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Observational Study
. 2017 Jun 1;64(11):1502-1508.
doi: 10.1093/cid/cix128.

Implications of Failure to Routinely Diagnose Resistance to Second-Line Drugs in Patients With Rifampicin-Resistant Tuberculosis on Xpert MTB/RIF: A Multisite Observational Study

Karen R Jacobson  1 , Marinus Barnard  2 , Mary B Kleinman  3 , Elizabeth M Streicher  4 , Elizabeth J Ragan  1 , Laura F White  5 , Ofer Shapira  6 , Tania Dolby  2 , John Simpson  2 , Lesley Scott  7 , Wendy Stevens  7 , Paul D van Helden  4 , Annelies Van Rie  8   9 , Robin M Warren  4
Affiliations
Observational Study

Implications of Failure to Routinely Diagnose Resistance to Second-Line Drugs in Patients With Rifampicin-Resistant Tuberculosis on Xpert MTB/RIF: A Multisite Observational Study

Karen R Jacobson et al. Clin Infect Dis. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Clin Infect Dis. 2017 Oct 15;65(8):1431-1433. doi: 10.1093/cid/cix563. Clin Infect Dis. 2017. PMID: 29017252 Free PMC article. No abstract available.

Abstract

Background.: Xpert MTB/RIF (Xpert) detects rifampicin-resistant tuberculosis (RR-tuberculosis), enabling physicians to rapidly initiate a World Health Organization-recommended 5-drug regimen while awaiting second-line drug-susceptibility test (DST) results. We quantified the second-line DST results time and proportion of patients potentially placed on suboptimal therapy.

Methods.: We included RR-tuberculosis patients detected using Xpert at the South African National Health Laboratory Services (NHLS) of the Western Cape between November 2011 and June 2013 and at Eastern Cape, Free State, and Gauteng NHLS between November 2012 and December 2013. We calculated time from specimen collection to phenotypic second-line DST results. We identified isoniazid and ethionamide resistance mutations on line probe assay and performed pyrazinamide sequencing.

Results.: Among 1332 RR-tuberculosis patients, only 44.7% (596) had second-line DST for both fluoroquinolones and second-line injectable: 55.8% (466 of 835) in the Western Cape and 26.2% (130 of 497) in the other provinces. Patients with smear negative disease and age ≤10 years were less likely to have a result (risk ratio [RR] = 0.72; 95% CI, 0.64-0.81 and RR = 0.49; 95% CI, 0.26-0.79). Median time to second-line DST was 53 days (range, 8-259). Of the 252 patients with complete second-line DST, 101 (40.1%) potentially initiated a suboptimal regimen: 46.8% in the Western Cape and 25.3% in the other provinces.

Conclusions.: Many South Africans diagnosed with RR-tuberculosis by Xpert initiate a suboptimal regimen, with information to adjust therapy available in half of all patients after a median 7 weeks. Algorithm completion and time delays remain challenging.

Keywords: South Africa; drug resistance.; drug susceptibility; multidrug-resistant tuberculosis; tuberculosis.

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Figures

Figure 1.
Figure 1.
Flow diagrams of patients from Western Cape Province (11) and Eastern Cape, Free State, and Gauteng provinces (11) included in the study. Abbreviations: DST, drug-susceptibility test; MTB, Mycobacterium tuberculosis; NTM, nontuberculous mycobacteria; RIF, rifampin.
Figure 2.
Figure 2.
Percentage of patients with number of likely effective drugs in standardized 5-drug multidrug-resistant tuberculosis regimen: Western Cape Province (N = 173) and Eastern Cape, Free State, Gauteng provinces (N = 79).
See this image and copyright information in PMC

References

    1. World Health Organization. Tuberculosis Diagnostics: Xpert MTB/RIF Test 2014. Available at: http://apps.who.int/iris/bitstream/10665/112469/1/9789241506700_eng.pdf. Accessed on 14 July 2016.
    1. Van Rie A, Page-Shipp L, Hanrahan CF, et al. Point-of-care Xpert MTB/RIF for smear-negative tuberculosis suspects at a primary care clinic in South Africa. Int J Tuberc Lung Dis 2013; 17(11):368–72. - PMC - PubMed
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    1. Ahuja SD, Ashkin D, Avendano M, et al. Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients. PLoS Med 2012; 9:e1001300. - PMC - PubMed

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