{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:27:11Z","timestamp":1793406431882,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Acinetobacter baumannii (CRAB) pose significant therapeutic challenges due to their high resistance and global spread. Combination therapy with colistin (COL) and meropenem (MEM) was used to enhance antimicrobial activity. This study evaluated the COL-MEM combination against CRKP and CRAB isolates with a high resistance profile. A total of 58 carbapenem-resistant clinical isolates (31 CRKP and 27 CRAB), including extensively resistant and pandrug-resistant strains, were collected over a period of 12 months. Synergy between COL and MEM was assessed by microdilution checkerboard (MCB) and time-kill (TKA) assays. Carbapenemase genes were detected using molecular methods. The results showed that the COL-MEM combination yielded synergy (35.5% and 40.7%, respectively) and additive effects (35.5% and 37.0%, respectively), while no antagonism was observed. TKA confirmed bactericidal activity, especially at doubled MCB-detected concentrations, indicating dose-dependent activity. The significant reduction in the minimum inhibitory concentration in the combination indicated its potential for dose optimization, minimizing COL-associated toxicities. Genotypic profiling showed that the expression of blaNDM and blaOxa-48 can reduce synergy. These findings, obtained with isolates of high resistance, support the efficacy of this combination therapy and could reduce the dose-related side effects of COL. However, they also highlight genotype-specific variations and COL resistance mechanisms as limiting variables.<\/jats:p>","DOI":"10.3390\/pathogens15020214","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T16:09:32Z","timestamp":1770998972000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In Vitro Evaluation of Colistin\u2013Meropenem Activity Against XDR and PDR Carbapenemase-Producing Klebsiella pneumoniae and Acinetobacter baumannii"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2916-6226","authenticated-orcid":false,"given":"Shahinda","family":"Rezk","sequence":"first","affiliation":[{"name":"Microbiology Department, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt"},{"name":"Institute of Virology, Medical Center, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada Younis","family":"Elwakeel","sequence":"additional","affiliation":[{"name":"Microbiology Department, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt"},{"name":"El Amereya General Hospital, Ministry of Health, Alexandria 23711, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer","family":"Ghazal","sequence":"additional","affiliation":[{"name":"Microbiology Department, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6368-2596","authenticated-orcid":false,"given":"Amel","family":"Elsheredy","sequence":"additional","affiliation":[{"name":"Microbiology Department, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1963-9838","authenticated-orcid":false,"given":"Daniel","family":"Baecker","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Stra\u00dfe 2+4, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3610-4592","authenticated-orcid":false,"given":"Ahmed Noby","family":"Amer","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology Department, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Canal El Mahmoudia Street, Beside Green Plaza Complex, Alexandria 21648, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Busi, S., and Prasad, R. 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