Understanding the risk of emerging bacterial resistance to over the counter antibiotics in topical sore throat medicines

Aims The aims of this study were to explore the development of bacterial resistance and cross‐resistance in four common human pathogens following realistic exposure to antibiotics found in over‐the‐counter (OTC) sore throat medicines: gramicidin, neomycin, bacitracin and tyrothricin. Methods and Results Bacterial exposure to in‐use (concentration in the product before use) and diluted concentration (i.e. during use ) of antibiotic where conducted in broth for 24 h or until growth was visible. The changes in bacterial susceptibility profile before and after exposure was determined using standardized ISO microdilution broth. Antibiotic testing was performed according to EUCAST guidelines. We demonstrated that test bacteria were able to survive exposure to the in‐use concentrations of some antibiotics used in OTC medicines. Exposure to during use concentrations of bacitracin resulted in stable increase in minimal inhibitory concentration (MIC) (>8‐fold) in Staphylococcus aureus and Acinetobacter baumannii . Exposure to tyrothricin resulted in a stable increase in MIC (2·4‐fold) in Klebsiella pneumoniae , and exposure to neomycin resulted in a stable increase MIC (5000‐fold higher than the baseline) in Streptococcus pyogenes . Clinical cross‐resistance to other antibiotics (ciprofloxacin, fusidic acid, gentamicin, cefpodoxime, amoxicillin/clavulanic acid and cefotaxime) was also demonstrated following exposure to bacitracin or tyrothricin. Bacitracin exposure lead to a stable bacterial resistance after 10 passages. Conclusions Our results indicate that OTC antibiotic medicines have the potential to drive resistance and cross‐resistance in vitro . Significance and Impact of the Study Tackling antibiotic resistance is a high worldwide priority. It is widely accepted that the overuse and misuse of antibiotics increase the risk of the development and spread of antibiotic resistance within communities. A number of OTC sore throat products, widely available across the world for topical use in respiratory indications, contain locally delivered antibiotics. Our findings showed that these antibiotics in OTC medicines present a risk for emerging cross‐resistance in a number of bacterial respiratory pathogens

Effect of exposure to chlorhexidine residues at “during use” concentrations on antimicrobial susceptibility profile, efflux, conjugative plasmid transfer, and metabolism of Escherichia coli

There is no standardized protocol to predict the concentration levels of microbicides that are left on surfaces as a result of the use of these products, and there is no standardized method to predict the potential risk that such levels pose to emerging antibacterial resistance. The ability to distinguish between selection and adaption processes for antimicrobial resistance in bacteria and the impact of different concentrations of microbicide exposure have not been fully investigated to date. This study considers the effect of exposure to a low concentration of chlorhexidine digluconate (CHX) on selected phenotypes of Escherichia coli and relates the findings to the risk of emerging antimicrobial resistance. A concentration of 0.006 mg/ml CHX is a realistic “during use” exposure concentration measured on surfaces. At this concentration, it was possible for CHX-susceptible bacteria to survive, adapt through metabolic alterations, exhibit a transient decrease in antimicrobial susceptibility, and express stable clinical cross-resistance to front-line antibiotics. Efflux activity was present naturally in tested isolates, and it increased in the presence of 0.00005 mg/ml CHX but ceased with 0.002 mg/ml CHX. Phenotypic microarray assays highlighted a difference in metabolic regulation at 0.00005 mg/ml and 0.002 mg/ml CHX; more changes occurred after growth with the latter concentration. Metabolic phenotype changes were observed for substrates involved with the metabolism of some amino acids, cofactors, and secondary metabolites. It was possible for one isolate to continue transferring ampicillin resistance in the presence of 0.00005 mg/ml CHX, whilst 0.002 mg/ml CHX prevented conjugative transfer. In conclusion, E. coli phenotype responses to CHX exposure are concentration dependent, with realistic residual CHX concentrations resulting in stable clinical cross-resistance to antibiotics

Effect of Exposure to Chlorhexidine Residues at “During Use” Concentrations on Antimicrobial Susceptibility Profile, Efflux, Conjugative Plasmid Transfer, and Metabolism of Escherichia coli

There is no standardized protocol to predict the concentration levels of microbicides that are left on surfaces as a result of the use of these products, and there is no standardized method to predict the potential risk that such levels pose to emerging antibacterial resistance. The ability to distinguish between selection and adaption processes for antimicrobial resistance in bacteria and the impact of different concentrations of microbicide exposure have not been fully investigated to date. This study considers the effect of exposure to a low concentration of chlorhexidine digluconate (CHX) on selected phenotypes of Escherichia coli and relates the findings to the risk of emerging antimicrobial resistance. </jats:p

Impact of artificial accelerated ageing of PVC surfaces and surface degradation on disinfectant efficacy

Background Standardized efficacy surface tests for disinfectants are performed on pristine surfaces. There is a growing interest in understanding the impact of surface ageing on disinfectant activity, owing for example to the increased usage of ultraviolet (UV) radiation and oxidative chemistries for surface decontamination. This acknowledges that general surface ‘wear and tear’ following UV radiation and oxidative biocide exposure may impact biocidal product efficacy. Methods PVC surfaces were aged through thermal and UV-A radiation (340 nm wavelength) following the use of standard ageing surface protocols to simulate natural surface degradation. Surface roughness, contact angle and scanning electron microscopy were performed to evaluate physical changes in PVC surfaces before and after artificial ageing. The efficacy of five pre-impregnated disinfectant wipes were evaluated using the ASTM E2967-15 on stainless-steel (control) and PVC surfaces (aged and non-aged). Results The type of formulation and the organism tested remained the most significant factors impacting disinfectant efficacy, compared with surface type. Both thermal ageing and UV-A exposure of PVC surfaces clearly showed signs of surface degradation, notably an increase in surface roughness. Physical changes were observed in the roughness of PVC after artificial ageing. A difference in disinfectant efficacy dependent on aged PVC surfaces was observed for some, but not all formulations. Conclusion We showed that surface type and surface ageing can affect biocidal product efficacy, although in a non-predictable manner. More research is needed in this field to ascertain whether surface types and aged surfaces should be used in standardized efficacy testing

Impact of a dry inoculum deposition on the efficacy of copper-based antimicrobial surfaces

Background The introduction of antimicrobial surfaces into healthcare environments is believed to impact positively on the rate of healthcare-associated infections by significantly decreasing pathogen presence on surfaces. Aim To report on a novel efficacy test that uses a dry bacterial inoculum to measure the microbicidal efficacy of antimicrobial surfaces. Methods An aerosolized dry inoculum of Staphylococcus aureus or Acinetobacter baumannii was deposited on copper alloy surfaces or a hospital-grade stainless-steel surface. Surviving bacteria were enumerated following incubation of the inoculated surfaces at an environmentally relevant temperature and relative humidity. Damage caused to bacteria by the aerosolization process and by the different surfaces was investigated. Findings Dry inoculum testing showed a <2-log 10 reduction in S. aureus or A. baumannii on the copper alloy surfaces tested after 24 h at 20°C and 40% relative humidity. Potential mechanisms of action included membrane damage, DNA damage and arrested cellular respiration. The aerosolization process caused some damage to bacterial cells. Once this effect was taken into account, the antimicrobial activity of copper surfaces was evident. Conclusions Our test provided a realistic deposition of a bacterial inoculum to a surface and, as such, a realistic protocol to assess the efficacy of dry antimicrobial environmental surfaces in vitro