In vitro inhibitory and intracellular bactericidal activity of omadacycline against Mycobacterium abscessus

doi:10.19982/j.issn.1000-6621.20240274

Abstract

Abstract:

Objective: To evaluate the antimicrobial and bactericidal activities of omadacycline against Mycobacterium abscessus (MAB) and provide insights into optimizing drug combinations for the treatment of MAB infections. Methods: A total of 58 clinical isolates of MAB, obtained from patients at the Beijing Chest Hospital between 2015 and 2016, as well as a reference strain (ATCC 19977), were included in this study. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of omadacycline against the reference strain were measured using microdilution, alongside determining the MIC₉₀ for the clinical isolates. The checkerboard assay was employed to evaluate the effects of drug combinations on the reference strain, while intracellular bactericidal activity was assessed to measure the drugs’ efficacy against intracellular bacteria. Results: Omadacycline demonstrated MIC of 0.5 μg/ml and MBC of 4 μg/ml against the reference strain, with MIC₉₀ of 0.5 μg/ml for the clinical isolates. Synergistic effects were observed when omadacycline was combined with clarithromycin, linezolid, and bedaquiline, with fractional inhibitory concentration indices (FICIs) of 0.250, 0.375, and 0.375, respectively. Additive effects were noted when combined with clofazimine, azithromycin, and rifabutin, with FICIs of 0.750, 0.625 and 0.560. The combination of omadacycline and bedaquiline produced the most substantial reduction in MBC, decreasing from 4 μg/ml to 0.05 μg/ml, representing a 98.75% reduction compared to omadacycline monotherapy. For intracellular bacteria, the combination of omadacycline and azithromycin demonstrated the most pronounced bactericidal effect at 24 hours, reducing the bacterial count from (7.02±0.06) log₁₀ CFU to (5.36±0.10) log₁₀ CFU (t=3.241, P<0.001). At 48 hours, the combination of omadacycline and clofazimine reduced the intracellular bacterial load from (7.36±0.10) log₁₀ CFU to (5.33±0.35) log₁₀ CFU (t=8.265, P=0.004). Similarly, the combination of omadacycline and imipenem resulted in a reduction of intracellular bacteria from (6.87±0.15) log₁₀ CFU to (5.10±0.17) log₁₀ CFU (t=13.190, P<0.001). The combination of omadacycline and linezolid reduced the intracellular bacterial count from (6.95±0.05) log₁₀ CFU to (5.26±0.24) log₁₀ CFU (t=11.920, P=0.005). Similarly, the combination of omadacycline and rifabutin lowered the intracellular bacterial load from (6.98±0.07) log₁₀ CFU to (5.65±0.16) log₁₀ CFU (t=13.440, P=0.001). Conclusion: Omadacycline combined with other drugs demonstrates significant inhibitory and bactericidal activity against MAB. These findings suggest that omadacycline holds promise as a therapeutic option for treating MAB infections.

Key words: Mycobacterium abscessus, Mycobacterial infections, Antibacterial agents, Omadacycline, In vitro studies

CLC Number:

R378.91

Ma Shiran, Chen Suting, Huang Hairong, Duan Hongfei. In vitro inhibitory and intracellular bactericidal activity of omadacycline against Mycobacterium abscessus[J]. Chinese Journal of Antituberculosis, 2024, 46(12): 1442-1447. doi: 10.19982/j.issn.1000-6621.20240274

Figures/Tables 2

药物	24h				48h
药物	单用 ( $x ˉ$ ±s, log₁₀ CFU)	联合奥马环素 ( $x ˉ$ ±s, log₁₀ CFU)	t值	P值	单用 ( $x ˉ$ ±s, log₁₀ CFU)	联合奥马环素 ( $x ˉ$ ±s, log₁₀ CFU)	t值	P值
二甲基亚砜	7.69±0.09	-	-	-	7.82±0.07	-	-	-
奥马环素	7.16±0.15	-	-	-	6.20±0.17	-	-	-
贝达喹啉	6.49±0.20	6.26±0.24	1.289	0.269	6.26±0.24	5.46±0.15	4.862	0.013
阿奇霉素	7.02±0.06	5.36±0.10	24.000	<0.001	6.80±0.04	5.36±0.10	22.940	<0.001
氯法齐明	7.36±0.10	6.83±0.13	5.581	0.006	7.36±0.10	5.33±0.35	8.265	0.004
克拉霉素	6.86±0.09	6.59±0.11	3.241	0.034	6.26±0.24	5.26±0.24	5.076	0.007
阿米卡星	6.82±0.04	6.46±0.15	4.025	0.046	5.80±0.17	5.20±0.17	4.243	0.013
亚胺培南	7.09±0.09	6.46±0.15	6.183	0.007	6.87±0.15	5.10±0.17	13.190	<0.001
利奈唑胺	7.10±0.17	6.30±0.30	3.983	0.025	6.95±0.05	5.26±0.24	11.920	0.005
利福布汀	6.68±0.52	6.83±0.13	0.318	0.780	6.98±0.07	5.65±0.16	13.440	0.001

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