1. Quali sono i principali tipi di infezione?
E come si manifestano?
Dr Vincenzo Galati
INMI L. Spallanzani

2. PRINCIPALI LOCALIZZAZIONI DELLE
INFEZIONI NOSOCOMIALI
varie
18%
vie urinarie
30%
cute
6%
app.
sito chirurgico app.
digerente
14% respiratorio
8%
24%
Fonte: NNIS

3. HAI IN ICU
US NHSN 2006-2007 EUROPE EPIC 2 - 2007
• lungs 64%
• abdomen 20%
• bloodstream 15%
• renal tract/genitourinary
system 14%
JAMA, December 2, 2009—Vol 302, No. 21

4. HAI IN ICU

5. HAI IN ICU

7. Pneumonia classification
CAP

8. Pneumonia classification
CAP
HAP

9. Pneumonia classification
CAP
non-VAP
HAP
VAP

10. Pneumonia classification
CAP
HCAP
non-VAP
HAP
VAP

11. Pneumonia classification
CAP
HCAP NHAP
non-VAP
HAP
VAP

12. PATOGENESI DELLA VAP
ENDOGENA ESOGENA
Colonizzazione del
Colonizzazione del
circuito ventilatorio,
tratto aereo-digestivo
contaminazione
superiore (EGNB)
luminale (crociata)
Aspirazione Inalazione
Colonizzazione del tratto respiratorio
inferiore
POLMONITE

13. POLMONITE - Diagnosi microbiologica
 Coltura dell’espettorato: può riflettere una colonizzazione
dell’orofaringe, più che la presenza di microrganismi nelle basse vie
respiratorie. CRITERI DI BARTLETT per giudicare l’adeguatezza del
campione: >25 leucociti e <10 cellule epiteliali per campo.
 Coltura da sangue o liquido pleurico (in casi piuttosto rari).
 Da aspirato endotracheale, BAL (bronchoalveolar lavage), o PSB
(protected specimen brush) (effettuati più spesso su pazienti intubati);
 Colture quantitative (da aspirato endotracheale, BAL o PSB) :
vengono utilizzate per distinguere la colonizzazione/contaminazione
all’infezione.

14. N Engl J Med 362;19 may
13, 2010

15. VAP - FATTORI DI RISCHIO
Chastre J, Fagon JY. Am J Resp Crit Care Med, 2002

16. Timing e microbiologia
•VAP precoce (Early onset): durante i primi 4 giorni- MSSA, H.
influenzae, S. pneumoniae, Enterobacteriaceae
•VAP tardiva (late onset): dal 5° (7°) giorno- P. aeruginosa,
Acinetobacter spp, MRSA, bacilli gram-negativi antibiotico-
multiresistenti
•HAP ad insorgenza precoce (entro 3-5gg): S. pneumoniae, H.
influenzae, M. catarrhalis
•HAP ad insorgenza tardiva (dopo 5 gg): Enterobacteriaceae
(K.pneumoniae, Enterobacter spp, E. coli), P. aeruginosa
Am J Infect Contr 24:380, 1996; Crit Care Clin 14:119,1998; Am J Respir Crit Care Med 165:867-903, 2002

17. CAP
 Incidence: 3-40 cases /1,000
population per year
- 80 % outpatient: low risk of mortality
- 18% non-ICU inpatient: 5-8% mortality
- 2% ICU inpatient: 10-20% mortality
 Hospitalization rate is increasing in recent years up to
40-60%, mainly among elderly patients and those with
multiple comorbidities
Fry AM et al. JAMA 2005,
Torres and Rello Am J Resp Crit Care Med 2010
Ruuskanen O et al. Lancet 2011

18. CAP
Expected CAP pathogen distribution, by site of care
Outpatient Non-ICU inpatient ICU inpatient
S. pneumoniae S. pneumoniae S. pneumoniae
M. pneumoniae M. pneumoniae S. aureus (CA-MRSA)
H. influenzae C. pneumoniae Legionella sp.
C. pneumoniae H. influenzae Gram-negative bacilli
Resp. viruses Legionella sp. H. Influenzae
Aspiration pneumonia
Resp. viruses
File TM. Lancet 2003
Vardakas KZ Eur Respir J 2009

19. HAP-VAP
 Incidence: 5-10 cases/1,000 admitted patients
- increasing 6-20 folds in mechanically ventilated pts
- VAP incidence: 20%, 10-15 cases/1,000 days of MV
 Prolonged LOS,
increased healthcare
costs, and a 15–45%
attributable mortality
Hortal J, Giannella M, and Bouza E Intensive Care Med 2009
Esperatti E et al. Am J Respir Crit Care Med 2010
Torres and Rello Am J Respir Crit Care Med 2010

20. HAP-VAP
Causative pathogens of HAP and VAP in the SENTRY
Antimicrobial Surveillance Programme, 2004-2008 (North
America, Europe, Latin America) N=7,496
HAP VAP
S. aureus 26.6% (MRSA 59%) 19.5% (MRSA 51%)
P. aeruginosa 22.4% 26.6%
Enterobacter spp. 7.5% 7%
Klebsiella spp. 10.5% 10.2%
Serratia spp. 4.1% 4.1%
A. baumannii 8.3% 14.3%
CAP pathogens* 2.6% 4.1%
*S. pneumoniae, H. influenzae, M. catarrhalis
Jones RN Clin Infect Dis 2010

21. Origins of HCAP
CAP ATS 1996 HAP, VAP
Morin and Hadler
Community onset MRSA bacteremia
J Infect Dis 2001
Friedman et al. MDR bloodstream infections
Ann Intern Med 2002
Tacconelli et al.
Community onset MRSA bacteremia
JAC 2004
HCAP
ATS guidelines 2005

22. Definition of HCAP
Contact with the health system
Prior Residence in a Chronic IV/wound care at
hospitalization nursing home or hemodialysis home
and/or surgery LTCF Chemotherapy

23. Epidemiology of HCAP patients
 Median age 64-81 years
 High rate of comorbidities (CHF, COPD,
cerebrovascular disease)
 Poor functional status
 Risk factors for aspiration pneumonia
 Treatment restrictions
CAP << HCAP = HAP
Kollef et al. Chest 2005; Carratala et al. Arch Intern Med 2007;
Shindo et al Chest 2009; Venditti et al. Ann Intern Med 2009;
Chalmers et al Clin Infect Dis 2011; Jung et al. BMC Infect Dis 2011

24. The concept of HCAP
 HCAP presents an etiological
pattern similar to that of HAP
 Failure to cover MDR pathogens leads to inadequate
initial antimicrobial coverage and accounts for excess
mortality
 HCAP patients should be identified and treated with
initial broad-spectrum antibiotic therapy

25. NHAP
 Pneumonia is the second most common infection in
nursing home residents
 High mortality (15-60%) and common cause for
hospital transfer
 Functional status may play a role in:
-Risk of drug resistant pathogen
-Mortality
Mylotte JM Drugs Aging 2006
El-Solh et al. AA Clin Infect Dis 2004

29. Infezioni correlate a catetere vascolare

30. CVC-related blodstream infections

31. CVC-related blodstream infections

32. DEFINIZIONI di BATTERIEMIA correlata
a CVC (CDC 2002)
 FEBBRE + SEGNI e SINTOMI di SIRS + in ASSENZA di ALTRE FONTI
d’INFEZIONE
 ISOLAMENTO dello STESSO MICRORGANISMO in EMOCOLTURA da VASO
PERIFERICO e in COLTURA SEMI-QUANTITATIVA del CATETERE
 IN ASSENZA di DATI MICROBIOLOGICI: DEFERVESCENZA /SCOMPARSA DEI
SINTOMI ENTRO 24 h dalla RIMOZIONE del CATETERE VENOSO
 EMOCOLTURE QUANTITATIVE (eseguite in contemporanea) POSITIVE sia da
CATETERE VASCOLARE che da VASO PERIFERICO, con CRESCITA da 5 a 10
VOLTE SUPERIORE nel SANGUE PRELEVATO da CATETERE ovvero con
CRESCITA SIGNIFICATIVAMENTE PIU’ RAPIDA da CVC rispetto a VP.

33. LCBI - Laboratory-confirmed bloodstream infection
LCBI must meet at least 1 of the following criteria:
1. Patient has a recognized pathogen cultured from 1 or more blood cultures
and
organism cultured from blood is not related to an infection at another site.
2. Patient has at least 1 of the following signs or symptoms: fever (>38°C),
chills, or hypotension
and
signs and symptoms and positive laboratory results are not related to an
infection at another site
and
common skin contaminant (ie, diphtheroids [Corynebacterium spp], Bacillus
[not B anthracis] spp, Propionibacterium spp, coagulase-negative
staphylococci [including S epidermidis], viridans group streptococci,
Aerococcus spp, Micrococcus spp) is cultured from 2 or more blood cultures
drawn on separate occasions.

34. BATTERIEMIA CORRELATA A CATETERE
VENOSO- DIAGNOSI
Tempo differenziale di positività della coltura
da catetere rispetto alla coltura da vena
periferica ≥120 min.:
- sensibilità 81% e specificità 92% per
cateteri a breve termine
- sensibilità 93% e specificità 75% per
cateteri a lungo termine
Ann Intern Med 2004; 140: 18-25

36.  Most CRBSIs emanate from the insertion site, hub, or both. For
long-term catheters—particularly tunneled catheters— the catheter
hub is a prominent source of microbes causing bloodstream
infection.
 the 4 groups of microbes that most commonly cause CRBSI
associated with percutaneously inserted, noncuffed catheters
are: coagulase- negative staphylococci, S. aureus, Candida species,
and enteric gram-negative bacilli.
For surgically implanted catheters and peripherally inserted
CVCs, they are coagulase-negative staphylococci, enteric gram-
negative bacilli, S. aureus, and P. aeruginosa [8].

37.  Semiquantitative (roll plate) or quantitative catheter culture
techniques (luminal flushing or sonication methods) are the most
reliable diagnostic methodologies and have much greater specificity
than qualitative broth cultures.
 A recently inserted catheter (i.e., one that had been indwelling for
<14 days) is most commonly colonized from a skin microorganism
along the external surface of the catheter. Thus, the roll-plate method
has high sensitivity.
 Intraluminal spread of microbes from the catheter hub into the
bloodstream is increasingly important for long-term catheters (i.e.,
those that have been indwelling ≥14 days).

38.  Blood cultures that are positive for S. aureus, coagulase-
negative staphylococci, or Candida species, in the absence
of other identifiable sources of infection, should increase the
suspicion for CRBSI.
 Improved symptomatology within 24 h after catheter
removal suggests but does not prove that the catheter is the
source of infection.

40. Although catheter colonization with
accompanying systemic signs of infection suggests
catheter- related infection, a
definitive diagnosis of CRBSI requires positive
percutaneous blood culture results with concordant
microbial growth from the catheter tip or catheter-
drawn cultures that meet the quantitative culture or
DTP criteria.

41. Definizioni di Sepsi, Sepsi Grave e Shock Settico
Da Consensus Conference ACCP/SCCM
Bone RC, Balk RA, Cerra FB e al. American College of Chest
Physicians/Society of Critical Care Medicine Consensus
Conference: Definitions for sepsis and organ failure and
gudelines for the use of innovative therapies in sepsis. Chest
101: 1644-1655, 1992

42. Infezione
Sepsi Shock
Sepsi
grave Settico
Gravità in aumento della risposta
sistemica all'infezione

43. SIRS = sindrome della risposta
infiammatoria sistemica
Infezione/ Sepsi Shock
SIRS Sepsi Settico
Trauma Grave
Risposta infiammatoria sistemica ad una moltitudine di
insulti clinici severi manifestata da due o più delle seguenti
condizioni:
1. Temperatura >38°C o <36°C.
2. Frequenza Cardiaca >90 battiti/min.
3. Frequenza respiratoria >20/min o PaCO2 <32 mm Hg.
4. Conta dei leucociti >12.000/mm3 o <4.000/mm3 o
neutrofili immaturi (cellule "a bande") >10%.
Bone RC, Chest 101: 1644-1655, 1992

44. Sepsi. Risposta infiammatoria
sistemica
Infezione/ Sepsi Shock
SIRS Sepsi Settico
Trauma Grave
La risposta infiammatoria sistemica ad una infezione documentata.
Le manifestazioni della sepsi associate all'infezione sono le stesse
definite per la SIRS (due o più).
Deve essere accertato se tali manifestazioni sono una risposta
sistemica diretta alla presenza di un processo infettivo e
rappresentano un'alterazione acuta rispetto alle condizioni di base
in assenza di altre ragioni conosciute responsabili di queste
anomalie.
Bone RC, Chest 101: 1644-1655, 1992

45. Batteriemia Altro
Fungemia Trauma
Infezione Sepsi SIRS
Viremia Ustioni
Altro Pancreatite

46. Sepsi Grave
Infezione/ Sepsi Shock
SIRS Sepsi Settico
Trauma Grave
Sepsi (SIRS) associata a disfunzione d’organo,
ipoperfusione o ipotensione. L’ipoperfusione e le alterazioni
della perfusione possono includere acidosi lattica, oliguria e
alterazioni acute dello stato mentale.
Bone RC Chest 101: 1644-1655, 1992

47. Ipotensione Sepsi (SIRS) –
Indotta.
Pressione sistolica < 90 mmHg o una
riduzione  40 mmHg
rispetto al basale in assenza
di altre cause di ipotensione.
Bone RC, Balk RA, Cerra FB e al. American College of Chest Physicians/Society of Critical Care Medicine Consensus
Conference: Definitions for sepsis and organ failure and gudelines for the use of innovative therapies in sepsis.
Chest 101: 1644-1655, 1992

48. Shock settico
Infezione/ Sepsi Shock
SIRS Sepsi Settico
Trauma Grave
Sottogruppo delle Sepsi Gravi e delle ipotensioni Sepsi (SIRS)- indotte
che, malgrado adeguata reintegrazione di liquidi mostrano segni di
ipoperfusione che può includere acidosi lattica, oliguria o alterazione
acuta dello stato mentale.
I pazienti che ricevono agenti inotropi o vasopressori possono non
essere più ipotesi al momento in cui manifestano alterazioni delle
perfusione o disfunzione d'organo, tuttavia dovrebbero ancora essere
classificati come Shock Settico (SIRS).
Bone RC, Balk RA, Cerra FB e al. American College of Chest Physicians/Society of Critical Care Medicine
Consensus Conference: Definitions for sepsis and organ failure and gudelines for the use of innovative therapies
in sepsis. Chest 101: 1644-1655, 1992

49. Sindrome da Disfunzione d'Organo
Multipla (MODS)
Presenza di alterazione della
funzione d'organo in un paziente
acuto tale che l'omeostasi non possa
essere mantenuta senza intervento.
Bone RC, Balk RA, Cerra FB e al. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions
for sepsis and organ failure and gudelines for the use of innovative therapies in sepsis. Chest 101: 1644-1655, 1992

50. Levy et al, Crit Care Med 2003

51. Levy et al, Crit Care Med 2003

53. Objective: To define the frequency and prognostic
implications of SIRS criteria in critically ill patients
hospitalized in European ICUs
Design and setting: Cohort, multicentre, observational
study of 198 ICUs in 24 European countries.
Patients and interventions: All 3,147 new adult admissions
to participating ICUs between 1 and 15 May 2002 were
included. Data were collected prospectively, with common
SIRS criteria.

58. Discussion
ICU outcome did not differ according to individual SIRS criteria at admission,
and the maximum number of SIRS criteria did not differ according to the site of
infection or stage of sepsis
There was, however, a higher frequency of three or four SIRS criteria vs. two
SIRS criteria in infected then in non-infected patients.
 All infected patients had at least two SIRS criteria
As the number of SIRS criteria at the time of admission increased, mortality
increased in patients without infections and also for those patients with
infections at the various grades of sepsis.
It is clear from this study and others that SIRS has a great prognostic
importance in predicting infections, length of stay, severity of disease, organ
failure and outcome.

59. GRAZIE PER L’ATTENZIONE