High frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South african patients with extensively drug-resistant tuberculosis

dc.contributor.authorPietersen, Elizeen_ZA
dc.contributor.authorPeter, Jonnyen_ZA
dc.contributor.authorStreicher, Elizabethen_ZA
dc.contributor.authorSirgel, Friken_ZA
dc.contributor.authorRockwood, Neeshaen_ZA
dc.contributor.authorMastrapa, Barbaraen_ZA
dc.contributor.authorTe Riele, Julianen_ZA
dc.contributor.authorDavids, Malikaen_ZA
dc.contributor.authorvan Helden, Paulen_ZA
dc.contributor.authorWarren, Robinen_ZA
dc.contributor.authorDheda, Keertanen_ZA
dc.date.accessioned2016-01-11T06:56:08Z
dc.date.available2016-01-11T06:56:08Z
dc.date.issued2015en_ZA
dc.description.abstractBACKGROUND: There are limited data about the epidemiology and treatment-related outcomes associated with capreomycin resistance in patients with XDR-TB. Capreomycin achieves high serum concentrations relative to MIC but whether capreomycin has therapeutic benefit despite microbiological resistance remains unclear. METHODS: We reviewed the susceptibility profiles and outcomes associated with capreomycin usage in patients diagnosed with XDR-TB between August 2002 and October 2012 in two provinces of South Africa. Patients whose isolates were genotypically tested for capreomycin resistance were included in the analysis. RESULTS: Of 178 XDR-TB patients 41% were HIV-infected. 87% (154/178) isolates contained a capreomycin resistance-conferring mutation [80% (143/178) rrs A1401G and 6% (11/178) were heteroresistant (containing both the rrs A1401G mutation and wild-type sequences)]. Previous MDR-TB treatment, prior usage of kanamycin, or strain type was not associated with capreomycin resistance. 92% (163/178) of XDR-TB patients were empirically treated with capreomycin. Capreomycin resistance decreased the odds of sputum culture conversion. In capreomycin sensitive and resistant persons combined weight at diagnosis was the only independent predictor for survival (p=<0.001). By contrast, HIV status and use of co-amoxicillin/clavulanic acid were independent predictors of mortality (p=<0.05). Capreomycin usage was not associated with survival or culture conversion when the analysis was restricted to those whose isolates were resistant to capreomycin. CONCLUSION: In South Africa the frequency of capreomycin conferring mutations was extremely high in XDR-TB isolates. In those with capreomycin resistance there appeared to be no therapeutic benefit of using capreomycin. These data inform susceptibility testing and the design of treatment regimens for XDR-TB in TB endemic settings.en_ZA
dc.identifier.apacitationPietersen, E., Peter, J., Streicher, E., Sirgel, F., Rockwood, N., Mastrapa, B., ... Dheda, K. (2015). High frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South african patients with extensively drug-resistant tuberculosis. <i>PLoS One</i>, http://hdl.handle.net/11427/16303en_ZA
dc.identifier.chicagocitationPietersen, Elize, Jonny Peter, Elizabeth Streicher, Frik Sirgel, Neesha Rockwood, Barbara Mastrapa, Julian Te Riele, et al "High frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South african patients with extensively drug-resistant tuberculosis." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/16303en_ZA
dc.identifier.citationPietersen, E., Peter, J., Streicher, E., Sirgel, F., Rockwood, N., Mastrapa, B., ... & Dheda, K. (2015). High frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South african patients with extensively drug-resistant tuberculosis. PloS one, 10(4), e0123655. doi:10.1371/journal.pone.0123655en_ZA
dc.identifier.ris TY - Journal Article AU - Pietersen, Elize AU - Peter, Jonny AU - Streicher, Elizabeth AU - Sirgel, Frik AU - Rockwood, Neesha AU - Mastrapa, Barbara AU - Te Riele, Julian AU - Davids, Malika AU - van Helden, Paul AU - Warren, Robin AU - Dheda, Keertan AB - BACKGROUND: There are limited data about the epidemiology and treatment-related outcomes associated with capreomycin resistance in patients with XDR-TB. Capreomycin achieves high serum concentrations relative to MIC but whether capreomycin has therapeutic benefit despite microbiological resistance remains unclear. METHODS: We reviewed the susceptibility profiles and outcomes associated with capreomycin usage in patients diagnosed with XDR-TB between August 2002 and October 2012 in two provinces of South Africa. Patients whose isolates were genotypically tested for capreomycin resistance were included in the analysis. RESULTS: Of 178 XDR-TB patients 41% were HIV-infected. 87% (154/178) isolates contained a capreomycin resistance-conferring mutation [80% (143/178) rrs A1401G and 6% (11/178) were heteroresistant (containing both the rrs A1401G mutation and wild-type sequences)]. Previous MDR-TB treatment, prior usage of kanamycin, or strain type was not associated with capreomycin resistance. 92% (163/178) of XDR-TB patients were empirically treated with capreomycin. Capreomycin resistance decreased the odds of sputum culture conversion. In capreomycin sensitive and resistant persons combined weight at diagnosis was the only independent predictor for survival (p=<0.001). By contrast, HIV status and use of co-amoxicillin/clavulanic acid were independent predictors of mortality (p=<0.05). Capreomycin usage was not associated with survival or culture conversion when the analysis was restricted to those whose isolates were resistant to capreomycin. CONCLUSION: In South Africa the frequency of capreomycin conferring mutations was extremely high in XDR-TB isolates. In those with capreomycin resistance there appeared to be no therapeutic benefit of using capreomycin. These data inform susceptibility testing and the design of treatment regimens for XDR-TB in TB endemic settings. DA - 2015 DB - OpenUCT DO - 10.1371/journal.pone.0123655 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - High frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South african patients with extensively drug-resistant tuberculosis TI - High frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South african patients with extensively drug-resistant tuberculosis UR - http://hdl.handle.net/11427/16303 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16303
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0123655
dc.identifier.vancouvercitationPietersen E, Peter J, Streicher E, Sirgel F, Rockwood N, Mastrapa B, et al. High frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South african patients with extensively drug-resistant tuberculosis. PLoS One. 2015; http://hdl.handle.net/11427/16303.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2015 Pietersen et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherExtensively drug-resistant tuberculosisen_ZA
dc.subject.otherDrug therapyen_ZA
dc.subject.otherMulti-drug-resistant tuberculosisen_ZA
dc.subject.otherSputumen_ZA
dc.subject.otherTuberculosis diagnosis and managementen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherHIV diagnosis and managementen_ZA
dc.subject.otherDrug screeningen_ZA
dc.titleHigh frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South african patients with extensively drug-resistant tuberculosisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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