Evidence map›Paper›PMID 25909847›Full record

ArticlePloS one2015

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

Elize Pietersen, Jonny Peter, Elizabeth Streicher, Frik Sirgel, Neesha Rockwood, Barbara Mastrapa, Julian Te Riele, Malika Davids, Paul van Helden, Robin Warren and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 5 pooled it
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 5 syntheses or guidelines pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. A systematic review on extensively drug-resistant tuberculosis from 2009 to 2020: special emphases on treatment outcomes.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2023
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  11. Toll-like Receptor 4 Signaling and Downstream Neutrophilic Inflammation Mediate Endotoxemia-Enhanced Blood-Labyrinth Barrier Trafficking.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 2 countries.

Elize PietersenLung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Jonny PeterLung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Elizabeth StreicherDepartment of Science and Technology/National Research Foundation Centre for Excellence for Biomedical Tuberculosis Research/South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Science, Stellenbosch University, Tygerberg, South Africa.
Frik SirgelDepartment of Science and Technology/National Research Foundation Centre for Excellence for Biomedical Tuberculosis Research/South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Science, Stellenbosch University, Tygerberg, South Africa.
Neesha RockwoodDepartment of Medicine, Imperial College London, London, United Kingdom.
Barbara MastrapaGordonia Provincial Hospital, Upington, South Africa.
Julian Te RieleBrooklyn Chest Hospital, Cape Town, South Africa.
Malika DavidsLung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Paul van HeldenDepartment of Science and Technology/National Research Foundation Centre for Excellence for Biomedical Tuberculosis Research/South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Science, Stellenbosch University, Tygerberg, South Africa.
Robin WarrenDepartment of Science and Technology/National Research Foundation Centre for Excellence for Biomedical Tuberculosis Research/South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Science, Stellenbosch University, Tygerberg, South Africa.
Keertan DhedaLung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
University of Cape Town · ZANational Research Foundation · ZABrooklyn Chest Hospital · ZAImperial College London · GBSouth African Medical Research Council · ZAStellenbosch University · ZA

Funding

Wellcome Trust 100693
6 · The paper itself

Abstract

backgroundThere 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.

methodsWe 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.

resultsOf 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.

conclusionIn 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.

Indexed as

Drug Resistance, Multiple, BacterialAdultAntitubercular AgentsCoinfectionExtensively Drug-Resistant TuberculosisFemaleHIV InfectionsHumansMaleMicrobial Sensitivity TestsMutationMycobacterium tuberculosisRetrospective StudiesSouth AfricaTreatment FailureTreatment OutcomeAntitubercular Agents

Identifiers

PMID25909847
PMCPMC4409172
OpenAlexW2008996157

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.