Which is the right management and treatment of patients with CAP and HAP? Which are the risk factors?

1. Francesco Blasi
Department of Physiopathology and Transplantation
University of Milan
Managing CAP and HAP

2. GLOSSARY
CAP- is defined as a pulmonary infection developing in
the community or <48 hours of hospital admission.
These patients may be managed in ER, the general
ward or admitted directly to the ICU.
HAP is defined as a pulmonary infection developing
during hospitalisation, 48 hours or more after
admission, and not present or incubating at the time
of admission.
VAP is defined as a pneumonia that arises more than
48–72 hours after endotracheal intubation.

4. Torres A, et al. Thorax 2013;68:1057–65.

6. Estimated cost of median length of stay for patients with CAP in European hospitals

8. This was an observational, prospective study of consecutive
patients coming from the community who were admitted to the
Policlinico Hospital, Milan, Italy, with a diagnosis of
pneumonia between April 2008 and April 2010.
A total of 935 consecutive patients with pneumonia were
enrolled during the study period
Aliberti A, et al CID 2012;54(4):470-8.

9. Risk Factors Analysis: MDR pathogens
Aliberti A, et al CID 2012;54(4):470-8.
MDR multi drug resustant
HCAP health care associated pneumonia

10. Aliberti A, et al CID 2012;54(4):470-8.
MDR multi drug resistant
COPD chronic obstructive pulmonary disease

11. Aliberti S et al. Thorax 2013;68:997-9

12. New approach: Stratify risk factors
New findings:
• Different risk factors have different importance for MDR prediction
•Chronic renal failure is an independent risk factor for MDR
(A window of patient’s functional status)
•Patient’s targeted approach for empiric antibiotic therapy is possible
Aliberti A, et al CID 2012;54(4):470-8MDR multi drug resistant

14. CASE REPORT
n. 1

15. Male, 74 y/o
Active smoker. Former parachutist.
Past medical history:
10-year history of COPD (dystrophic bullae) in LTOT since 1 year (2
L/m- 1.5 L/m).
Chronic heart failure, pleural effusions since 4 years.
Benign prostatic hyperplasia, depression, peptic ulcer.
Discharged 2 months before from the Internal Medicine
Dpt with a diagnosis of UTI treated with ciprofloxacin.
FEV1: 64%
DLCO 47%
BGA (O2:1 L/m): pH: 7.49 PaCO2: 36 PaO2:64 HCO3: 22

16. Since the day before: fever (38 °C)
and dyspnea.
BP: 150/60 mmHg HR: 80 bpm RR: 20 bpm T: 39 °C
Chest examination: not wheezing
K: 3.25 Na: 133 CRP: 5.8 WBC: 20.000

17. PNEUMONIA
LIVER
Diaphragm

18. PNEUMONIA
B LINES

20. TREATMENT?

21. • Ceftriaxone 2gr ev
• Azithromycin 500 mg ev
Since the day before: fever (38 °C) and
SOB.
BP: 150/60 mmHg HR: 80 bpm RR: 20 bpm T: 39 °C
Chest examination: non wheezing
K: 3.25 Na: 133 CRP: 5.8 WBC: 20.000

22. ?

23. STRATIFYING RISK FACTORS

24. Aliberti A, et al CID 2012;54(4):470-8.
MDR multi drug resistant
COPD chronic obstructive pulmonary disease

25. D1
Ceftriaxone 2gr
20.000
5.8 ---
18.000
14.6
WBC
CRP
T
Azithromycina 500
D2 D3
Ab anti-Legionella pneumophila: negative
Swab: bacteria and fungi: neg
Urinary antigens LP and SP: negative
Blood culture: negative
Ab anti-Mycoplasma: IgG negative and IgM negative
Naso-pharyngeal swab DNA CP, MP, LP: negative
Tracheal aspirate : Gram negative +++

26. In VII giornataOn day 3
Pleural effusion

27. Tracheal aspirate

28. WOULD YOU CHANGE?

29. Ceftriaxone 2gr
20.000
5.8 ---
18.000
14.6
15.000
---
14.200
5.6
WBC
CRP
T
Azithromycina 500 stop
stop
Imipenem 1g q8 EV
Tracheal aspirate
D1 D2 D3 D4 D5
Ab anti-Legionella pneumophila: negative
Swab: bacteria and fungi: neg
Urinary antigens LP and SP: negative
Blood culture: negative
Ab anti-Mycoplasma: IgG negative and IgM negative
Naso-pharyngeal swab DNA CP, MP, LP: negative

30. Ceftriaxone 2gr
20.000
5.8 ---
18.000
14.6
15.000
---
14.200
5.6
12.400
---
WBC
CRP
T
Azithromycina 500 stop
stop
Imipenem 1g q8 EV
D1 D2 D3 D4 D5 D6
Ab anti-Legionella pneumophila: negative
Swab: bacteria and fungi: neg
Urinary antigens LP and SP: negative
Blood culture: negative
Ab anti-Mycoplasma: IgG negative and IgM negative
Naso-pharyngeal swab DNA CP, MP, LP: negative
Tracheal aspirate

31. Discharged on Day 20…

32. TREATMENT OPTIONS FOR HOSPITALIZED PATIENTS
WITH COMMUNITY-ACQUIRED PNEUMONIA
(no need for intensive care treatment) (in alphabetical order) [C4]
INSIDE HOSPITAL: CAP
Aminopenicillin  macrolide *#
Aminopenicillin / ß-lactamaseinhibitor # macrolide *
Non-antipseudomonal cephalosporin cefotaxime or ceftriaxone
macrolide *
Levofloxacin #
Moxifloxacin #§
Penicillin G  macrolide

33. TREATMENT OPTIONS FOR PATIENTS WITH SEVERE
COMMUNITY-ACQUIRED PNEUMONIA [C4]
(ICU OR INTERMEDIATE CARE)
INSIDE HOSPITAL: CAP
NO RISK FACTORS FOR P. aeruginosa
Non-antipseudomonal cephalosporin III + macrolide *
or
moxifloxacin or levofloxacin ± non-antipseudomonal cephalosporin III
RISK FACTORS FOR P. aeruginosa
Antipseudomonal cephalosporin ** or
acylureidopenicillin / ß-lactamaseinhibitor or carbapenem
(meropenem preferred, up to 6 g possible, 3x2 in 3hours infusion)
PLUS
Ciprofloxacin^
OR PLUS
Macrolide* + aminoglycoside (gentamicin, tobramycin or amikacin)

34. WHAT EMPIRICAL ANTIBIOTIC TREATMENT IS
RECOMMENDED FOR ASPIRATION PNEUMONIA?
INSIDE HOSPITAL: CAP
Hospital ward admitted from home
Oral or iv-lactam/-lactamase inhibitor
or Clindamycin
or iv cephalosporin + oral metronidazole
or moxifloxacin
ICU or admitted from Nursing Home
Clindamycin + cephalosporin
or
Cephalosporin + metronidazole

46. CASE REPORT
n. 2

47. Male, 56 y/o
He was referred to our ER because of new cough with sputum
production, fever off and on (Tmax: 38°C) and mild dyspnea since 72
hours.
He also reported a 6-day history of malaise, sore throat and chills
during the previous 15 days. Symptoms persisted in spite of NSAID
Past medical history:
-COPD (GOLD III)
- Hepatitis C, not on treatment
Allergy Hx: denied; Food exposure: denied; recent travel:
denied; Family Hx: non-contributory
He was on aspirin
Tobacco 1-2 packs per day x 25 years, but no cigarettes in
the prior 8 days due to feeling poorly. Trader.
He was hospitalized for 16 days during the past 2 months for surgery
(bowel obstruction) and treated with different antibiotics.

48. VentiMask (FiO2: 31%)
Vital sign
BP: 120/70 mmHg
HR: 125 r
RR: 28 bpm
T: 38 °C
SpO2: 83% on RA
PSI RC: IV
Physical examination revealed
decreased breathing sound on right
chest with fine moist rales on the lower
lobe
In the ER:

49. What kind of treatment?

50. In the ward:
- Ceftriaxone 2 g iv + azithromycin 500 mg iv
Pneumonia screening: sputum/BAL; blood culture, urinary antigens,
serology for atypical pathogens
D1 D2 D3
-Ceftriaxone 2 g iv +
azithromycin 500 mg iv
18.600
7
12.500
12
10.420
6
WBC
CRP
T
Ab anti-Legionella pneumophila: negative
Swab: bacteria and fungi: neg
Urinary antigens LP and SP: negative
Blood culture: negative
Ab anti-Mycoplasma: IgG negative and IgM negative
Naso-pharyngeal swab DNA CP, MP, LP: negative
0.30 0.25 0.10PCT

51. D1 D2 D3
-Ceftriaxone 2 g iv +
azithromycin 500 mg iv
18.600
7
12.500
12
10.420
6
WBC
CRP
T
0.30 0.25 0.10PCT
9.000
3
0.08
D4

52. ….AND NOW?

53. DISCHARGED ON DAY 6

65. Pneumonia and Cardiovascular events
PATHOPHYSIOLOGICAL MECHANISMS
Corrales-Medina. Lancet 2012

67. Which patients in hospital are at risk?
Lines and
Medical devices
Burns
Renal dialysis
Transplant
recipients
Cancer
Post-surgery
High dependency
Elderly
Neonates
Hospital

68. HAP
(SENTRY surveillance system - n=31,436)
Jones et al – CID 2010
Incidence, %
Pathogen All regions
United
States
Europe
Latin
America
Staphylococcus aureus 28.0 36.3 23.0 20.1
Pseudomonas aeruginosa 21.8 19.7 20.8 28.2
Klebsiella spp. 9.8 8.5 10.1 12.1
Escherichia coli 6.9 4.6 10.1 5.5
Acinetobacter spp. 6.8 4.8 5.6 13.3
Enterobacter spp. 6.3 6.5 6.2 6.2
Serratia spp. 3.5 4.1 3.2 2.4
Stenotroph. maltophilia 3.1 3.3 3.2 2.3
Streptococcus pneumoniae 2.9 2.5 3.6 2.4
Haemophilus influenzae 2.7 2.5 3.7 1.3

69. MRSA trends, Europe
EARS-NET

70. MDR Gram-negatives causing pneumonia
Pseudomonas aeruginosa
Acinetobacter
Enterobacteriaceae
Stenotrophomonas maltophilia

71. 0
5
10
15
20
25
30
35
40
2006 2007 2008 2009 2010 2011
EARS-NET
Proportion%
Year
AMG
FQ
NEM
PIP
CAZ
Pseudomonas aeruginosa resistance trends, Italy

72. 0
5
10
15
20
25
30
35
40
45
50
2005 2006 2007 2008 2009 2010 2011
Proportion%
Year
Klebsiella pneumoniae and resistance to
3rd gen. cephalosporins and fluoroquinolones, Italy
EARS-NET
R to 3GC
R to FQ
Increasing role of carbapenems

73. Giani et al – JCM 2009
Santoriello et al – unpublished
Fontana et al – BMC Res Notes 2010
Marchese et al – J Chemother 2010
Ambretti et al – New Microb 2010
Gaibani et al – Eurosurv 2011
Mezzatesta et al – CMI 2011
Agodi et al – JCM 2011
Richter et al – JCM 2011
Di Carlo et al – BMC Gastroenterol 2011
Rossolini GM – unpublished
late 2008
The first reported
cases of KPC-Kp
KPC-producing K. pneumoniae – the Italian epidemic
early 2011
AMCLI – CoSA CRE network
Frasson et al – JCM 2012
ARISS – CoSA survey 2012
late 2012

74. AMCLI-CoSA – Italian national surveillance 2011
CRAB detected in ALL CENTERS
Nationwide cross-sectional survey, 2011
(6 weeks / 25 centers / N=585 isolates)
Carbapenem-R Acinetobacter, Italy

75. 0
10
20
30
40
50
60
70
80
90
100 C-02
C-19
C-01
C-25
C-09
C-13
C-16
C-23
C-21
C-08
C-20
C-17
C-11
C-14
C-12
C-05
C-03
C-15
C-07
C-06
C-04
C-24
C-18
C-22
C-10
CRAB proportion by center – Italian surveillance
Centers
CRABproportion(%)
AMCLI-CoSA – Italian national surveillance 2011
Mean, 43%

77. CASE 3

78. Female, 86 y/o
She was referred to our ER because of a 7-day history of dyspnea. She
also reported a history of recurrent urinary infections
Her past history was remarkable for:
- NIDDM associated with retinopathy
- Chronic vascular encephalopathy
- Essential hypertension
- Left knee joint prosthesis (25 years back)
She was on: aspirin, ibesartan, nifedipine, metformin, furosemide
She was a former worker. Non-smoker. Non-allergic.
She was admitted to the internal medicine department with a diagnosis
of decompensated chronic heart failure.

79. AFTER 4 DAYS
BP: 190/90 mmHg
HR: 115 bpm
RR: 26 bpm
T: 39 °C
SpO2: 88% in RA
Glucose: 369
Abnormal chest sounds (rales and
rhonchi) were detected bilaterally in the
lower lobes
EKG: sinusal rhythm; HR 115, PQ: 0.20,
no modifications of ventricular
reporalization

81. Your Diagnosis?

82. VentiMask (FiO2: 50%)
BP: 190/90 mmHg
HR: 115 bpm
RR: 26 bpm
T: 39 °C
SpO2: 88% in RA
Glucose: 369
Abnormal chest sounds (rales and
rhonchi) were detected bilaterally in the
lower lobes
EKG: sinusal rhythm; HR 115, PQ: 0.20,
no modifications of ventricular
reporalization

83. WHICH TREATMENT?

84. In the ward (Internal Medicine):
- Ceftriaxone 2 gr
- Levofloxacin 500 mg x 2 EV
Pneumonia screening: sputum/BAL; blood culture, urinary antigens,
serology for atypical pathogens
D1 D2 D3
Ceftriaxone 2gr
22.220
19
18.700
18
17.400
18
WBC
CRP
T
Levofloxacin 500 q12
Ab anti-Legionella pneumophila: negative
Swab: bacteria and fungi: neg
Urinary antigens LP and SP: negative
Tracheal aspirate: GRAM POSITIVE
Blood culture: pending
Ab anti-Mycoplasma: IgG negative and IgM negative
Naso-pharyngeal swab DNA CP, MP, LP: negative
0.44 0.42 0.49PCT

85. WOULD YOU CHANGE?

87. Ceftriaxone 2gr
22.220
19
18.700
18
17.400
18
WBC
CRP
T
Levofloxacin 500 q12
0.44 0.42 0.49
Vancomycin 500 mg in 50 cc F at 5 ml/h
Stop
D1 D2 D3
PCT

88. Ceftriaxone 2gr
22.220
19
18.700
18
17.400
20
WBC
CRP
T
Levofloxacin 500 q12
0.44 0.42 ---
Vancomycin 500 mg in 50 cc F at 5 ml/h
12.800
14
0.28
11.000
11
0.21
11.550
12
0.20
11.400
13
0.20
D1 D2 D3 D4 D5 D6 D7
PCT

89. DAY 8:
Episode of ACPE with sudden dyspnea and hypoxemia. Good response
with furosemide, nitroderivates and helmet CPAP.
On Day 8, once the episode of
ACPE was treated, patient was on
CPAP…

90. After 2 hours from that CXR, patient was still on CPAP:
Sudden hypoxemia with a SpO2 of 88% on CPAP - 10 cmH2O and FiO2:
40%-
BP: 160/90
HR: 110 R
RR: 24 bpm
Active urinary
output
CPAP
10 cmH2O
FiO2: 80%
SpO2: 80%
BP: 160/90
HR: 110 RS
RR: 24 bpm
Active urinary
output
Hypoxemia was unresponsive to high pressures and FiO2
Echocardiograpy: Normal RA and RV
Normal LV function

92. Because of the CXR findings, patient underwent Thorax CT scan:

93. Because of the CXR findings, patient underwent Thorax CT scan:

94. Levofloxacin 500 q12
Vancomycin 500 mg in 50 cc F at 5
ml/h
12.800
14
0.28
11.000
11
0.21
11.550
12
0.20
11.400
13
0.20
Blood was found during a bronchoscopy with a SpO2 75%  98%.
Patient was put on Ventimask 35%
Stop
Stop
Linezolid 600 mg q12 EV
Tobramycin EV
Imipenem 1 g q8 EV
D5 D6 D7 D8
WBC
CRP
T
PCT

95. EXITUS on DAY 10

97. HAP or VAP
Obtain lower respiratory tract sample for culture
(quantitative or semiquantitative) & microscopy
Begin empiric antimicrobial therapy using algorithm and
local microbiologic data (unless low clinical suspicion and
Negative microscopy of LRT sample)
Days 2 & 3: Check cultures & assess clinical response:
(Temperature, WBC, CXR, Oxygenation, sputum purulence,
Haemodynamic changes and organ function)
Clinical Improvement at 48-72 hours?
Am J Respir Crit Care Med 2005;171:388-416

98. HAP, VAP
Clinical Improvement at 48-72 hours?
NO YES
Cultures - Cultures + Cultures - Cultures +
Search for other
Pathogens,
Complications,
Other Diagnoses
or Other Sites of
infection
Adjust antibiotic
Therapy, search
For other
Pathogens,
Complications
Or other sies
Of infection
Consider
Stopping
antibiotics
De-escalate
Antibiotics, if
Possible.
Treat selected
Patients for
7-8 days and
reassess
Am J Respir Crit Care Med 2005;171:388-416

99. HAP, VAP
Late onset (5days) or risk factors for
multidrug resistant pathogens
NO YES
Limited Spectrum
Ceftriaxone (1 x 2g) or
Fluoroquinolone (Levofloxacin 1x750mg or
Moxifloxacin 1x400mg) or
Ampicillin / sulbactam (3x3g) or
Ertapenem (1x1g)
Broad Spectrum
Antipseudomonal cephalosporin (Ceftazidime 3x2g)
or
Antipseudomonal carbapenem (Imipenem/Cilastin
3x1g, Meropenem 3x1g)
or
-lactam/-lactamase inhibitor (Piperacillin/tazobactam
3x4.5g)
Plus
Antipseud fluoroquinolone (Ciprofloxacin 3x400mg,
Levofloxacin 1x750mg)
or
Aminoglycoside (Amikacin 15mg/kg/d divided bid, max
1.5g/d)
(MRSA – linezolid (2x600mg) or vancomycin (2x1g
initial, control blood levels))
Am J Respir Crit Care Med 2005;171:388-416

101. • The lack of initial improvement in PaO2/FiO2, along with an
increase in the SOFA score, was the two clinical evolutionary
findings that predicted mortality in a multivariate model.
• These feasible and low-cost variables should be evaluated in
future trials to test interventions in patients with ICUAP.

102. Four Major Principles
1. Avoid inadequate treatment
2. Variable bacteriology between hospital sites
and over time
3. Avoid antibiotic overuse – accurate diagnosis and
pathogen directed therapy
4. Prevention strategies for modifiable risk factors
Am J Respir Crit Care Med 2005;171:388-416