Effect of Different Media on the Bactericidal Activity of Colistin and on the Synergistic Combination With Azidothymidine Against mcr-1-Positive Colistin-Resistant Escherichia coli

Abstract

Antimicrobial susceptibility testing (AST) performed according to defined guidelines is important to identify resistance and to predict the clinical success or failure of specific antibiotic therapy. However, these guidelines do not cover all physiological conditions that can have a tremendous impact on in vivo resistance. In this study, we tested the susceptibility of thirteen mcr-1-positive Escherichia coli strains against colistin, one of the last resort antibiotics for treating multi-drug resistant pathogens, in media recommended for ASTs as well as-physiologically more relevant-in human serum and artificial urine (AU). Minimal inhibitory concentration (MIC) values in heat-inactivated human serum were similar to those in cation-adjusted Mueller-Hinton broth (CAMHB), but reduced in native serum for almost all strains that could grow in this media. In AU MIC values for mcr-1 positive E. coli were increased significantly up to 16-fold compared to that in CAMBH, which did not apply to the colistin-susceptible E. coli strains tested. Although different growth media could affect the MIC of colistin alone, their impact on the synergistic effect of the combination with the antiviral drug azidothymidine was minimal. The higher divalent cation concentration combined with acidic pH values is most likely responsible for the increased MIC values of the mcr-1 harboring E. coli strains tested against colistin in AU compared to that in CAMHB. Antimicrobial susceptibility screening procedures for colistin using CAMHB only could lead to an underestimation of resistance under different physiological conditions. Therefore, not only pharmacokinetic but also pharmacodynamic studies in urine are as important as in serum or plasma.

In vitroassessment of the antibacterial effects of the combinations of fosfomycin, colistin, trimethoprim and nitrofurantoin against multi‐drug–resistantEscherichia coli

“…Remarkably, the majority of UPEC in the present study were susceptible to FOS and COL. These findings are in agreement with those reported in previous studies, which demonstrated that FOS (Raja 2019;Loose et al 2020;Rosana et al 2020) and COL (Ku et al 2015;Kim et al 2016;Lee and Le 2018;Loose et al 2020) remain the most effective antimicrobial against ESBL-UTIs.…”

“…Fosfomycin (FOS), nitrofurantoin (NIT) and trimethoprim (TRI) are recommended for the treatment of uncomplicated cystitis as a first-line empiric therapy (Bonkat et al 2017;Kot 2019;L opez-Montesinos and Horcajada 2019), whereas colistin (COL) is recommended as a last line antibiotic defense for treatment of UTI caused by multi-drug-resistant (MDR) Gram-negative bacteria (Karakkattu et al 2017;Loose et al 2020). Unfortunately, the resistance of UPEC to these antimicrobial agents was relatively increased in Egypt and (Abdelkhalik et al 2018;Kotb et al 2019;Metwally and Elnagar 2019) and other countries (Poirel et al 2017;Lee and Le 2018;Ram ırez-Castillo et al 2018).…”

Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter baumannii

“…Colistin first binds to the LPS at the cell surface followed by displacing the divalent cations (Ca 2+ and Mg 2+ ) to disturb the integrity of the outer membrane, resulting in bacterial cell death. Previous reports showed that the MIC values in serum was lower than those in other culture media (Loose et al, 2020). Therefore, the enhanced antibacterial effect in the presence of serum is likely attributed to the combination effect of colistin and depolymerase on the bacterial cell surface facilitating the host immune attack.…”

Anti-Biofilm Effect of Octenidine and Polyhexanide on Uropathogenic Biofilm-Producing Bacteria

“…The following disinfectants were tested: FARCO-fill ® Protect (triclosan 3,000 mg/L; Farco-Pharma, Köln, Germany), LAVAN-OX ® (<0.08% sodium hypochlorite <800 mg/L; Serag Wiessner, Naila, Germany), Octenisept ® (octenidine 1,000 mg/L; Schülke & Mayr, Norderstedt, Germany), and Prontosan ® (polyhexanide 1,000 mg/L; B. Braun Melsungen AG, Melsungen, Germany). MIC and MBC determinations were described elsewhere [20]. All determinations were repeated thrice.…”