Antibacterials/antituberculars

Abstract

Antibacterials/antituberculars Development of drug resistance and treatment failure: 8 case reportsIn a prospective cohort study (NCT03162107; PRAXIS study conducted between November 2016 and January 2019) of 297 adult patients, 8 adult patients [sexes and exact ages not stated] were described, of whom, 7 patients exhibited treatment failure during treatment with linezolid, terizidone, aminosalicylic acid [para-amino salicylic acid], imipenem, pyrazinamide, ethionamide, ethambutol, isoniazid, delamanid, bedaquiline, clofazimine or unspecified fluoroquinolones for extensively drug-resistant tuberculousis (XDR-TB). Additionally, five of these patients and the remaining one patient developed drug resistance during treatment with bedaquiline and clofazimine [routes, dosages and duration of treatments to reaction onsets not stated].Patient-A: The adult patient, who had pre-XDR TB and HIV infection, had been receiving unspecified antiretroviral therapy for HIV infection. Concomitantly, the patient started receiving pyrazinamide, unspecified fluoroquinolones, bedaquiline, clofazimine, ethionamide, linezolid, terizidone and aminosalicylic acid for tuberculosis. At a 6-month follow-up, the patient experienced treatment failure. Subsequently, the patient was lost to follow-up.Patient-B: The adult patient, who had pre-XDR TB and HIV infection, had been receiving unspecified antiretroviral therapy for HIV infection. Concomitantly, the patient started receiving pyrazinamide, unspecified fluoroquinolones, bedaquiline, clofazimine, linezolid, terizidone, aminosalicylic acid and iminipem for tuberculosis. Initially, the patient had a baseline Rv0678 variant (associated with bedaquiline resistance; R109L, R159fs) allele frequency of 72%; however, 2 months following treatment initiation, the patient's Mycobacterium tuberculosis minimum inhibitory concentration (MIC) for bedaquiline increased from 0.03 µg/mL to 0.25 µg/mL due to within-patient evolution of the infecting strain. Further, the frequency of Rv0678 variant allele increased to 96%, indicating drug resistance secondary to bedaquiline and clofazimine. At a 6-month follow-up, the patient exhibited treatment failure with pyrazinamide, unspecified fluoroquinolones, terizidone, aminosalicylic acid and iminipem. Eventually, the patient died [immediate cause of death not stated].Patient-D: The adult patient, who had XDR-TB and HIV infection, had been receiving unspecified antiretroviral therapy for HIV infection. Concomitantly, the patient started receiving isoniazid, pyrazinamide, unspecified fluoroquinolones, bedaquiline, clofazimine, terizidone and aminosalicylic acid for XDR-TB. At a 6-month follow-up, the patient exhibited treatment failure. Eventually, the patient died [immediate cause of death not stated].Patient-F: The adult patient, who had XDR-TB and HIV infection, had been receiving unspecified antiretroviral therapy for HIV infection. Concomitantly, the patient started receiving pyrazinamide, unspecified fluoroquinolones, bedaquiline, clofazimine, linezolid, terizido...