C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 NTIMICROIL RESISTNCE SURVEILLNCE FROM SENTINEL PULIC HOSPITLS, SOUTH FRIC, Olga Perovic,2, Verushka Chetty Centre for Opportunistic, Tropical & Hospital Infections, NICD 2 Department of Clinical Microbiology and Infectious Diseases, University of the Witwatersrand Introduction ntimicrobial resistance (MR) is a significant public health concern that threatens effective treatment of severe infections, both locally and globally. Surveillance is conducted to determine the extent and pattern of resistance amongst the most common pathogens Enterobacter cloacae complex, Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. Routine electronic data were collected from sentinel sites (mostly tertiary academic hospitals) (Table ). causing infections in humans. Integrated data on bacterial resistance are obtained from an electronic database of bacterial antimicrobial susceptibility results generated by public sector diagnostic laboratories in South frica. ntimicrobial susceptibility reporting was based on Clinical Laboratory Standards Institute (CLSI) guidelines. 3 The various laboratory methods used included Microscan, Vitek and disk diffusion. Due to sitespecific differences in testing methodologies and data The objectives of the MR surveillance programme are to determine the number of isolates of selected pathogens reported from selected hospitals by month and to describe antimicrobial susceptibility to the most important treatment regimens by pathogen and by hospital. capture on the LIS, extensive cleaning and recoding of data were necessary. This was done within the CDW. The CDW linking algorithm was used to create unique patient identifiers that enabled the generation of patientlevel data and de-duplication within a 2-day patient episode, which was initiated from the first occurrence of resistance to a given antibiotic for a given pathogen. Methods ll data for this report were sourced from the National Health Laboratory Service (NHLS) Corporate Data Warehouse (CDW). This is a national repository for laboratories serving all public sector hospitals in South frica and contains archived data from the Laboratory Information System (LIS). 2 Vancomycin resistance is not reported for Staphylococcus aureus due to the lack of confirmatory test methods (pending agreement with the South frican Society for Clinical Microbiology (SSCM)). Data were omitted for those sites that tested fewer than 3 organisms for resistance to a particular antibiotic. loodstream infections over the period uary- ember were extracted for the following ESKPE pathogens: cinetobacter baumannii complex, 56
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 Table : Hospitals participating in antimicrobial resistance surveillance by province, South frica, and their characteristics. Hospital Site Province cademic Hospital No of beds Frere Hospital Eastern Cape No 96 Livingstone Hospital Eastern Cape Yes 66 Nelson Mandela cademic Hospital/Mthatha Tertiary (NMH) Eastern Cape Yes 52 Universitas Hospital (UH) Free State Yes 65 Charlotte Maxeke Johannesburg cademic Hospital (CMJH) Gauteng Yes 88 Chris Hani aragwanath Hospital (CHH) Gauteng Yes 32 Dr George Mukhari Hospital (DGMH) Gauteng Yes 2 Steve iko cademic Hospital (SH) Gauteng Yes 832 Helen Joseph Hospital (HJH) Gauteng Yes 7 Grey s Hospital (GH) KwaZulu-Natal Yes 53 Inkosi lbert Luthuli Central Hospital (ILCH) KwaZulu-Natal Yes 846 King Edward VIII Hospital (KEH) KwaZulu-Natal Yes 922 Mahatma Gandhi Hospital (MGH) KwaZulu-Natal No 35 RK Khan Hospital (RKKH) KwaZulu-Natal No 543 Tygerberg Hospital (TH) Western Cape Yes 3 Groote Schuur Hospital (GSH) Western Cape Yes 893 Results Data for bloodstream infections and antimicrobial susceptibility tests are summarised for cinetobacter baumannii complex (Figure ), Enterobacter cloacae complex (Figure 2), Enterococcus faecalis (Figure 3), Enterococcus faecium (Figure 4), Escherichia coli (Figure 5), Klebsiella pneumoniae (Figure 6), Pseudomonas aeruginosa (Figure 7) and Staphylococcus aureus (Figure 8). For each organism, the total number of isolates, as well as their susceptibility profiles and percentage susceptibility to selected antimicrobial agents by site were analysed (Figures -8). cinetobacter baumannii complex cinetobacter baumannii showed resistance to the majority of antimicrobial agents tested. This was likely due to its ability to encode and upregulate various mechanisms of resistance such as the loss of outer membrane porins and permeability, efflux systems, mpc β-lactamases and others. The proportions of isolates resistant to imipenem, cefepime and ceftazidime were high at 82%, 8% and 78%, respectively, whereas resistance proportions were 68% to ciprofloxacin, 5% to amikacin and 6% to tobramycin. The extent of resistance to most agents changed in comparison to 24 i.e. there was a significant decrease in resistance to imipenem (23% in 24 vs. 8% ; p<.) while resistance to carbapenems, cephalosporins (3 rd and 4 th generations) and aminoglycosides increased in, with the exception of resistance to colistin which was only 2% in compared to 5% in 24. From referral isolates sent to the ntimicrobial Resistance Laboratory (MRL) of the NICD, no colistin resistance conferred by the mcr gene was confirmed. Except for these few isolates no confirmation of colistin resistance is performed at the MRL. 57
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 6 4 2 8 6 4 2 26 3 22 22 pr 38 7 36 39 36 39 ug 98 25 Tobramycin Ceftazidime Imipenem Ciprofloxacin Colistin 583 453 39 86 39 27 262 264 447 799 595 976 542 68 7 44 6 59 954 3 % 2% 4% 6% 8% % 2 Figure :. cinetobacter baumannii cases by month, and. Numbers and percentages of susceptible and resistant. baumannii complex isolates from blood cultures at public-sector sentinel sites,. Total number of isolates analyzed = 529. 58
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 Enterobacter cloacae complex The prevalence of presumptive (i.e. no molecular confirmation) resistance of Enterobacter cloacae complex to ertapenem of 8% has decreased in comparison to the 24 resistance prevalence of %. Resistance to imipenem and meropenem has remained stable at 2%. Resistance to ceftazidime has decreased since 24 (p=.2) while resistance to piperacillintazobactam remained stable in. Resistance to cefepime (3%) is suggestive of mpc hyper-production due to de-repressed mpc mutants which confer resistance to all cephalosporins. These data may also indicate co-carriage of an extended-spectrum β- lactamase (ESL). 8 6 4 55 4 64 52 56 46 47 6 46 66 4 52 2 pr ug Gentamicin Piperacillin-tazobactam Cefoxitin Cefotaxime/ceftriaxone Ceftazidime Cefepime Ertapenem Imipenem Meropenem Ciprofloxacin Levofloxacin 9 487 38 376 56 33 337 35 464 522 527 445 3 52 6 2 99 6 89 52 42 5 2 % % 2% 3% 4% 5% 6% 7% 8% 9% % Figure 2:. Enterobacter cloacae cases by month, and. Numbers and percentages of susceptible and resistant E. cloacae complex isolates from blood cultures at public-sector sentinel sites,. Total number of isolates analyzed = 624. 59
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 Enterococcus faecalis Enterococcus faecalis exhibited 4% resistance to penicillins and % (non-confirmed) resistance to vancomycin, both of which are slightly reduced from the corresponding prevalences of 24 (7% to penicillins and 2% to vancomycin). There were no other significant changes in comparison to 24. 8 6 4 2 69 56 72 64 pr 73 69 7 7 7 73 ug 54 8 Penicillin/ampicillin Teicoplanin Linezolid 2 3 27 3 344 762 6 8 4 4 7 24 % 2% 4% 6% 8% % Figure 3:. Enterococcus faecalis cases by month, and. Numbers and percentages of susceptible and resistant E. faecalis isolates from blood cultures at public-sector sentinel sites,. Total number of isolates analyzed = 823. 6
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 Enterococcus faecium Enterococcus faecium is inherently resistant to β-lactam agents. Resistance to vancomycin remained unchanged at 5% in. 8 6 4 2 68 5 67 64 67 pr 93 69 89 ug 64 88 64 65 mpicillin/amoxycillin Quinupristin-dalfopristin Vancomycin 34 7 2 4 77 345 373 769 72 43 2 % 2% 4% 6% 8% % Figure 4:. Enterococcus faecium cases by month, and. Numbers and percentages of susceptible and resistant E. faecium isolates from blood cultures at public-sector sentinel sites,. Total number of isolates analyzed = 849. 6
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 Escherichia coli Escherichia coli showed no change in resistance to piperacillin-tazobactam and ciprofloxacin compared to 24 and no significant increased resistance to the β- lactam group over a two-year period. Resistance to 3 rd generation cephalosporins indicates the presence of extended spectrum β-lactamases (ESLs) and was recorded in 22% of isolates. 25 2 5 5 47 35 27 4 49 64 49 4 49 pr ug 74 64 63 mpicillin/amoxycillin Cefazolin/cephalexin Cefotaxime/ceftriaxone Cefepime Imipenem Ciprofloxacin Trimethoprim-sulfamethoxazole 245 87 65 49 49 486 37 338 37 637 684 723 237 8 48 78 3 254 5 42 384 367 8 9 2 465 2 % 2% 4% 6% 8% % Figure 5:. Escherichia coli cases by month, and. Numbers and percentages of susceptible and resistant E. coli isolates from blood cultures at public-sector sentinel sites,. Total number of isolates analyzed = 882. 62
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 Klebsiella pneumoniae Klebsiella pneumoniae was resistant to multiple antimicrobials, including 3 rd generation cephalosporins that indicate production of ESLs (69%), ciprofloxacin (33%) and piperacillin-tazobactam (5%). The proportion of isolates resistant to ertapenem (4%) has remained unchanged over a 2-year period. Resistance prevalences to imipenem (6%) and meropenem (6%) showed significant increases compared to 24 (p<.). lthough resistance to other carbapenems was generally low, the rapid emergence of strains with carbapenemase production threatens the efficacy and use of this vital class of antimicrobials as a therapeutic option. Thus, knowledge of local hospital epidemiology and monitoring of carbapenem resistance is essential. 4 3 2 267 28 258 28 23 259 235 27 24 236 284 35 pr ug Piperacillin-tazobactam Cefotaxime/ceftriaxone Cefepime Imipenem Ciprofloxacin 772 783 792 3 987 248 638 2 89 2 89 2 276 2 32 2 34 499 27 7 686 666 8 82 382 323 97 59 55 % 2% 4% 6% 8% % Figure 6:. Klebsiella pneumoniae cases by month, and. Numbers and percentages of susceptible and resistant K. pneumoniae isolates from blood cultures at public-sector sentinel sites,. Total number of isolates analyzed = 292. 63
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 Pseudomonas aeruginosa Thirty percent of Pseudomonas aeruginosa isolates were resistant to piperacillin-tazobactam and 27% were resistant to cefepime. Colistin resistance was low (%). However, this was not confirmed by reference or molecular methods. 8 6 4 49 7 65 6 59 54 59 34 54 6 44 6 2 pr ug Piperacillin-tazobactam Cefepime Meropenem Levofloxacin 474 436 39 447 42 47 423 44 2 4 22 59 7 43 57 8 69 46 5 % 2% 4% 6% 8% % Figure 7:. Pseudomonas aeruginosa cases by month, and. Numbers and percentages of susceptible and resistant P. aeruginosa isolates from blood cultures at public-sector sentinel sites,. Total number of isolates analyzed = 67. 64
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 Staphylococcus aureus No S. aureus isolates were reported to be vancomycin resistant in. Resistance to methicillin/oxacillin and all other β-lactams showed a minor increase compared to 24. Cefoxitin resistance was indicative of methicillin resistance (MRS). Resistance rates to erythromycin and clindamycin remained unchanged. 3 25 2 5 5 254 77 25 239 24 pr 22 9 85 84 ug 22 99 99 Penicillin/ampicillin Cefoxitin Clindamycin Ciprofloxacin Rifampicin Vancomycin 58 2 346 453 25 487 783 235 25 498 2 86 9 2 22 98 733 794 6 775 484 667 6 654 % 2% 4% 6% 8% % 5 54 Figure 8:. Staphylococcus aureus cases by month, and. Numbers and percentages of susceptible and resistant S. aureus isolates from blood cultures at public-sector sentinel sites,. Total number of isolates analyzed = 257. 65
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 Carbapenemase-producing Enterobacteriaceae (CPE) The ntimicrobial Resistance Laboratory confirmed the public laboratories following phenotypic confirmation of carbapenem resistance (Table 2). Few organisms presented with more than one CPE gene. presence of carbapenemase genes in Enterobacteriaceae isolates that were referred from Table 2: Numbers of confirmed carbapenemase-producing Enterobactericeae by species and genoptype Carbapenemases producing Enterobacteriaceae No. of isolates Species Citrobacter freundii 9 Enterobacter aerogenes 8 Enterobacter asburiae 3 Enterobacter cloacae 4 Enterobacter kobei 2 Enterobacter spp. 2 Escherichia coli 64 Klebsiella oxytoca 2 Klebsiella pneumoniae 552 Klebsiella spp. 3 Morganella morganii Proteus mirabilis 2 Proteus spp. Providencia rettgeri 23 Providencia vermicola Raoutella ornithinolytica Serratia marcescens 55 Genotype OX-48 like 234 VIM 55 NDM 438 GES 2 KPC IMP 8 Discussion and conclusion Certain limitations are inherent in the data presented. Data may be incomplete due to missing cases not captured on the LIS or non-standardised coding of pathogens and antibiotics. Testing methods and microbiological practice vary between sites and this and results presented here are reported as captured on the LIS. Thus, while some results may suggest the occurrence of an outbreak, it is not possible to confirm this. For certain sites, not all organisms are represented. This may be due to organisms not being identified at a particular site for. could account for variation in the results presented. Confirmatory antimicrobial susceptibility test (ST) methods were not performed for any of these organisms Surveillance for CPEs is currently being conducted at 4 national sites. Due to the limitations mentioned above 66
C O M M U N I C L E D I S E S E S S U R V E I L L N C E U L L E T I N V O L U M E 4, N O. 3 there is a continuous need for improvement in the quality of data obtained by electronic surveillance. The data presented in this report nevertheless highlight the importance of surveillance for antimicrobial resistance patterns. Disclaimer Data are reported as received through the CDW. No demographic, epidemiological, clinical or molecular data were available to distinguish between hospitalassociated and community-acquired infections. cknowledgements Sue Candy and the NHLS CDW team are thanked for cleaning the data and preparing the tables and figures. shika Singh-Moodley is thanked for CPE gene identification. The SSCM editorial committee members are thanked for their comments and suggestions. References. Langmuir D. The surveillance of communicable diseases of national importance. N Engl J Med 963; 268: 82-92. 2. Garner JS, et al. CDC definitions for nosocomial infections. m J Infect Control 988; 6: 28-4. 3. Performance Standards for ntimicrobial Susceptibility Testing. Clinical and Laboratory Standards Institute (CLSI), 26; M -S26. The Communicable Diseases Surveillance ulletin is published by the National Institute for Communicable Diseases (NICD) of the National Health Laboratory Services (NHLS), Private ag X4, Sandringham, 23, Johannesburg, South frica. Suggested citation: [uthors names or National Institute for Communicable Diseases (if no author)]. [rticle title]. Communicable Diseases Surveillance ulletin 26; 4(3): [page numbers]. Editorial and Production Staff asil rooke Editor Irma Latsky Nombuso Shabalala Production Editorial Committee Cheryl Cohen John Frean Halima Said Veerle Msimang Vanessa Quan Tendesayi Kufa-Chakezha Jaishree Raman Nicola Page Requests for e-mail subscription are invited - please send request to Mrs Irma Latsky: irmal@nicd.ac.za Material from this publication may be freely reproduced provided due acknowledgement is given to the author, the ulletin and the NICD. This bulletin is available on the NICD website: http://www.nicd.ac.za 67