Abstract
BackgroundLack of rapid and reliable susceptibility testing for second-line drugs used in the treatment of multidrug-resistant tuberculosis (MDR-TB) may limit treatment success.MethodsMycobacterium tuberculosis isolates from patients referred to Kibong’oto National TB Hospital in Tanzania for second-line TB treatment underwent confirmatory speciation and susceptibility testing. Minimum inhibitory concentration (MIC) testing on MYCOTB Sensititre plates was performed for all drugs available in the second-line formulary. We chose to categorize isolates as borderline susceptible if the MIC was at or one dilution lower than the resistance breakpoint. M. tuberculosis DNA was sequenced for resistance mutations in rpoB (rifampin), inhA (isoniazid, ethionamide), katG (isoniazid), embB (ethambutol), gyrA (fluoroquinolones), rrs (amikacin, kanamycin, capreomycin), eis (kanamycin) and pncA (pyrazinamide).ResultsOf 22 isolates from patients referred for second-line TB treatment, 13 (59%) were MDR-TB and the remainder had other resistance patterns. MIC testing identified 3 (14%) isolates resistant to ethionamide and another 8 (36%) with borderline susceptibility. No isolate had ofloxacin resistance, but 10 (45%) were borderline susceptible. Amikacin was fully susceptible in 15 (68%) compared to only 11 (50%) for kanamycin. Resistance mutations were absent in gyrA, rrs or eis for all 13 isolates available for sequencing, but pncA mutation resultant in amino acid change or stop codon was present in 6 (46%). Ten (77%) of MDR-TB patients had at least one medication that could have logically been modified based on these results (median 2; maximum 4). The most common modifications were a change from ethioniamide to para-aminosalicylic acid, and the use of higher dose levofloxacin.ConclusionsIn Tanzania, quantitative second-line susceptibility testing could inform and alter MDR-TB management independent of drug-resistance mutations. Further operational studies are warranted.
Highlights
Lack of rapid and reliable susceptibility testing for second-line drugs used in the treatment of multidrug-resistant tuberculosis (MDR-TB) may limit treatment success
Despite individualized treatment existing as the standard of care in areas with adequate expertise and laboratory capacity [4], the lack of second-line susceptibility testing is common in resource-limited settings where the vast majority of MDR-TB occurs, and in such locations empiric regimens have been advocated [1]
In the following study we describe the potential application of quantitative susceptibility testing for drug-resistant TB management in Tanzania
Summary
Lack of rapid and reliable susceptibility testing for second-line drugs used in the treatment of multidrug-resistant tuberculosis (MDR-TB) may limit treatment success. Management of multidrug-resistant tuberculosis (MDRTB) poses a major challenge, since resistance to isoniazid and rifampin precludes the use of two key drugs in the anti-TB regimen. The lack of rapid and reliable susceptibility testing for the drugs which compose the MDR-TB regimen further limits the ability to assign the ideal combination to an individual patient. Despite individualized treatment existing as the standard of care in areas with adequate expertise and laboratory capacity [4], the lack of second-line susceptibility testing is common in resource-limited settings where the vast majority of MDR-TB occurs, and in such locations empiric regimens have been advocated [1]. Meta-analysis found improved cure rates with use of a later generation fluoroquinolone among patients with extensively drug-resistant isolates resistant to ofloxacin [7]
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