In vitro minimal inhibitory concentrations of rifampin and ethambutol, and treatment outcome in Mycobacterium avium complex lung disease [PublishAheadOfPrint]

Although it is known that in vitro minimal inhibitory concentrations (MICs) of rifampin and ethambutol are poorly correlated with clinical response in Mycobacterium avium complex lung disease (MAC-LD), its evidence is limited. This study investigated the association between treatment outcome and in vitro MICs of rifampin and ethambutol in patients with MAC-LD. Among patients diagnosed with macrolide-susceptible MAC-LD between January 2008 and December 2013, 274 patients treated with a standard regimen for ≥12 months until August 2017 and whose in vitro MIC results were available were enrolled at a tertiary referral center in South Korea. The MIC of antimicrobial agents was determined using the broth microdilution method. The mean age of the included patients was 60.4 years. The overall treatment success rate was 79.6% (218/274 patients) and tended to decrease with increasing MICs of rifampin and ethambutol, particularly at MICs ≥8 μg/ml. Treatment success was significantly different between MAC isolates with MIC ≥8 μg/ml for rifampin and ethambutol and those with MIC <8 μg/ml for rifampin and/or ethambutol (64.9% vs. 85.3%, P <0.001). Multivariate analysis showed that a MIC ≥8 μg/ml for both drugs and initial sputum acid-fast bacilli smear positivity were independent factors for unfavorable response (adjusted odds ratio [lsqb]OR[rsqb] 3.154, 95% confidence interval [lsqb]CI[rsqb] 1.641–6.063, P = 0.001; adjusted OR 2.769, 95% CI 1.420–5.399, P = 0.003, respectively). These findings suggested that in vitro MICs of rifampin and ethambutol may be related to treatment outcome in MAC-LD.

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