of NBSAP. Secondary outcomes             Categoric variables were compared by the Pearson 2 test or
included the following: (1) clinical response; (2) microbiological     Fisher exact test, and continuous variables were compared by the
response; and (3) cost of hospitalization after the onset of           Student t test or Mann-Whitney U test. Multivariate analyses
NBSAP.                                                                 were performed to determine the independent association of
  For the early treatment vs delayed treatment analyses, patients      antibiotic resistance and delayed treatment with the clinical
who died within 72 h of the onset of infection were excluded.          outcome of interest while adjusting for confounding variables.
Clinical and microbiological outcomes were assessed at the             Clinical features significantly associated with the outcome by
following four time points: day 3; day 7; day 10; and at the end of    univariate analysis were included in the explanatory multivariate

1416                                                                                                                   Clinical Investigations

               Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                                    © 2005 American College of Chest Physicians
model. The univariate predictors had to represent 10% of the             tive Staphylococcus sp. The most common concom-
cohort to prevent overfitting of the multivariate model. Dichot-         itant respiratory organisms were P aeruginosa (nine
omous outcomes (eg, IRM and clinical status) were analyzed with
standard logistic regression. A p value of 0.05 was considered
                                                                         cases); A baumannii (eight cases); Klebsiella spp
to be significant for two-tailed tests. A statistical software package   (seven cases); Escherichia coli (six cases); Candida
(SPSS, version 10.0; SPSS; Chicago, IL) was used for all of the          albicans (four cases); Enterobacter spp (three cases);
calculations.                                                            and nine others.
                                                                            The clinical and microbiological success rates at
                                                                         the end of treatment were 56.7% and 53.3%, respec-
                            Results                                      tively. Thirty-three patients (55.5%) died during
                                                                         hospitalization, and 24 (40.0%) died secondary to
Baseline Data
                                                                         NBSAP (ie, IRM). Nine patients died for reasons not
   Of the 206 patients identified either by Interna-                     attributable to the pneumonia. In seven cases, treat-
tional Classification of Diseases, ninth revision, codes                 ment for NBSAP had stopped at least 2 weeks before
for S aureus pneumonia and/or by concomitant                             the patient died. Withdrawal from support occurred
blood and respiratory cultures positive for S aureus,                    in two patients irrespective of the concomitant pneu-
60 met the strict inclusion criteria as assessed for                     monia.
NBSAP. The primary reasons for exclusion from the                           The relationship between APACHE II score and
study included a lack of clinical or radiologic findings                 death is shown in Figure 1. A linear relationship
supporting a pneumonia diagnosis (n 46), alter-                          existed demonstrating that patients who were more
nate clinical diagnoses (n 43), infection that was                       acutely ill at the time of admission to the ICU had a
not nosocomial (n 26), time correlation between                          greater mortality rate (R2 0.74).
microbiological findings (n 25), and chart not
available (n 6). Alternative clinical diagnoses po-                      Outcomes of Bacteremic MRSA vs Methicillin-
tentially causing the infection isolated more than                       Sensitive S aureus Pneumonia MSSAP
once included the following: endocarditis (n 12);
IV line-related sepsis (n 16); alternative pathogen                         Of the 60 patients, 42 patients (70%) were in-
most likely caused infection (n 5); and pelvic                           fected with MRSA. A comparison of clinical features
abscess (n 2). Overall, the mean ( SD) age was                           between MRSA and methicillin-sensitive S aureus
55.5 15.0 years, and the median APACHE II score                          (MSSA) patients is presented in Table 1. By univar-
was 20 (range, 3 to 41). Most patients were men                          iate analysis, MRSA patients were more likely than
(66.7%), and were predominantly African American                         MSSA patients to have received prior antibiotic
(56.7%) and white (38.3%). An equal number of                            treatment and had a longer median length of stay
patients were admitted to surgery (41.7%) and med-                       prior to the onset of NBSAP. In addition, a signifi-
icine services (41.7%), and 16.7% of the patients                        cant difference existed between the two groups with
were admitted to the burn unit. Twenty-three pa-                         respect to appropriate treatment. In the MSSA
tients (38.3%) underwent surgery 1 month prior                           group, 72.2% of patients received appropriate ther-
to the development of NBSAP. Bilateral infiltrates                       apy within 44.75 h of the onset of infection com-
were evident on chest radiography in 75% of the                          pared with only 50% of patients in the MRSA
patients identified. Most patients were in the ICU at
time of onset of NBSAP (93.3%), and 83.3% of
patients were receiving mechanical ventilation. The
median length of stay prior to the onset of NBSAP
was 9 days (range, 2 to 81 days).
   The origin of the respiratory cultures used for the
microbiological determination of pneumonia came
from aspirated sputum in 90% of the cases, and from
BAL fluid in 10% of cases. Of the 60 patients, 42
patients (70%) were infected with MRSA. Forty-four
patients (73.3%) had concomitant organisms (6 in
blood only, 7 in blood and respiratory cultures, and
31 in respiratory cultures only). The most common
concomitant organisms in the blood were as follows:
Enterococcus spp (five cases); Acinetobacter bau-
mannii (three cases); Streptococcus viridans (two
                                                                         Figure 1. IRM grouped by APACHE II score. APACHE II
cases); Klebsiella pneumoniae (one case); Streptococ-                    scores grouped in values of 10. Dotted line represented linear
cus pneumoniae (one case); and one cogulase-nega-                        regression line.

www.chestjournal.org                                                                          CHEST / 128 / 3 / SEPTEMBER, 2005   1417

               Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                                    © 2005 American College of Chest Physicians
Table 1—Characteristics of MSSA vs MRSA                      median length of time needed to switch to optimal
                    Pneumonia                                       therapy for the eight patients who had been empir-
                                 MSSA         MRSA                  ically treated with vancomycin was 71.5 h (range, 16
       Characteristics          (n 18)       (n 42)       p Value   to 123 h). Of the 42 MRSA patients, 24 (57.1%)
Age, yr                       55.2 17.6     58.4 13.9       0.45
                                                                    received empiric vancomycin treatment, 8 (19.0%)
APACHE II score               20.5 (5–41)   20.0 (3–36)     0.72    received -lactam agents, 6 (14.3%) received clinda-
Charlson index score           2 (0–6)       2 (0–7)        0.53    mycin, 3 (7.1%) received trimethoprim/sulfamethox-
Diabetes                       3 (16.7)     15 (35.7)       0.14    azole, 1 was started on therapy with levofloxacin; and
Decubitus ulcers               0             7 (16.7)       0.09    1 patient died before receiving appropriate antibiotic
Prior antibiotics              3 (16.7)     30 (71.4)       0.01
Vent at NBSAP onset           13 (72.2)     37 (88.1)       0.13
                                                                    treatment. Once susceptibility data were available,
LOS prior to NBSAP onset, d    4 (2–31)     11.5 (4–81)     0.03    40 patients (95.2%) received vancomycin for primary
ICU LOS prior to NBSAP         3 (0–31)      9 (0–58)       0.059   antimicrobial treatment of pneumonia. Two patients
   onset, d                                                         were never appropriately treated with antibiotics.
Time to adequate therapy, h   24 (8–51)     44 (1–149)      0.013   Nine patients (50.0%) in the MSSA subgroup were
*Values given as mean SD, No. of patients (%), or median (range),   treated with combination therapy compared with
 unless otherwise indicated. LOS length of stay; Vent receiving     seven patients (16.7%) in the MRSA subgroup. The
 mechanical ventilation.
                                                                    median duration of combination therapy was 3 days
                                                                    in both groups (MSSA group range, 1 to 10 days;
                                                                    MRSA group range, 1 to 8 days). Eleven vancomycin
subgroup (p 0.01) [Fig 2]. Furthermore, MSSA                        trough levels were collected in a total of nine patients
pneumonia patients received appropriate treatment                   with a median value of 17.4 g/mL (range, 9.2 to
in significantly less time than did MRSA pneumonia                  26.7 g/mL).
patients (24 h [range, 8 to 51 h] vs 44 h [range, 1 to                 The comparison values of hospital mortality, IRM,
149 h], respectively; p 0.013). No difference was                   and IR-LOS between MSSA and MRSA patients are
detected in the duration of therapy between the two                 displayed in Figure 3. No significant differences in
groups (MSSA group, 10 days [range, 2.5 to 25.0                     these primary end points were observed between the
days]; MRSA group, 11 days [range, 1.0 to 21.5                      groups. Similarly, no significant differences in hos-
days]).                                                             pital mortality, IRM, and IR-LOS were noted for the
   Of the 18 MSSA patients, 8 patients (44.4%) were                 different empiric antibiotic regimens, stratified by
empirically treated with vancomycin, 7 patients                     methicillin susceptibility. Multivariate analyses were
(38.9%) were empirically treated with a -lactam, 1                  performed, and the associations between methicillin
patient was empirically treated with clindamycin, 1                 susceptibility and outcomes were identical to those
patient was empirically treated with levofloxacin, and              from the univariate analyses.
1 patient died prior to identification of the causative                IRM was higher in the empiric vancomycin group
organism and subsequent appropriate antibiotic                      than in the empiric -lactam group; however, this
therapy. Once sensitivity reports were obtained,                    was not statistically significant. For the 18 patients
77.8% of the MSSA patients received a -lactam                       infected with MSSA, the hospital mortality and IRM
agent as the primary antimicrobial treatment. The                   rates in the patients receiving empiric -lactams
                                                                    were 57.1% and 28.6%, respectively, compared with
                                                                    62.5% and 50.0%, respectively, in the empiric van-
                                                                    comycin group. For the 42 patients infected with
                                                                    MRSA, the hospital mortality and IRM rates in
                                                                    patients receiving empiric vancomycin were 50.0%
                                                                    and 45.8%, respectively, compared with 62.5% and
                                                                    25.0%, respectively, in the empiric -lactam group.
                                                                    These findings, however, were not statistically signif-
                                                                    icant, and an additional evaluation of this subset
                                                                    revealed that patients who had been empirically
                                                                    treated with -lactams tended to be younger (me-
                                                                    dian age, 52 vs 56 years, respectively) and to have
                                                                    lower APACHE II scores (median, 17 vs 21, respec-
                                                                    tively).
                                                                       Overall clinical success was achieved in 59.5% of
                                                                    MRSA patients compared with 50.0% of MSSA
Figure 2. Receipt of adequate treatment within the 44.75-h          patients. No differences in clinical or microbiological
breakpoint established for S aureus bacteremia.                     success were determined at days 3, 7, or 10, or at the

1418                                                                                                       Clinical Investigations

              Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                                   © 2005 American College of Chest Physicians
Figure 3. Outcomes of NBSAP based on MSSA vs MRSA pneumonia.




end of antimicrobial therapy for any treatment reg-            no significant difference in the rate of response was
imen, stratified by methicillin susceptibility. Simi-          seen at days 3, 7, and 10, and at the end of
larly, because 83.3% of patients were receiving me-            antimicrobial therapy or the first day to clinical
chanical ventilation at the time of onset, no                  improvement (5 days [range, 2 to 14 days] vs 5 days
difference in clinical response was observed in this           [range, 2 to 11 days], respectively). In the CART
VAP subset of patients compared with the whole                 analysis that was performed to identify a specific
cohort. Of note, the overall clinical cure rate in             “time to therapy” for the bacteremic S aureus pneu-
patients receiving vancomycin was 56.3%; 58.3% in              monia cohort, no additional time breakpoint in ap-
the subset of MRSA patients.                                   propriate antibiotic treatment was found that pro-
                                                               duced an increased probability of IRM.
Outcomes in Delayed vs Early Appropriate                          The evaluation of the appropriateness of therapy
Therapy                                                        for concomitant pathogens was also assessed. Alter-
                                                               native pathogens were appropriately treated 85% of
   Five patients were excluded in the appropriate              the time based on the susceptibility profile. The
therapy analyses secondary to death within 72 h of             clinical success was 59.5% for patients treated ap-
the onset of infection. Of the remaining 55 patients,          propriately for both NBSAP and the alternative
24 patients (43.6%) did not receive appropriate                pathogen. This result was similar to the clinical
antibiotic treatment within 44.75 h of the onset of            success rate observed for the entire cohort (56.7%).
infection, and 31 patients (56.4%) received appro-                Complete, infection-related cost data were avail-
priate antibiotic treatment within 44.75 h of the              able for 22 of the 60 patients. The greatest reason for
onset of infection. There were no significant differ-          increased cost was length of hospitalization. In the
ences between the two groups (delayed vs early) with           patients who lived, the median total cost was $35,072
respect to the APACHE II score at time of admission            (range, $19,764 to $312,511) compared with $22,098
to the ICU (20.5 [range, 5 to 41] vs 18 [range, 4 to           (range, $1,218 to $66,351) in the patients who died.
40], respectively; p 0.6) and Charlson comorbidity             No differences in cost were evident in patients based
index score (2 [range, 0 to 6] vs 2 [range, 0 to 6],           on methicillin susceptibility or early empiric treat-
respectively; p 0.9). The median time to the start             ment.
of appropriate treatment was 68.5 h (range, 45 to
149 h) in the delayed-treatment group and 25 h
(range, 4 to 44 h) in the early-treatment group. Only                              Discussion
16 patients received appropriate antibiotic treatment
within 24 h of the onset of infection                            The previous literature specifically focusing on S
   No differences existed with respect to the primary          aureus nosocomial pneumonia is limited. Our review
outcomes based on the receipt of delayed vs early              of 60 patients is one of the largest reports of a
appropriate antibiotic therapy (Fig 4). In addition,           real-world experience describing the outcomes of

www.chestjournal.org                                                             CHEST / 128 / 3 / SEPTEMBER, 2005   1419

               Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                                    © 2005 American College of Chest Physicians
Figure 4. Outcomes of NBSAP based on early vs delayed treatment.




bacteremic staphylococcal pneumonia. The distribu-            pneumonia patients. In the 55 patients with bacteri-
tion of pathogens responsible for nosocomial pneu-            ologically evaluable S aureus pneumonia, the overall
monia differs depending on factors such as the                clinical success rate in vancomycin-treated patients
length of hospital admission before onset of the              was 50.9% compared with 44.4% in the 18 patients
disease, admission to the ICU, and duration of                infected with MRSA. Stevens et al14 specifically
mechanical ventilation.25 S aureus pneumonia typi-            evaluated therapy with linezolid vs therapy with
cally develops in patients who have had a longer              vancomycin for the treatment of MRSA infections.
length of hospital stay before onset of disease, have         Data from 29 patients with MRSA pneumonia re-
received mechanical ventilation for       5 days (ie,         vealed that a clinical cure was achieved in 75.0% of
late-onset VAP), and have been exposed to previous            patients treated with either agent. In a study analyz-
antimicrobial therapy. A prediction model26 has               ing data from two previous double-blind studies of
been developed to determine which characteristics             patients with S aureus nosocomial pneumonia, Wun-
predict for the development of MRSA in patients               derink et al15 found that there was no difference in
with S aureus bacteremia. The greatest risk factor            clinical cure between the use of linezolid and van-
was previous antibiotic exposure with an odds ratio           comycin among all of the S aureus nosocomial
of 9.2 (95% confidence interval, 4.8 to 17.9). Rello          pneumonia patients (51.5% vs 43.4%, respectively;
and Diaz3 also found previous antimicrobial therapy           p 0.182). However, in the subset of 133 MRSA
to be a risk factor for MRSA pneumonia as well. Our           nosocomial pneumonia patients, a significant differ-
findings for this cohort of 60 patients concur with           ence was found (59% vs 35.5%, respectively;
this description. The median length of hospital stay          p 0.009). Kollef et al16 examined clinical cures in
before the first positive culture finding was 9 days.         patients who specifically had VAP and found signif-
Most of our patients (93.3%) were in the ICU                  icant differences in favor of the empiric use of
receiving mechanical ventilation (83.3%) at the onset         linezolid over vancomycin in both the S aureus VAP
of disease, and 55% of patients received antibiotic           group (48.9% vs 35.2%, respectively; p 0.06) and
therapy prior to the onset of pneumonia. Further-             the MRSA VAP group (62.2% vs 21.2%, respectively;
more, 71.4% of patients who developed MRSA                    p 0.001). Our findings were similar to these re-
pneumonia had received previous antibiotic therapy            ported values. Overall clinical success was achieved
within 30 days prior to the onset of nosocomial               in 56.7% of all patients and in 59.5% of the subset of
pneumonia. This was significantly different from the          MRSA patients compared with 50.0% of the subset
16.7% of MSSA pneumonia patients (p 0.01).                    of MSSA patients. Highlighting the empiric use of
   Clinical success has been reported in S aureus             vancomycin, the overall clinical success rate was
nosocomial pneumonia in a number of trials, mostly            56.3%, with 58.3% cure rates in the MRSA patient
comparing vancomycin with the newer agents quinu-             population. Among patients with MRSA, the IRM
pristin/dalfopristin and linezolid. Fagon et al27 com-        rate was higher in patients receiving empiric vanco-
pared the efficacy of therapy with quinupristin/              mycin (45.8%) compared with that in patients receiv-
dalfopristin and vancomycin in Gram-positive                  ing empiric -lactam agents (25.0%). These findings

1420                                                                                               Clinical Investigations

            Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                                 © 2005 American College of Chest Physicians
were not statistically significant, and an additional          not predict clinical success or decreased mortality.
evaluation of this subset of patients revealed that            Another reason may be in part attributable to the
patients empirically treated with -lactam agents               slow activity or lack of efficacy of vancomycin, such
tended to be younger and to have lower APACHE II               that even the early administration of this agent is
scores, partially explaining this finding. Because             associated with poor clinical outcomes.31,32
    80% of patients were already receiving mechani-               The greatest limitation of our study was the small
cal ventilation at the onset of NBSAP, these percent-          number of patients (n 60) who met our strict
ages did not change after analyzing this subset of             inclusion criteria. The main reason that so few
patients.                                                      patients were available for inclusion over the 5 years
   Patients included in this analysis were critically ill      was the requirement for patients to have concomi-
and had numerous underlying chronic comorbidities,             tant S aureus bacteremia, as well as pneumonia. This
as evidenced by a median APACHE II score of 20
                                                               requirement was essential because of the retrospec-
(range, 3 to 41). Consequently, the mortality rate was
                                                               tive design of our investigation and the high rate of
high in our study, with an associated crude mortality
                                                               tracheal aspirates used as the respiratory source of
rate of 55.5% and an IRM rate of 40.0%. These
values also correlate well with those from previous            this pathogen. We wanted to be confident that the
literature6,7,28 –30 in which the mortality rate attribut-     patients who were involved in this analysis developed
able to S aureus has ranged between 28% and 50%.               bacteremia secondary to nosocomial pneumonia and
The mortality rate among nosocomial acquired bac-              not by hematogenous spread of S aureus, as can
teremic pneumonia patients was found to be 52.5%               occur in other conditions, such as endocarditis,
in a previous study.5                                          which was one of the exclusion criteria.
   The most surprising outcomes from our results                  Additional limitations were inherent to the retro-
were a lack of difference with respect to overall              spective design of the study. Characterizing NBSAP
hospital mortality rate, IRM rate, and IR-LOS based            was difficult, although stringent inclusion criteria
on the receipt of early vs delayed antibiotic therapy.         were used. Many patients who likely had nosocomial
Numerous reports8 –11 have been published stating              S aureus pneumonia were excluded from the analysis
that mortality significantly increases in patients who         because of the lack of a concomitant positive blood
develop pneumonia if empiric antibiotic therapies              culture finding. Also, numerous comorbidities con-
are not started at the time of clinical suspicion,             founded the accurate assessment of IRM. To ac-
before cultures have been collected and sensitivity            count for this, an independent reviewer with no
has been reported. Our lack of ability to detect a             knowledge of the culture and sensitivity data or of
difference may be a product of a small sample size             the choice and timing of antibiotic therapy was
leading to a potential type II error. In a previous            designated to determine the primary outcome based
study12 examining S aureus bacteremia, a delay in              on clinical data recorded throughout the course of
therapy of 44.75 h was found to be associated with             the patient’s hospital stay.
a 3.8 times higher rate of IRM. The 44.75-h break-                In conclusion, this investigation includes one of
point for appropriate therapy, however, was not                the largest collections of patients to have bacteremic
predictive in this series of pneumonia patients. In            nosocomial pneumonia that was specifically attribut-
addition, an additional breakpoint of time to appro-           able to S aureus. S aureus pneumonia developed late
priate therapy was not identified using CART. Some             in the patient’s hospital stay and in ICU patients who
potential reasons for no differences being detected            had previously received mechanical ventilation, and
are the low number of patients (n 60) and the high             was associated with a high crude mortality and IRM
mortality rate (55%) associated with this series. In           rates. No significant differences were detected with
addition, only 16 patients received appropriate anti-          respect to crude mortality, IRM, or IR-LOS between
biotic therapy within 24 h of the onset of infection. It       patients who developed MSSA vs those who devel-
may be difficult to ascertain the impact of delayed            oped MRSA pneumonia or depending on whether
therapy given the high rate of delayed treatment.              the patient had received early vs delayed appropriate
   Of interest, as demonstrated in Figure 1, a linear          antibiotic therapy. The small sample size may have
relationship existed with respect to IRM and increas-          precluded our ability to detect a difference in these
ing APACHE II score. Because of the requirement                groups. Patients who were empirically treated with
of concomitant bacteremia, this subset of pneumonia            vancomycin for MSSA and MRSA pneumonia expe-
patients likely represents those patients who are              rienced a high mortality rate. These findings suggest
most severely ill with rapid disease progression. The          that newer agents with enhanced clinical activity in
severe illness exhibited in these patients may be the          NBSAP are needed and that these should be evalu-
main factor determining mortality and may serve as             ated in a real-world setting, where outcomes of the
the reason why appropriate antibiotic treatment did            sickest patients can be assessed. The group of pa-

www.chestjournal.org                                                             CHEST / 128 / 3 / SEPTEMBER, 2005   1421

               Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                                    © 2005 American College of Chest Physicians
tients who will experience the greatest benefit from                       linezolid with vancomycin. Intensive Care Med 2004; 30:
these newer agents remains to be determined.                               388 –394
                                                                      17   American Thoracic Society. Hospital-acquired pneumonia in
                                                                           adults: diagnosis, assessment of severity, initial antimicrobial
                                                                           therapy, and preventive strategies: a consensus statement;
                        References                                         American Thoracic Society, November 1995. Am J Respir
 1 Hoffken G, Niederman MS. Nosocomial pneumonia: the                      Crit Care Med 1996; 153:1711–1725
   importance of a de-escalating strategy for antibiotic treatment    18   Micek ST, Ward S, Fraser VJ, et al. A randomized controlled
   of pneumonia in the ICU. Chest 2002; 122:2183–2196                      trial of an antibiotic discontinuation policy for clinically
 2 Lynch JP III. Hospital-acquired pneumonia: risk factors,                suspected ventilator-associated pneumonia. Chest 2004; 125:
   microbiology, and treatment. Chest 2001; 119:373S–384S                  1791–1799
 3 Rello J, Diaz E. Pneumonia in the intensive care unit. Crit        19   Rubinstein E, Cammarata S, Oliphant T, et al. Linezolid
   Care Med 2003; 31:2544 –2551                                            (PNU-100766) versus vancomycin in the treatment of hospi-
 4 Gonzalez C, Rubio M, Romero-Vivas J, et al. Bacteremic                  talized patients with nosocomial pneumonia: a randomized,
   pneumonia due to Staphylococcus aureus: a comparison of                 double-blind, multicenter study. Clin Infect Dis 2001; 32:
   disease caused by methicillin-resistant and methicillin-sus-            402– 412
   ceptible organisms. Clin Infect Dis 1999; 29:1171–1177             20   Beck KD, Gastmeier P. Clinical or epidemiologic diagnosis of
 5 Gonzalez C, Rubio M, Romero-Vivas J, et al. Staphylococcus              nosocomial pneumonia: is there any difference? Am J Infect
   aureus bacteremic pneumonia: differences between commu-                 Control 2003; 31:331–335
   nity and nosocomial acquisition. Int J Infect Dis 2003;            21   Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for
   7:102–108                                                               nosocomial infections, 1988. Am J Infect Control 1988;
 6 Rello J, Torres A, Ricart M, et al. Ventilator-associated               16:128 –140
   pneumonia by Staphylococcus aureus: comparison of methi-           22   Charlson ME, Pompei P, Ales KL, et al. A new method of
   cillin-resistant and methicillin-sensitive episodes. Am J Respir        classifying prognostic comorbidity in longitudinal studies:
   Crit Care Med 1994; 150:1545–1549                                       development and validation. J Chronic Dis 1987; 40:373–383
 7 Combes A, Luyt CE, Fagon JY, et al. Impact of methicillin          23   Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a
   resistance on outcome of Staphylococcus aureus ventilator-              severity of disease classification system. Crit Care Med 1985;
   associated pneumonia. Am J Respir Crit Care Med 2004;                   13:818 – 829
   170:786 –792                                                       24   National Committee for Clinical Laboratory Standards.
 8 Luna CM, Vujacich P, Niederman MS, et al. Impact of BAL                 Methods for dilution antimicrobial susceptibility tests for
   data on the therapy and outcome of ventilator-associated                bacteria that grow aerobically: approved standard M7–A6.
   pneumonia. Chest 1997; 111:676 – 685                                    Wayne, PA: National Committee for Clinical Laboratory
 9 Rello J, Gallego M, Mariscal D, et al. The value of routine             Standards, 2004
   microbial investigation in ventilator-associated pneumonia.        25   Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J
   Am J Respir Crit Care Med 1997; 156:196 –200                            Respir Crit Care Med 2002; 165:867–903
10 Kollef MH, Ward S. The influence of mini-BAL cultures on           26   Lodise TP Jr, McKinnon PS, Rybak M. Prediction model to
   patient outcomes: implications for the antibiotic management            identify patients with Staphylococcus aureus bacteremia at
   of ventilator-associated pneumonia. Chest 1998; 113:412– 420            risk for methicillin resistance. Infect Control Hosp Epidemiol
11 Alvarez-Lerma F. Modification of empiric antibiotic treat-              2003; 24:655– 661
   ment in patients with pneumonia acquired in the intensive          27   Fagon J, Patrick H, Haas DW, et al. Treatment of Gram-
   care unit: ICU-Acquired Pneumonia Study Group. Intensive                positive nosocomial pneumonia: prospective randomized
   Care Med 1996; 22:387–394                                               comparison of quinupristin/dalfopristin versus vancomycin;
12 Lodise TP, McKinnon PS, Swiderski L, et al. Outcomes                    Nosocomial Pneumonia Group. Am J Respir Crit Care Med
   analysis of delayed antibiotic treatment for hospital-acquired          2000; 161:753–762
   Staphylococcus aureus bacteremia. Clin Infect Dis 2003;            28   Kaye MG, Fox MJ, Bartlett JG, et al. The clinical spectrum of
   36:1418 –1423                                                           Staphylococcus aureus pulmonary infection. Chest 1990;
13 Sandiumenge A, Diaz E, Bodi M, et al. Therapy of ventilator-            97:788 –792
   associated pneumonia: a patient-based approach based on the        29   Musher DM, Lamm N, Darouiche RO, et al. The current
   ten rules of “The Tarragona Strategy.” Intensive Care Med               spectrum of Staphylococcus aureus infection in a tertiary care
   2003; 29:876 – 883                                                      hospital. Medicine (Baltimore) 1994; 73:186 –208
14 Stevens DL, Herr D, Lampiris H, et al. Linezolid versus            30   Iwahara T, Ichiyama S, Nada T, et al. Clinical and epidemi-
   vancomycin for the treatment of methicillin-resistant Staph-            ologic investigations of nosocomial pulmonary infections
   ylococcus aureus infections. Clin Infect Dis 2002; 34:1481–             caused by methicillin-resistant Staphylococcus aureus. Chest
   1490                                                                    1994; 105:826 – 831
15 Wunderink RG, Rello J, Cammarata SK, et al. Linezolid vs           31   Levine DP, Fromm BS, Reddy BR. Slow response to vanco-
   vancomycin: analysis of two double-blind studies of patients            mycin or vancomycin plus rifampin in methicillin-resistant
   with methicillin-resistant Staphylococcus aureus nosocomial             Staphylococcus aureus endocarditis. Ann Intern Med 1991;
   pneumonia. Chest 2003; 124:1789 –1797                                   115:674 – 680
16 Kollef MH, Rello J, Cammarata SK, et al. Clinical cure and         32   Small PM, Chambers HF. Vancomycin for Staphylococcus
   survival in Gram-positive ventilator-associated pneumonia:              aureus endocarditis in intravenous drug users. Antimicrob
   retrospective analysis of two double-blind studies comparing            Agents Chemother 1990; 34:1227–1231




1422                                                                                                                  Clinical Investigations

               Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                                    © 2005 American College of Chest Physicians
Epidemiology, Treatment, and Outcomes of Nosocomial Bacteremic
                 Staphylococcus aureus Pneumonia*
 C. Andrew DeRyke, Thomas P. Lodise, Jr., Michael J. Rybak and Peggy S.
                             McKinnon
                     Chest 2005;128; 1414-1422
                    DOI 10.1378/chest.128.3.1414
                 This information is current as of April 17, 2011
Updated Information & Services
Updated Information and services can be found at:
http://chestjournal.chestpubs.org/content/128/3/1414.full.html
References
This article cites 31 articles, 17 of which can be accessed free at:
http://chestjournal.chestpubs.org/content/128/3/1414.full.html#ref-list-1
Cited Bys
This article has been cited by 4 HighWire-hosted articles:
http://chestjournal.chestpubs.org/content/128/3/1414.full.html#related-urls
Permissions & Licensing
Information about reproducing this article in parts (figures, tables) or in its entirety can be
found online at:
http://www.chestpubs.org/site/misc/reprints.xhtml
Reprints
Information about ordering reprints can be found online:
http://www.chestpubs.org/site/misc/reprints.xhtml
Citation Alerts
Receive free e-mail alerts when new articles cite this article. To sign up, select the
"Services" link to the right of the online article.
Images in PowerPoint format
Figures that appear in CHEST articles can be downloaded for teaching purposes in
PowerPoint slide format. See any online figure for directions.




    Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011
                         © 2005 American College of Chest Physicians

Weitere ähnliche Inhalte

Was ist angesagt?

CAP 2010 Guidelines
CAP 2010 GuidelinesCAP 2010 Guidelines
CAP 2010 Guidelinescap_0009
 
Approach to fever in the transplant patient
Approach to fever in the transplant patientApproach to fever in the transplant patient
Approach to fever in the transplant patientFarooq Khan
 
Role of ct chest in covid management
Role of ct chest in covid managementRole of ct chest in covid management
Role of ct chest in covid managementDrVeereshDhanni
 
Severe Community Acquired Pneumonia (SCAP)
Severe Community Acquired Pneumonia (SCAP)Severe Community Acquired Pneumonia (SCAP)
Severe Community Acquired Pneumonia (SCAP)Apollo Hospitals
 
COMMUNITY AQUIRED PNEUMONIA
COMMUNITY AQUIRED PNEUMONIACOMMUNITY AQUIRED PNEUMONIA
COMMUNITY AQUIRED PNEUMONIAmauryaramgopal
 
Clinical features of patients infected with 2019 novel copy
Clinical features of patients infected with 2019 novel   copyClinical features of patients infected with 2019 novel   copy
Clinical features of patients infected with 2019 novel copyMadhumitaSingh23
 
Cytokines and T-Lymphocyte count in patients in the acute and chronic phases ...
Cytokines and T-Lymphocyte count in patients in the acute and chronic phases ...Cytokines and T-Lymphocyte count in patients in the acute and chronic phases ...
Cytokines and T-Lymphocyte count in patients in the acute and chronic phases ...Dr. Juan Rodriguez-Tafur
 
CV of Professor Gamal Agmy June 2016
CV of Professor Gamal Agmy June 2016CV of Professor Gamal Agmy June 2016
CV of Professor Gamal Agmy June 2016Gamal Agmy
 
A review of the covid 19 pandemic and the role of medical laboratory scientis...
A review of the covid 19 pandemic and the role of medical laboratory scientis...A review of the covid 19 pandemic and the role of medical laboratory scientis...
A review of the covid 19 pandemic and the role of medical laboratory scientis...ArchanDomReyes
 
A novel coronavirus from patients with pneumonia in china, 2019
A novel coronavirus from patients with pneumonia in china, 2019A novel coronavirus from patients with pneumonia in china, 2019
A novel coronavirus from patients with pneumonia in china, 2019MANUELPERALTA33
 
Radiological Presentation of COVID 19
Radiological Presentation of COVID 19Radiological Presentation of COVID 19
Radiological Presentation of COVID 19Gamal Agmy
 
Opportunistic infections in covid 19
Opportunistic infections in covid 19Opportunistic infections in covid 19
Opportunistic infections in covid 19Neha Sharma
 
Mers co v - journal reading
Mers co v - journal readingMers co v - journal reading
Mers co v - journal readingSoroy Lardo
 
nosocomial pneumonia
nosocomial pneumonianosocomial pneumonia
nosocomial pneumoniashabeel pn
 
Bedside to Bench: How Clinical Imaging of Patients with COVID-19 is Informing...
Bedside to Bench: How Clinical Imaging of Patients with COVID-19 is Informing...Bedside to Bench: How Clinical Imaging of Patients with COVID-19 is Informing...
Bedside to Bench: How Clinical Imaging of Patients with COVID-19 is Informing...Scintica Instrumentation
 
Ventilator associated pneumonia
Ventilator associated pneumoniaVentilator associated pneumonia
Ventilator associated pneumoniaBeena Philip
 
Ct scans can determine severity of coronavirus
Ct scans can determine severity of coronavirusCt scans can determine severity of coronavirus
Ct scans can determine severity of coronavirusAtlantis Worldwide LLC
 
Coronavirus infectious disease, MERS, SARS
Coronavirus infectious disease, MERS, SARSCoronavirus infectious disease, MERS, SARS
Coronavirus infectious disease, MERS, SARSBibhash Kumar
 

Was ist angesagt? (20)

CAP 2010 Guidelines
CAP 2010 GuidelinesCAP 2010 Guidelines
CAP 2010 Guidelines
 
Approach to fever in the transplant patient
Approach to fever in the transplant patientApproach to fever in the transplant patient
Approach to fever in the transplant patient
 
Role of ct chest in covid management
Role of ct chest in covid managementRole of ct chest in covid management
Role of ct chest in covid management
 
Severe Community Acquired Pneumonia (SCAP)
Severe Community Acquired Pneumonia (SCAP)Severe Community Acquired Pneumonia (SCAP)
Severe Community Acquired Pneumonia (SCAP)
 
COMMUNITY AQUIRED PNEUMONIA
COMMUNITY AQUIRED PNEUMONIACOMMUNITY AQUIRED PNEUMONIA
COMMUNITY AQUIRED PNEUMONIA
 
Clinical features of patients infected with 2019 novel copy
Clinical features of patients infected with 2019 novel   copyClinical features of patients infected with 2019 novel   copy
Clinical features of patients infected with 2019 novel copy
 
Cytokines and T-Lymphocyte count in patients in the acute and chronic phases ...
Cytokines and T-Lymphocyte count in patients in the acute and chronic phases ...Cytokines and T-Lymphocyte count in patients in the acute and chronic phases ...
Cytokines and T-Lymphocyte count in patients in the acute and chronic phases ...
 
CV of Professor Gamal Agmy June 2016
CV of Professor Gamal Agmy June 2016CV of Professor Gamal Agmy June 2016
CV of Professor Gamal Agmy June 2016
 
A review of the covid 19 pandemic and the role of medical laboratory scientis...
A review of the covid 19 pandemic and the role of medical laboratory scientis...A review of the covid 19 pandemic and the role of medical laboratory scientis...
A review of the covid 19 pandemic and the role of medical laboratory scientis...
 
A novel coronavirus from patients with pneumonia in china, 2019
A novel coronavirus from patients with pneumonia in china, 2019A novel coronavirus from patients with pneumonia in china, 2019
A novel coronavirus from patients with pneumonia in china, 2019
 
Radiological Presentation of COVID 19
Radiological Presentation of COVID 19Radiological Presentation of COVID 19
Radiological Presentation of COVID 19
 
Opportunistic infections in covid 19
Opportunistic infections in covid 19Opportunistic infections in covid 19
Opportunistic infections in covid 19
 
Mers co v - journal reading
Mers co v - journal readingMers co v - journal reading
Mers co v - journal reading
 
nosocomial pneumonia
nosocomial pneumonianosocomial pneumonia
nosocomial pneumonia
 
Bedside to Bench: How Clinical Imaging of Patients with COVID-19 is Informing...
Bedside to Bench: How Clinical Imaging of Patients with COVID-19 is Informing...Bedside to Bench: How Clinical Imaging of Patients with COVID-19 is Informing...
Bedside to Bench: How Clinical Imaging of Patients with COVID-19 is Informing...
 
CAP
CAPCAP
CAP
 
Ventilator associated pneumonia
Ventilator associated pneumoniaVentilator associated pneumonia
Ventilator associated pneumonia
 
Ct scans can determine severity of coronavirus
Ct scans can determine severity of coronavirusCt scans can determine severity of coronavirus
Ct scans can determine severity of coronavirus
 
NEUMONIA ASOCIADA AL VENTILADOR GUIA IDSA 2016
NEUMONIA ASOCIADA AL VENTILADOR GUIA IDSA 2016NEUMONIA ASOCIADA AL VENTILADOR GUIA IDSA 2016
NEUMONIA ASOCIADA AL VENTILADOR GUIA IDSA 2016
 
Coronavirus infectious disease, MERS, SARS
Coronavirus infectious disease, MERS, SARSCoronavirus infectious disease, MERS, SARS
Coronavirus infectious disease, MERS, SARS
 

Ähnlich wie Epidemiology treatment and_outcomes_of_sa_nosocomial_pneumonia_chest_2005-1

Repeated Hemoptysis with Progressive Bronchiectasis: a case report of Lady Wi...
Repeated Hemoptysis with Progressive Bronchiectasis: a case report of Lady Wi...Repeated Hemoptysis with Progressive Bronchiectasis: a case report of Lady Wi...
Repeated Hemoptysis with Progressive Bronchiectasis: a case report of Lady Wi...komalicarol
 
Annals of Clinical and Medical Case Reports - Acmcasereport
Annals of Clinical and Medical Case Reports - AcmcasereportAnnals of Clinical and Medical Case Reports - Acmcasereport
Annals of Clinical and Medical Case Reports - Acmcasereportsemualkaira
 
ventilator-associated pneumonia.ppt
ventilator-associated pneumonia.pptventilator-associated pneumonia.ppt
ventilator-associated pneumonia.pptssuser0622881
 
( Journal Club ) Procalcitonin as a diagnostic biomarker of sepsis: A tertiar...
( Journal Club ) Procalcitonin as a diagnostic biomarker of sepsis: A tertiar...( Journal Club ) Procalcitonin as a diagnostic biomarker of sepsis: A tertiar...
( Journal Club ) Procalcitonin as a diagnostic biomarker of sepsis: A tertiar...Abdullatif Al-Rashed
 
Characteristic and outcomes of patients with ptb requiring icu care
Characteristic and outcomes of patients with ptb requiring icu careCharacteristic and outcomes of patients with ptb requiring icu care
Characteristic and outcomes of patients with ptb requiring icu careEArl Copina
 
Covid 19 convalescent plasma therapy
Covid 19 convalescent plasma therapyCovid 19 convalescent plasma therapy
Covid 19 convalescent plasma therapySumit Kumar
 
Sepsis newer aspects
Sepsis newer aspectsSepsis newer aspects
Sepsis newer aspectsAbdul Sathar
 
Case Study Of Pneumonia And Chronic Pulmonary Disease
Case Study Of Pneumonia And Chronic Pulmonary DiseaseCase Study Of Pneumonia And Chronic Pulmonary Disease
Case Study Of Pneumonia And Chronic Pulmonary DiseaseEvelyn Donaldson
 
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...YogeshIJTSRD
 
Neumonia Adquirida en la Comunidad
Neumonia Adquirida en la ComunidadNeumonia Adquirida en la Comunidad
Neumonia Adquirida en la ComunidadVictor Grau Cuba
 
Update management of CAP
Update management of CAPUpdate management of CAP
Update management of CAPSaher Farghly
 
Arterial CO2 Tension on Admission as a marker of in-hospital mortality
Arterial CO2 Tension on Admission as a marker of in-hospital mortality Arterial CO2 Tension on Admission as a marker of in-hospital mortality
Arterial CO2 Tension on Admission as a marker of in-hospital mortality GerardJamero1
 
jcm-08-00698-v2.pdf
jcm-08-00698-v2.pdfjcm-08-00698-v2.pdf
jcm-08-00698-v2.pdfTonyNouh
 
BMJ Open-2016-Conway Morris--2
BMJ Open-2016-Conway Morris--2BMJ Open-2016-Conway Morris--2
BMJ Open-2016-Conway Morris--2Tracey Mare
 
pediatric Pneumonia.pptx
pediatric Pneumonia.pptxpediatric Pneumonia.pptx
pediatric Pneumonia.pptxSayed Ahmed
 
Management Of Community Acquired Pneumonia
Management  Of Community Acquired PneumoniaManagement  Of Community Acquired Pneumonia
Management Of Community Acquired PneumoniaAshraf ElAdawy
 

Ähnlich wie Epidemiology treatment and_outcomes_of_sa_nosocomial_pneumonia_chest_2005-1 (20)

Repeated Hemoptysis with Progressive Bronchiectasis: a case report of Lady Wi...
Repeated Hemoptysis with Progressive Bronchiectasis: a case report of Lady Wi...Repeated Hemoptysis with Progressive Bronchiectasis: a case report of Lady Wi...
Repeated Hemoptysis with Progressive Bronchiectasis: a case report of Lady Wi...
 
Annals of Clinical and Medical Case Reports - Acmcasereport
Annals of Clinical and Medical Case Reports - AcmcasereportAnnals of Clinical and Medical Case Reports - Acmcasereport
Annals of Clinical and Medical Case Reports - Acmcasereport
 
ventilator-associated pneumonia.ppt
ventilator-associated pneumonia.pptventilator-associated pneumonia.ppt
ventilator-associated pneumonia.ppt
 
( Journal Club ) Procalcitonin as a diagnostic biomarker of sepsis: A tertiar...
( Journal Club ) Procalcitonin as a diagnostic biomarker of sepsis: A tertiar...( Journal Club ) Procalcitonin as a diagnostic biomarker of sepsis: A tertiar...
( Journal Club ) Procalcitonin as a diagnostic biomarker of sepsis: A tertiar...
 
Infectious diseases
Infectious diseasesInfectious diseases
Infectious diseases
 
BCMJ_52Vol6_tularemia
BCMJ_52Vol6_tularemiaBCMJ_52Vol6_tularemia
BCMJ_52Vol6_tularemia
 
Characteristic and outcomes of patients with ptb requiring icu care
Characteristic and outcomes of patients with ptb requiring icu careCharacteristic and outcomes of patients with ptb requiring icu care
Characteristic and outcomes of patients with ptb requiring icu care
 
Covid 19 convalescent plasma therapy
Covid 19 convalescent plasma therapyCovid 19 convalescent plasma therapy
Covid 19 convalescent plasma therapy
 
Sepsis newer aspects
Sepsis newer aspectsSepsis newer aspects
Sepsis newer aspects
 
Case Study Of Pneumonia And Chronic Pulmonary Disease
Case Study Of Pneumonia And Chronic Pulmonary DiseaseCase Study Of Pneumonia And Chronic Pulmonary Disease
Case Study Of Pneumonia And Chronic Pulmonary Disease
 
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...
 
Neumonia Adquirida en la Comunidad
Neumonia Adquirida en la ComunidadNeumonia Adquirida en la Comunidad
Neumonia Adquirida en la Comunidad
 
Update management of CAP
Update management of CAPUpdate management of CAP
Update management of CAP
 
Arterial CO2 Tension on Admission as a marker of in-hospital mortality
Arterial CO2 Tension on Admission as a marker of in-hospital mortality Arterial CO2 Tension on Admission as a marker of in-hospital mortality
Arterial CO2 Tension on Admission as a marker of in-hospital mortality
 
Pneumonia without..
Pneumonia without..Pneumonia without..
Pneumonia without..
 
jcm-08-00698-v2.pdf
jcm-08-00698-v2.pdfjcm-08-00698-v2.pdf
jcm-08-00698-v2.pdf
 
BMJ Open-2016-Conway Morris--2
BMJ Open-2016-Conway Morris--2BMJ Open-2016-Conway Morris--2
BMJ Open-2016-Conway Morris--2
 
pediatric Pneumonia.pptx
pediatric Pneumonia.pptxpediatric Pneumonia.pptx
pediatric Pneumonia.pptx
 
Nosocomial infections
Nosocomial infectionsNosocomial infections
Nosocomial infections
 
Management Of Community Acquired Pneumonia
Management  Of Community Acquired PneumoniaManagement  Of Community Acquired Pneumonia
Management Of Community Acquired Pneumonia
 

Mehr von Christian Wilhelm

Taquicardias de complejo «qrs» estrecho
Taquicardias de complejo «qrs» estrechoTaquicardias de complejo «qrs» estrecho
Taquicardias de complejo «qrs» estrechoChristian Wilhelm
 
Cuando iniciar tratamiento arv
Cuando iniciar tratamiento arvCuando iniciar tratamiento arv
Cuando iniciar tratamiento arvChristian Wilhelm
 
Treatment of hospital acquired, ventilator-associated, and healthcare-associa...
Treatment of hospital acquired, ventilator-associated, and healthcare-associa...Treatment of hospital acquired, ventilator-associated, and healthcare-associa...
Treatment of hospital acquired, ventilator-associated, and healthcare-associa...Christian Wilhelm
 
Clinical presentation and diagnosis of ventilator associated pneumonia
Clinical presentation and diagnosis of ventilator associated pneumoniaClinical presentation and diagnosis of ventilator associated pneumonia
Clinical presentation and diagnosis of ventilator associated pneumoniaChristian Wilhelm
 
Insuficiencia renal crónica
Insuficiencia renal crónicaInsuficiencia renal crónica
Insuficiencia renal crónicaChristian Wilhelm
 
Neumonía asociada a ventilación mecánica
Neumonía asociada a ventilación mecánicaNeumonía asociada a ventilación mecánica
Neumonía asociada a ventilación mecánicaChristian Wilhelm
 
Complicaciones diabetes mellitus
Complicaciones diabetes mellitusComplicaciones diabetes mellitus
Complicaciones diabetes mellitusChristian Wilhelm
 
Cap07 Las Causas De Muerte SúBita En Atletas. DiagnóStico Y PrevencióN
Cap07   Las Causas De Muerte SúBita En Atletas. DiagnóStico Y PrevencióNCap07   Las Causas De Muerte SúBita En Atletas. DiagnóStico Y PrevencióN
Cap07 Las Causas De Muerte SúBita En Atletas. DiagnóStico Y PrevencióNChristian Wilhelm
 

Mehr von Christian Wilhelm (20)

Reumatología y ejercicio
Reumatología y ejercicioReumatología y ejercicio
Reumatología y ejercicio
 
Tratamiento antiretroviral
Tratamiento antiretroviralTratamiento antiretroviral
Tratamiento antiretroviral
 
Taquicardias de complejo «qrs» estrecho
Taquicardias de complejo «qrs» estrechoTaquicardias de complejo «qrs» estrecho
Taquicardias de complejo «qrs» estrecho
 
Obesidad
ObesidadObesidad
Obesidad
 
Cuando iniciar tratamiento arv
Cuando iniciar tratamiento arvCuando iniciar tratamiento arv
Cuando iniciar tratamiento arv
 
Hiv, Cancer y cardiología
Hiv, Cancer  y cardiologíaHiv, Cancer  y cardiología
Hiv, Cancer y cardiología
 
Treatment of hospital acquired, ventilator-associated, and healthcare-associa...
Treatment of hospital acquired, ventilator-associated, and healthcare-associa...Treatment of hospital acquired, ventilator-associated, and healthcare-associa...
Treatment of hospital acquired, ventilator-associated, and healthcare-associa...
 
Clinical presentation and diagnosis of ventilator associated pneumonia
Clinical presentation and diagnosis of ventilator associated pneumoniaClinical presentation and diagnosis of ventilator associated pneumonia
Clinical presentation and diagnosis of ventilator associated pneumonia
 
Insuficiencia renal crónica
Insuficiencia renal crónicaInsuficiencia renal crónica
Insuficiencia renal crónica
 
Esquizofrenia
EsquizofreniaEsquizofrenia
Esquizofrenia
 
Neumonía asociada a ventilación mecánica
Neumonía asociada a ventilación mecánicaNeumonía asociada a ventilación mecánica
Neumonía asociada a ventilación mecánica
 
Tuberculosis
TuberculosisTuberculosis
Tuberculosis
 
ECV Hemorrágico
ECV HemorrágicoECV Hemorrágico
ECV Hemorrágico
 
Olmesartan
OlmesartanOlmesartan
Olmesartan
 
Complicaciones diabetes mellitus
Complicaciones diabetes mellitusComplicaciones diabetes mellitus
Complicaciones diabetes mellitus
 
Cap07 Las Causas De Muerte SúBita En Atletas. DiagnóStico Y PrevencióN
Cap07   Las Causas De Muerte SúBita En Atletas. DiagnóStico Y PrevencióNCap07   Las Causas De Muerte SúBita En Atletas. DiagnóStico Y PrevencióN
Cap07 Las Causas De Muerte SúBita En Atletas. DiagnóStico Y PrevencióN
 
Nuevas Perspectivas
Nuevas PerspectivasNuevas Perspectivas
Nuevas Perspectivas
 
Aliskiren And Valsartan
Aliskiren And ValsartanAliskiren And Valsartan
Aliskiren And Valsartan
 
Beta Bloqueadores Vrs Ieca
Beta Bloqueadores Vrs IecaBeta Bloqueadores Vrs Ieca
Beta Bloqueadores Vrs Ieca
 
Nuevas Perspectivas
Nuevas PerspectivasNuevas Perspectivas
Nuevas Perspectivas
 

Kürzlich hochgeladen

ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptxWINCY THIRUMURUGAN
 
ORAL HYPOGLYCAEMIC AGENTS - PART 2.pptx
ORAL HYPOGLYCAEMIC AGENTS  - PART 2.pptxORAL HYPOGLYCAEMIC AGENTS  - PART 2.pptx
ORAL HYPOGLYCAEMIC AGENTS - PART 2.pptxNIKITA BHUTE
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project reportNARMADAPETROLEUMGAS
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologyDeepakDaniel9
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdfHongBiThi1
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.kishan singh tomar
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxkomalt2001
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Vaikunthan Rajaratnam
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdfHongBiThi1
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfDolisha Warbi
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfDolisha Warbi
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentsaileshpanda05
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxMAsifAhmad
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxNaveenkumar267201
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsMedicoseAcademics
 

Kürzlich hochgeladen (20)

ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
 
Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
ORAL HYPOGLYCAEMIC AGENTS - PART 2.pptx
ORAL HYPOGLYCAEMIC AGENTS  - PART 2.pptxORAL HYPOGLYCAEMIC AGENTS  - PART 2.pptx
ORAL HYPOGLYCAEMIC AGENTS - PART 2.pptx
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project report
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacology
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
 
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptx
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing student
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functions
 

Epidemiology treatment and_outcomes_of_sa_nosocomial_pneumonia_chest_2005-1

  • 1. Epidemiology, Treatment, and Outcomes of Nosocomial Bacteremic Staphylococcus aureus Pneumonia* C. Andrew DeRyke, Thomas P. Lodise, Jr., Michael J. Rybak and Peggy S. McKinnon Chest 2005;128;1414-1422 DOI 10.1378/chest.128.3.1414 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/128/3/1414.full.html Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright2005by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692 Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 2. Epidemiology, Treatment, and Outcomes of Nosocomial Bacteremic Staphylococcus aureus Pneumonia* C. Andrew DeRyke, PharmD; Thomas P. Lodise, Jr., PharmD; Michael J. Rybak, PharmD, MS; and Peggy S. McKinnon, PharmD Objective: To describe outcomes associated with nosocomial bacteremic Staphylococcus aureus pneumonia (NBSAP) and to determine whether delay in adequate antimicrobial treatment is a risk factor for negative clinical and microbiological outcomes. Design: Retrospective cohort analysis. Setting: This study was conducted at Detroit Receiving Hospital and University Health Center, which is a 279-bed, level 1 trauma center in Detroit, MI. Patients: All episodes of NBSAP identified from January 1, 1999, to April 30, 2004. Results: Of 206 patients identified over a 5-year period with positive blood and respiratory cultures for S aureus, 60 patients met strict clinical, radiographic, and microbiological criteria for NBSAP. The overall mean ( SD) characteristics include the following: age, 55.5 15.0 years; acute physiology and chronic health evaluation II score, 20 (range, 3 to 41); ICU at onset, 93.3%; mechanical ventilation, 83.3%; length of stay (LOS) prior to NBSAP, 9 days (range, 2 to 81 days); methicillin-resistant S aureus (MRSA) rate, 70%; and all-cause hospital and infection-related mortality (IRM), 55.5% and 40.0%, respectively. Overall, S aureus pneumonia developed late in the patient’s hospital stay in ICU patients previously receiving mechanical ventilation and was associated with high crude mortality and IRM rates. No significant difference existed with respect to mortality or infection-related LOS between patients who had received early appropriate antibiotic therapy vs those who had received delayed appropriate antibiotic therapy at the onset of pneumonia or in patients with methicillin-sensitive S aureus pneumonia vs those with MRSA pneumonia. Conclusion: IRM from NBSAP is high, and standard therapies evaluated at the time of this study resulted in poor clinical outcomes. Delayed therapy was not found to be a predictor of adverse outcomes; however, this lack of ability to detect a difference may be a product of small sample size. These findings suggest that newer agents with enhanced clinical activity in NBSAP are needed and that these should be evaluated in a real-world setting, where outcomes of the most ill patients can be assessed. (CHEST 2005; 128:1414 –1422) Key words: bacteremia; clinical outcomes; critical care; cross-infection; hospital mortality; ICU; infection; staphylo- coccal infections; staphylococcal pneumonia; ventilator-associated pneumonia Abbreviations: APACHE acute physiology and chronic health evaluation; CART classification and regression tree analysis; IR-LOS infection-related length of stay; IRM infection-related mortality; NBSAP nosocomial bactere- mic Staphylococcus aureus pneumonia; MRSA methicillin-resistant Staphylococcus aureus; MSSA methicillin- sensitive Staphylococcus aureus; VAP ventilator-associated pneumonia N osocomial pneumonia is infection and second most common hospital currently the is the monia ranges from 7.8 to 68.0%, and is influenced by the duration of hospital and ICU stay, the specific leading cause of death from hospital-acquired infec- diagnostic method used for pathogen detection, and tions.1 The incidence of acquiring nosocomial pneu- the patient population studied.1 The rate of nosoco- mial pneumonia secondary to Staphylococcus aureus *From the Anti-Infective Research Laboratory, Wayne State has increased steadily over the past 2 decades.2 In University, Detroit, MI (Drs. Rybak and McKinnon); the De- partment of Pharmacy, Barnes Jewish Hospital, St. Louis, MO Reproduction of this article is prohibited without written permission (Dr. McKinnon); the Center for Anti-Infective Research and from the American College of Chest Physicians (www.chestjournal. Development, Hartford Hospital, Hartford, CT (Dr. DeRyke); org/misc/reprints.shtml). and Albany College of Pharmacy, Albany, NY (Dr. Lodise). Correspondence to: Peggy S. McKinnon, PharmD, Barnes-Jewish Manuscript received December 23, 2004; revision accepted Hospital, Mailstop 90 –52-411, 216 South Kings Hwy, St. Louis, January 26, 2005. MO 63110; e-mail: psm9154@bjc.org 1414 Clinical Investigations Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 3. one review3 of three major studies examining the University Human Investigation Committee. This investigation etiology of ventilator-associated pneumonia (VAP), S included all of the episodes of NBSAP identified from January 1, 1999, to April 30, 2004. Nosocomial pneumonia, or hospital- aureus was the most frequently isolated Gram-posi- acquired pneumonia, was defined as pneumonia occurring 48 tive organism and the second-most isolated organism h after hospital admission and excluding any infection that was only behind Pseudomonas aeruginosa. Most studies incubating at the time of hospital admission.17 estimate that S aureus accounts for 15 to 35% of all For the purposes of this investigation, the diagnosis of NBSAP nosocomial pneumonia cases; however, the true in- was defined based on clinical, radiographic, and microbiological cidence depends on many factors, such as patient criteria.18 –21 Within 72 h of the first positive culture, a chest demographics, local susceptibility patterns, and radiograph must also have been abnormal, and the patient must have had signs and symptoms consistent with nosocomial pneu- methods of diagnosis.3 monia. In order to fulfill the requirement for bacteremic pneu- monia, at least one S aureus-positive blood culture not related to For editorial comment see page 1093 another source of infection and one S aureus-positive respiratory culture must have been obtained within 72 h of each other as Although there is increased recognition of S au- well. Possible respiratory cultures included positive growth in the reus as a major pathogen causing nosocomial pneu- culture of pleural fluid, positive sputum culture/tracheal aspirate monia, there are few studies4 –7 with descriptive data (defined as secretions from the lungs, bronchi, or trachea that specifically evaluating patient outcomes of S aureus contain numerous or a moderate number of neutrophils and rare pneumonia. In addition, in the last decade, evidence or few squamous epithelial cells) findings, and a positive quanti- tative culture result from minimally contaminated lower respira- has accumulated demonstrating that initial inappro- tory tract specimens (eg, BAL fluid with 10,000 cfu/mL). priate antibiotic treatment is an important indepen- Radiographic criteria for pneumonia were met if the chest dent predictor of excess mortality in patients with radiograph yielded a new or progressive and persistent infiltrate, nosocomial pneumonia.8 –11 To our knowledge, no consolidation, or cavitation. Persistence of an infiltrate was data exist examining the impact of delayed appropri- defined as having the infiltrate present radiographically for at ate antibiotic treatment specifically for bacteremic S least 72 h. Patients were defined as symptomatic if one of the aureus pneumonia. In a retrospective study12 evalu- following were present: fever (ie, temperature 38°C or 100.4°F) or hypothermia (ie, temperature 35°C or 95°F) with ating S aureus bacteremia, a delay in treatment with no other recognized cause; leukopenia (ie, WBC count, 4,000 antibiotics for 44.75 h was found to be an inde- cells/ L) or leukocytosis (ie, WBC count, 10,000 cells/ L); or, pendent predictor of infection-related mortality for adults 70 years old, altered mental status with no other (IRM) [adjusted odds ratio, 3.8; 95% confidence recognized cause. Patients also had to exhibit one of the following interval, 1.3 to 11.0; p 0.01]. It is unknown if this signs: new onset of purulent sputum, change in the character of 44.75-h breakpoint is applicable to patients with the sputum, increased respiratory secretions, or increased suc- bacteremic S aureus pneumonia. Although the im- tioning requirements; new onset or worsening of cough, dyspnea, or tachypnea (respiratory rate, 25 breaths/min); or worsening pact of methicillin resistance on the outcomes of gas exchange (eg, O2 desaturation [Pao2/fraction of inspired patients with S aureus bacteremia has been exten- oxygen ratio of 240], increased oxygen requirements, or in- sively evaluated, little information exists on the im- creased ventilation demand). pact of the methicillin resistance of patients with Medical charts were screened to exclude the following possible nosocomial bacteremic S aureus pneumonia (NBSAP). alternative causes for fever and radiographic chest densities. The Furthermore, less information exists on the impact of presence of atelectasis was defined by the complete disappear- empirical antibiotic selection on NBSAP. Over the past ance of radiographic densities within 48 h of evaluation. Conges- tive heart failure with pulmonary edema was defined as a few years, studies13–16 have suggested that vancomycin resolution of pulmonary infiltrates following diuresis. A pulmo- may not be optimal for the treatment of S aureus nary embolism was defined by the presence of at least two pneumonia, especially in the subset of patients who segmental or larger mismatched perfusion abnormalities on a have been infected with methicillin-resistant S aureus ventilation-perfusion scan or suggestive radiographic findings on (MRSA). To evaluate the epidemiology, treatment, and pulmonary angiography and spiral CT scan. outcomes of NBSAP, a retrospective cohort analysis Patients with endovascular infections, including endocarditis, was performed. Specifically, we examined the impact of were excluded because of the potential for hematogenous spread of S aureus to the lungs, thus complicating our retrospective methicillin resistance, empirical therapy, and delayed diagnosis of S aureus pneumonia. Patients with endocarditis were treatment on the outcomes of patients with NBSAP. identified by transthoracic or transesophageal echocardiography and/or documentation of the diagnosis in the medical record. Materials and Methods Study Design Study Population To evaluate the epidemiology, treatment, and outcomes of NBSAP, a retrospective cohort analysis was performed. Specifi- This study was conducted at Detroit Receiving Hospital and cally, we examined the impact of methicillin resistance, empirical University Health Center, which is a 279-bed, level 1 trauma therapy, and delayed treatment on the outcomes of patients with center in Detroit, MI, and was approved by the Wayne State NBSAP. www.chestjournal.org CHEST / 128 / 3 / SEPTEMBER, 2005 1415 Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 4. Data Collection antimicrobial therapy. To prevent bias, investigators involved in the outcome assessments were blinded to both susceptibility data Clinical Data: Data extracted from the patient medical records and treatment data, including the time to receipt of treatment. and pharmacy database included the following: age; sex; comor- bidities present; prior antibiotic use (within 30 days prior to NBSAP); length of hospitalization before the onset of nosocomial Definitions pneumonia (total hospitalization and hospitalization in the ICU); mechanical ventilation at the onset of nosocomial pneumonia; Clinical outcomes were evaluated as successes or failures. Charlson comorbidity index score22; and severity of illness based Clinical success included clinical resolution, which was defined as on APACHE (acute physiology and chronic health evaluation) II the complete resolution of all signs and symptoms of pneumonia scores at the time of admission to the ICU.23 If the patients were (return to preinfection baseline) along with improvement, or lack not admitted to the ICU, the APACHE II score was determined of progression, of all abnormalities on the chest radiograph, and at hospital admission. clinical improvement, which was defined in patients if a partial The following comorbid conditions were documented: diabe- resolution of clinical signs and symptoms occurred such that no tes mellitus; heart failure; COPD; asthma; hepatic dysfunction; additional antimicrobial therapy was required, along with the renal failure (as indicated by the necessity for dialysis); malig- improvement or stabilization of chest radiographic findings. nancy; HIV infection; alcoholism; presence of decubitus ulcers Patients who died or whose conditions did not improve were (stage II to IV); administration of immunosuppressive drugs (ie, deemed as having clinical failure. Clinical failure was defined as receipt of 20 mg prednisone or an equivalent corticosteroid the persistence of clinical signs and symptoms, the persistence of per day for 14 days before the onset of nosocomial pneumonia positive culture findings, and/or a lack of resolution of infiltrates or the receipt of any neoplastic chemotherapy in the 3 months on the chest radiograph. before the onset of nosocomial pneumonia); surgery requiring Microbiological outcomes were categorized as eradication or 48 h of hospitalization in the 30 days before the onset of persistence. Microbiological eradication included documented nosocomial pneumonia; and the presence of burns on 30% of eradication, defined as the elimination of baseline pathogens the body surface area. based on subsequent negative blood and respiratory culture Microbiological Data: Collected microbiological data included findings, and presumed eradication, which was denoted in pa- all of the positive blood or respiratory culture findings, irrespec- tients in whom presumed eradication occurred based on clinical tive of the pathogen identified. Susceptibility testing was per- resolution, but no subsequent cultures were obtained. Microbi- formed using the microtiter-well method, and the results were ological persistence included documented persistence, which was interpreted according to National Committee for Clinical Labo- defined as the persistence of bacteria despite the appropriate use ratory Standards guidelines24 by the clinical microbiological of antibiotic therapy based on in vitro susceptibility results, and laboratory. presumed persistence, which was denoted in patients in whom Treatment Data: All of the antimicrobial agents administered presumed microbiological failure occurred based on clinical to provide activity against S aureus isolates were noted. Empiric failure, but no subsequent cultures were obtained. treatment was the first antibiotic regimen provided following the Death was considered to be related to NBSAP (ie, IRM) if one onset of infection. Treatment was considered to be appropriate or more of the following criteria were present: (1) blood and/or on the basis of the following two factors: the timing of treatment respiratory cultures were positive for S aureus at the time of relative to the first positive blood or respiratory culture finding; death; (2) death occurred before the resolution of signs and and the in vitro susceptibility of the blood or respiratory isolate. symptoms of the nosocomial pneumonia; (3) death occurred Timing was evaluated based on a previously described breakpoint 14 days after the onset of nosocomial pneumonia without of 44.75 h, which was determined by classification and regression another explanation; (4) autopsy findings indicated pneumonia as tree analysis (CART) as an independent predictor of mortality in a cause of death; and (5) pneumonia was indicated as a cause of S aureus bactermia.12 If a patient had received at least one IV death on the death certificate. antibiotic to which the S aureus blood or respiratory isolate was The calculation of IR-LOS was measured from the time when susceptible and the antibiotic had been administered within the first positive blood or respiratory culture finding was col- 44.75 h, it was considered to be appropriate early treatment. For lected until the end of antimicrobial treatment, death, or hospital example, an individual with MRSA bacteremia receiving vanco- discharge. The calculation of IR-LOS excluded patients who died mycin within 44.75 h would be classified as having received early secondary to nosocomial pneumonia. appropriate treatment. A patient with MRSA initially treated with An infection-related cost of hospitalization was determined for a -lactam but not receiving vancomycin within 44.75 h would be each patient. The Detroit Receiving Hospital accounting depart- considered as having received delayed treatment. In addition, we ment supplied the cost figures. For patients who lived or did not utilized CART analysis to determine whether there was a differ- die secondary to NBSAP, the cost was calculated from the onset ent breakpoint to better describe the critical time to appropriate of infection until the last day that antimicrobial therapy active antibiotic treatment for this cohort of NBSAP patients. against S aureus was administered (ie, the IR-LOS). For those patients who died because of NBSAP, the cost was calculated from the onset of infection until the day of the patient’s death. Outcome Assessment The following primary end points were assessed: (1) IRM; (2) Statistical Analysis hospital (crude) mortality; and (3) infection-related length of stay length (IR-LOS) after the onset of NBSAP. Secondary outcomes Categoric variables were compared by the Pearson 2 test or included the following: (1) clinical response; (2) microbiological Fisher exact test, and continuous variables were compared by the response; and (3) cost of hospitalization after the onset of Student t test or Mann-Whitney U test. Multivariate analyses NBSAP. were performed to determine the independent association of For the early treatment vs delayed treatment analyses, patients antibiotic resistance and delayed treatment with the clinical who died within 72 h of the onset of infection were excluded. outcome of interest while adjusting for confounding variables. Clinical and microbiological outcomes were assessed at the Clinical features significantly associated with the outcome by following four time points: day 3; day 7; day 10; and at the end of univariate analysis were included in the explanatory multivariate 1416 Clinical Investigations Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 5. model. The univariate predictors had to represent 10% of the tive Staphylococcus sp. The most common concom- cohort to prevent overfitting of the multivariate model. Dichot- itant respiratory organisms were P aeruginosa (nine omous outcomes (eg, IRM and clinical status) were analyzed with standard logistic regression. A p value of 0.05 was considered cases); A baumannii (eight cases); Klebsiella spp to be significant for two-tailed tests. A statistical software package (seven cases); Escherichia coli (six cases); Candida (SPSS, version 10.0; SPSS; Chicago, IL) was used for all of the albicans (four cases); Enterobacter spp (three cases); calculations. and nine others. The clinical and microbiological success rates at the end of treatment were 56.7% and 53.3%, respec- Results tively. Thirty-three patients (55.5%) died during hospitalization, and 24 (40.0%) died secondary to Baseline Data NBSAP (ie, IRM). Nine patients died for reasons not Of the 206 patients identified either by Interna- attributable to the pneumonia. In seven cases, treat- tional Classification of Diseases, ninth revision, codes ment for NBSAP had stopped at least 2 weeks before for S aureus pneumonia and/or by concomitant the patient died. Withdrawal from support occurred blood and respiratory cultures positive for S aureus, in two patients irrespective of the concomitant pneu- 60 met the strict inclusion criteria as assessed for monia. NBSAP. The primary reasons for exclusion from the The relationship between APACHE II score and study included a lack of clinical or radiologic findings death is shown in Figure 1. A linear relationship supporting a pneumonia diagnosis (n 46), alter- existed demonstrating that patients who were more nate clinical diagnoses (n 43), infection that was acutely ill at the time of admission to the ICU had a not nosocomial (n 26), time correlation between greater mortality rate (R2 0.74). microbiological findings (n 25), and chart not available (n 6). Alternative clinical diagnoses po- Outcomes of Bacteremic MRSA vs Methicillin- tentially causing the infection isolated more than Sensitive S aureus Pneumonia MSSAP once included the following: endocarditis (n 12); IV line-related sepsis (n 16); alternative pathogen Of the 60 patients, 42 patients (70%) were in- most likely caused infection (n 5); and pelvic fected with MRSA. A comparison of clinical features abscess (n 2). Overall, the mean ( SD) age was between MRSA and methicillin-sensitive S aureus 55.5 15.0 years, and the median APACHE II score (MSSA) patients is presented in Table 1. By univar- was 20 (range, 3 to 41). Most patients were men iate analysis, MRSA patients were more likely than (66.7%), and were predominantly African American MSSA patients to have received prior antibiotic (56.7%) and white (38.3%). An equal number of treatment and had a longer median length of stay patients were admitted to surgery (41.7%) and med- prior to the onset of NBSAP. In addition, a signifi- icine services (41.7%), and 16.7% of the patients cant difference existed between the two groups with were admitted to the burn unit. Twenty-three pa- respect to appropriate treatment. In the MSSA tients (38.3%) underwent surgery 1 month prior group, 72.2% of patients received appropriate ther- to the development of NBSAP. Bilateral infiltrates apy within 44.75 h of the onset of infection com- were evident on chest radiography in 75% of the pared with only 50% of patients in the MRSA patients identified. Most patients were in the ICU at time of onset of NBSAP (93.3%), and 83.3% of patients were receiving mechanical ventilation. The median length of stay prior to the onset of NBSAP was 9 days (range, 2 to 81 days). The origin of the respiratory cultures used for the microbiological determination of pneumonia came from aspirated sputum in 90% of the cases, and from BAL fluid in 10% of cases. Of the 60 patients, 42 patients (70%) were infected with MRSA. Forty-four patients (73.3%) had concomitant organisms (6 in blood only, 7 in blood and respiratory cultures, and 31 in respiratory cultures only). The most common concomitant organisms in the blood were as follows: Enterococcus spp (five cases); Acinetobacter bau- mannii (three cases); Streptococcus viridans (two Figure 1. IRM grouped by APACHE II score. APACHE II cases); Klebsiella pneumoniae (one case); Streptococ- scores grouped in values of 10. Dotted line represented linear cus pneumoniae (one case); and one cogulase-nega- regression line. www.chestjournal.org CHEST / 128 / 3 / SEPTEMBER, 2005 1417 Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 6. Table 1—Characteristics of MSSA vs MRSA median length of time needed to switch to optimal Pneumonia therapy for the eight patients who had been empir- MSSA MRSA ically treated with vancomycin was 71.5 h (range, 16 Characteristics (n 18) (n 42) p Value to 123 h). Of the 42 MRSA patients, 24 (57.1%) Age, yr 55.2 17.6 58.4 13.9 0.45 received empiric vancomycin treatment, 8 (19.0%) APACHE II score 20.5 (5–41) 20.0 (3–36) 0.72 received -lactam agents, 6 (14.3%) received clinda- Charlson index score 2 (0–6) 2 (0–7) 0.53 mycin, 3 (7.1%) received trimethoprim/sulfamethox- Diabetes 3 (16.7) 15 (35.7) 0.14 azole, 1 was started on therapy with levofloxacin; and Decubitus ulcers 0 7 (16.7) 0.09 1 patient died before receiving appropriate antibiotic Prior antibiotics 3 (16.7) 30 (71.4) 0.01 Vent at NBSAP onset 13 (72.2) 37 (88.1) 0.13 treatment. Once susceptibility data were available, LOS prior to NBSAP onset, d 4 (2–31) 11.5 (4–81) 0.03 40 patients (95.2%) received vancomycin for primary ICU LOS prior to NBSAP 3 (0–31) 9 (0–58) 0.059 antimicrobial treatment of pneumonia. Two patients onset, d were never appropriately treated with antibiotics. Time to adequate therapy, h 24 (8–51) 44 (1–149) 0.013 Nine patients (50.0%) in the MSSA subgroup were *Values given as mean SD, No. of patients (%), or median (range), treated with combination therapy compared with unless otherwise indicated. LOS length of stay; Vent receiving seven patients (16.7%) in the MRSA subgroup. The mechanical ventilation. median duration of combination therapy was 3 days in both groups (MSSA group range, 1 to 10 days; MRSA group range, 1 to 8 days). Eleven vancomycin subgroup (p 0.01) [Fig 2]. Furthermore, MSSA trough levels were collected in a total of nine patients pneumonia patients received appropriate treatment with a median value of 17.4 g/mL (range, 9.2 to in significantly less time than did MRSA pneumonia 26.7 g/mL). patients (24 h [range, 8 to 51 h] vs 44 h [range, 1 to The comparison values of hospital mortality, IRM, 149 h], respectively; p 0.013). No difference was and IR-LOS between MSSA and MRSA patients are detected in the duration of therapy between the two displayed in Figure 3. No significant differences in groups (MSSA group, 10 days [range, 2.5 to 25.0 these primary end points were observed between the days]; MRSA group, 11 days [range, 1.0 to 21.5 groups. Similarly, no significant differences in hos- days]). pital mortality, IRM, and IR-LOS were noted for the Of the 18 MSSA patients, 8 patients (44.4%) were different empiric antibiotic regimens, stratified by empirically treated with vancomycin, 7 patients methicillin susceptibility. Multivariate analyses were (38.9%) were empirically treated with a -lactam, 1 performed, and the associations between methicillin patient was empirically treated with clindamycin, 1 susceptibility and outcomes were identical to those patient was empirically treated with levofloxacin, and from the univariate analyses. 1 patient died prior to identification of the causative IRM was higher in the empiric vancomycin group organism and subsequent appropriate antibiotic than in the empiric -lactam group; however, this therapy. Once sensitivity reports were obtained, was not statistically significant. For the 18 patients 77.8% of the MSSA patients received a -lactam infected with MSSA, the hospital mortality and IRM agent as the primary antimicrobial treatment. The rates in the patients receiving empiric -lactams were 57.1% and 28.6%, respectively, compared with 62.5% and 50.0%, respectively, in the empiric van- comycin group. For the 42 patients infected with MRSA, the hospital mortality and IRM rates in patients receiving empiric vancomycin were 50.0% and 45.8%, respectively, compared with 62.5% and 25.0%, respectively, in the empiric -lactam group. These findings, however, were not statistically signif- icant, and an additional evaluation of this subset revealed that patients who had been empirically treated with -lactams tended to be younger (me- dian age, 52 vs 56 years, respectively) and to have lower APACHE II scores (median, 17 vs 21, respec- tively). Overall clinical success was achieved in 59.5% of MRSA patients compared with 50.0% of MSSA Figure 2. Receipt of adequate treatment within the 44.75-h patients. No differences in clinical or microbiological breakpoint established for S aureus bacteremia. success were determined at days 3, 7, or 10, or at the 1418 Clinical Investigations Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 7. Figure 3. Outcomes of NBSAP based on MSSA vs MRSA pneumonia. end of antimicrobial therapy for any treatment reg- no significant difference in the rate of response was imen, stratified by methicillin susceptibility. Simi- seen at days 3, 7, and 10, and at the end of larly, because 83.3% of patients were receiving me- antimicrobial therapy or the first day to clinical chanical ventilation at the time of onset, no improvement (5 days [range, 2 to 14 days] vs 5 days difference in clinical response was observed in this [range, 2 to 11 days], respectively). In the CART VAP subset of patients compared with the whole analysis that was performed to identify a specific cohort. Of note, the overall clinical cure rate in “time to therapy” for the bacteremic S aureus pneu- patients receiving vancomycin was 56.3%; 58.3% in monia cohort, no additional time breakpoint in ap- the subset of MRSA patients. propriate antibiotic treatment was found that pro- duced an increased probability of IRM. Outcomes in Delayed vs Early Appropriate The evaluation of the appropriateness of therapy Therapy for concomitant pathogens was also assessed. Alter- native pathogens were appropriately treated 85% of Five patients were excluded in the appropriate the time based on the susceptibility profile. The therapy analyses secondary to death within 72 h of clinical success was 59.5% for patients treated ap- the onset of infection. Of the remaining 55 patients, propriately for both NBSAP and the alternative 24 patients (43.6%) did not receive appropriate pathogen. This result was similar to the clinical antibiotic treatment within 44.75 h of the onset of success rate observed for the entire cohort (56.7%). infection, and 31 patients (56.4%) received appro- Complete, infection-related cost data were avail- priate antibiotic treatment within 44.75 h of the able for 22 of the 60 patients. The greatest reason for onset of infection. There were no significant differ- increased cost was length of hospitalization. In the ences between the two groups (delayed vs early) with patients who lived, the median total cost was $35,072 respect to the APACHE II score at time of admission (range, $19,764 to $312,511) compared with $22,098 to the ICU (20.5 [range, 5 to 41] vs 18 [range, 4 to (range, $1,218 to $66,351) in the patients who died. 40], respectively; p 0.6) and Charlson comorbidity No differences in cost were evident in patients based index score (2 [range, 0 to 6] vs 2 [range, 0 to 6], on methicillin susceptibility or early empiric treat- respectively; p 0.9). The median time to the start ment. of appropriate treatment was 68.5 h (range, 45 to 149 h) in the delayed-treatment group and 25 h (range, 4 to 44 h) in the early-treatment group. Only Discussion 16 patients received appropriate antibiotic treatment within 24 h of the onset of infection The previous literature specifically focusing on S No differences existed with respect to the primary aureus nosocomial pneumonia is limited. Our review outcomes based on the receipt of delayed vs early of 60 patients is one of the largest reports of a appropriate antibiotic therapy (Fig 4). In addition, real-world experience describing the outcomes of www.chestjournal.org CHEST / 128 / 3 / SEPTEMBER, 2005 1419 Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 8. Figure 4. Outcomes of NBSAP based on early vs delayed treatment. bacteremic staphylococcal pneumonia. The distribu- pneumonia patients. In the 55 patients with bacteri- tion of pathogens responsible for nosocomial pneu- ologically evaluable S aureus pneumonia, the overall monia differs depending on factors such as the clinical success rate in vancomycin-treated patients length of hospital admission before onset of the was 50.9% compared with 44.4% in the 18 patients disease, admission to the ICU, and duration of infected with MRSA. Stevens et al14 specifically mechanical ventilation.25 S aureus pneumonia typi- evaluated therapy with linezolid vs therapy with cally develops in patients who have had a longer vancomycin for the treatment of MRSA infections. length of hospital stay before onset of disease, have Data from 29 patients with MRSA pneumonia re- received mechanical ventilation for 5 days (ie, vealed that a clinical cure was achieved in 75.0% of late-onset VAP), and have been exposed to previous patients treated with either agent. In a study analyz- antimicrobial therapy. A prediction model26 has ing data from two previous double-blind studies of been developed to determine which characteristics patients with S aureus nosocomial pneumonia, Wun- predict for the development of MRSA in patients derink et al15 found that there was no difference in with S aureus bacteremia. The greatest risk factor clinical cure between the use of linezolid and van- was previous antibiotic exposure with an odds ratio comycin among all of the S aureus nosocomial of 9.2 (95% confidence interval, 4.8 to 17.9). Rello pneumonia patients (51.5% vs 43.4%, respectively; and Diaz3 also found previous antimicrobial therapy p 0.182). However, in the subset of 133 MRSA to be a risk factor for MRSA pneumonia as well. Our nosocomial pneumonia patients, a significant differ- findings for this cohort of 60 patients concur with ence was found (59% vs 35.5%, respectively; this description. The median length of hospital stay p 0.009). Kollef et al16 examined clinical cures in before the first positive culture finding was 9 days. patients who specifically had VAP and found signif- Most of our patients (93.3%) were in the ICU icant differences in favor of the empiric use of receiving mechanical ventilation (83.3%) at the onset linezolid over vancomycin in both the S aureus VAP of disease, and 55% of patients received antibiotic group (48.9% vs 35.2%, respectively; p 0.06) and therapy prior to the onset of pneumonia. Further- the MRSA VAP group (62.2% vs 21.2%, respectively; more, 71.4% of patients who developed MRSA p 0.001). Our findings were similar to these re- pneumonia had received previous antibiotic therapy ported values. Overall clinical success was achieved within 30 days prior to the onset of nosocomial in 56.7% of all patients and in 59.5% of the subset of pneumonia. This was significantly different from the MRSA patients compared with 50.0% of the subset 16.7% of MSSA pneumonia patients (p 0.01). of MSSA patients. Highlighting the empiric use of Clinical success has been reported in S aureus vancomycin, the overall clinical success rate was nosocomial pneumonia in a number of trials, mostly 56.3%, with 58.3% cure rates in the MRSA patient comparing vancomycin with the newer agents quinu- population. Among patients with MRSA, the IRM pristin/dalfopristin and linezolid. Fagon et al27 com- rate was higher in patients receiving empiric vanco- pared the efficacy of therapy with quinupristin/ mycin (45.8%) compared with that in patients receiv- dalfopristin and vancomycin in Gram-positive ing empiric -lactam agents (25.0%). These findings 1420 Clinical Investigations Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 9. were not statistically significant, and an additional not predict clinical success or decreased mortality. evaluation of this subset of patients revealed that Another reason may be in part attributable to the patients empirically treated with -lactam agents slow activity or lack of efficacy of vancomycin, such tended to be younger and to have lower APACHE II that even the early administration of this agent is scores, partially explaining this finding. Because associated with poor clinical outcomes.31,32 80% of patients were already receiving mechani- The greatest limitation of our study was the small cal ventilation at the onset of NBSAP, these percent- number of patients (n 60) who met our strict ages did not change after analyzing this subset of inclusion criteria. The main reason that so few patients. patients were available for inclusion over the 5 years Patients included in this analysis were critically ill was the requirement for patients to have concomi- and had numerous underlying chronic comorbidities, tant S aureus bacteremia, as well as pneumonia. This as evidenced by a median APACHE II score of 20 requirement was essential because of the retrospec- (range, 3 to 41). Consequently, the mortality rate was tive design of our investigation and the high rate of high in our study, with an associated crude mortality tracheal aspirates used as the respiratory source of rate of 55.5% and an IRM rate of 40.0%. These values also correlate well with those from previous this pathogen. We wanted to be confident that the literature6,7,28 –30 in which the mortality rate attribut- patients who were involved in this analysis developed able to S aureus has ranged between 28% and 50%. bacteremia secondary to nosocomial pneumonia and The mortality rate among nosocomial acquired bac- not by hematogenous spread of S aureus, as can teremic pneumonia patients was found to be 52.5% occur in other conditions, such as endocarditis, in a previous study.5 which was one of the exclusion criteria. The most surprising outcomes from our results Additional limitations were inherent to the retro- were a lack of difference with respect to overall spective design of the study. Characterizing NBSAP hospital mortality rate, IRM rate, and IR-LOS based was difficult, although stringent inclusion criteria on the receipt of early vs delayed antibiotic therapy. were used. Many patients who likely had nosocomial Numerous reports8 –11 have been published stating S aureus pneumonia were excluded from the analysis that mortality significantly increases in patients who because of the lack of a concomitant positive blood develop pneumonia if empiric antibiotic therapies culture finding. Also, numerous comorbidities con- are not started at the time of clinical suspicion, founded the accurate assessment of IRM. To ac- before cultures have been collected and sensitivity count for this, an independent reviewer with no has been reported. Our lack of ability to detect a knowledge of the culture and sensitivity data or of difference may be a product of a small sample size the choice and timing of antibiotic therapy was leading to a potential type II error. In a previous designated to determine the primary outcome based study12 examining S aureus bacteremia, a delay in on clinical data recorded throughout the course of therapy of 44.75 h was found to be associated with the patient’s hospital stay. a 3.8 times higher rate of IRM. The 44.75-h break- In conclusion, this investigation includes one of point for appropriate therapy, however, was not the largest collections of patients to have bacteremic predictive in this series of pneumonia patients. In nosocomial pneumonia that was specifically attribut- addition, an additional breakpoint of time to appro- able to S aureus. S aureus pneumonia developed late priate therapy was not identified using CART. Some in the patient’s hospital stay and in ICU patients who potential reasons for no differences being detected had previously received mechanical ventilation, and are the low number of patients (n 60) and the high was associated with a high crude mortality and IRM mortality rate (55%) associated with this series. In rates. No significant differences were detected with addition, only 16 patients received appropriate anti- respect to crude mortality, IRM, or IR-LOS between biotic therapy within 24 h of the onset of infection. It patients who developed MSSA vs those who devel- may be difficult to ascertain the impact of delayed oped MRSA pneumonia or depending on whether therapy given the high rate of delayed treatment. the patient had received early vs delayed appropriate Of interest, as demonstrated in Figure 1, a linear antibiotic therapy. The small sample size may have relationship existed with respect to IRM and increas- precluded our ability to detect a difference in these ing APACHE II score. Because of the requirement groups. Patients who were empirically treated with of concomitant bacteremia, this subset of pneumonia vancomycin for MSSA and MRSA pneumonia expe- patients likely represents those patients who are rienced a high mortality rate. These findings suggest most severely ill with rapid disease progression. The that newer agents with enhanced clinical activity in severe illness exhibited in these patients may be the NBSAP are needed and that these should be evalu- main factor determining mortality and may serve as ated in a real-world setting, where outcomes of the the reason why appropriate antibiotic treatment did sickest patients can be assessed. The group of pa- www.chestjournal.org CHEST / 128 / 3 / SEPTEMBER, 2005 1421 Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 10. tients who will experience the greatest benefit from linezolid with vancomycin. Intensive Care Med 2004; 30: these newer agents remains to be determined. 388 –394 17 American Thoracic Society. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies: a consensus statement; References American Thoracic Society, November 1995. Am J Respir 1 Hoffken G, Niederman MS. Nosocomial pneumonia: the Crit Care Med 1996; 153:1711–1725 importance of a de-escalating strategy for antibiotic treatment 18 Micek ST, Ward S, Fraser VJ, et al. A randomized controlled of pneumonia in the ICU. Chest 2002; 122:2183–2196 trial of an antibiotic discontinuation policy for clinically 2 Lynch JP III. Hospital-acquired pneumonia: risk factors, suspected ventilator-associated pneumonia. Chest 2004; 125: microbiology, and treatment. Chest 2001; 119:373S–384S 1791–1799 3 Rello J, Diaz E. Pneumonia in the intensive care unit. Crit 19 Rubinstein E, Cammarata S, Oliphant T, et al. Linezolid Care Med 2003; 31:2544 –2551 (PNU-100766) versus vancomycin in the treatment of hospi- 4 Gonzalez C, Rubio M, Romero-Vivas J, et al. Bacteremic talized patients with nosocomial pneumonia: a randomized, pneumonia due to Staphylococcus aureus: a comparison of double-blind, multicenter study. Clin Infect Dis 2001; 32: disease caused by methicillin-resistant and methicillin-sus- 402– 412 ceptible organisms. Clin Infect Dis 1999; 29:1171–1177 20 Beck KD, Gastmeier P. Clinical or epidemiologic diagnosis of 5 Gonzalez C, Rubio M, Romero-Vivas J, et al. Staphylococcus nosocomial pneumonia: is there any difference? Am J Infect aureus bacteremic pneumonia: differences between commu- Control 2003; 31:331–335 nity and nosocomial acquisition. Int J Infect Dis 2003; 21 Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for 7:102–108 nosocomial infections, 1988. Am J Infect Control 1988; 6 Rello J, Torres A, Ricart M, et al. Ventilator-associated 16:128 –140 pneumonia by Staphylococcus aureus: comparison of methi- 22 Charlson ME, Pompei P, Ales KL, et al. A new method of cillin-resistant and methicillin-sensitive episodes. Am J Respir classifying prognostic comorbidity in longitudinal studies: Crit Care Med 1994; 150:1545–1549 development and validation. J Chronic Dis 1987; 40:373–383 7 Combes A, Luyt CE, Fagon JY, et al. Impact of methicillin 23 Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a resistance on outcome of Staphylococcus aureus ventilator- severity of disease classification system. Crit Care Med 1985; associated pneumonia. Am J Respir Crit Care Med 2004; 13:818 – 829 170:786 –792 24 National Committee for Clinical Laboratory Standards. 8 Luna CM, Vujacich P, Niederman MS, et al. Impact of BAL Methods for dilution antimicrobial susceptibility tests for data on the therapy and outcome of ventilator-associated bacteria that grow aerobically: approved standard M7–A6. pneumonia. Chest 1997; 111:676 – 685 Wayne, PA: National Committee for Clinical Laboratory 9 Rello J, Gallego M, Mariscal D, et al. The value of routine Standards, 2004 microbial investigation in ventilator-associated pneumonia. 25 Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Am J Respir Crit Care Med 1997; 156:196 –200 Respir Crit Care Med 2002; 165:867–903 10 Kollef MH, Ward S. The influence of mini-BAL cultures on 26 Lodise TP Jr, McKinnon PS, Rybak M. Prediction model to patient outcomes: implications for the antibiotic management identify patients with Staphylococcus aureus bacteremia at of ventilator-associated pneumonia. Chest 1998; 113:412– 420 risk for methicillin resistance. Infect Control Hosp Epidemiol 11 Alvarez-Lerma F. Modification of empiric antibiotic treat- 2003; 24:655– 661 ment in patients with pneumonia acquired in the intensive 27 Fagon J, Patrick H, Haas DW, et al. Treatment of Gram- care unit: ICU-Acquired Pneumonia Study Group. Intensive positive nosocomial pneumonia: prospective randomized Care Med 1996; 22:387–394 comparison of quinupristin/dalfopristin versus vancomycin; 12 Lodise TP, McKinnon PS, Swiderski L, et al. Outcomes Nosocomial Pneumonia Group. Am J Respir Crit Care Med analysis of delayed antibiotic treatment for hospital-acquired 2000; 161:753–762 Staphylococcus aureus bacteremia. Clin Infect Dis 2003; 28 Kaye MG, Fox MJ, Bartlett JG, et al. The clinical spectrum of 36:1418 –1423 Staphylococcus aureus pulmonary infection. Chest 1990; 13 Sandiumenge A, Diaz E, Bodi M, et al. Therapy of ventilator- 97:788 –792 associated pneumonia: a patient-based approach based on the 29 Musher DM, Lamm N, Darouiche RO, et al. The current ten rules of “The Tarragona Strategy.” Intensive Care Med spectrum of Staphylococcus aureus infection in a tertiary care 2003; 29:876 – 883 hospital. Medicine (Baltimore) 1994; 73:186 –208 14 Stevens DL, Herr D, Lampiris H, et al. Linezolid versus 30 Iwahara T, Ichiyama S, Nada T, et al. Clinical and epidemi- vancomycin for the treatment of methicillin-resistant Staph- ologic investigations of nosocomial pulmonary infections ylococcus aureus infections. Clin Infect Dis 2002; 34:1481– caused by methicillin-resistant Staphylococcus aureus. Chest 1490 1994; 105:826 – 831 15 Wunderink RG, Rello J, Cammarata SK, et al. Linezolid vs 31 Levine DP, Fromm BS, Reddy BR. Slow response to vanco- vancomycin: analysis of two double-blind studies of patients mycin or vancomycin plus rifampin in methicillin-resistant with methicillin-resistant Staphylococcus aureus nosocomial Staphylococcus aureus endocarditis. Ann Intern Med 1991; pneumonia. Chest 2003; 124:1789 –1797 115:674 – 680 16 Kollef MH, Rello J, Cammarata SK, et al. Clinical cure and 32 Small PM, Chambers HF. Vancomycin for Staphylococcus survival in Gram-positive ventilator-associated pneumonia: aureus endocarditis in intravenous drug users. Antimicrob retrospective analysis of two double-blind studies comparing Agents Chemother 1990; 34:1227–1231 1422 Clinical Investigations Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians
  • 11. Epidemiology, Treatment, and Outcomes of Nosocomial Bacteremic Staphylococcus aureus Pneumonia* C. Andrew DeRyke, Thomas P. Lodise, Jr., Michael J. Rybak and Peggy S. McKinnon Chest 2005;128; 1414-1422 DOI 10.1378/chest.128.3.1414 This information is current as of April 17, 2011 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/128/3/1414.full.html References This article cites 31 articles, 17 of which can be accessed free at: http://chestjournal.chestpubs.org/content/128/3/1414.full.html#ref-list-1 Cited Bys This article has been cited by 4 HighWire-hosted articles: http://chestjournal.chestpubs.org/content/128/3/1414.full.html#related-urls Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions. Downloaded from chestjournal.chestpubs.org at 97185 Health Organization on April 17, 2011 © 2005 American College of Chest Physicians