Abstract
BackgroundNontuberculous mycobacteria (NTM) are ubiquitous organisms and the incidence of NTM infections has been increasing in recent years. Mycobacteroides abscessus (M. abscessus) is one of the most antimicrobial-resistant NTM; however, no reliable antibiotic regimen can be officially advocated. We evaluated the efficacy of clarithromycin in combination with various antimicrobial agents against the M. abscessus complex.ResultsTwenty-nine clinical strains of M. abscessus were isolated from various clinical samples. Of the isolates, 10 (34.5%) were of M. abscessus subsp. abscessus, 18 (62.1%) of M. abscessus subsp. massiliense, and 1 (3.4%) of M. abscessus subsp. bolletii. MICs of three antimicrobial agents (amikacin, imipenem, and moxifloxacin) were measured with or without clarithromycin. The imipenem-clarithromycin combination significantly reduced MICs compared to clarithromycin and imipenem monotherapies, including against resistant strains. The association between susceptibility of the M. abscessus complex and each combination of agents was significant (p = 0.001). Adjusted residuals indicated that the imipenem-clarithromycin combination had the synergistic effect (adjusted residual = 3.1) and suppressed the antagonistic effect (adjusted residual = − 3.1). In subspecies of M. abscessus complex, the association with susceptibility of M. abscessus subsp. massiliense was similarly statistically significant (p = 0.036: adjusted residuals of synergistic and antagonistic effect respectively: 2.6 and − 2.6). The association with susceptibility of M. abscessus subsp. abscessus also showed a similar trend but did not reach statistical significance.ConclusionOur data suggest that the imipenem-clarithromycin combination could be the recommended therapeutic choice for the treatment of M. abscessus complex owing to its ability to restore antimicrobial susceptibility.
Highlights
Nontuberculous mycobacteria (NTM) are ubiquitous organisms and the incidence of NTM infections has been increasing in recent years
Clinical features of three subspecies of M. abscessus complex Twenty-nine clinical strains of M. abscessus were isolated from various clinical samples at the Juntendo university hospital from 2011 to 2019
Twenty-two of 29 (75.9%) patients were diagnosed with M. abscessus complex from
Summary
Nontuberculous mycobacteria (NTM) are ubiquitous organisms and the incidence of NTM infections has been increasing in recent years. The incidence of M. abscessus-infected pulmonary disease has dramatically increased in Japan, from 0.1 cases/100,000 person/year in 2001 to 0.5 cases/100,000 person/year in 2014. M. abscessus is one of the treatment-refractory NTM, characterized by rapid growth and multidrug resistance. Massiliense lacks the erm (41) gene associated with macrolide resistance, and the macrolide susceptibility among M. abscessus subsp. Abscessus and bolletii is different [10, 11] For this reason, some experts recommend non-macrolide combinations for treatment for macrolide-resistant M. abscessus subspecies, based on identified in vitro susceptibilities [12]. We propose new insights into the synergistic effects on M. abscessus susceptibility achieved in vitro by clarithromycin in combination with other antimicrobials
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