An In Vitro Perspective on What Individual Antimicrobials Add to Mycobacterium avium Complex Therapies.
Antimicrob Agents Chemother
; 65(8): e0273020, 2021 07 16.
Article
em En
| MEDLINE
| ID: mdl-33972258
ABSTRACT
For Mycobacterium avium complex pulmonary disease (MAC-PD), current treatment regimens yield low cure rates. To obtain an evidence-based combination therapy, we assessed the in vitro activity of six drugs, namely, clarithromycin (CLR), rifampin (RIF), ethambutol (EMB), amikacin (AMK), clofazimine (CLO), and minocycline (MIN), alone and in combination, against Mycobacterium avium and studied the contributions of individual antibiotics to efficacy. The MICs of all antibiotics against M. avium ATCC 700898 were determined by broth microdilution. We performed kinetic time-kill assays of all single drugs and clinically relevant two-, three-, four-, and five-drug combinations against M. avium. Pharmacodynamic interactions of these combinations were assessed using area under the time-kill curve-derived effect size and Bliss independence. Adding a second drug yielded an average increase of the effect size (E) of 18.7% ± 32.9%, although antagonism was seen in some combinations. Adding a third drug showed a smaller increase in effect size (+12.2% ± 11.5%). The RIF-CLO-CLR (E of 102 log10 CFU/ml · day), RIF-AMK-CLR (E of 101 log10 CFU/ml · day), and AMK-MIN-EMB (E of 97.8 log10 CFU/ml · day) regimens proved more active than the recommended RIF-EMB-CLR regimen (E of 89.1 log10 CFU/ml · day). The addition of a fourth drug had little impact on effect size (+4.54% ± 3.08%). In vitro, several two- and three-drug regimens are as effective as the currently recommended regimen for MAC-PD. Adding a fourth drug to any regimen had little additional effect. In vitro, the most promising regimen would be RIF-AMK-macrolide or RIF-CLO-macrolide.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complexo Mycobacterium avium
/
Infecção por Mycobacterium avium-intracellulare
Limite:
Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Holanda