Background and objectives: Multidrug-resistant (MDR) Escherichia coli is a global concern. E. coli exhibits resistance through extended-spectrum beta-lactamase (ESBL) production, efflux pumps, and biofilm formation. Fosfomycin alone and in combination with amikacin and ciprofloxacin is effective against MDR E. coli. We conducted this study to evaluate the in vitro activity of fosfomycin, alone and in combination with amikacin and ciprofloxacin, against clinical MDR E. coli isolates, including ESBL and biofilm producers. We assessed the in vitro effects by calculating the minimum inhibitory concentration (MIC). The biofilm grades were evaluated using a spectrophotometer. We also assessed the drug interactions of fosfomycin with amikacin and ciprofloxacin using the fractional inhibitory concentration index (FICI) and Epsilometer test (E-test) cross methods. Methods: This study was conducted from April 2023 to March 2025 at Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, India. We included MDR E. coli isolates collected from clinical specimens (i.e., urine, blood, cerebrospinal fluid, respiratory samples, pus, and tissues) of adult patients of both sexes. The bacteria in the specimens were cultivated using enriched and selective media, such as MacConkey agar and 5% sheep blood agar. Antibiotic susceptibility pattern of E. coli evaluated by VITEK AST card N-235 and N-405 (BioMérieux, Marcy-l'Étoile, France) for urinary and non-urinary isolates, respectively. The MDR strains were noted. The biofilm grades were assessed using a spectrophotometer by measuring optical density (OD). The higher OD values were suggestive of stronger biofilms by the MDR E. coli isolates. The drug interactions of fosfomycin with amikacin and ciprofloxacin were assessed through FICI and E-test cross methods. Lower FICI values indicated additive and synergistic interactions. We analyzed the data through R software (version 4.5.2) (R Foundation for Statistical Computing, Vienna, Austria). Results: We analyzed 422 MDR E. coli isolates during the study period. The majority of the samples were urine samples (306, 72.5%). Most of the MDR E. coli isolates were ESBL producers (364, 86.3%). Biofilm production was seen in only 131 (31.0%) isolates. The median OD value of all 422 isolates was 0.073 (0.066-0.129). The majority of isolates were either biofilm non-producers or weak biofilm producers. The MIC90 values of fosfomycin, amikacin, and ciprofloxacin were 32, 8, and 0.5 micrograms/ml, respectively. The FICI values of the combinations of fosfomycin with amikacin and ciprofloxacin were 0.62 and 0.86 microgram/ml, respectively. These values supported the synergistic and additive interactions among the drugs. Drug combinations were more effective than monotherapy across all categories of biofilm producers. Conclusion: The MDR E. coli isolates were more common in urine specimens. Most of them were ESBL producers. Around one-third of isolates were biofilm producers. The drug combinations were more effective than monotherapy with the three antimicrobials. We recommend prospective studies with larger sample sizes to confirm the clinical relevance of our findings.
Choudhury et al. (Mon,) studied this question.