TY - JOUR
T1 - High Prevalence of Multidrug-Resistant Clostridioides difficile Following Extensive Use of Antimicrobials in Hospitalized Patients in Kenya
AU - Mutai, Winnie C.
AU - Mureithi, Marianne W.
AU - Anzala, Omu
AU - Revathi, Gunturu
AU - Kullin, Brian
AU - Burugu, Magdaline
AU - Kyany’a, Cecilia
AU - Odoyo, Erick
AU - Otieno, Peter
AU - Musila, Lillian
N1 - Funding Information:
We would like to thank Prof. Sharon Reid and Prof. Valerie Abratt (University of Cape Town, SA) and Prof. Andrew Whitelaw (University of Stellenbosch, SA) for support in anaerobic bacteriology and molecular assay training. The authors would also like to thank the Kenya Medical Research Institute/Walter Reed Army Institute of Research microbiology team, the research assistants (Grace Ndichu, William Musyoka and the late Tom Ouko), and the University of Nairobi Medical Microbiology lab team for their invaluable contributions in data collection and analysis. This project would not have been possible without the participation of the research participants, who responded to the questionnaires and provided stool samples for microbiological analysis. Part of the data in this manuscript was presented at the American Society for Microbiology (ASM) microbe 2019 in San Francisco, CA, June 20–24, 2019, and at the Young Scientist Symposium on Infectious Diseases in Durban, South Africa, 27–28 May 2019.
Funding Information:
WM was supported by the Consortium for Advanced Research Training in Africa (CARTA). CARTA is jointly led by the African Population and Health Research Center and the University of the Witwatersrand and funded by the Carnegie Corporation of New York (Grant No.: B 8606.R02), Sida (Grant No.: 54100029), the DELTAS Africa Initiative (Grant No: 107768/Z/15/Z). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS) ‘s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (UK) (Grant No.: 107768/Z/ 15/Z) and the UK government. This work was also partially supported by funds from National Research Fund Kenya (NRF) (2017/2018), University of Nairobi Deans Research Grant (2015/ 2016), and AstraZeneca (2014/2015). The funder bodies were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Publisher Copyright:
© Copyright © 2021 Mutai, Mureithi, Anzala, Revathi, Kullin, Burugu, Kyany’a, Odoyo, Otieno and Musila.
PY - 2021/2/8
Y1 - 2021/2/8
N2 - Introduction: Clostridioides difficile is a neglected pathogen in many African countries as it is generally not regarded as one of the major contributors toward the diarrheal disease burden in the continent. However, several studies have suggested that C. difficile infection (CDI) may be underreported in many African settings. The aim of this study was to determine the prevalence of CDI in hospitalized patients, evaluate antimicrobial exposure, and detect toxin and antimicrobial resistance profiles of the isolated C. difficile strains. Methods: In this cross-sectional study, 333 hospitalized patients with hospital-onset diarrhoea were selected. The stool samples were collected and cultured on cycloserine-cefoxitin egg yolk agar (CCEY). Isolates were presumptively identified by phenotypic characteristics and Gram stain and confirmed by singleplex real-time PCR (qPCR) assays detecting the species-specific tpi gene, toxin A (tcdA) gene, toxin B (tcdB) gene, and the binary toxin (cdtA/cdtB) genes. Confirmed C. difficile isolates were tested against a panel of eight antimicrobials (vancomycin, metronidazole, rifampicin, ciprofloxacin, tetracycline, clindamycin, erythromycin, and ceftriaxone) using E-test strips. Results: C. difficile was detected in 57 (25%) of diarrheal patients over the age of two, 56 (98.2%) of whom received antimicrobials before the diarrheal episode. Amongst the 71 confirmed isolates, 69 (97.1%) harbored at least one toxin gene. More than half of the toxigenic isolates harbored a truncated tcdA gene. All isolates were sensitive to vancomycin, while three isolates (2.1%) were resistant to metronidazole (MIC >32 mg/L). High levels of resistance were observed to rifampicin (65/71, 91.5%), erythromycin (63/71, 88.7%), ciprofloxacin (59/71, 83.1%), clindamycin (57/71, 80.3%), and ceftriaxone (36/71, 50.7.8%). Among the resistant isolates, 61 (85.9%) were multidrug-resistant. Conclusion: Multidrug-resistant C. difficile strains were a significant cause of healthcare facility-onset C. difficile infections in patients with prior antimicrobial exposure in this Kenyan hospital.
AB - Introduction: Clostridioides difficile is a neglected pathogen in many African countries as it is generally not regarded as one of the major contributors toward the diarrheal disease burden in the continent. However, several studies have suggested that C. difficile infection (CDI) may be underreported in many African settings. The aim of this study was to determine the prevalence of CDI in hospitalized patients, evaluate antimicrobial exposure, and detect toxin and antimicrobial resistance profiles of the isolated C. difficile strains. Methods: In this cross-sectional study, 333 hospitalized patients with hospital-onset diarrhoea were selected. The stool samples were collected and cultured on cycloserine-cefoxitin egg yolk agar (CCEY). Isolates were presumptively identified by phenotypic characteristics and Gram stain and confirmed by singleplex real-time PCR (qPCR) assays detecting the species-specific tpi gene, toxin A (tcdA) gene, toxin B (tcdB) gene, and the binary toxin (cdtA/cdtB) genes. Confirmed C. difficile isolates were tested against a panel of eight antimicrobials (vancomycin, metronidazole, rifampicin, ciprofloxacin, tetracycline, clindamycin, erythromycin, and ceftriaxone) using E-test strips. Results: C. difficile was detected in 57 (25%) of diarrheal patients over the age of two, 56 (98.2%) of whom received antimicrobials before the diarrheal episode. Amongst the 71 confirmed isolates, 69 (97.1%) harbored at least one toxin gene. More than half of the toxigenic isolates harbored a truncated tcdA gene. All isolates were sensitive to vancomycin, while three isolates (2.1%) were resistant to metronidazole (MIC >32 mg/L). High levels of resistance were observed to rifampicin (65/71, 91.5%), erythromycin (63/71, 88.7%), ciprofloxacin (59/71, 83.1%), clindamycin (57/71, 80.3%), and ceftriaxone (36/71, 50.7.8%). Among the resistant isolates, 61 (85.9%) were multidrug-resistant. Conclusion: Multidrug-resistant C. difficile strains were a significant cause of healthcare facility-onset C. difficile infections in patients with prior antimicrobial exposure in this Kenyan hospital.
KW - Africa
KW - Clostridioides difficile
KW - antimicrobial use
KW - multidrug resistance
KW - toxin types
UR - http://www.scopus.com/inward/record.url?scp=85101207729&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2020.604986
DO - 10.3389/fcimb.2020.604986
M3 - Article
C2 - 33628744
AN - SCOPUS:85101207729
SN - 2235-2988
VL - 10
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 604986
ER -
