Culture conversion and macrolide resistance in Mycobacterium abscessus complex pulmonary disease

Abstract

The Mycobacterium abscessus complex (MABC) is highly resistant to antibiotics, making the pulmonary disease it causes, known as MABC-PD, difficult to treat. Macrolide antibiotics are the main treatment for MABC-PD, but there is ongoing debate about whether to favor azithromycin (AZI) or clarithromycin (CLA). We compared how well AZI and CLA work against MABC and monitored the risk of developing resistance. MABC-PD patients were enrolled, and their primary isolates were collected. The minimum inhibitory concentrations (MICs) of CLA and AZI against these isolates over various incubation times were determined. The incidences of the acquired and inducible resistance of the isolates to both antibiotics were compared, and their association with culture conversion was monitored. The transcription levels of the erm(41) gene were quantified. A total of 61 MABC-PD patients who underwent a macrolide-containing treatment regimen were enrolled. The MICs of AZI against the MABC clinical isolates were found to be approximately four to eight times higher than those of CLA. Inducible macrolide resistance was observed in the subspecies Mycobacterium abscessus, which possessed the functional erm(41) gene. Inducible resistance to AZI happened more rapidly than to CLA, and the transcription of the erm(41) elevated significantly after prolonged exposure to macrolides. Patients infected with isolates with functional erm(41) gene or rrl mutation experienced lower rates of culture conversion compared to those without such mutations. Acquired and inducible resistance to macrolides significantly contributes to the treatment failures of MABC-PD. The in vitro sensitivity and the inducible resistance occurrence all favor CLA over AZI for MABC-PD treatment.

Importance: The Mycobacterium abscessus complex (MABC) is highly resistant to antibiotics, making Mycobacterial abscessus pulmonary disease (MAPD) difficult to treat. Macrolide antibiotics are the main treatment, but there is debate over whether azithromycin (AZI) or clarithromycin (CLA) is more effective. In our study of 61 MAPD patients, we compared the effectiveness of AZI and CLA while tracking resistance. We found that the minimum inhibitory concentrations (MICs) of AZI were four to eight times higher than those of CLA. Isolates with the functional erm(41) gene exhibited macrolide resistance, with AZI developing resistance faster than CLA. Patients with these resistant strains had lower rates of successful treatment. Overall, the in vitro sensitivity and the inducible resistance occurrence all favor CLA over AZI for MABC-PD treatment.

Keywords: Mycobacterium abscessus complex; culture conversion; inducible resistance; macrolides.