Carbapenem-resistant Enterobacterales among hospitalized patients in Cape Town, South Africa: clinical and microbiological epidemiology
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PROVIDER: S-EPMC10959510 | biostudies-literature | 2024 Mar
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Project description:BackgroundThe molecular epidemiology of carbapenem-resistant Enterobacterales in Cape Town remains largely unknown.ObjectivesThis study aimed to describe the molecular epidemiology, resistome, virulome and mobilome of carbapenem-resistant Klebsiella pneumoniae (CRKP) within Cape Town to guide therapy, antimicrobial stewardship and infection prevention and control practices.MethodsEighty-five CRKP isolates from hospitalized patients underwent WGS as part of a prospective, multicentre, cross-sectional study, conducted between 1 November 2020 and 30 November 2022, across public-sector and private-sector hospitals in Cape Town, South Africa.ResultsMLST revealed three novel types, ST6785, ST6786 and ST6787, while the most common were ST219, ST307, ST17, ST13 and ST2497. Different predominant clones were noted in each hospital. The most common carbapenemase gene was blaOXA-48-like, detected in 71% of isolates, with blaNDM detected in 5%. Notably, co-detection of two carbapenemase genes (blaOXA-48-like and blaNDM) occurred in 13% of isolates. The yersiniabactin siderophore was detected in 73% of isolates, and was most commonly associated with the ICEKp5 mobile element. All carbapenemases were located on plasmids. The genes blaOXA-181 and blaOXA-232 colocalized with a ColKP3 replicon type on assembled contigs in 83% and 100% of cases, respectively.ConclusionsCRKP epidemiology in Cape Town reflects institutionally dominant, rather than regional, clones. The most prevalent carbapenemase gene was blaOXA-48-like, in keeping with CRKP epidemiology in South Africa in general. Emerging clones harbouring both blaOXA-48-like and blaNDM, such as ST17, ST2497 and the novel ST6787, are a concern due to the limited availability of appropriate antimicrobial agents in South Africa.
| S-EPMC10963078 | biostudies-literature
Project description:CRE in Cape Town, South Africa
| PRJEB81144 | ENA
Project description:BackgroundCarbapenem resistant Enterobacterales (CRE) have become established as leading pathogens in South African healthcare facilities. The aim of this study is to describe the epidemiology of CRE carriage and clinical infection episodes at healthcare facilities in the Western Cape Province of South Africa (2016-2020), and identify factors associated with mortality in CRE infected patients.MethodologyWe used routine data from the Provincial Health Data Centre to track the emergence of CRE in healthcare facilities in the Western Cape Province of South Africa. We included all CRE episodes (clinical and carriage) at Western Cape hospitals (including day and inpatients) from 2016 to 2020 to determine the distribution of CRE, patient demographics and antibiotic resistance phenotypes. Logistic regression was performed to identify factors associated with mortality from clinical CRE episodes.Results2242 CRE episodes (1580 [70.5%] clinical and 662 [29.5%] carriage) were identified. From these, 2281 CRE isolates were identified, with Klebsiella species predominating (1644, 72.1%). Affected patients had a median age of 31 (IQR 0-52) years, and 1167 (52.0%) were male. Most CRE episodes were recorded in central hospitals (70.0%, p < 0.001). Where outcome data was available, crude in-hospital mortality rates were 26.9% (371/1379) for CRE clinical episodes versus 6.4% (41/640) for CRE carriage episodes (p < 0.001). Factors that showed a statistically significant association with in-hospital mortality were female sex [adjusted odd ratio (aOR) 1.40 (95% confidence interval (CI) 1.09-1.560)], adult patients [aOR 1.76 (95% CI 1.20-2.57)], CRE isolation from a sterile specimen [aOR 0.41 (95% CI 0.32-0.53)], and >3 days between hospital admission and specimen collection [aOR 1.56 (95% CI 1.11-2.18)].ConclusionsCRE episodes at Western Cape healthcare facilities are concentrated at tertiary hospitals, with high case fatality rates in patients with clinical CRE episodes. Infection control interventions must be strengthened to reduce transmission of CRE, and to reduce infection risks.
| S-EPMC11346644 | biostudies-literature
Project description:Staphylococci are responsible for a wide range of infections in animals. The most common species infecting animals include Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus intermedius. Recent increases in antibiotic use and antibiotic resistance in animals highlight the need to understand the potential role of commercial livestock as a reservoir of staphylococci and antibiotic resistance genes. Nasal swabs were collected from 143 apparently healthy pigs and 21 pig farm workers, and 45 environmental swabs of feed and water troughs, from two commercial pig farms in the Western Cape, South Africa. Staphylococci were isolated, identified using mass-spectrometry, and antimicrobial susceptibility testing and Illumina whole genome sequencing were performed. One hundred and eighty-five (185) Staphylococcus spp. isolates were obtained, with Mammalicoccus sciuri (n = 57; 31%) being the most common, followed by S. hyicus (n = 40; 22%) and S. aureus (n = 29; 16%). S. epidermidis was predominantly identified in the farm workers (n = 18; 86%). Tetracycline resistance was observed across all species, with rates ranging from 67 to 100%. Majority of M. sciuri isolates (n = 40; 70%) were methicillin resistant, with 78% (n = 31) harbouring mecA. M. sciuri isolates had genes/elements which were associated with SCCmec_type_III (3A) and SCCmec_type_VIII(4A) and were mostly observed in ST61 strains. ST239 strains were associated with SCCmec_type_III(3A). High rates of tetracycline resistance were identified among staphylococci in the pig farms in Western Cape, South Africa. This highlights the need for policy makers to regulate the use of this antibiotic in pig farming.
| S-EPMC11347665 | biostudies-literature
Project description:BackgroundExperimental data show that drug-resistance-conferring mutations are often associated with a decrease in the replicative fitness of bacteria in vitro, and that this fitness cost can be mitigated by compensatory mutations; however, the role of compensatory evolution in clinical settings is less clear. We assessed whether compensatory evolution was associated with increased transmission of rifampicin-resistant tuberculosis in Khayelitsha, Cape Town, South Africa.MethodsWe did a genomic epidemiological study by analysing available M tuberculosis isolates and their associated clinical data from individuals routinely diagnosed with rifampicin-resistant tuberculosis in primary care and hospitals in Khayelitsha, Cape Town, South Africa. Isolates were collected as part of a previous study. All individuals diagnosed with rifampicin-resistant tuberculosis and with linked biobanked specimens were included in this study. We applied whole-genome sequencing, Bayesian reconstruction of transmission trees, and phylogenetic multivariable regression analysis to identify individual and bacterial factors associated with the transmission of rifampicin-resistant M tuberculosis strains.FindingsBetween Jan 1, 2008, and Dec 31, 2017, 2161 individuals were diagnosed with multidrug-resistant or rifampicin-resistant tuberculosis in Khayelitsha, Cape Town, South Africa. Whole-genome sequences were available for 1168 (54%) unique individual M tuberculosis isolates. Compensatory evolution was associated with smear-positive pulmonary disease (adjusted odds ratio 1·49, 95% CI 1·08-2·06) and a higher number of drug-resistance-conferring mutations (incidence rate ratio 1·38, 95% CI 1·28-1·48). Compensatory evolution was also associated with increased transmission of rifampicin-resistant disease between individuals (adjusted odds ratio 1·55; 95% CI 1·13-2·12), independent of other patient and bacterial factors.InterpretationOur findings suggest that compensatory evolution enhances the in vivo fitness of drug-resistant M tuberculosis genotypes, both within and between patients, and that the in vitro replicative fitness of rifampicin-resistant M tuberculosis measured in the laboratory correlates with the bacterial fitness measured in clinical settings. These results emphasise the importance of enhancing surveillance and monitoring efforts to prevent the emergence of highly transmissible clones capable of rapidly accumulating new drug resistance mutations. This concern becomes especially crucial at present, because treatment regimens incorporating novel drugs are being implemented.FundingFunding for this study was provided by a Swiss and South Africa joint research award (grant numbers 310030_188888, CRSII5_177163, and IZLSZ3_170834), the European Research Council (grant number 883582), and a Wellcome Trust fellowship (to HC; reference number 099818/Z/12/Z). ZS-D was funded through a PhD scholarship from the South African National Research Foundation and RMW was funded through the South African Medical Research Council.
| S-EPMC10319636 | biostudies-literature
Project description:Carbapenem-resistant Klebsiella pneumoniae South Africa
| PRJEB63361 | ENA
Project description:BackgroundCarbapenem-resistant Enterobacterales (CRE) is a global threat. Enterobacterales develops carbapenem resistance through several mechanisms, including the production of carbapenemases. We aim to describe the prevalence of Carbapenem-resistant Enterobacterales (CRE) with and without carbapenemase production and distribution of carbapenemase-producing (CP) genes in Thailand using 2016-2018 data from a national antimicrobial resistance surveillance system developed by the Thailand National Institute of Health (NIH).MethodsCRE was defined as any Enterobacterales resistant to ertapenem, imipenem, or meropenem. Starting in 2016, 25 tertiary care hospitals from the five regions of Thailand submitted the first CRE isolate from each specimen type and patient admission to Thailand NIH, accompanied by a case report form with patient information. NIH performed confirmatory identification and antimicrobial susceptibility testing and performed multiplex polymerase chain reaction testing to detect CP-genes. Using 2016-2018 data, we calculated proportions of CP-CRE, stratified by specimen type, organism, and CP-gene using SAS 9.4.ResultsOverall, 4,296 presumed CRE isolates were submitted to Thailand NIH; 3,946 (93%) were confirmed CRE. Urine (n = 1622, 41%) and sputum (n = 1380, 35%) were the most common specimen types, while blood only accounted for 323 (8%) CRE isolates. The most common organism was Klebsiella pneumoniae (n = 2660, 72%), followed by Escherichia coli (n = 799, 22%). The proportion of CP-CRE was high for all organism types (range: 85-98%). Of all CRE isolates, 2909 (80%) had one CP-gene and 629 (17%) had > 1 CP-gene. New Delhi metallo-beta-lactamase (NDM) was the most common CP-gene, present in 2392 (65%) CRE isolates. K. pneumoniae carbapenemase (KPC) and Verona integron-encoded metallo-β-lactamase (VIM) genes were not detected among any isolates.ConclusionCP genes were found in a high proportion (97%) of CRE isolates from hospitals across Thailand. The prevalence of NDM and OXA-48-like genes in Thailand is consistent with pattern seen in Southeast Asia, but different from that in the United States and other regions. As carbapenemase testing is not routinely performed in Thailand, hospital staff should consider treating all patients with CRE with enhanced infection control measures; in line with CDC recommendation for enhanced infection control measures for CP-CRE because of their high propensity to spread.
| S-EPMC8180034 | biostudies-literature
Project description:BackgroundEvidence shows that antiretroviral (ART) exposure is associated with neurodevelopmental delays in human immunodeficiency virus (HIV)-exposed uninfected (HEU) children. However, there are few insights into modifiable maternal and child factors that may play a role in improving neurodevelopment in HEU children. We used a parent-centric neurodevelopment tool, Ages & Stages Questionnaire (ASQ) to examined neurodevelopment in HEU children at 12-24 months of age, and associations with maternal and child factors.Methods505 HIV-infected women (initiated ART pre- or during pregnancy) with live singleton births attending primary health care were enrolled; 355 of their HEU children were assessed for neurodevelopment (gross motor, fine motor, communication, problem solving and personal-social domains) at 12-24 months using age-specific ASQ administered by a trained fieldworker. Associations with maternal and child factors were examined using logistic regression models.ResultsAmong mothers (median age 30 years, IQR, 26-34), 52% initiated ART during pregnancy; the median CD4 count was 436 cells/μl (IQR, 305-604). Most delayed neurodevelopment in HEU children was in gross (9%) and fine motor (5%) functions. In adjusted models, maternal socio-economic status (aOR 0.42, 95% CI 0.24-0.76) was associated with reduced odds of delayed gross-fine motor neurodevelopment. Maternal age ≥35 years (aOR 0.22, 95% CI 0.05-0.89) and maternal body mass index (BMI) <18.5 (aOR 6.76, 95% CI 1.06-43.13) were associated with delayed communication-problem-solving-personal-social neurodevelopment. There were no differences in odds for either domain by maternal ART initiation timing.ConclusionsDelayed neurodevelopment was detected in both gross and fine motor functions in this cohort of HEU children, with strong maternal predictors that may be explored as potentially modifiable factors associated with neurodevelopment at one to two years of age.
| S-EPMC7673492 | biostudies-literature
Project description:BackgroundBedaquiline is a life-saving tuberculosis drug undergoing global scale-up. People at risk of weak tuberculosis drug regimens are a priority for novel drug access despite the potential source of Mycobacterium tuberculosis-resistant strains. We aimed to characterise bedaquiline resistance in individuals who had sustained culture positivity during bedaquiline-based treatment.MethodsWe did a retrospective longitudinal cohort study of adults (aged ≥18 years) with culture-positive pulmonary tuberculosis who received at least 4 months of a bedaquiline-containing regimen from 12 drug-resistant tuberculosis treatment facilities in Cape Town, South Africa, between Jan 20, 2016, and Nov 20, 2017. Sputum was programmatically collected at baseline (ie, before bedaquiline initiation) and each month to monitor treatment response per the national algorithm. The last available isolate from the sputum collected at or after 4 months of bedaquiline was designated the follow-up isolate. Phenotypic drug susceptibility testing for bedaquiline was done on baseline and follow-up isolates in MGIT960 media (WHO-recommended critical concentration of 1 μg/mL). Targeted deep sequencing for Rv0678, atpE, and pepQ, as well as whole-genome sequencing were also done.FindingsIn total, 40 (31%) of 129 patients from an estimated pool were eligible for this study. Overall, three (8%) of 38 patients assessable by phenotypic drug susceptibility testing for bedaquiline had primary resistance, 18 (47%) gained resistance (acquired or reinfection), and 17 (45%) were susceptible at both baseline and follow-up. Several Rv0678 and pepQ single-nucleotide polymorphisms and indels were associated with resistance. Although variants occurred in Rv0676c and Rv1979c, these variants were not associated with resistance. Targeted deep sequencing detected low-level variants undetected by whole-genome sequencing; however, none were in genes without variants already detected by whole-genome sequencing. Patients with baseline fluoroquinolone resistance, clofazimine exposure, and four or less effective drugs were more likely to have bedaquiline-resistant gain. Resistance gain was primarily due to acquisition; however, some reinfection by resistant strains occurred.InterpretationBedaquiline-resistance gain, for which we identified risk factors, was common in these programmatically treated patients with sustained culture positivity. Our study highlights risks associated with implementing life-saving new drugs and shows evidence of bedaquiline-resistance transmission. Routine drug susceptibility testing should urgently accompany scale-up of new drugs; however, rapid drug susceptibility testing for bedaquiline remains challenging given the diversity of variants observed.FundingDoris Duke Charitable Foundation, US National Institute of Allergy and Infectious Diseases, South African Medical Research Council, National Research Foundation, Research Foundation Flanders, Stellenbosch University Faculty of Medicine Health Sciences, South African National Research Foundation, Swiss National Science Foundation, and Wellcome Trust.
| S-EPMC10842724 | biostudies-literature
Project description:Uptake of contraceptive implants has declined in South Africa since their introduction in 2014, with side effects and inadequate health provider training cited as primary contributors underlying a poor community perception of implants. In this paper we explore a theme that emerged unexpectedly during analysis of our research in Cape Town that may be an additional factor in this decline: narratives of women being assaulted by robbers who physically remove the implants for smoking as drugs. Narratives were described consistently across interviews and focus groups with youth (aged 18-24 years) and in interviews with health providers, with six participants (two young people, four health providers) sharing personal experiences of robbery. While there was a range of perspectives on whether narratives are based on real experiences or are myths, there was strong consensus that narratives of implant robbery may be influencing women's decisions around implant use in Cape Town. This is a potent example of how perceptions of new products can affect uptake and offers important lessons for implementers to reflect on in planning for rollout of other health technologies.
| S-EPMC7529647 | biostudies-literature