Implementation of Public Health Surveillance of Carbapenemase- Producing Enterobacteriaceae in Victoria, Australia

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1 Implementation of Public Health Surveillance of Carbapenemase- Producing Enterobacteriaceae in Victoria, Australia C.R. Lane*, J. Brett, M.B. Schultz, K. Stevens, A. van Diemen, S.A. Ballard, N.L. Sherry, J.C. Kwong, D.R.M. Cameron, D.A. Williamson, M. Easton, B.P. Howden Communicable Disease Control Conference 27 th June 217 Background Carbapenemase producing enterobacteriaceae (CPE) Carbapenemases, enzymes that confer resistance to carbapenems Increased morbidity and mortality Outbreak potential Source: Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 213. Atlanta, GA,

2 Common Carbapenemases Class Name Abbreviation Major sub-types A Klebsiella pneumoniae carbapenemase -2, -3 New-delhi metallo-betalactamase -1, -, -7 B Imipenemase metallo-betalactamase -4 Verona imipenemase metallo-betalactamase -1, -2 D carbapenemases OXA-48, OXA-181, OXA-232 OXA-23-like carbapenemases OXA-23-like OXA-23 Victorian -2 Outbreak 2

3 Public Health Surveillance of CPE Identify transmission Implement standardised control measures Oversight by a centralised incident management team (VCIMT) Communicate CPE risk to other facilities Inform response & empiric treatment (antibiograms) 3

4 Number of Cases (monthly) Victorian CPE Surveillance and Response Unit Suspected CPE isolate identified Isolate referred to MDU PHL DHHS and VICNISS notified Infection control actions initiated Confirmatory testing performed Monitor trends CPE Confirmed Not CPE (rejected) Epidemiological data collected Genomic relatedness to other isolates assessed No further action Epidemiological and genomic data evaluated for local transmission Local transmission suspected? Yes No If changes observed Outbreak investigation Transmission risk area may be designated by Vic CPE Incident management team Gene(s) detected, Other OXA^ SME * J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D Specimen collection date ^Includes carbapenem degarding only, such as OXA-23-like, OXA-24/4-like and OXA-1-like genes *October 212, MDU PHL conducted a one month snapshot of CRE in Victoria. Implementation of the Victorian Guideline on CPE Patients with CPE identified at MDU PHL, by month and carbapenemase gene type, 1 January December Total cases/year 4

5 Number of Cases Number of Cases, SME Location at Specimen Collection 216 Victorian CPE Cases N % Hospital Admitted 67 (7%) Hospital Emergency/Outpatients 18 (19%) Medical clinic (inc. GP) (%) Aged care facility 1 (1%) Total 96 Clinical Presentation N % Colonisation 7 (9%) Infection 33 (34%) Urinary tract 21 Bacteraemia Unknown 2 (6%) OXA-232 OXA-48 OXA SME-3 SME SME Carbapenemase Genes NB: Genes included will exceed total number of isolates, due to 3 isolates with multiple gene types detected. Risk Factors Differ by Carbapenemase Majority (91%) overseas travellers, most hospitalised Some putative community acquisition in India South and Central Asia South East Asia Middle East China Greece Other No Unknown Carbapenemase Gene Group

6 Number of Cases Number of Cases,, SME SME Risk Factors Differ by Carbapenemase Majority (91%) overseas travellers, most hospitalised Some putative community acquisition in India Found in travellers (76%) and non-travellers (24%), suggesting some unrecognised local transmission South and Central Asia South East Asia Middle East China Greece Other No Unknown Carbapenemase Gene Group Risk Factors Differ by Carbapenemase Majority (91%) overseas travellers, most hospitalised Some putative community acquisition in India Found in travellers (76%) and non-travellers (24%), suggesting some unrecognised local transmission Small number of cases with overseas hospitalisation (Greece) Most within well defined local K. pneumoniae outbreaks South and Central Asia South East Asia Middle East China Greece Other No Unknown Carbapenemase Gene Group 6

7 Number of Cases, SME Risk Factors Differ by Carbapenemase Majority (91%) overseas travellers, most hospitalised Some putative community acquisition in India Found in travellers (76%) and non-travellers (24%), suggesting some unrecognised local transmission Small number of cases with overseas hospitalisation (Greece) Most within well defined local K. pneumoniae outbreaks Rarely associated with travel Widely distributed across species Local transmission observed in multiple species 3 E. coli 3 K. pneumoniae 2 E. cloacae complex 2 S. 1marcescens K. oxytoca C. freundii C. farmeri South and Central Asia South East Asia Middle East China Greece Other No Unknown Gene(s) detected, SME Carbapenemase Number of Gene Cases Group Local Transmission of CPE Gene Species 216 cases -2 K. pneumoniae 6-2 C. farmeri 2-4 K. pneumoniae 3-4 K. pneumoniae 2-4 K. oxytoca 4?Unidentified transmission networks 7

8 Why? Long colonisation periods Cases temporally/geographically dispersed at CPE identification Same carbapenemase gene, bacterial species +/- multi locus sequence type Epidemiological and genomic investigation Person, place and time Consistent with transmission Hypothesis for time and place of transmission (direct or indirect) Aged care facility, adjacent rooms Phylogenetic tree of Victorian -2 K. pneumoniae ST28, Non-overlapping admissions to ward 8

9 Number of Cases (monthly) Centralised combined epidemiological and genomic investigation needed: Long time frames Frequent and complex patient movements Transmission at multiple facilities Aged care facility, adjacent rooms Multiple possible exposures. Phylogenetic tree of Victorian -2 K. pneumoniae ST28, Non-overlapping admissions to ward 2 1 Gene(s) detected, Other OXA^ SME * IMI 217 so far J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J Specimen collection date ^Includes carbapenem degrading only, such as OXA-23-like, OXA-24/4-like and OXA-1-like genes Version 2 guideline released Total cases/year 9

10 Australian data (CARAlert) Source: CARAlert Progress Report 17 March to 31 December 216 < Conclusions Local acquisition mainly limited to -4 and -2 Considerable importation of CPE Centralised combined epi and genomic surveillance critical to: Identifying local transmission networks Implementing targeted control measures

11 MDU PHL Mark Schultz Kerrie Stevens Donna Cameron Ben Howden Jason Kwong Susan Ballard Acknowledgements DHHS Marion Easton Annaleise van Diemen Suzana Talevska VCIMT members VICNISS Judy Brett Ann Bull -4 Complexity 11

12 Number of Patients Local transmission networks Gene Species 216 cases Facilities of suspected transmission -2 K. pneumoniae C. farmeri K. pneumoniae K. pneumoniae K. oxytoca 4 1 All cases identified at facility where transmission is suspected Patient Demographics Carbapenemase gene detected All Yes No Sex, n (%) Female 213/382 (6%) 43/96 (4%) 17/286 (9%) Age, median (range) Years 72 ( 99) 66 (3 9) 74 ( 99)^ ^Age unknown for two rejected cases Gene(s) detected, SME Age Group (yrs) 12

13 Number of episodes, SME Overseas travel N % 4 years prior to detection Yes 49 (1%) Overseas healthcare 41 No 4 (47%) Unknown 2 (2%) Total 96 Country of travel South & Central Asia (India, Sri Lanka, Bangladesh, Pakistan, 24 Afghanistan) South East Asia (Vietnam, Cambodia, Thailand, Philippines, Malaysia) 11 Greece 4 Middle East (Turkey, Lebanon) 4 China 2 Other 4 Travel South and Central Asia South East Asia Middle East China Greece Other No Unknown Carbapenemase Gene Type Parallel Outbreak investigations Genomics --- Epidemiology Consistent with transmission Commonality in person, place and time. Hypothesis for time and place of transmission (direct or indirect - enviro, staff, colonisation) Transmission risk area 13

14 Number of Patients Travel location(s) Overseas Travel group Gene Organism (12 months prior to identification) hospitalisation Greece -2 K. pneumoniae Greece~ Yes R R R R R >=16 t tes NoR R R R S R R R S R NoR R NoNo 214 Greece~ Yes R R R R R >=16 t tes NoR R R R S R R R S R NoS S NoNo 214 Greece~ Yes R R R R R >=16 t tes NoR R R R S R R R S R NoS S NoNo 214 Greece~ Yes R R R R R >=16 R NoR R R R R R R R S S NoR R S S 214 Greece~ Yes R R R R R >=16 t tes NoR R R R R R R R S R NoR R NoNo 21 Greece~ Yes R R R R R >=16 t tes NoR R R R R R R R S R NoR R NoNo 216 Greece~ Yes R R R R R >=16 t tes NoR R R R S R R S S S NoS S NoNo K. pneumoniae Greece~ Yes R R R R R >=16 t tes NoR R R R I R R I S S NoR R NoNo 21-1 K. pneumoniae Greece~ Yes R S S S S <=.2t tes NoR S R I S I S I S S NoR R NoNo 21 India and -1 E. coli Bangladesh~ Yes R R R R R >=16 t tes NoR R R R R R R R R R I R R NoNo 216 south Asia India~ Yes R R R R R >=16 R R R R R R R R R R R R I R R S S E. coli India No R R R R R >=16 t tes NoR R R R R R R R R R S R R NoNo 216 India No R R R R R >=16 t tes NoR R R R R R R S S S S R R NoNo 216 India~ Yes R R R R R >=16 t tes NoR R R R R R R R R R I R R NoNo 216 India No R R R R R >=16 t tes NoR R R R R R R R R R S R R NoNo 216 India No R R R R R 8 t tes NoR R R R R R R R R R S R R NoNo 216 India~ Yes R R R R R >=16 t tes NoR R R R R R R S S S I S S NoNo 216 India No R R R R R >=16 t tes NoR R R R R R R R R R R R R NoNo 216 India~ Yes R R R R R >=16 R R R R R R R R R S S S R R R S S 216 India~ Yes R I I R R 4 S R R R R R R R R R R S S R R S S 216 India~ Yes R R R R R >=16 S S R R R R I R R S S S R R R S S 216 India~ Yes R R R R R >=16 R R R R R R R R R R R R S R R S S E. coli Pakistan~ Yes R R R R R >=16Not tested Not Rtested R R R R R R R R R Not Stested S Not Not tested 21 tested OXA-181 E. coli India No R R R R S <=.2 S Not Rtested R R R R R R R R S I R R S S 21 India No R R R R I 2 S Not Rtested R R R I R R S S S S S S S S 21 India, Jordan No R R R R S 1 S Not Rtested R R R S R R S S S I S S S S 21 India No R R R R S 1Not tested Not Rtested R R R R R R R S S S S S Not Not tested 216 tested OXA-232 K. pneumoniae India~ Yes R R R R R >=16 R Not Rtested R R S S R R R S I Not Rtested R R S 21 India~ Yes R R R R R >=16Not tested Not Rtested R R S S R R R R R Not Rtested R Not Not tested 21 tested India~ Yes R R R R R >=16Not tested Not Rtested R R R R R R R R I Not Rtested R Not Not tested 21 tested South-east -2 K. pneumoniae Vietnam No R R R R R >=16Not tested Not Rtested R R R R R R R R S Not Stested S Not Not tested 214 tested Asia Vietnam~, Thailand~ Yes R R R R R >=16Not tested Not Rtested R R R S R R R S R Not Stested S Not Not tested 214 tested -1 E. coli Thailand~ Yes R R R R R >=16Not tested Not Rtested R R R I R R R R S S R R Not Not tested 216 tested - E. coli Cambodia~, Vietnam Yes R R R R R >=16Not tested Not Rtested R R R R R R R R S R R R Not Not tested 216 tested -7 E. coli Philippines~ Yes R R R R R >=16Not tested Not Rtested R R R R R R S S S I R R Not Not tested 216 tested OXA-181 K. pneumoniae Vietnam~ Yes R R R R R >=16Not tested Not Rtested R R R R R R R S S Not Stested S Not Not tested 21 tested Thailand~ Yes R R R R I 2 S S R S S S S S S S S S Not Stested S S S 216 OXA-48 E. coli Malaysia~, India, Egypt, Israel, Jordan Yes R R R R I 2Not tested Not Rtested R R R S S S S S S S R R Not Not tested 216 tested Vietnam~ Yes R R R R S 1Not tested Not Rtested R R R R R R R S S I R R Not Not tested 216 tested Other -2 K. pneumoniae New Zealand No R R R R R >=16 R R R R R R R R R R S R Not Rtested R R I 212 USA, New Zealand No R R R R R >=16Not tested Not Rtested I R R R R R R S R Not Stested S Not Not tested 216 tested -1 E. coli China~ Yes R R R R R >=16 S S R R R R S S S S S S S R R S S E. coli China~, USA, Europe NFS Yes R R R R R >=16Not tested Not Rtested R R R R R R R R S S R R Not Not tested 216 tested OXA-48 E. coli Lebanon~ Yes R R R R S.Not tested Not Rtested S R R S S S S S S I S S Not Not tested 216 tested Turkey~ Yes R R R R S. S S R R S S S R R R S S S R R S S 216 OXA-48 K. pneumoniae Turkey No R R R R R >=16 R Not Rtested R R S S R R R R S Not Rtested R S S 21 Malta~ Yes R R R R R 8 S Not Rtested S R R S R R R R S Not Rtested R S S 21 ~Location of hospitalisation Ampicillin Amoxicillin Clavulanic Acid Ticarcillin Clavulanic Acid Piperacillin Tazobactam Meropenem Meropenem MIC (Vitek) Meropenem e-test Aztreonam e-test Cefazolin Cefoxitin Ceftriaxone Ceftazidime Cefepime Ciprofloxacin Norfloxacin Tobramycin Gentamicin Amikacin Nitrofurantoin Trimethoprim Cotrimoxazole Colistin e-test Fosfomycin e-test Year 12 Just 8 6 * 4 2 J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D Specimen collection date ^Includes carbapenem degarding only, such as OXA-23-like, OXA-24/4-like and OXA-1-like genes *October 212, MDU PHL conducted a one month snapshot of CRE in Victoria. 14

15 Number of Patients Just 4 * J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D Specimen collection date ^Includes carbapenem degarding only, such as OXA-23-like, OXA-24/4-like and OXA-1-like genes *October 212, MDU PHL conducted a one month snapshot of CRE in Victoria. Current and Future Research Understanding local -4 diversity and transmission networks Prevalence and role of environmental contamination Duration and role of long term colonisation Screening sensitivity, antibiotic exposure 1

16 Carbapenemase status, by species High % carbapenemase producers Low % carbapenemase producers Carbapenemase producers Non-carbapenemase producers 16