National sentinel site surveillance for antimicrobial resistance in Klebsiella pneumoniae isolates in South Africa, 2010-2012

PKBackground: The increasing rates of antimicrobial resistance observed in the nosocomial pathogen Klebsiella pneumoniae are of major public health concern worldwide. Objectives: To describe the antibiotic susceptibility profiles of K. pneumoniae isolates from bacteraemic patients submitted by sentinel laboratories in five regions of South Africa from mid-2010 to mid-2012. Molecular methods were used to detect the most commonly found extended-spectrum beta-lactamase (ESBL) and carbapenemase resistance genes. Methods: Thirteen academic centres serving the public healthcare sector in Gauteng, KwaZulu-Natal, Free State, Limpopo and Western Cape provinces submitted K. pneumoniae isolates from patients with bloodstream infections. Vitek 2 and MicroScan instruments were used for organism identification and susceptibility testing. Multiplex polymerase chain reactions (PCRs) were used to detect blaCTX-M, blaSHV and blaTEM genes in a proportion of the ESBL isolates. All isolates exhibiting reduced susceptibility to carbapenems were PCR tested for blaKPC and blaNDM-1 resistance genes. Results: Overall, 68.3% of the 2 774 isolates were ESBL-positive, showing resistance to cefotaxime, ceftazidime and cefepime. Furthermore, 46.5% of all isolates were resistant to ciprofloxacin and 33.1% to piperacillin-tazobactam. The major ESBL genes were abundantly present in the sample analysed. Most isolates (95.5%) were susceptible to the carbapenems tested, and no isolates were positive for blaKPC or blaNDM-1. There was a trend towards a decrease in susceptibility to most antibiotics. Conclusion: The high proportion of ESBL-producing K. pneumoniae isolates observed, and the prevalence of ESBL genes, are of great concern. Our findings represent a baseline for further surveillance in SA, and can be used for policy and treatment decisions

Molecular detection of carbapenemase-producing genes in referral Enterobacteriaceae in South Africa: A short report

Molecular confirmation of carbapenemase-producing Enterobacteriaceae (CPE) was introduced in South Africa (SA) at the end of 2011. We report on the detection of these resistance genes based on referral isolates. Enterobacteriaceae with non-susceptibility to any of the carbapenems according to defined criteria for antimicrobial susceptibility testing results were sent to a reference laboratory. A proportion of isolates had limited demographic, epidemiological and clinical data available. Organism identification was reconfirmed using reference laboratory methods, and the presence of carbapenemases was confirmed with a real-time polymerase chain reaction. We analysed 1 503 significant isolates received for confirmation from the National Health Laboratory Service and some private laboratories during 2012 - 2015 and confirmed one or more carbapenemase-producing genes in 68% of isolates, the most common organism being Klebsiella pneumoniae (60%). The most common carbapenemase genes were blaNDM, followed by blaOXA-48 and its variants. BlaOXA-48 and its variants demonstrated non-susceptibility to ertapenem in 89% of the isolates when analysed by the phenotypic method, and to ceftazidime in 34%. Overall, the detection rate for carbapenemases in K. pneumoniae blood isolates in the public sector was 1.9% during the 4-year period. This report indicates the presence of CPE in SA, and it is important for all healthcare workers to be aware of this major public health threat so that infection prevention and control measures can be implemented to prevent the spread of CPE in healthcare facilities

Phenotypic and genotypic correlation of carbapenememase-producing Enterobacteriaceae and problems experienced in routine screening

Background. The emergence and transmission of carbapenem-resistant Enterobacteriaceae (CRE) is a concern in both the clinical and public health arenas. Reliable and accurate detection of these organisms is required for patient management and infection prevention and control purposes. In the routine laboratory, phenotypic methods are utilised for identification of CRE.Objectives. To investigate the phenotypic profiles of suspected carbapenemase-producing Enterobacteriaceae (CPE) isolates generated by the automated MicroScan Walkaway system making use of the Clinical and Laboratory Standards Institute (CLSI) guidelines, and correlate these with carbapenemase production by molecular methods.Methods. Antimicrobial susceptibility testing was performed using the MicroScan Walkaway system, and the presence of six carbapenemase genes (blaNDM, blaVIM, blaIMP, blaOXA-48and variants, blaGESand blaKPC) was screened for using a multiplex real-time polymerase chain reaction.Results. A total of 2 678 isolates were evaluated. Klebsiella pneumoniae accounted for 62.9% of the isolates (n=1 685), followed by Enterobacter cloacae (n=361, 13.5%). Carbapenemases accounted for 75.2% of isolates; blaOXA-48 and its variants predominated (n=978, 36.5%), followed by blaNDM (n=904, 33.8%), blaVIM (n=108, 4.0%), blaIMP (n=35, 1.3%), blaGES (n=24, 0.9%) and blaKPC (n=18, 0.7 %).Conclusions. A considerable number of isolates expressing a carbapenemase or carbapenemases (the majority of which were blaOXA-48 producing) were susceptible to third-and fourth-generation cephalosporins and carbapenems, demonstrating that confirmed carbapenemase-producing isolates are not presenting as possible carriers of carbapenemases using routine diagnostic methods. Similar results were obtained when CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints were applied and are suitable for the purpose of patient management. However, since genotyping assays are costly, it is suggested that routine laboratories first perform comprehensive phenotypic screening for CPE

Carbapenem-resistant Enterobacterales in patients with bacteraemia at tertiary academic hospitals in South Africa, 2019 - 2020: An update

Background. The emergence of carbapenem-resistant Enterobacterales (CRE) has become a serious and significant public health threat worldwide, owing to the limited antimicrobial therapy options, and the elevated mortality rates associated with these infections. Objectives. To present an update on the epidemiology of CRE bloodstream infections among hospitalised patients reported under the Group for Enteric, Respiratory and Meningeal Diseases Surveillance in South Africa (GERMS-SA) between January 2019 and December 2020. Methods. Patients of all ages with CRE bacteraemia were included and isolates, when available, were sent to the reference laboratory for confirmatory testing and molecular characterisation. Multivariable logistic regression analysis was performed to assess factors associated with in-hospital mortality. Results. We included 2 144 patients with CRE bacteraemia with a median age of 33 (interquartile range 1 - 51) years, of whom 1 145 (54.2%) were male. Klebsiella pneumoniae accounted for 79.8% of infections (n=863/1 082), of which 89.5% (n=611/683) were healthcare associated (HA). The most common carbapenemase genes were carbapenem-hydrolysing oxacillinase-48 (blaOXA-48-like) (76.8%; n=761/991), New Delhi metallo-β-lactamase (blaNDM) (21.1%; n=209/991) and Verona integron-encoded metallo-β-lactamase (blaVIM) (1.3%; n=13/991). None of the screened isolates with a colistin minimum inhibitory concentration >2 μg/mL harboured the mobilised colistin resistance (mcr)-1 to mcr-5 genes. The crude in-hospital mortality rate was 36.6% (n=377/1 029). Patients aged ≥60 years (v. 1.6 - 9 years) (adjusted odds ratio (aOR) 4.53; 95% confidence interval (CI) 2.21 - 9.28), those with comorbidities (diabetes, malignancy, renal and/or cardiovascular failure) (aOR 1.72; 95% CI 1.17 - 2.52), those with altered mental state (aOR 5.36; 95% CI 3.21 - 8.92) and those with previous antimicrobial use (aOR 1.88; 95% CI 1.27 - 2.77) had increased odds of in-hospital mortality. Conclusion. The epidemiology of CRE bloodstream infections remained similar compared with the previous surveillance report. Most infections were HA and caused by OXA-48-like carbapenemase-producing K. pneumoniae with no plasmid-mediated colistin resistance. Standard infection control measures should be strengthened

Pseudomonas aeruginosa bacteraemia in an academic hospital in South Africa

This study aimed at determining the clinical manifestations, outcome and prognostic factors associated with P. aeruginosa bacteraemia at the Chris Hani Baragwanath Hospital during the period 1998-99; to describe and quantify resistance to anti-pseudomonal drugs, and characterization of bacteraemic isolates, investigate the genetic relationship among drug susceptible and multiply resistant strains in the hospital. Clinical and laboratory investigations, culture and antimicrobial susceptibility testing were performed. Bacteraemic isolates were typed by endonuclease macrorestriction. Those with ≥97% band pattern similarity were assigned genotype status. Of 91 P. aeruginosa blood isolates, 52 (57%) were nosocomially acquired. Underlying conditions associated with episodes were burns in 24 (26.4%) and HIV infection in 21 (23%). Multi-drug resistance was present in 14 isolates (15.4%). Outcome was poor and death was associated with 36 (45.56%) of episodes. Case fatality rates were 60% in adults and 27.3% in children. Being a child, receiving appropriate antimicrobial treatment and admission to specialized care units were significantly associated with improved prognosis. P. aeruginosa bacteraemia was associated with outbreaks caused by two multiply resistant genotypes. Eighteen, antimicrobial susceptible isolates from bacteraemic episodes in paediatric wards, 9 in HIV-seropositive children, could be linked to small outbreaks in both hospitalised and community-based children. South African Medical Journal Vol. 98 (8) 2008: pp. 626-62

Molecular detection of carbapenemase-producing genes in referral Enterobacteriaceae in South Africa: A short report

Molecular confirmation of carbapenemase-producing Enterobacteriaceae (CPE) was introduced in South Africa (SA) at the end of 2011. We report on the detection of these resistance genes based on referral isolates. Enterobacteriaceae with non-susceptibility to any of the carbapenems according to defined criteria for antimicrobial susceptibility testing results were sent to a reference laboratory. A proportion of isolates had limited demographic, epidemiological and clinical data available. Organism identification was reconfirmed using reference laboratory methods, and the presence of carbapenemases was confirmed with a real-time polymerase chain reaction. We analysed 1 503 significant isolates received for confirmation from the National Health Laboratory Service and some private laboratories during 2012 - 2015 and confirmed one or more carbapenemase-producing genes in 68% of isolates, the most common organism being Klebsiella pneumoniae (60%). The most common carbapenemase genes were blaNDM, followed by blaOXA-48 and its variants. BlaOXA-48 and its variants demonstrated non-susceptibility to ertapenem in 89% of the isolates when analysed by the phenotypic method, and to ceftazidime in 34%. Overall, the detection rate for carbapenemases in K. pneumoniae blood isolates in the public sector was 1.9% during the 4-year period. This report indicates the presence of CPE in SA, and it is important for all healthcare workers to be aware of this major public health threat so that infection prevention and control measures can be implemented to prevent the spread of CPE in healthcare facilities

NDM-1 imported from India – first reported case in South Africa

Carbapenem-resistant Enterobacteriaceae have been increasingly reported throughout the world. The first South African report of a New Delhi metallo-beta-lactamase was from Gauteng in August 2011. Despite maintaining a high degree of vigilance, the first such case was seen in KwaZulu-Natal almost a year later. Other cases have been unable to confirm a definite link to any other affected areas; this is the first case in South Africa showing this direct epidemiological link

Surveillance and comparison of antimicrobial susceptibility patterns of ESKAPE organisms isolated from patients with bacteraemia in South Africa, 2016 - 2017

Background. In South Africa (SA), the National Department of Health has developed an Antimicrobial Resistance National Strategy Framework document to manage antimicrobial resistance (AMR). One of the strategic objectives is to optimise surveillance and early detection of AMR. At the National Institute for Communicable Diseases (NICD), an analysis of selected organisms and antimicrobial agents from both the public and the private sectors was conducted.Objectives. The relevance of surveillance for AMR is increasingly recognised in the light of global action plans to combat resistance. In this report, we present an overview of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) organisms and Escherichia coli reported from public and private sector laboratories in SA for the period 2016 - 2017.Methods. Antimicrobial susceptibility testing (AST) profiles on selected ESKAPE organisms and E. coli isolated from blood cultures from the public and private sectors in 2016 and 2017 were analysed. AST data were extracted from a web-based electronic platform created by the NICD. Drug-bug combinations following the World Health Organization’s Global Antimicrobial Surveillance System guidelines were included in the analysis.Results. A total of 28 920 ESKAPE organisms and E. coli were reported in 2016 and 32 293 in 2017 across the two health sectors. Proportions of some organisms differed between the two health sectors, such as E. coli (19% in the public sector and 36% in the private sector), A. baumannii (14% public and 4% private), P. aeruginosa (7% public and 11% private) and S. aureus (27% public and 17% private). Susceptibility data indicated changing patterns in both sectors towards an increase in non-susceptibility to carbapenems in K. pneumoniae (p<0.01). However, we demonstrated an increase in susceptibility to cloxacillin in S. aureus (p<0.01) in both sectors.Conclusions. The key clinically important finding is the rapidly decreasing carbapenem susceptibility among Enterobacteriaceae reported in SA, irrespective of sector. In addition, the analysis provides information that could be used to monitor the effectiveness of interventions implemented at a national level under the guidance and direction of the national AMR framework.