Once-a-week tigecycline for the treatment of drug-resistant TB

The Journal of Antimicrobial Chemotherapy
Devyani DeshpandeTawanda Gumbo

Abstract

MDR-TB and XDR-TB have poor outcomes. To examine the efficacy of tigecycline monotherapy in the hollow fibre system model of TB. We performed pharmacokinetic/pharmacodynamic studies using tigecycline human-like concentration-time profiles in the hollow fibre system model of TB in five separate experiments using Mycobacterium tuberculosis in log-phase growth or as semi-dormant or intracellular bacilli, as monotherapy. We also compared efficacy with the isoniazid/rifampicin/pyrazinamide combination (standard therapy). We then applied extinction mathematics, morphisms and Latin hypercube sampling to identify duration of therapy with tigecycline monotherapy. The median tigecycline MIC for 30 M. tuberculosis clinical and laboratory isolates (67% MDR/XDR) was 2 mg/L. Tigecycline monotherapy was highly effective in killing M. tuberculosis in log-phase-growth and semi-dormant and intracellular M. tuberculosis. Once-a-week dosing had the same efficacy as daily therapy for the same cumulative dose; thus, tigecycline efficacy was linked to the AUC0-24/MIC ratio. Tigecycline replacement by daily minocycline after 4 weeks of therapy was effective in sterilizing bacilli. The AUC0-24/MIC ratio associated with optimal kill was 42.3. Tigecyclin...Continue Reading

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Citations

Jan 29, 2021·Journal of Global Antimicrobial Resistance·Shashikant SrivastavaTawanda Gumbo

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