Spread of carbapenems resistant Enterobacteriaceae in South Africa; report from National Antimicrobial Resistance Reference Laboratory Olga Perovic*, Ashika Singh-Moodley, Samantha Iyaloo 5 th November 15 Antimicrobial Reference Laboratory at NICD and University of Witwatersrand*
Introduction The spread of carbapenem-non-susceptible Enterobacteriaceae poses a threat to healthcare and patient safety globally and in South Africa. Since the first case of carbapenemase producing Enterobacteriaceae (NDM1) in a private healthcare facility in Gauteng 2011, the Antimicrobial Resistance Laboratory (AMRL) at the National Institute for Communicable Diseases (NICD) has been receiving carbapenem non-susceptible Enterobacteriaceae clinically significant isolates from public and private health sectors for confirmatory and molecular testing. 2
Objectives To analyze CREs trend over 4 years period. To identify the most common organisms effected by presence of CPE genes. To highlight importance of surveillance.
Case report form
Labortaory methodology Confirmatory identification of organisms was done on VITEK II (biomèrieux, France) and on MALDI-TOF. Antimicrobial susceptibility testing was performed using automated systems the MicroScan Walkaway system (Siemens, USA). The interpretation of susceptibility was done according to the Clinical and Laboratory Standards Institute (CLSI) guidelines 11. DNA was extracted from the phenotypic carbapenem-resistant isolates. The supernatant was harvested and screened for bla NDM, bla KPC, bla OXA-48 and its variants, bla GES, bla IMP and bla VIM using realtime polymerase chain reaction (PCR) (LightCycler 480 II, Roche Applied Science, LightCycler 480 Probes Master kit and the individual LightMix Modular kits (Roche Diagnostics, IN, USA). 5
Results A total of 1618 carbapenem non-susceptible isolates from all specimen types were received by the AMRL since 2012. We confirmed presence of cabapenemase genes in 1043 (83%) Enterobacteriaceae from total of 1258 isolates. Approximately 12% of patients had more than one specimen with non-susceptible isolates.
Distribution of 1258 Enterobacteriaceae 700 600 571 613 500 400 363 300 200 71 0
Distribution of referral isolates per province 400 350 341 300 281 250 220 200 150 111 50 0 1 75 77 63 70 67 39 28 15 16 6 7 5 2 3 2 6 8 1 13 Group1 EC FS GA KZ LP NW WC
Numbers Number of 1249 isolates from public and private sectors 450 400 The majority of isolates were received from public hospitals 1025 (82%). 392 350 300 277 313 250 200 150 43 76 53 73 50 22 0 Isolates per year Private Public
Numbers Ward types at public sector from 1024 patients 250 221 236 200 202 150 122 89 50 26 6 11 32 24 21 34 0 Ward types ADULT PAED UNK
Gender distribution among 1190 patients 300 267 250 200 201 181 185 174 150 146 50 0 14 22 Female Male
Numbers Specimen types 350 300 250 200 150 50 0 43 328 Urine and blood were the most common specimens (25% and 28.5%, respectively) 92 82 49 2 11 31 51 64 1 10 8 26 35 1 4 1 2 5 3 1 610 9 52 275 Total 1302 Private Public
Numbers The most common organisms 600 500 400 300 200 0 37 36 39 1 17 62 12 62 1 308 349 221 10 23 36 14 15 4 44 20 4 85 68 42 56 8 10 41 42 64 19 8 12 All rganisms Serratia marcescens Salmonella spp. Providencia rettgeri Proteus mirabilis Morganella morganii Klebsiella pneumoniae Klebsiella oxytoca Escherichia coli Enterobacter cloacae complex Enterobacter cloacae Enterobacter aerogenes Citrobacter freundii
KPC OXA-48 Variants IMP OXA-48 NDM GES KPC OXA-48 Variants VIM IMP OXA-48 NDM GES KPC VIM OXA-48 NDM VIM OXA-48 NDM Percentages Confirmed CPEs, 1043 (83%) from total 1258 isolates 50% 45% 40% 35% 30% 31% 25% 20% 15% 12% 14% 10% 5% 0% 0% 0% 0% 0% 3% 1% 1% 0% 2% 3% 5% 0% 0% 4% 8% 4% 9% Confirmed CPEs Confirmed CPEs Confirmed CPEs Confirmed CPEs
Numbers Isolates with OXA-48 variants 90 91 80 84 70 60 50 40 45 30 20 10 0 1 OXA-48 Variants
Percenatges Distribution of carbapenemase genes among K. pneumoniae and E. cloacae 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% VIM OXA-48 Variants OXA-48 NDM KPC IMP GES 0% E. cloacae K. pneumo E. cloacae E. cloacae com K. pneumo E. cloacae E. cloacae com K. pneumo E. cloacae K. pneumo The most common organisms
Distribution of 274 CPEs per wards 50% 45% 40% 35% 30% 25% 20% 15% VIM OXA-48 Variants OXA-48 NDM KPC IMP GES 10% 5% 0% ADULT ICU PAEDIATRIC OUTPATIENT
CPEs in K. pneumoniae 50% Klebsiella pneumoniae was the predominant organism 920 (73%) and carbapenemases were detected in 623 (68%) isolates including 372 (60%) NDM as the most predominate gene with a substantial increase in positivity rate from 46% in 2014 to 71% in 2015. 45% 40% 35% 30% 25% 20% 15% K. pneumo - VIM K. pneumo - OXA-48 Variants K. pneumo - OXA-48 K. pneumo - NDM K. pneumo - KPC K. pneumo - GES 10% 5% 0%
Numbers Numbers Scarces clinical information 300 300 250 260 228 218 250 267 253 200 200 180 150 121 150 125 89 50 0 43 27 2 5 5 50 0 48 42 39 19 11 3 1 Group1 Group1 Antibiotics use Underlying conditions N U Y Poly. (U) N U Y Poly. (U)
Conclusions We presented carbapenem resistant Enterobacteriaceae referred for confirmatory testing and molecular identification of carbapenemases with increasing percentage of CPE cases over 4 years. Real prevalence of the resistance is not established as these were all referral isolates but structured enhanced surveillance is recommended to establish the hospital burden and infection control and prevention measures should be implemented at all healthcare facilities. 20
THE END I would like to thank AMRL-CC staff for their support and audience for their attention. 21