Priming with biocides: A pathway to antibiotic resistance?

Abstract

Aims To investigate the priming effects of sub‐inhibitory concentrations of biocides on antibiotic resistance in bacteria. Methods and results Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were exposed to sub‐inhibitory concentrations of biocides via a gradient plate method. Minimum inhibitory concentration (MIC) and antibiotic susceptibility were determined, and efflux pump inhibitors (thioridazine and chlorpromazine) were used to investigate antibiotic resistance mechanism(s). Escherichia coli displayed a twofold increase in MIC (32–64 mg l−1) to H2O2 which was stable after 15 passages, but lost after 6 weeks, and P. aeruginosa displayed a twofold increase in MIC (64–128 mg l−1) to BZK which was also stable for 15 passages. There were no other tolerances observed to biocides in E. coli, P. aeruginosa or S. aureus; however, stable cross‐resistance to antibiotics was observed in the absence of a stable increased tolerance to biocides. Sixfold increases in MIC to cephalothin and fourfold to ceftriaxone and ampicillin were observed in hydrogen peroxide primed E. coli. Chlorhexidine primed S. aureus showed a fourfold increase in MIC to oxacillin, and glutaraldehyde‐primed P. aeruginosa showed fourfold (sulphatriad) and eightfold (ciprofloxacin) increases in MIC. Thioridazine increased the susceptibility of E. coli to cephalothin and cefoxitin by fourfold and twofold, respectively, and both thioridazine and chlorpromazine increased the susceptibility S. aureus to oxacillin by eightfold and fourfold, respectively. Conclusions These findings demonstrate that sub‐inhibitory concentrations of biocides can prime bacteria to become resistant to antibiotics even in the absence of stable biocide tolerance and suggests activation of efflux mechanisms may be a contributory factor. Significance and Impact of the Study This study demonstrates the effects of low‐level exposure of biocides (priming) on antibiotic resistance even in the absence of obvious increased biocidal tolerance.

Biocide Susceptibility and Antimicrobial Resistance of Escherichia coli Isolated from Swine Feces, Pork Meat and Humans in Germany

“…The diversity of bacterial protection mechanisms might be one possible explanation for the weak correlations we observed. Further, it has been shown that prolonged bacterial exposure to low biocide concentrations may result in AMR development, which is not accompanied by a stable decrease in biocide susceptibility [64,65]. Because this pathway to antimicrobial resistance induced by biocides is unrelated to changes in biocide MICs, it cannot be detected with the approach of our study.…”

Photodynamic inactivation of different pathogenic bacteria on human skin using a novel photosensitizer hydrogel

“…Another important aspect is that antibiotics in dermatology are often used for prolonged courses, with significant potential for microbiome alteration and antibiotic‐related adverse effects 1,9,10 . Biocidal substances frequently used for the decolonization of human skin increasingly encounter the development of resistant bacteria, sometimes accompanied by cross‐resistance to antibiotics 6,59 . Clones of Escherichia coli were recently detected, which were even less sensitive to povidone‐iodine.…”

“…1,9,10 Biocidal substances frequently used for the decolonization of human skin increasingly encounter the development of resistant bacteria, sometimes accompanied by cross-resistance to antibiotics. 6,59 Clones of Escherichia coli were recently detected, which were even less sensitive to povidone-iodine. These clones additionally showed crossresistance with different antibiotics.…”

In Vitro and In Vivo Antileishmanial Activity of Thioridazine

“…The recommended dose in adults is 50 mg to 100 mg three times daily, increasing based upon effect and tolerance to a maximum of 800 mg daily [ 34 ]. Despite its side effects, thioridazine has been the recent focus of repurposing as an anticancer drug [ 15 , 16 , 35 , 36 ], as an antibacterial [ 17 – 20 , 37 , 38 ] and as an antiviral [ 39 ].…”