Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>
<i>Pseudomonas aeruginosa</i> is an opportunistic nosocomial pathogen associated with high morbidity and mortality rates. Combination of antibiotics has been found to combat multi-drug resistant or extensively drug resistance <i>P. aeruginosa</i>. In this study we investigate...
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Autores principales: | , , , , , , |
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Formato: | article |
Lenguaje: | EN |
Publicado: |
MDPI AG
2021
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Materias: | |
Acceso en línea: | https://doaj.org/article/d57ec8ea27144e16b83c7826fe5d21e3 |
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Sumario: | <i>Pseudomonas aeruginosa</i> is an opportunistic nosocomial pathogen associated with high morbidity and mortality rates. Combination of antibiotics has been found to combat multi-drug resistant or extensively drug resistance <i>P. aeruginosa</i>. In this study we investigate the in vitro and in vivo effect of amikacin and imipenem combination against resistant <i>P. aeruginosa</i>. The checkerboard technique and time-killing curve have been performed for in vitro studies showed synergistic effect for combination. A peritonitis mouse model has been used for evaluation of the therapeutic efficacy of this combination which confirmed this synergistic effect. The in vitro and in vivo techniques showed synergistic interaction between tested drugs with fractional inhibitory concentration indices (FICIs) of ≤0.5. Conventional PCR and quantitative real-time PCR techniques were used in molecular detection of <i>bla <sub>IMP</sub></i> and <i>aac(6′)-Ib</i> as 35.5% and 42.2% of <i>P. aeruginosa</i> harbored <i>bla <sub>IMP</sub></i> and <i>aac(6′)-Ib</i> respectively. Drug combination viewed statistically significant reduction in bacterial counts (<i>p</i> value < 0.5). The lowest <i>bla <sub>IMP</sub></i> and <i>aac(6′)-Ib</i> expression was observed after treatment with 0.25 MIC of imipenem + 0.5 MIC of amikacin. Morphological changes in <i>P. aeruginosa</i> isolates were detected by scanning electron microscope (SEM) showing cell shrinkage and disruption in the outer membrane of <i>P. aeruginosa</i> that were more prominent with combination therapy than with monotherapy. |
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