Prof George Dimopoulos MD,PhD,FCCP
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1 14 th Symposium on Infections and Sepsis Porto, 1-3 April 2009 Outbreak control Prof George Dimopoulos MD,PhD,FCCP Department of Respiratory and Intensive Care University Hospital ATTIKON Medical School, University of Athens
2 Glossary used for outbreaks
3 Benchmark - Use of either internal or external information to compare a sample to a population Baseline - Objective quantitative data collected to determine endemic infection rates or rates of risk factors in a population Cohort - A group of patients exposed to a common factor(s) who are compared to an unexposed group to see what the effect of the factor is on the disease or situation.
4 Cohorting - Grouping of patients or staff members together who have had the same infection or exposure and segregating them from those who have not had the exposure or do not have the infection Colonization - Presence of a microorganism at a body site not associated with active invasion of the host, causing no tissue damage Common (point) source outbreak - Outbreak of infections attributed to the same single exposure source Contamination - The presence of microorganisms on inanimate objects or in substances
5 Denominator - Number to be divided by, which represents the population at risk Endemic - The usual or expected occurrence of disease Epidemic - An excess over the expected incidence of disease within a geographic area or population, during a specific time frame Epidemiology -The study of the distribution and determinants of disease Nosocomial infection - An infection acquired h after the admission
6 What is an Outbreak? An increase over the background or 'endemic' rate of infection in a geographic area (f.i ICU) with a particular microbe (f.i methicillin-resistant Staphylococcus aureus) or of a specific type of infection such as SSI or BSI. Only 8% of BSI are related to an outbreak Checko PJ: Text of Infection Control and Epidemiolog T (2000 edition). Washington DC, 2000, pp , Doebbeling BN, Prevention and Control of Nosocomial Infections (ed 2). Boston, MA, Little, Brown, 1992, pp
7 Outbreaks I. - the procedure for the definition - I. The gold standard definitions of NNIS II. The NNIS system collaboration between 315 voluntary member hospitals and the CDC III. Member hospitals follow the NNIS definitions for infection and then submit their infection surveillance data to the CDC Division of Healthcare Quality Promotion, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services: National Nosocomial Surveillance System Report Data Summarv January 1992-June Am J Infect Control :
8 Outbreaks II. - the procedure for the definition - IV. CDC - pools the data - creates benchmarks for both infection rates and device utilization - publishes the data for other hospitals to use as a comparison The infection ratio denominator used by the CDC NNIS system is device days Division of Healthcare Quality Promotion, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services: National Nosocomial Surveillance System Report Data Summarv January 1992-June Am J Infect Control :
9 How to approach an Outbreak? 3 main Steps 1. to confirm that an outbreak exists 2. a multidisciplinary team should be formed 3. a literature search should be conducted once an outbreak has been detected
10 Once an ourbreak has been confirmed Alert - hospital administration, - patients, - specific services environmental cleaning biomedical engineering respiratory therapy pharmacy occupational health service
11 Once an ourbreak has been confirmed Microbiology department keep all related specimens and isolates for further molecular testing clinical specimens, surveillance cultures of patients, staff, and the environment that are obtained as part of the outbreak investigation
12 Once an ourbreak has been confirmed Multidisciplinary team - immediate measures to prevent colonization and/or infection and to plan strategies to identify new cases.
13 Finding the Source (I) Patient care items - medications, enteral feeds, equipment Person-to person transmission Environmental reservoirs Environmental reservoirs - Contamination of infusions, enteral feeds, medications may occur during manufacture is referred as "intrinsic" contamination
14 Environmental reservoirs In this case - the products are contaminated before they reach the hospital and staff practices are not implicated in the outbreak. Outbreaks of intrinsically contaminated products Outbreaks of intrinsically contaminated products - can span large geographical areas and may require assistance from wordwide recognized organizations (CDC, FDA)
15 Water environment and colonization of ICU patients with Pseudomonas aeruginosa Prospective, single-centre study in two adult ICUs Environmental samples from the water fittings of rooms once per week, during a 8-week period P. aeruginosa = in 193 (86.2%) of the 224 U-bend samples and in 10 of the 224 samples from the tap (4.5%) 17 / 193 patients were colonized 1 / 17 patients was colonized by a clone present in the water environment of his room before the patient s first positive sample Water fittings seem to play a smaller role in non-epidemic situations than expected. Cholley et al, Intensive Care Med (2008) 34:
16 Finding the Source (II) Efforts to locate the source of an outbreak include assessment and culturing - staff - equipment and/or - the environment.
17 Person-to-Person Transmission Transfer of organisms from the hands of healthcare workers - Transiently or persistently colonized with organisms from patients or contaminated equipment (blood pressure cuffs, stethoscopes, or bedrails) The organisms the patients Other person-to-person transmission staff members are either working while ill have lesions or rashes on their skin or have asymptomatic carriage of organisms such as methicillin resistant S. aureus
18 The role of Surveillance Surveillance systematic approach using standardized definitions for infection, providing a means to recognize problems and to effectively target infection control measures Haas JP et al. Seminars in Perinatology 2002; 26(5 )
19 Development of a surveillance program Involves - selection of definitions of infections - determination of the types of infection - monitoring of the methods of cases finding - denominator data Haas JP et al. Seminars in Perinatology 2002; 26(5 )
20 Surveillance of microbial resistance in European Intensive Care Units 35 ICUs Microbial resistance, antibiotic consumption and infection control stewardship measures were evaluated Median (range) antibiotic consumption 1,254 (range 348 4,992) DDD per 1,000 occupied bed days The proportion MRSA median 11.6% (range 0 100) ESBL phenotype of E. coli 3.9% (0 80) and K. pneumoniae 14.3% (0 77.8) carbapenem resistant P. aeruginosa 22.5% (0 100) Wide variation in antibiotic consumption, microbial resistance and infection control measures. Hanberger et al, Intensive Care Med DOI /s y
21 Concordance between VAP and BSI pathogenic isolates and prior respiratory tract (RT) or gastrointestinal tract (GT) colonization Surveillance cultures Acinetobacter, Pseudomonas, Klebsiella VAP - PPV = 67 94% - NPV = % Bacteremia - PPV = 43 54% - NPV = % Surveillance-guided initial antibiotic therapy - appropriate in 91 and 86% of patients with VAP and bacteremia, respectively. Papadomichelakis et al Intensive Care Med (2008) 34:
22 Pattern of MRSA carriage screening swabs Batra et al, Intensive Care Med (2008) 34: (34%) patients were detected only by throat or rectal swabs Combined throat and rectal swabs had higher sensitivity than pooled keratinised skin swabs (76 vs. 60%, p = ) Swabs from all carriage sites together detected 95% (100) of MRSA positive patients, with five patients being positive at wound sites only.
23 Acinetobacter spp. Outbreaks Villegas et al, Infect Control and Hosp Epidemiol 2003;24: All studies were descriptive, 75% of the reports described ICU-related outbreaks or clusters
24 Outbreak of Infection with a Multiresistant Klebsiella pneumoniae Strain Associated with Contaminated Roll Boards in Operating Rooms van t Veen et al, J Clin Microbiol 2005, p
25 The contribution of beds to healthcareassociated infection Only the bedrail is evaluated Potential reservoirs of infection mattresses and pillows All the bed components have to be adequately decontaminated to minimise the risk of crossinfection In outbreaks,investigation assessment of mattresses and pillow contamination Creamer et al, Journal of Hospital Infection (2008) 69, 8e23
26 Reported outbreaks VIM-producing E. coli VIM-producing K. pneumoniae MBL-producing P. mirabilis MBL-producing Enterobacter cloacae, E. aerogenes, Morganella morganii, Providencia stuartii Vatopoulos A. Eurosurveillance 2008;23(1-3):1-6
27 Components of a Surveillance Program for Healthcare-acquired acquired Infections Variable Options for Data Positive~Negative Attributes Standard Infection Definitions Type of infection CDC-NNIS Vermont Oxford Hospital specific NNIS Catheter related BSI, UTI, SSI and ventilator-associated pneumonia. All BSI, UTI, pneumonia, conjunctivitis, skin infection, gastroenteritis. All sites of infection in the unit Can compare to NNIS. Selected infections only, no specific pathogen information recorded. Compare to self Compare to self over time only Can compare to NNIS Compare to self over time only Assess for problem infections in unit
28 Components of a Surveillance Program for Healthcare-acquired acquired Infections Variable Case-finding Options for Data Microbiology laboratory reports Pharmacy record surveillance Radiology report surveillance Chart review. Combination Positive~Negative Attributes Recognition of the source Usually not specific enough. Review of the charts with use of microbiology / pharmacy / radiology systems. Denominator No. of cases/100 patient discharges No. of cases/100 patient-days No. of cases/100 procedures No. of cases/i,000 device-days Easily obtained /not comparable with NNIS. Used for SSI surveillance Comparable with NNIS / not routinely obtained by hospital
29 Clinical microbiology issues MICs - CLSI or EUCAST standards - Various automatic sensitivity testing systems Discrepancies = phantom zone Discrepancies = phantom zone - Etest strips containing imipemen and EDTA produce a synergy image between imipenem and EDTA
30 Rapid laboratory detection of carbapenemresistant Enterobacteriaceae (CRE) PCR a highly sensitive and specific method is unavailable for daily use in many laboratories new chromogenic medium, CHROMagar KPC CHROMagar Orientation supplemented with agents that inhibit the growth of gram-positive/gram-negative carbapenem-sensitive bacteria. Samra et al, J Clin Microb 2008, p
31 Molecular epidemiology issues I. Genes - f.i. VIM-1 type (gene cassete) or VIM-2 - type base element and number of nucleotides II. Integrons - different structure suggests a different evolution process rather than a transfer - various transposons III. Plasmids
32 REP-PCR PCR molecular typing Patient A bloodstream infection A1 blood, A2 tracheal aspirate, A3 stool, A4 pus Patient B VAP B5 tracheal aspirate, B6 BAL Patient C VAP C7 tracheal aspirate, C8 stool, C9 BAL, C10 pus Patient D bloodstream infection, D11 stool, D12 blood Papadomichelakis et al Intensive Care Med (2008) 34:
33 Molecular epidemiology for endemic infections Two isolates that were considered as (A) identical are then considered as (B) different after a third isolate was typed. Blanc et al, Infection, Genetics and Evolution 4 (2004)
34 Genotype analysis of 42 KPC-Kp isolates rep-pcr results (a) 25 isolates from #3 to #27 a single genotype, 5 (from #31 to #35) another clone type (b) a single major KPC-Kp clone was identified among the 42 isolates analysed Endimiani et al, Journal of Antimicrobial Chemotherapy doi: /jac/dkn547
35 Use of antibiotics - biological markers - how to break the vicious circle of resistance
36 The soluble triggering receptor expressed on myeloid cells-1 in bacterial infection strem-1 represents a reliable biological marker of bacterial infection, not a sufficient biological marker for infection of the urinary tract as a result of its low sensitivity. sensitivity, 0.82 (95% CI, ) specificity, 0.86 (95% CI, ) Whether strem-1 guidance can reduce antibiotic use as well as the measurement of strem-1 in different types of infection will require additional prospective studies. Jiyong et al, Intens Care Med DOI /s z
37 Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia ROC curves day-1 PCT (bold line) PCT increase (dotted line) areas under the curves of 0.51 (95% CI ) and 0.62 (95% CI ) Crude values and procalcitonin rise had poor diagnostic value for VAP and thus should not be used to initiate antibiotics when VAP is clinically suspected Luyt et al, Intensive Care Med (2008) 34:
38 Serial Procalcitonin to Guide Duration of Community-Acquired Pneumonia Therapy (ProCAP Study) 302 Swiss patients with radiographic communityacquired pneumonia randomized to procalcitonin (PCT)-guided vs standard treatment Antibiotic treatment Strongly discouraged at <0.1 µg/l Discouraged at <0.25 µg/l Encouraged at >0.25 µg/l Strongly encouraged at >0.5 µg/l Measure PCT on admit, 6 24 hours (if withheld), days 4, 6, and 8 28% with PCT <0.25 µg/l and 15% in PCT group as a whole had antibiotic withheld Shorter duration of treatment in PCT group vs control group (median of 5 days vs 12 days, respectively) 8% were not withdrawn from treatment despite recommendation from algorithm Antibiotic started P<0.001 Time to Antibiotic Discontinuation (Days) Christ-Crain M, et al. Am J Respir Crit Care Med. 2006;174:
39 The vicious circle of antibiotic overuse Marc Leone and Claude Martin Current Opinion in Critical Care 2008, 14:
40 The vicious circle can be broken by a good knowledge of each parameter interfering with antibiotic prescription. Marc Leone and Claude Martin Current Opinion in Critical Care 2008, 14:
41 Algorithm to assist the decision for treating patients with life-threatening infection in intensive care unit Leone et al 2007, Leone et al 2003, American Thoracic Society 2005
42 Categories of Isolation Precautions, Protective Measures and Relevant Pathogens Isolation Precautions for Hospitalized Patients Personal Protective Equipment Engineering Controls Needed Pathogens Standard Gown if soiling of uniform likely, Gloves if coming into contact with body secretions, excretions or open lesions, Mask and eye protection if splashing of body fluids is anticipated No specific pathogen used for all patients all the time Contact Gown, gloves Multi-drug resistant organisms, respiratory syncytial virus, rotavirus Droplet Gown, gloves regular surgical mask Influenza, pertussis, adenovirus Airborne N-95 respirator (for TB) Negative pressure environment Tuberculosis, measles, varicella
43 Conclusions Outbreal control - alert - multidisciplinary team - identification of the source - isolation of the patients - surveillance program
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