• Kumburu, Happiness
• Kibiki, Gibson
• Heysell, Scott K.
• Mpagama, Stellah G.
• Stroup, Suzanne
• Gratz, Jean
• Houpt, Eric R.

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:italic>Mycobacterium tuberculosis</jats:italic> 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. <jats:italic>M. tuberculosis</jats:italic> DNA was sequenced for resistance mutations in <jats:italic>rpoB</jats:italic> (rifampin), <jats:italic>inhA</jats:italic> (isoniazid, ethionamide), <jats:italic>katG</jats:italic> (isoniazid), <jats:italic>embB</jats:italic> (ethambutol), <jats:italic>gyrA</jats:italic> (fluoroquinolones), <jats:italic>rrs</jats:italic> (amikacin, kanamycin, capreomycin), <jats:italic>eis</jats:italic> (kanamycin) and <jats:italic>pncA</jats:italic> (pyrazinamide).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of 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 <jats:italic>gyrA</jats:italic>, <jats:italic>rrs</jats:italic> or <jats:italic>eis</jats:italic> for all 13 isolates available for sequencing, but <jats:italic>pncA</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In Tanzania, quantitative second-line susceptibility testing could inform and alter MDR-TB management independent of drug-resistance mutations. Further operational studies are warranted.</jats:p></jats:sec>

Topics

• electrochemical-induced impedance spectroscopy
• size-exclusion chromatography
• susceptibility