Combined genomic and epidemiological investigation of a state-wide outbreak of KPCproducing Enterobacteriaceae Lane CR, Kwong JC, Romanes F, Easton M, Cronin K, Waters MJ, Stevens K, Schultz MB, Sherry NL, Tai A, Ballard SA, Seemann T, Stinear T & Howden BP Communicable Disease Control Conference 28 th June 2017 CPE and KPC Carbapenemase producing enterobacteriaceae (CPE) Enzymes that confer resistance to carbapenem antibiotics Limited treatment - Increased morbidity and mortality Klebsiella pneumoniae carbapenemase (KPC) Large, clonal outbreaks overseas particularly K. pneumoniae 1
Victorian KPC - K. pneumoniae Epidemic curve, KPC positive K. pneumoniae by location at specimen collection, 2012-2014 Victorian KPC - K. pneumoniae Patients with KPC-2 positive Klebsiella pneumoniae, by postcode of residence, Victoria 2012-2014 2
KPC Investigation Extent and setting of KPC transmission in Victoria? - Number of affected health services? - Inter-health service transmission? - Transmission in residential or long term care facilities, community? Detailed genomic and descriptive epidemiological investigation Methods January 2012 December 2015 Isolates referred to MDU PHL from primary laboratories Molecular characterisation Carbapenemase gene detection, multi-locus sequence typing, phylogenetic analysis Patient/NoK interview and record review Travel (since 1996), Health care contact and movements (3 years prior to detection) Qualitative interview with infection control (subset) 3
Isolates and Demographics 69 included patients 57 clonal complex (cc) 258 K. pneumoniae Sex, n (%) Male 33/57 (58%) Age, median (range) Years 74 (20 95) Clinical Infection 35/57 (61%) Travel KPC endemic in Greece, Israel, Italy and NE United States <50% travel since 1996 12 months prior: 8/57 (14%) international travel 100% inpatient hospitalisation in Australia Local transmission? 4
Healthcare Exposure 41 facilities, 113 data requests, 2,165 admissions 12 months prior: Median 63 inpatient days (range 0-182) 19 facilities with >1 patient 41 (72%) patients, Facility F Four major clusters Likely three importation events Sub-clusters B and C Significant differences in inpatient facilities by cluster Combined with patient movement data 5
Cluster D In Detail Room contacts screened Ward contact No direct patient overlap?unidentified colonised patients/environment 6
Infection Control Interviews Contributing factors identified by infection control staff: Missed patient contact screening (ie. only room, not ward) Absence of CPE alerts on patient records on representation Environmental contamination of patient bathrooms Lack of single bathrooms for colonised patients No centralised patient registry Difficulties in inter-facility communication Findings Limited to four discrete outbreaks in a small number of healthcare institutions Multiple importation events Unrecognised colonised patients drive transmission Identification of high risk patients (case contacts, travelers) Inter-health service communication needed Combined genomic and epidemiological data critical Systematic centralised surveillance of CPE 7
Epidemic curve, KPC-2 all species by travel history, 2012-2017 8
MDU PHL Jason Kwong Ben Howden Kerrie Stevens Acknowledgements Donna Cameron Susan Ballard DHHS Finn Romanes Marion Easton Annaleise van Diemen Suzana Talevska Brett Sutton Infection control, microbiology and record staff at affected health services Cluster A (n=4) B1 (n=28) B2 (n=16) C (n=5) Unclustered (n=8) Total (n=57) Age, yrs (median, range) 76 (74-83) 67 (20-90) 81 (52-95) 74 (58-78) 82 (73-88) 74 (20 95) Male (n, %) 1 (25) 14 (50) 11 (69) 3 (60) 4 (100) 33 (58) Colonised patients 0 (0) 4 (7) 9 (56) 2 (40) 3 (75) 18 (32) Infected patients (n, %) a 4 (100) 22 (79) 5 (31) 3 (60) 1 (25) 35 (61) Urinary tract 4 (100) 13 (46) 4 (14) 2 (40) 1 (25) 24 (42) Intrabdominal - 5 (18) - - - 5 (9) Pulmonary & pleural - 3 (11) 1 (4) - - 4 (7) Intravascular line-related - 1 (4) - - - 1 (2) Skin/soft tissue - - - 1 (4) - 1 (2) Sepsis 1 (25) 15 (54) 3 (19) 2 (40) 1 (25) 22 (39) Comorbidities Kidney/renal disease 2 (50) 15 (54) 12 (75) 1 (20) 1 (25) 31 (54) Type 2 diabetes 2 (50) 7 (25) 8 (50) 1 (20) - 18 (32) Liver disease 1 (25) 10 (36) 1 (6) - - 12 (21) Prior chemo/radiotherapy - 7 (25) 16 (13) - 1 (25) 10 (18) Antibiotic therapy > 1 month 2 (50) 8 (29) 5 (31) 3 (60) 1 (25) 19 (33) Overseas travel in prior 12 months - 1 (4) 1 (6) 2 (40) 4 (100) 8 (14) Country of travel b Greece - - - 1 (20) 4 (100) 5 (9) New Zealand - 1 (4) - - - 1 (2) Vietnam - - 1 (6) 1 (20) - 2 (4) Thailand - - - 1 (20) - 1 (2) Hong Kong - - - 1 (20) - 1 (2) Overseas hospitalisation - - - 2 (40) 4 (100) 6 (11) a Sum may exceed total where patients report multiple sites of infection b Sum may exceed total where patients report multiple travel destinations 9
Infection Control Feedback Factors identified by infection control staff contributing to KPC transmission Bundled measures undertaken in every instance where ongoing transmission was halted Missed identification of patient contacts e.g. only room contacts screened, with subsequent transmission to other contacts on the same ward Use of contact screening Enhanced cleaning Isolation of cases in contact precautions Absence of permanent patient alerts for discharged patient contacts, or colonised patients requiring staff use of personal protective equipment (gloves and gown) and promotion of hand hygiene Environmental contamination of patient bathrooms Bundled measures undertaken in some instances where ongoing transmission was halted Staff cohorting Shared bathrooms for colonised patients, due to the unavailability of single bathroom facilities Lack of a central colonised patient registry, and inability of healthcare facilities to identify KPC colonised patients identified at other facilities Screening of patient transfers Notification of KPC cases and contacts to receiving facilities Environmental screening & decontamination 10