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. 2014 Aug 15;59(4):465-72.
doi: 10.1093/cid/ciu372. Epub 2014 May 20.

Mortality among tuberculosis patients with acquired resistance to second-line antituberculosis drugs--United States, 1993-2008

Julia V Ershova  1 , Ekaterina V Kurbatova  1 , Patrick K Moonan  1 , J Peter Cegielski  1
Affiliations

Mortality among tuberculosis patients with acquired resistance to second-line antituberculosis drugs--United States, 1993-2008

Julia V Ershova et al. Clin Infect Dis. .

Abstract

Background: Resistance to second-line antituberculosis drugs (SLDs) severely compromises treatment options of drug-resistant tuberculosis. We assessed the association between acquisition of resistance (AR) to second-line injectable drugs (SLIs) or fluoroquinolones (FQs) and mortality among tuberculosis cases confirmed by positive culture results with available initial and final drug susceptibility test (DST) results.

Methods: We analyzed data from the US National Tuberculosis Surveillance System, 1993-2008. Acquired resistance was defined as drug susceptibility at initial DST but resistance to the same drug at final DST. We compared survival with Kaplan-Meier curves and analyzed the association between AR and mortality using a univariate extended Cox proportional hazards model adjusted for age.

Results: Of 2329 cases with both initial and final DSTs to SLIs, 49 (2.1%) acquired resistance; 13 of 49 (26.5%) had treatment terminated by death compared with 222 (10.0%) of those without AR to SLIs (P < .001). Of 1187 cases with both initial and final DSTs to FQs, 32 (2.8%) acquired resistance; 12 of 32 (37.5%) had treatment terminated by death compared with 121 (10.9%) of those without AR to FQs (P = .001). Controlling for age, mortality was significantly greater among cases with AR to SLDs than among cases without AR (adjusted hazard ratio [aHR] for SLIs: 2.8; 95% confidence interval [CI],1.4-5.4; aHR for FQ: 1.9; 95% CI, 1.0-3.5). Multidrug-resistant tuberculosis at treatment initiation, positive human immunodeficiency virus status, and extrapulmonary disease were also significantly associated with mortality.

Conclusions: Mortality was significantly greater among tuberculosis cases with AR to SLDs. Providers should consider AR to SLDs early in treatment, monitor DST results, and avoid premature deaths.

Keywords: acquired drug resistance; tuberculosis.

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Figures

Figure 1
Figure 1
Figure 1(a). Selection of cases with initial DST to any SLD (31,733) Notes: DST: drug susceptibility test, SLD: second-line drugs, FLD: first-line drugs, MDR: multidrug resistance, *: percentage calculated from the number in the above box Figure 1(b). Selection of study population: second-line injectable drugs Notes: DST: drug susceptibility test, SLI: second-line injectable drugs, AR: acquired resistance Figure 1(c). Selection of study population: fluoroquinolones Notes: DST: drug susceptibility test, FQ: fluoroquinolones, AR: acquired resistance
Figure 1
Figure 1
Figure 1(a). Selection of cases with initial DST to any SLD (31,733) Notes: DST: drug susceptibility test, SLD: second-line drugs, FLD: first-line drugs, MDR: multidrug resistance, *: percentage calculated from the number in the above box Figure 1(b). Selection of study population: second-line injectable drugs Notes: DST: drug susceptibility test, SLI: second-line injectable drugs, AR: acquired resistance Figure 1(c). Selection of study population: fluoroquinolones Notes: DST: drug susceptibility test, FQ: fluoroquinolones, AR: acquired resistance
Figure 1
Figure 1
Figure 1(a). Selection of cases with initial DST to any SLD (31,733) Notes: DST: drug susceptibility test, SLD: second-line drugs, FLD: first-line drugs, MDR: multidrug resistance, *: percentage calculated from the number in the above box Figure 1(b). Selection of study population: second-line injectable drugs Notes: DST: drug susceptibility test, SLI: second-line injectable drugs, AR: acquired resistance Figure 1(c). Selection of study population: fluoroquinolones Notes: DST: drug susceptibility test, FQ: fluoroquinolones, AR: acquired resistance
Figure 2
Figure 2. Survival during treatment among TB cases with and without acquired resistance to second-line injectable drugs, United States, 1993 – 2008
Notes: AR: acquired resistance
Figure 3
Figure 3. Survival during treatment among TB cases with and without acquired resistance to fluoroquinolones, United States, 1993 – 2008
Notes: AR: acquired resistance
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