by author Epidemiology of infections in the ICU

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1 Epidemiology of infections in the ICU Anastasia Antoniadou Internal Medicine Infectious Diseases Assistant Professor Athens University Medical School University General Hospital ATTIKON

2 Epidemiology of infections in the ICU Contemporary published information about infection surveillance data in the ICU setting from surveillance systems and multicenter studies Definitions Common sites of ICU-acquired infections, rates and pathogens The problem of drug resistant microorganisms Emerging pathogens Infection outbreaks

3 Epidemiology of infections in the ICU Infections in the ICU are a significant cause of morbidity, mortality and cost 20% of patients develop infection during their ICU stay In point prevalence studies (PPS), prevalence of nosocomial infections on any given day in acute care hospitals is on average 7%. This value climbs to 48-51% for ICU patients Length of stay(los) and mortality for infected patients is considerably increased, as well as are healthcare costs

4 Epidemiology of infections in the ICU ICU-acquired infections =infections presenting 48 hours or more after ICU admission Device- associated infections in the ICU(DAI)= Infections presenting with the device at least 48 hours in place (except for urinary catheters which should be 7 or more days in place) CDC s definitions have been updated in 2005 and the European s of HAI-NET have been recently set and validated (much similar) All recorded infections are symptomatic and documented

5 Epidemiology of infections in the ICU The most common infections in the ICU have been for decades LRTI, BSI, UTI, followed by SSI (abdomen) The majority of them >80% related to a device

6 10.50% 17% Common sites of infection in the ICU Nosocomial infections whole hospital 19.30% 27% UTI 24% ECDC NI EPIDEMIOLOGICAL REPORT LRTI SSI BSI OTHER ICU-Acquired infections CDC/NHSN 35.30% 18.60% 30.10% 15.90% CAUTI VAP SSI CLABSI 31% 40% CAUTI 9% 20% Infect Control Hosp Epidemiol 2008;29:996 Am J Infect Control 2009;37:783 VAP SSI CLABSI

7 Common sites/rates of infection in the ICU Catheter related blood-stream infections (CLABSI) Ventilator associated pneumoniae (VAP) Catheter- associated urinary tract infections (CAUTI) The infections included in the ICU-Infections surveillance systems and point prevalence major studies Rates are followed as quality indicators Rates are expressed as number of infections per 1000 device days. In multicenter networks the pooled mean value is presented

8 Common sites/rates of infection in the ICU The National Healthcare Safety Network (NHSN)(former NNIS) >1500 healthcare facilities ICU TYPE CLABSI VAP CAUTI CORONARY CARDIOTHORACIC MEDICAL MED/SURG SURGICAL NEUROSURGICAL PEDIATRIC TRAUMA BURN RESPIRATORY NICU AJIC 2004;32:470 AJIC 2009;37:783 NHSN Data summary 2009 at

9 Common sites/rates of infection in the ICU International Nosocomial Infection Control Consortium (INICC) Founded in Argentina in Includes 173 ICUs from 25 countries from Latin America, Asia, Africa and Europe, considered with low resources. Methodology of surveillance is the NHSN s and definitions of infections the CDC s Surveillance includes also LOS, mortality and hand hygiene compliance First report presents the surveillance data 155,358 patients and 923,624 patient/device days Device utilization rate was similar to NHSN Am J Infect Control 2010;38:95-106

10 Common sites/rates of infection in the ICU INICC ICU TYPE CLABSI VAP CAUTI HAND HYGIENE COMPLIANCE CORONARY % S/CARDIOTHORASIC % MEDICAL % MED/SURG % NEUROSURGICAL % PEDIATRIC % SURGICAL % TRAUMA % BURN % NICU % OVERALL Am J Infect Control 2010;38:95-106

11 MORTALITY/ LOS Infection in the ICU : INICC CRUDE MORTALITY RATE ADULTS WITHOUT HAI 14.4% 5 LOS ADULTS WITH CLABSI 38.1% 17.1 ADULTS WITH VAP 43.7% 15.6 ADULTS WITH CAUTI 32.9% 14.5 INFANTS WITHOUT HAI 8.1% 11.2 INFANTS WITH CLABSI 34.5% 33.3 INFANTS WITH VAP 27.1% 27.3 Am J Infect Control 2010;38:95-106

12 Comparison of DAI rates, per 1000 device days, in the ICUs of the INICC and the NHSN Am J Infect Control 2010;38:95-106

13 These higher DAI rates may reflect the typical ICU situation in limited-resources countries. in the majority of these countries, there are still no legally enforceable rules or regulations concerning the implementation of infection control programs. adherence to the rules is most irregular hospital accreditation is not mandatory this lack of official regulations is strongly correlated to the considerable variability found in the compliance with hand hygiene guidelines administrative and financial support in most INICC hospitals is insufficient to fund infection control programs and invariably results in extremely low nurse-to-patient staffing ratios (which have proved to be highly connected to high DAI rates in ICUs),hospital overcrowding, lack of medical supplies, and in an insufficient number of experienced nurses or trained health care workers.

14 Epidemiology of infections in the ICU THE EPIC STUDIES EPIC STUDY EUROPEAN PREVALENCE OF INFECTION IN THE ICU EUROPEAN EPIC II STUDY EXTENDED PREVALENCE OF INFECTION AND OUTCOME IN ICU INTERNATIONAL DAY OF PPS : 29/4/1992 DAY OF PPS : 8/5/ ICUs in 17 western European countries 1265 ICUs in 75 countries 667 from W. Europe, 210 from Central/South America, 137 from Asia, 97 from E. Europe, 83 from N. America, 54 from Oceania, 17 from Africa patients patients, 13796>18y JAMA 1995;274:639 JAMA 2009;302:2323

15 Epidemiology of infections in the ICU THE EPIC STUDIES EPIC I EPIC II INFECTED 44.8% 51% ICU-ACQUIRED 20.6% - RESPIRATORY 64.7% 64% UTI 17.6% 14% BSI 12% 15% WOUND 7% - ABDOMEN - 20% POS CX 85% 70% ON ANTIBIOTICS - 71% JAMA 1995;274:639 JAMA 2009;302:2323

16 EPIC I Intensive Care Med 2000;26:S3 VARIATIONS BETWEEN COUNTRIES

17 Infection correlates to increased mortality and LOS CCM 2008;36: % LRTI 30% BSIs

18 88% lung/bsi/uti. All device related 60.4% Gram negatives (20% Acinetobacter), 39.7% Gram positives (25% CNS) 88% on antibiotics 2-3 times higher than NHSN, much lower CAUTI 8 ICUs 19% of ICU pts 28.5/1000 pt/days ICHE 2007;28:602

19 Device-associated infections in the intensive care units of Cyprus: results of the first national incidence study. Total rate: 15.8 infections/1000 pt/days 80.4% BSI/LRTI/UTI. 88% Device-related CLABSI 18.6/1000 device/days VAP 6.4/1000 device/days CAUTI 2.8/1000 device/days Pseudomonas 21.6% (30% carba R) CNS 11.7% Enterococcus 11.3% S.aureus 9.2% (68% MRSA) Crude mortality 33.2% 21.6 LOS post infection Infection 2010; 38: 165

20 Prevalence of infections and mortality VARIATIONS BETWEEN COUNTRIES Intensive Care Med 2000;26:S3

21 EPIC II JAMA 2009;302:2323

22 Epidemiology of infections in the ICU THE EPIC STUDIES Epic II : ICU and hospital mortality were 18% and 24% respectively. Infection increased mortality rates to 25 and 33% respectively and prolonged LOS by more than 14 days Risk factors for death were ICU-acquired pneumonia (1.9), clinical sepsis (3.5) and BSI (1.7), high severity scores and comorbidities Intensive care unit and hospital mortality rates were highest in ICUs from Central and South America and Eastern Europe and lowest in ICUs from Oceania. There was a significant relationship between the percentage of infected patients and hospital mortality. JAMA 2009;302:2323

23 Epidemiology of infections in the ICU THE EPIC II STUDY Infection rates were related to health care expenditure, with higher rates of infection reported in countries that had a lower proportion of gross domestic product devoted to health care (61.9% infection rate in countries devoting 5% of gross domestic product to health; 53.8% in those devoting 5%- 9%; 48.0% in those devoting 9%; P<001) JAMA 2009;302:2323

24 Epidemiology of infections in the ICU THE EPIC STUDIES: Microbiology Library EPIC I EPIC II Lecture S.aureus 30% 20% MRSA 60% 50% CoNS 19% 11% VRE - 3.8% Online Pseudomonas 29% 20% Enterobacteriaceae 34% 36% Acinetobacter 9% 8.8% Fungi ESCMID 17% 19% Infection with Acinetobacter, Pseudomonas or Enterococcus had increased mortality in EPIC II More prevalent in low resources countries

25 May ICUs in 24 European countries 3,147 adult pts admitted and followed up until death or discharge or 60 days of hospitalization 37.4% sepsis (25% ICU-acquired) 40% clinical sepsis 60% with pos cultures Lung 68% Abdomen 22% Candida Acinetobacter Enterobacteriaceae Pseudomonas S.aureus 4% 14% 17% 29% Crit Care Med 2006;34: % 0% 5% 10% 15% 20% 25% 30% 35% ICU-acquired sepsis and pseudomonal sepsis correlated with higher ICU mortality

26 EPIC II SITE OF INFECTION BY GEOGRAPHIC REGION JAMA 2009;302:2323

27 EPIC II JAMA 2009;302:2323

28 KISS : the Hospital Infection Surveillance System of Germany A Network of 586 ICUs Methodology and rates similar to NHSN S.aureus and Pseudomonas the predominant pathogens

29 KISS : Stable MRSA rates, increasing ESBL and VRE rates

30 Resistance is higher in low resource countries

31 DAI in NHSN : Antimicrobial Resistance rates OVERALL RESISTANCE (%) MRSA 56.2% 5% VRE 33.3% 35% P. aeruginosa R FQ R AP-penicillins R CARBA K. pneumonia R 3 rd gen cephal. R CARBA 30.7% 17.5% 25.3% 25% 10% ACINETOBACTER R CARBA 35% - E.Coli R FQ R 3 rd gen cephal. R CARBA 30% 10% 2% Semin Resp Crit Care Med 2011;32:115 %INCREASE RESISTANCE % - 54% 104% % -

32 Epidemiology of infections in the ICU : Microbiology The most common pathogens remain stable the last at least decade: S.aureus, CoNS, Enterococcus, P. aeuginosa, Enterobacteriaceae, Acinetobacter MRSA and VRE were past threats that remain. MRSA rates are decreasing in developed countries, VRE are stable or increasing ESBL producing Enterobacteriaceae are endemic. The new threat of the new decade are the carbapenemase producing microorganisms, posing a challenge to infection control practices by their ease horizontal transmission and the lack of treatment choices due to their multiresistant profile

33 EARS-NET 2009 : MRSA RATES IN EUROPE

34 EARS-NET 2009 : VRE RATES IN EUROPE E. faecalis E. faecium

35 EARS-NET 2009 : klebsiella resistant to 3 rd gen cephalosporins

36 EARS-NET 2009 : klebsiella resistant to FQs

37 EARS-NET 2009 : klebsiella resistant to Carbapenems

38 EARS-NET 2009 : Pseudomonas resistant to FQs

39 EARS-NET 2009 : Pseudomonas resistant to PIP/TAZO

40 EARS-NET 2009 : Pseudomonas resistant to Carbapenems Acinetobacter is 4-85% resistant to Carbapenems (Souli et al. Eurosurveillane 2008)

41 VRE : %, ALL SPECIMENS WHONET - GREECE WARDS ICU

42 MRSA : %, ALL SPECIMENS WHONET - GREECE MEDICAL SURGICAL ICU

43 IMIPENEM RESISTANT ACINETOBACTER (% ALL SPECIMENS ) WHONET GREECE WARDS ICU

44 WHONET GREECE IMIPENEM-R K.pneumoniae (%,all specimens of Greek hospitals ) Medical Wds Surgical Wds ICU

45 WHONET GREECE IMIPENEM-R P.aeruginosa (% all specimens ) Medical Wds Surgical Wds ICU

46 Carbapenemases: the new threat fro public health

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48 Geographic distribution of KPC worldwide Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase producing bacteria. Lancet Infect Dis 2009; 9:

49 Ηealth Prodection Agency. July 2009 Multi-resistant hospital bacteria linked to India and Pakistan A National Resistance Alert, issued in January 2009 [1], warned of an increasing number of carbapenem-resistant strains of Enterobacteriaceae being identified in UK hospital patients, a significant proportion of whom had received medical treatment abroad....this situation resembles that with producers of VIM and KPC carbapenemases where we have seen multiple importations via patients previously hospitalised in Greece, Cyprus and Israel along with locally acquired infections. However the population flow between the UK and the Indian subcontinent is larger..

50 The November 2009 Eurosurveillance report underlines that NDM-1 is spreading across Europe, since between , 77 cases have been reported from 13 European countries (13 cases with possible nosocomial acquisition) Eurosurveillance, 12 November 2009

51 12 year ( ) antibiotic resistance surveillance of Klebsiella pneumoniae collected from intensive care and urology patients in 14 Dutch hospitals A significant increase in resistance among ICU isolates was observed for ceftazidime (4.2%-10.8%), ciprofloxacin (5.8%-18.5%) and trimethoprim/sulfamethoxazole (11.9%-23.1%), and for cefuroxime (2.8%-7.9%)! Among ICU isolates the prevalence of ESBLs increased significantly from 2% to 8%. Carbapenemase production was not demonstrated. Among ICU isolates the prevalence of multidrug resistance increased and has been 12% since Overall, resistance was significantly higher among ICU isolates. JAC 2011;66:855

52 95 participants from 24 European countries Methicillin-resistant Staphylococcus aureus (MRSA) and thirdgeneration cephalosporin resistant Enterobacteriaceae were the most frequently reported antibiotic-resistant bacteria with 69 (73%) and 67 (71%) participants reporting having treated at least one patient with such an infection during the preceding six months, respectively. Fifty (53%) participants declared having treated at least one patient infected with a bacterium totally or almost totally resistant to available antibiotics during the past six months, with 8 participants having treated more than 10 such patients and 13 having treated from 3 to 10 such patients. Eurosurveillance 2009

53 Candida infections epidemiology Candida sp. : the 3 rd more common pathogen in ICU BSI Candida is found in 17-19% of DAI in ICU Candida sp : The highest mortality as a cause of bacteremia Clin Infect Dis. 2004;39:

54 Candida spp epidemiology Species n (%) of each species according to origin ICU (N = 779) Non-ICU (N = 973) C. albicans 393 (50.4) 461 (47.4) C. glabrata 136 (17.5) 176 (18.1) C. parapsilosis 118 (15.1) 184 (18.9) C. tropicalis 82 (10.5) 93 (9.6) C. krusei 16 (2.1) 20 (2.1) Miscellaneous a 34 (4.4) 39 (4.0) Resistance both to azoles and echinocandins was uncommon in ICU and non-icu settings. Overall, fluconazole resistance was detected in 5.0% of ICU isolates. Candida glabrata was the only species in which resistance to azoles and echinocandins was noted. Pfaller MA. Int J Antimicrob Agents 2011 April (Sentry program)

55 Epidemiology of infections in the ICU CA-MRSA ( 10% of ICU MRSA, 30% of newly transmitted in the ICU) Hypervirulent C. Difficile (epidemics, 4% of ICU pts, 20% progression to fulminant colitis with 60% mortality. 17% attributed mortality) Aspergillus ( %, lung or bronchial disease, COPD patients, organ failure, steroids, DM, related to high mortality) CMV (active viremia/antigenemia in 0-36% of immunocompetent ICU patients after 5 days. Related to ICU death, question about active organ disease) Semin Resp Crit Care Med 2011;32:115, J Crit Care 2010;25:282 Infect Dis Clin North Am 2009;23:727 CCM 2009;37:1850, CCM 2009;37:2350 Ιntensive Care Med 2007;33: Clin Infect DIS 2007; 45: 205

56 Epidemiology of infections in the ICU Infection outbreaks may be related to an index case or an environmental source and may herald emerging endemicity for newly identified pathogens Outbreaks in the ICU occur with an estimated frequency of 9.8/100,000 admissions Between , 113 outbreaks in the ICU setting were reported Pneumonia or BSI were the commonest sites of infection Semin Resp Crit Care Med 2011;32:115

57 Epidemiology of infections in the ICU Acinetobacter spp (24%) was the most common isolate followed by Pseudomonas (12%) and S.aureus(12%) 65% of outbreaks involved resistant (mostly multiresistant) gram negatives. 46% involved NICU Compared to a report of the decade , MRSA outbreaks have decreased (9% from 25%) probably because of subsequent endemicity. Resistant gram negatives outbreaks have increased (from 36% to 46%) Probable sources were environmental reservoirs (19%), HCWs (16%), index patients (11%),and medical interventions (7%) Semin Resp Crit Care Med 2011;32:115

58 Epidemiology of infections in the ICU VAP Summary o22-47% OF ICU infections o90% related to mechanical ventilation omultiplies the risk of death by 2-10 times ocrude mortality 24-76% (attributed 33-50%) o /1000 ventilator-days AJRCCM, 15 Feb 2005 Semin Resp Crit Care Med 2011

59 Epidemiology of infections in the ICU BSI in the ICU Summary 27-68/1000 admissions 5-10 times higher incidence compared to wards 20% ICU-acquired (90% central line-associated) 50% Gram positives, 30-40% Gram negatives, 6-17% Candida 13.5 days longer LOS, $ 30,000 cost per survivor In Europe (F, G, It, UK), CLABSI/1000 cath.days, 12% mortality, million euro annual cost J Hosp Inf 2009;72:97, Infect Dis Clin North Am 2009;23:557-69

60 CAUTI Epidemiology of infections in the ICU Summary 20-30% of ICU infections Almost 100% CAUTI Mean rate in NHSN : /1000 cath-days Increases the LOS by 1.6 days In matched studies corrected for severity and morbidity, does not increase ICU mortality Gram negatives predominate, Candida 25%, Enterococci 14% $600 cost per episode J infect 2011;62:136 Crit Care Med 2011; 39:1167 Crit Care Med 2010;38:5

61 CLABSI Extremes of age Underlying illness severity Malnutrition Burns Neutropenia Heavy bacteria skin colonization Remote source of sepsis Hypergycemia RISK FACTORS FOR CLABSI, VAP, UTI VAP Advanced age Uderlying illness severity COPD Cancer diagnosis Impaired airway reflexes Cardiac disease/ arrest Immunosuppressive therapy Malnutririon Reason fornadmission Duration of MV Nasoorotracheal intubation, Duration of catheterization urgent,reintubation, Catheter site tracheostomy Urgent catheterization, over a Self- or accidentalexrubation guidewire, repeated Supine position Cath-related thrombosis Inadequate cuff pressure Parenteral nutririon Aspiration Hemodialysis Anacids, sedatives understaffing Enteral feeeding Maxillary sinusitis Semin Resp Crit Care Med 2011 CAUTI Advanced age Underlying illness severity Female DM Abnormal serum creatinine Rapidly fatal underlying disease Cathetrization other than fro surgery or urine output Duration of catheterization ICU LOS Errors in cath care Bactrial colonization of drainage bag Periurithral colonization

62 Epidemiology of infections in the ICU Infections acquired in the ICU have a stable profile over years Device associated BSI, VAP and UTIs are those surveyed by ICU surveillance systems Systematic surveillance provides the benchmark values we need to validate surveillance of infections in an individual ICU Rates of infection differ by ICU type, by country and by geographic region and by resources provided for healthcare Risk factors for infection and death remain stable over years. Infection is an independent risk factor of death for the infected patient

63 Epidemiology of infections in the ICU S. aureus, Pseudomonas, Enterbacteriaceae, CoNS, Enterococci and Candida are the pathogens predominating for years as cause of ICU infections Emerging microbial resistance and multiresistance is the contemporary threat and challenge for treating phycisians and infection control practicioners. The most recent threat represent the carbapenemase producing microorganisms An ICU infection outbreak in usually the way by which a new resistant pathogen is introduced in the ICU setting

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