amoxicillin-potassium-clavulanate-combination and Extensively-Drug-Resistant-Tuberculosis

Topics: Amoxicillin-Potassium Clavulanate Combination; Extensively Drug-Resistant Tuberculosis; Fanconi Syndrome; Humans; Meropenem; Tuberculosis, Multidrug-Resistant

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Therapy, Combination; Extensively Drug-Resistant Tuberculosis; Fanconi Syndrome; Humans; Meropenem; Microbial Sensitivity Tests; Thienamycins

Management of extensively drug-resistant tuberculosis (XDR-TB) and pre-XDR-TB is challenging, as effective drugs are lacking. Group 5 anti-tuberculosis drugs have an unclear role in the treatment of drug-resistant TB, and in children the efficacy, safety and effects of long-term use are not well described. We present clinical outcomes and adverse effects of a cohort of children with XDR-TB or pre-XDR-TB treated with Group 5 drugs in Tajikistan.. We conducted a retrospective analysis of eight children treated with one or more of the Group 5 drugs available under the Tajikistan National TB Programme-linezolid, amoxicillin-clavulanate, clofazimine and clarithromycin-given in combination with first- and second-line drugs. Time to sputum culture conversion, clinical outcomes and adverse effects were evaluated.. Two children were cured, one completed treatment, four achieved favourable interim outcomes and one died. Adverse effects attributable to linezolid that required drug cessation occurred in one child; adverse effects of the other Group 5 drugs were insignificant or absent, requiring no regimen changes.. Group 5 drugs can contribute to effective regimens in children with XDR and pre-XDR-TB. With proper monitoring and aggressive management of adverse effects, their safety profile might be acceptable, even in long-term use.

Topics: Adolescent; Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; Child; Child, Preschool; Clarithromycin; Clofazimine; Drug Combinations; Extensively Drug-Resistant Tuberculosis; Female; Follow-Up Studies; Humans; Linezolid; Male; Retrospective Studies; Sputum; Tajikistan; Treatment Outcome

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.

Topics: Acetamides; Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Humans; Levofloxacin; Linezolid; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Ofloxacin; Oxazolidinones; Pakistan; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary