Antibacterial Activity of Human Simulated Epithelial Lining Fluid Concentrations of Ceftazidime-Avibactam Alone or in Combination with Amikacin Inhale (BAY41-6551) against Carbapenem-Resistant Pseudomonas aeruginosa and Klebsiella pneumoniae.
Antimicrob Agents Chemother
; 62(7)2018 07.
Article
em En
| MEDLINE
| ID: mdl-29914950
ABSTRACT
The role of inhalational combination therapy when treating carbapenem-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae with newer beta-lactam/beta-lactamase inhibitors has not been established. Using a 72-h in vitro pharmacodynamic chemostat model, we simulated the human exposures achieved in epithelial lining fluid (ELF) following intravenous treatment with ceftazidime-avibactam (CZA) 2.5 g every 8 h (q8h) alone and in combination with inhaled amikacin (AMK-I) 400 mg q12h, a reformulated aminoglycoside designed for inhalational administration, against three P. aeruginosa isolates (CZA [ceftazidime/avibactam] MICs, 4/4 to 8/4 µg/ml; AMK-I MICs, 8 to 64 µg/ml) and three K. pneumoniae isolates (CZA MICs, 1/4 to 8/4 µg/ml; AMK-I MICs, 32 to 64 µg/ml). Combination therapy resulted in a significant reduction in 72-h CFU compared with that of CZA monotherapy against two of three P. aeruginosa isolates (-4.14 log10 CFU/ml, P = 0.027; -1.42 log10 CFU/ml, P = 0.020; and -0.4 log10 CFU/ml, P = 0.298) and two of three K. pneumoniae isolates (0.04 log10 CFU/ml, P = 0.963; -4.34 log10 CFU/ml, P < 0.001; and -2.34 log10 CFU/ml, P = 0.021). When measured by the area under the bacterial growth curve (AUBC) over 72 h, significant reductions were observed in favor of the combination regimen against all six isolates tested. AMK-I combination therapy successfully suppressed CZA resistance development in one K. pneumoniae isolate harboring blaKPC-3 that was observed during CZA monotherapy. These studies suggest a beneficial role for combination therapy with intravenous CZA and inhaled AMK when treating pneumonia caused by carbapenem-resistant Gram-negative bacteria.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
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Amicacina
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Ceftazidima
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Compostos Azabicíclicos
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Inibidores de beta-Lactamases
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Klebsiella pneumoniae
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Antibacterianos
Limite:
Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos