Omadacycline as a promising new agent for the treatment of infections with Mycobacterium abscessus

Abstract

Background: Despite intensive treatment regimens, the outcome of Mycobacterium abscessus infections is extremely poor and thus novel treatment regimens are needed. Although tigecycline seems to be one of the best options currently available, its long-term use is hampered by severe toxic side effects as well as the need for intravenous administration and the relatively high concentrations required for efficacy.

Objectives: To assess the in vitro activity of omadacycline against M. abscessus and compare it with the activity of tigecycline.

Methods: The concentration- and time-dependent killing capacities of omadacycline and tigecycline against M. abscessus subspecies abscessus were determined using a time-kill kinetics assay. Time-kill curves as well as concentration-effect curves were generated.

Results: Time-kill curves showed strong concentration-dependent antimicrobial activity for both omadacycline and tigecycline. Omadacycline showed inhibition of mycobacterial growth at 4 mg/L and mycobacterial killing at concentrations ≥16 mg/L. Tigecycline showed mycobacterial killing at concentrations ≥4 mg/L, achieving elimination at concentrations ≥16 mg/L. The concentration-effect curves after 7 days of exposure showed stasis, 1 log mycobacterial killing and 2 log mycobacterial killing at 3.3, 4.0 and 4.8 mg/L for omadacycline and 2.2, 2.7 and 3.4 mg/L for tigecycline, respectively.

Conclusions: The results of this in vitro study on omadacycline activity, together with its favourable (pharmacokinetic) properties, suggest that omadacycline is a potential new agent for the treatment of M. abscessus infections.

Figure 1.

Concentration- and time-dependent bactericidal activity of (a) omadacycline (OMC) and (b) tigecycline (TGC) against M. abscessus subsp. abscessus. Mycobacterial cultures were exposed to OMC or TGC for 7 days at 37°C under shaking conditions. On days 1, 3 and 7, samples were collected, centrifuged and subcultured onto antibiotic-free and OMC- or TGC-containing solid medium and incubated for 5 days at 37°C with 5% CO₂ to determine cfu. Experiments were performed in duplicate. Results shown are from one representative experiment.

Figure 2.

Concentration–effect curves of omadacycline (OMC, left) and tigecycline (TGC, right) against M. abscessus subsp. abscessus after 7 days of drug exposure. dlog, difference between the starting inoculum and the mycobacterial load at day 7.