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OBJECTIVES: This research examines the combined in vitro effectiveness of cefiderocol with other antibiotics against carbapenem-resistant Pseudomonas aeruginosa (CR-PA) obtained from Intensive Care Units. METHODS: Forty unique CR-PA isolates were evaluated for their minimum inhibitory concentrations (MICs) using broth microdilution. The bactericidal and synergistic effects of cefiderocol, alone or in conjunction with other antimicrobials, were assessed using time-kill curve experiments. RESULTS: Colistin had the lowest MIC50/MIC90 value of 1/2 mg/L, with cefiderocol following at 0.5/4 mg/L against the tested strains. Cefiderocol, levofloxacin, tobramycin, and meropenem showed bactericidal activity against various isolates. Moreover, the most effective synergistic interactions were seen with combinations of cefiderocol and eravacycline, cefiderocol and meropenem, and cefiderocol and ceftazidime/avibactam against the tested strains at 1xMIC concentrations after 24 hours. Antagonism against the analyzed CR-PA strains was not found. CONCLUSION: This study's results indicate that cefiderocol combined with eravacycline, meropenem, or ceftazidime/avibactam showed greater effectiveness against CR-PA bacteria. This dual treatment might be a substitute choice for CR-PA.

AIM: The point of this study was to compare and to contrast how well cefiderocol worked against a group of Achromobacter spp. and Stenotrophomonas maltophilia isolates in-vitro, both by itself and when mixed with other antibiotics. BACKGROUND: Cefiderocol, a new antibiotic, is highly effective against S. maltophilia and multidrug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. The U.S. Food and Drug Administration (FDA) approved it for treating nosocomial pneumonia (e.g., ventilator-associated pneumonia) and complicated urinary tract infections caused by susceptible aerobic Gram-negative bacteria. However, evidence is insufficient regarding cefiderocol combination therapy for Achromobacter spp. and S. maltophilia. METHODS: We determined the MICs of cefiderocol and the tested antibiotics for 40 isolates total of S. maltophilia and Achromobacter spp. We then tested various cefiderocol MICs in time-kill experiments, using cefiderocol alone and in combination with comparators. RESULTS: Cefiderocol was the agent with the highest susceptibility rate (100%). Cefiderocol also displayed the lowest MIC50 and MIC90 values. We observed synergy in time-kill experiments when we combined cefiderocol with levofloxacin or colistin at 1xMIC concentration. CONCLUSIONS: These data suggest that cefiderocol displays potent in vitro activity against S. maltophilia and Achromobacter spp. Our research shows that cefiderocol, levofloxacin, and colistin work well together in-vitro and could be used as an alternative to treat infections caused by S. maltophilia and Achromobacter spp. These results indicate the need for further investigations into cefiderocol, including more complex in vitro and in vivo model studies, to determine its role in treating this pathogen.

BACKGROUND: Achromobacter spp. may form biofilm in patients' respiratory tracts and cause serious infections. AIM: This research examined the bactericidal and synergistic effects of ceftazidime/avibactam (CZA) alone and in combination with different antibiotics against Achromobacter spp. Moreover, the antibiofilm activity of CZA alone or in combination with the antibiotics was assessed. METHODS: MICs of 52 distinct Achromobacter spp. were determined by broth microdilution. In-vitro time-kill curve experiments assessed CZA's bactericidal and synergistic properties alone and in combination with other antibiotics. RESULTS: Based on MIC90 values, CZA exhibited four times greater in-vitro activity against tested strains than ceftazidime. The most effective agent was meropenem, with a 92% susceptibility level on the tested strains. On the other hand, ciprofloxacin was found to be bactericidal at both 1x and 4xMIC concentrations. CZA, chloramphenicol and meropenem were observed to have bactericidal effects alone at 4xMIC concentrations against the tested isolates. CZA+CS and CZA+MEM showed synergy in three out of five and two out of five strains tested at 1xMIC, respectively. Furthermore, the pairing of CZA with colistin, CZA with meropenem and CZA with ciprofloxacin exhibited a synergistic impact at 4xMIC. Moreover, combination therapy CZA with the tested antibiotics showed reduced biofilm formation in a concentration-dependent manner at 24h. CONCLUSIONS: The outcomes of this research also suggest that CZA plus colistin, meropenem, or ciprofloxacin were more productive against Achromobacter spp. strains. To our knowledge, this is the first article to evaluate the synergistic and antibiofilm activities of CZA alone or in combination with different agents against Achromobacter species.

Phages are ubiquitous in freshwater, seawater, soil, the human body, and sewage water. They are potent biopharmaceuticals against antimicrobial-resistant bacteria and offer a promising alternative for treating infectious diseases. Also, combining phages with antibiotics enhances the antibiotics' efficacy. This study focused on two Pseudomonas aeruginosa phages isolated from lake and sewage water samples and one of them selected for further investigation. Isolated phages PA-56 and PA-18 infected 92 % and 86 % of the tested 25 clinical Pseudomonas aeruginosa strains, respectively. PA-56 with strong activity was chosen for detailed characterization, antimicrobial studies, and genome analysis. Combining PA-56 with ciprofloxacin or meropenem demonstrated phage-antibiotic synergism and increased antibiofilm efficacy. Genome analysis revealed a GC ratio of 54 % and a genome size of 42.761 bp, with no virulence or antibiotic resistance genes. Notably, PA-56 harboured the toxin-antitoxin protein, MazG. Overall, this study suggests that PA-56 holds promise for future applications in industry or medicine.

Objectives: Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Relatively little is known about its clinical impact and optimal management. In the present study, the in vitro bactericidal activities of meropenem, either alone or in combination with colistin, levofloxacin, or chloramphenicol, were assessed using A. xylosoxidans strains isolated from CF patients. The synergistic interactions of these combinations were also investigated. Methods: Minimal inhibitory concentrations (MICs) were determined by microbroth dilution. Bactericidal and synergistic effects of the tested antibiotic combinations were assessed by using the time-kill curve technique. Results: Based on the time-kill curves, we found that meropenem-colistin combinations have bactericidal and synergistic activities for 24 h against A. xylosoxidans strains, both at 1 × MIC and 4 × MIC. Although synergistic interactions were seen with meropenem-levofloxacin combinations, no bactericidal interactions were observed. Additionally, the meropenem-chloramphenicol combinations were found to be neither bactericidal nor synergistic. No antagonism was observed with any combination tested. Conclusions: This study’s findings could have important implications for empirical or combination antimicrobial therapy with tested antibiotics.