Synergistic effects of meropenem, amikacin, and ciprofloxacin against carbapenem resistant Pseudomonas aeruginosa isolates

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Abstract
Healthcare-associated infections (HAIs) caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) are considered a major problem in hospitals due to their resistance to the most effective classes of antibiotics. The aim of the present study was to determine the antimicrobial susceptibility patterns of P. aeruginosa isolates from clinical specimens, and the combination effect of meropenem, amikacin, and ciprofloxacin against CRPA isolates. This cross-sectional study analyzed 70 P. aeruginosa isolates collected from hospitalized patients between August and November 2023. Antimicrobial susceptibility testing was performed on all isolates, and carbapenemase production was assessed in CRPA isolates. Five carbapenemase genes (blaIMP, blaVIM, blaKPC, blaSIM, and blaOXA-48) were screened. Meropenem minimum inhibitory concentrations (MICs) were determined via microbroth dilution method, and synergistic effects of meropenem, amikacin, and ciprofloxacin were evaluated using a three-dimensional checkerboard method. The highest resistance was to colistin 52/70 (74.3%), followed by cefotaxime 33/70 (47.1%) and tobramycin 28/70 (40%). Conversely, the lowest resistance was for aztreonam 19/70 (27.1%); 26/70 (37.1%) of isolates were CRPA. The frequency of genes blaIMP and blaOXA-48 were 4/70 (5.7%) and 1/70 (1.4%) in P. aeruginosa isolates, respectively; blaKPC, blaVIM, and blaSIM were not detected. The three-dimensional checkerboard method was established on 8 selected non-susceptible carbapenem P. aeruginosa isolates and the synergistic effect was recorded for 5 of these tested isolates. This study presents a positive correlation between CRPA and multidrug resistance (MDR), including resistance to all tested antibiotics. However, synergistic effects observed in vitro with meropenem, amikacin, and ciprofloxacin combinations suggest that combination therapy holds promise for treating these infections.
Funding Information
  • Vice-chancellor for Research at Shiraz University of Medical Sciences (IR.SUMS.REC.01 27785)

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