Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant Pseudomonas aeruginosa

Pseudomonas aeruginosa 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 P. aeruginosa. In this study we investigate...

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Autores principales:	Sara Mahmoud Farhan, Mohamed Raafat, Mohammed A. S. Abourehab, Rehab Mahmoud Abd El-Baky, Salah Abdalla, Ahmed Osama EL-Gendy, Ahmed Farag Azmy
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Pseudomonas aeruginosa</i> drug combination imipenem amikacin FICs SEM Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d57ec8ea27144e16b83c7826fe5d21e3
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spelling	oai:doaj.org-article:d57ec8ea27144e16b83c7826fe5d21e32021-11-25T16:25:15ZEffect of Imipenem and Amikacin Combination against Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>10.3390/antibiotics101114292079-6382https://doaj.org/article/d57ec8ea27144e16b83c7826fe5d21e32021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1429https://doaj.org/toc/2079-6382<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.Sara Mahmoud FarhanMohamed RaafatMohammed A. S. AbourehabRehab Mahmoud Abd El-BakySalah AbdallaAhmed Osama EL-GendyAhmed Farag AzmyMDPI AGarticle<i>Pseudomonas aeruginosa</i>drug combinationimipenemamikacinFICsSEMTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1429, p 1429 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Pseudomonas aeruginosa</i> drug combination imipenem amikacin FICs SEM Therapeutics. Pharmacology RM1-950
spellingShingle	<i>Pseudomonas aeruginosa</i> drug combination imipenem amikacin FICs SEM Therapeutics. Pharmacology RM1-950 Sara Mahmoud Farhan Mohamed Raafat Mohammed A. S. Abourehab Rehab Mahmoud Abd El-Baky Salah Abdalla Ahmed Osama EL-Gendy Ahmed Farag Azmy Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>
description	<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.
format	article
author	Sara Mahmoud Farhan Mohamed Raafat Mohammed A. S. Abourehab Rehab Mahmoud Abd El-Baky Salah Abdalla Ahmed Osama EL-Gendy Ahmed Farag Azmy
author_facet	Sara Mahmoud Farhan Mohamed Raafat Mohammed A. S. Abourehab Rehab Mahmoud Abd El-Baky Salah Abdalla Ahmed Osama EL-Gendy Ahmed Farag Azmy
author_sort	Sara Mahmoud Farhan
title	Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>
title_short	Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>
title_full	Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>
title_fullStr	Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>
title_full_unstemmed	Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>
title_sort	effect of imipenem and amikacin combination against multi-drug resistant <i>pseudomonas aeruginosa</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d57ec8ea27144e16b83c7826fe5d21e3
work_keys_str_mv	AT saramahmoudfarhan effectofimipenemandamikacincombinationagainstmultidrugresistantipseudomonasaeruginosai AT mohamedraafat effectofimipenemandamikacincombinationagainstmultidrugresistantipseudomonasaeruginosai AT mohammedasabourehab effectofimipenemandamikacincombinationagainstmultidrugresistantipseudomonasaeruginosai AT rehabmahmoudabdelbaky effectofimipenemandamikacincombinationagainstmultidrugresistantipseudomonasaeruginosai AT salahabdalla effectofimipenemandamikacincombinationagainstmultidrugresistantipseudomonasaeruginosai AT ahmedosamaelgendy effectofimipenemandamikacincombinationagainstmultidrugresistantipseudomonasaeruginosai AT ahmedfaragazmy effectofimipenemandamikacincombinationagainstmultidrugresistantipseudomonasaeruginosai
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Effect of Imipenem and Amikacin Combination against Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>

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