title: Susceptibility testing of extensively drug-resistant and pre-extensively drug-resistant Mycobacterium tuberculosis against levofloxacin, linezolid, and amoxicillin-clavulanate.
abstract: Pakistan is a high-burden country for tuberculosis (TB). The emergence and increasing incidence of extensively drug-resistant (XDR) TB has been reported in Pakistan. Similarly, the prevalence of multidrug-resistant TB infections with fluoroquinolone resistance (pre-XDR) is also increasing. To treat these infections, local drug susceptibility patterns of alternate antituberculosis agents, including levofloxacin (LVX), linezolid (LZD), and amoxicillin-clavulanate (AMC), is urgently needed. The aim of this study was to determine the susceptibility frequencies of drug-resistant (DR) Mycobacterium tuberculosis against LVX, LZD, and AMC. All susceptibilities were determined on Middlebrook 7H10 agar. A critical concentration was used for LVX (1 μg/ml), whereas MICs were determined for LZD and AMC. M. tuberculosis H37Rv was used as a control strain. A total of 102 M. tuberculosis isolates (XDR, n = 59; pre-XDR, n = 43) were tested. Resistance to LVX was observed in 91.2% (93/102). Using an MIC value of 0.5 μg/ml as a cutoff, resistance to LZD (MIC ≥ 1 μg/ml) was noted in 5.9% (6/102). Although the sensitivity breakpoints are not established for AMC, the MIC values were high (>16 μg/ml) in 97.1% (99/102). Our results demonstrate that LZD may be effective for the treatment of XDR and pre-XDR cases from Pakistan. High resistance rates against LVX in our study suggest the use of this drug with caution for DR-TB cases from this area. Drug susceptibility testing against LVX and AMC may be helpful in complicated and difficult-to-manage cases.
authors.affiliation: Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan.
authors.forename: Imran
authors.initials: I
authors.lastname: Ahmed
authors.forename: Kauser
authors.initials: K
authors.lastname: Jabeen
authors.forename: Raunaq
authors.initials: R
authors.lastname: Inayat
authors.forename: Rumina
authors.initials: R
authors.lastname: Hasan
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D054908:Extensively Drug-Resistant Tuberculosis / Q000453:epidemiology / Q000382:microbiology*; D006801:Humans; D064704:Levofloxacin; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D015242:Ofloxacin / Q000494:pharmacology*; D023303:Oxazolidinones / Q000494:pharmacology*; D010154:Pakistan / Q000453:epidemiology; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000382:microbiology
chemical_list: D000081:Acetamides; D000995:Antitubercular Agents; D023303:Oxazolidinones; D064704:Levofloxacin; D019980:Amoxicillin-Potassium Clavulanate Combination; D015242:Ofloxacin; D000069349:Linezolid