An Update: Carbapenem resistant Enterobacteriaceae (CRE) Lynn Ramirez Avila Clinical Epidemiology and Infection Prevention May 26, 2014
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1 An Update: Carbapenem resistant Enterobacteriaceae (CRE) Lynn Ramirez Avila Clinical Epidemiology and Infection Prevention May 26, 2014
2 Outline Definitions Epidemiology Outcomes Treatment Prevention CRE in the UCLA HealthSystem
3 What are Enterobacteriaceae? Enterobacteriaceae Normal flora that inhabit the GI tract Gram negative rods Can cause infections in the community & healthcare setting More than 70 species Klebsiella pneumoniae Escherichia coli Enterobacter sp. Does not include Acinetobacter or Pseudomonas
4 Enterobacteriaceae Account for >21% of device related infections Beta lactam antibiotics have been the primary treatment of these organisms Penicillin derivatives such as cephalosporins, penicillin/beta lactamase combinations, carbapenems Resistance to the Beta lactam antibiotics emerged several years ago Logan CID 2012
5 Carbapenem resistant Enterobacteriaceae (CRE) uncommon prior to 1992 First described in 1996 in North Carolina as part of an outbreak investigation
6 Carbapenem resistant Enterobacteriaceae (CRE) /national/ _1_superbug antibioticresistant hospital borne infections; says nightmare bacteria cresuperbug killing h/
7 CDC Definition CRE Nonsusceptible meropenem, imipenem, doripenem Resistant to 3 rd generation cephalosporins Ceftriaxone, cefotaxime, ceftazadime Most common CRE in the United States Carbapenem resistant Klebsiella pneumonia (CRKP) CRKP produce Klebsiella pneumonia carbapenemase (KPC)
8 Enterobacteriaceae Other Gram negative rods CRE Not a CRE Pseudomonas Acinetobacter KPC NDM 1 IMP VIM OXA Amp C ESBL
9 Enterobacteriaceae Other Gram negative rods CRE Not a CRE Pseudomonas Acinetobacter KPC NDM 1 IMP VIM OXA Amp C ESBL
10 Enterobacteriaceae Other Gram negative rods CRE KPC NDM 1 IMP VIM OXA Not a CRE Amp C ESBL Produce beta lactamases that confer resistance to broad spectrum antibiotics Pseudomonas Acinetobacter Have different resistance mechanisms that confer resistance to broad spectrum antibiotics
11 Are enzymes that breakdown the antibiotic Different types Class A, B, D, MBL Most common is a Class A enzyme KPC plasmid based enzyme Most common clone ST258 Carbapenamases
12 Global Spread of CRE Molton et al CID 2013
13 CRE: A National Problem CDC, Get Smart Campaign materials/week/images/kpcstates.png
14 CRE Incidence Organism Klebsiella pneumoniae 1.6% 11% E coli 1% 1 2% Enterobacter spp. 1.4% 3.6% report 2013/pdf/ar threats pdf#page=53
15 03 vitalsigns.pdf
16 CDC Antibiotic Resistance Threat Report report 2013/pdf/
17 CRE at UCLA
18 How are CRE identified?
19 Susceptibility Profile and conditions/carbapenem resistantenterobacteriaceae/_documents/cdclinicianoutreach.pdf
20 CLSI 2012 Breakpoints
21 Phenotypic Testing Modified Hodge Test (MHT) Not used anymore
22 Who gets CRE?
23 Demographics Marquez et al ICHE 2013
24 Marquez et al ICHE 2013
25 Risk Factors for CRE Increased hospitalizations Prior extended spectrum cephalosporin and fluoroquinolone use Other studies have associated vancomycin Invasive procedures ICU stay Poor functional status Patel et al ICHE 2008
26 Patel et al ICHE 2008
27 03 vitalsigns.pdf
28 report 2013/pdf/
29 Why are CRE Clinically Important?
30 Why are CRE Clinically Important? High mortality rates associated with CRE and CRKP infection
31 CRE and Outcomes
32 Why are CRE Clinically Important? Mortality 50% mortality associated with CRE blood stream infections Pan resistant CRE strains cause 75% mortality Mortality Risk factors age, mechanical ventilation, malignancy, heart disease, and ICU stay Removal of the focus of infection (device, debridement, or drainage) associated with survival Gupta et al CID 2011
33 Why are CRE Clinically Important? Limited treatment options
34 Bad Bugs, No Drugs: Current Resistance Trends
35 CRE Treatment Options Limited treatment options Colistin Polymixin B Tigecycline Many KPC are pan resistant Aminoglycosides Fluoroquinolones
36 New Antibacterial Agents Approved Boucher et al. Clin Infect Dis. 2013; 56: 1685
37 Timeline for Development of a New Medication Stone, Scientific American, blog/2011/10/06/molecules tomedicine clinical trials for beginners/
38 Challenges for Antibiotic Research and Development Smaller market: Antibiotics work well and fast Compared with chronic, long term conditions Limited long term potential Bacteria become resistant!
39 Bad Bugs, No Drugs Infectious Diseases Society of America (IDSA) 2010
40 Why are CRE Epidemiologically Important?
41 Why are CRE Epidemiologically Important Resistance is highly transmissible Between organisms: plasmids and transposons Between patients: HANDS! These organisms are common causes of infection E. coli and urinary tract infections Acuity of patient population has increased dramatically in recent decade Increase number of transplant and oncology patients CRE have been documented in the community setting
42
43 Prevention
44 What do we do now? CRE are not endemic in most of the United States How do we keep it that way
45
46 Prevention Need to practice comprehensive infection control measures. Per CDC: Hand hygiene Contact precautions Education of healthcare workers Cohort staff/patients Notify laboratory Antimicrobial Stewardship CRE contact screening Consider Active surveillance cultures Chlorhexidine bathing CDC Guidance for Control of CRE 2012 CRE Toolkit
47 Transmission Pathways Munoz Price et al, Curr Opin 2013
48 Most important source of transmission of pathogens in the hospital setting Healthcare worker hands
49 Hand Hygiene Adherence in Hospitals Year of Study Adherence Rate Hospital Area 1994 (1) 29% General and ICU 1995 (2) 41% General 1996 (3) 41% ICU 1998 (4) 30% General 2000 (5) 48% General 1. Gould D, J Hosp Infect 1994;28: Larson E, J Hosp Infect 1995;30: Slaughter S, Ann Intern Med 1996;3: Watanakunakorn C, Infect Control Hosp Epidemiol 1998;19: Pittet D, Lancet 2000:356; CDC Hand Hygiene Slide Set
50 Efficacy of Hand Hygiene Preparations in Killing Bacteria Good Better Best Plain Soap Antimicrobial soap Alcohol-based handrub CDC Hand Hygiene Slide Set
51 Contact Precautions CDC Any person colonized or infected with CRE should be placed on Contact Precautions CRE colonization duration unknown though some studies report prolonged period (>6 mo) Risk factors: exposure to antibiotics, admission from another healthcare facility, and <3mos since first CRE test UCLA HealthSystem Any carbapenem resistant Enterobacteriaceae Klebsiella pneumoniae E coli Enterobacter sp. Contact isolation for the hospitalization and subsequent hospitalizations No clearance protocol available CDC Guidance for Control of CRE 2012 CRE Toolkit
52 Other Prevention Measures Healthcare personnel education Focus on hand hygiene and Contact precautions Minimize the use of devices Patient and staff cohorting Single patient room Dedicated staff to care for them Laboratory Notification Laboratory to notify infection prevention of any CRE CRE Screening Of any epidemiologically linked patient of CRE infected/colonized patient CDC Guidance for Control of CRE 2012 CRE Toolkit
53 Antibiotic Stewardship programs (ASP) Limited studies for CRE prevention Two studies include ASP as part of CRE bundle One study evaluated ASP as the sole intervention Reduction in the use of beta lactams ineffective in reducing CRE acquisition Use of fluoroquinolones associated with higher acquisition of fluorquinolone resistant CREs More studies needed to evaluate ASP Current goal to decrease total volume of antibiotics prescribed Munoz Price et al, Curr Opin 2013
54 Infection Prevention Department Pharmacy Director, Information Systems P&T Committee Antimicrobial Stewardship Program Microbiology Infectious Diseases Division Patient Safety Hospital Leadership John et al CID 1997; 24: 471
55 UCLA ASP Back end ASP program Adult: Started July 2010 Pediatric: Started March 2013 Targeted prospective audit with feedback Education/marketing Availability of expertise at the point of care Antibiotic handbook Antibiotic hotline Data monitoring Streamlining/de-escalation IV to PO Redundant coverage Education/marketing
56 UCLA Adult Antibiotic Use
57 The Environment Munoz Price et al, Curr Opin 2013
58 Supplemental Strategies Active surveillance testing Of any patient who may not be epidemiologically linked but who meet certain pre specified criteria Admission from a long term care facility Admission to a high risk setting Chlorhexidine (CHG) Has been used in CRE outbreak situations 3 studies have included CHG as part of their CRE bundle Difficult to assess utility of CHG in these studies as it was part of a package intervention Consider in certain settings CDC Guidance for Control of CRE 2012 CRE Toolkit; Munoz Price et al, Curr Opin 2013
59 Case Study: CRE in the UCLA HealthSystem
60 General Methods CRE defined as any of the Enterobacteriaceae that are resistant to meropenem For analysis, used cultures Jan 1, 2011 Dec 31, 2012 Reviewed patient charts to obtain additional data Each organism per patient was considered to be a separate event; all others were excluded from analysis 60 Serling Boyd, UCLA, 2013
61 Overview of CDC LabID Method Method for collecting and tracking positive lab results Does not take into consideration whether a culture represents colonization or true infection Used to assess burden of disease Separate events are considered to be organisms per patient per calendar month per hospital unit per specimen source Used different method for analysis to adapt data to be more relevant for RR/SM patient population 61 Serling Boyd, UCLA, 2013
62 Monthly number of cultures by facility by year RR SM Number of Cultures Jan Feb Mar Apr May June July Aug Sept Oct Nov Dec Month Number of Cultures Month RR: 76 cultures (35 from 2011; 41 from 2012) SM: 93 cultures (42 from 2011; 51 from 2012) 62 Serling Boyd, UCLA, 2013
63 Cultures by hospital unit (inpatients only) 18 RR 16 Number of Cultures icu 6icu 7icu 8icu 6n 8n emc 7e 7w 5ems pacu ecu 7ccu 2nicu 5picu 3f Hospital Unit RR: 64 inpatients Only takes into consideration discharge condition of admission encompassing positive culture (death during later admission not counted in this measure) 63 Serling Boyd, UCLA, 2013
64 Cultures by hospital unit (inpatients only) 30 SM Number of Cultures emr 2nici 3nw 3swpt 3st 4cwic 4cpic 4mn 4sw 5mn 5nw 6nt 6st 8st ccui sici ped Hospital Unit (SM) SM: 84 inpatients Only takes into consideration discharge condition of admission encompassing positive culture (death during later admission not counted in this measure) 64 Serling Boyd, UCLA, 2013
65 Patients with recent discharge from same facility in past 30 days Percent of patients Recent discharge in past 30 days RR: 76 cultures SM: 93 cultures Recent discharge from other facility or transfer from other hospital not included in this measure 0 RR SM Medical Center 65 Serling Boyd, UCLA, 2013
66 Admitting location (for inpatients only) 60 Percent of Inpatients RR SM Nursing home Home Hospital Other/unknown Admitting Location RR: 64 inpatient cultures, SM: 84 inpatient cultures Location obtained either from admission H&P or patient demographic information, when available Other/unknown include homeless patients (2 from SM) and various other types 66 of homes Serling Boyd, UCLA, 2013
67 40 Distribution of days from admission to positive culture Number of Cultures RR SM >30 Day or Range of Days from Admission RR: 64 inpatient cultures Mean time from admission to culture: 25 days SM: 84 inpatient cultures 67 Mean time from admission to culture: 11 days Serling Boyd, UCLA, 2013
68 Discharge condition (in hospital mortality) for inpatients only Percent of inpatients RR Medical Center SM Alive Dead RR: 64 inpatient cultures SM: 84 inpatient cultures Only takes into consideration discharge condition of admission encompassing positive culture (death during later admission not counted in this measure) 68 Serling Boyd, UCLA, 2013
69 60 and 90 day mortality (all patients) RR: 76 cultures 90 day mortality 60 day mortality RR SM SM: 93 cultures Takes into consideration any date of death included in CareConnect Used date to calculate number of days from time of culture Percent deceased 69 Serling Boyd, UCLA, 2013
70 UCLA Response Change in policy/practice Santa Monica Hospital Screen all geriatric patients via rectal swab All patients admitted from certain longterm care facilities, such as GoldStar placed on empiric contact precautions pending results of rectal swabs Ronald Reagan Medical Center CRE infected population different Long term hospitalized patients Importance of robust infection prevention practices and judicious antibiotic use KEY 70 Serling Boyd, UCLA, 2013
71 In Summary Carbapenem resistant Enterobacteriaceae (CRE) is growing problem Most common CRE is the Carbapenem Resistant Klebsiella pneumoniae (CRKP) that produces a Klebsiella pneumonia carbapenemase (KPC) Clinically Risk factors include hospitalization, antibiotic exposure, invasive devices, longterm acute care facility (LTAC), and increased acuity CRE associated with increased mortality Few treatment options exist Epidemiologically CRE resistance mechanisms can spread amongst bacteria CRE can spread amongst people Prevention via a bundled approach is key to halting the spread Adequate hand washing Contact precautions Cohorting Antibiotic Stewardship Contact tracing versus active surveillance
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