The Use of Machine Learning Methodologies to Analyse Antibiotic and Biocide Susceptibility in Staphylococcus aureus

Abstract

BackgroundThe rise of antibiotic resistance in pathogenic bacteria is a significant problem for the treatment of infectious diseases. Resistance is usually selected by the antibiotic itself; however, biocides might also co-select for resistance to antibiotics. Although resistance to biocides is poorly defined, different in vitro studies have shown that mutants presenting low susceptibility to biocides also have reduced susceptibility to antibiotics. However, studies with natural bacterial isolates are more limited and there are no clear conclusions as to whether the use of biocides results in the development of multidrug resistant bacteria.MethodsThe main goal is to perform an unbiased blind-based evaluation of the relationship between antibiotic and biocide reduced susceptibility in natural isolates of Staphylococcus aureus. One of the largest data sets ever studied comprising 1632 human clinical isolates of S. aureus originated worldwide was analysed. The phenotypic characterization of 13 antibiotics and 4 biocides was performed for all the strains. Complex links between reduced susceptibility to biocides and antibiotics are difficult to elucidate using the standard statistical approaches in phenotypic data. Therefore, machine learning techniques were applied to explore the data.ResultsIn this pioneer study, we demonstrated that reduced susceptibility to two common biocides, chlorhexidine and benzalkonium chloride, which belong to different structural families, is associated to multidrug resistance. We have consistently found that a minimum inhibitory concentration greater than 2 mg/L for both biocides is related to antibiotic non-susceptibility in S. aureus.ConclusionsTwo important results emerged from our work, one methodological and one other with relevance in the field of antibiotic resistance. We could not conclude on whether the use of antibiotics selects for biocide resistance or vice versa. However, the observation of association between multiple resistance and two biocides commonly used may be of concern for the treatment of infectious diseases in the future.

High Prevalence of Biocide Resistance Determinants in Staphylococcus aureus Isolates from Three African Countries

“…Similar chlorhexidine MICs (0.5 to 1 mg/liter) were found in MRSA and MSSA populations (85.0% [70/82 isolates] of MRSA versus 91.8% [201/219 isolates] of MSSA; P ϭ 0.1285), as previously reported for MRSA isolates from human and animal origins (10,31). To date, there is no breakpoint consensus to define biocide-reduced susceptibility, and independent reports have proposed different epidemiological cutoff (ECOFF) values based on the normal distribution of MICs in different S. aureus populations (27,32,33). In our study, an MIC cutoff of Ն1 mg/liter was defined, since Ͻ1% of the isolates showed an MIC of Ն2 mg/liter.…”

Genomics of antibiotic‐resistance prediction in Pseudomonas aeruginosa

“…In one of the largest phenotypic studies ever performed on biocides and on AMR, a total of 1632 worldwide clinical strains of S. aureus were analyzed …”

“…In one of the largest phenotypic studies ever performed on biocides and on AMR, a total of 1632 worldwide clinical strains of S. aureus were analyzed. 67 S. aureus is a major human pathogen, a major cause of nosocomial infections, and a significant cause of foodborne infection. By combining different machine learning methodologies, namely decision trees and clustering, to explore the data in order to find biologically and statistically significant results, it was demonstrated that reduced susceptibility to two common biocides, chlorhexidine and benzalkonium chloride, which belong to different structural families, is associated with multi-AMR.…”

Evaluation of Reduced Susceptibility to Quaternary Ammonium Compounds and Bisbiguanides in Clinical Isolates and Laboratory-Generated Mutants of Staphylococcus aureus

“…For this scope, we performed a comparative molecular and phenotypic characterization of the susceptibility to benzalkonium chloride and chlorhexidine (CHX) in the clinically relevant model organism S. aureus. This work is part of the multicenter BIOHYPO project, which aims to evaluate the impact of biocide use in the food chain on antimicrobial drug resistance of clinical relevance in enterobacteria, Gramnegative nonfermenters, staphylococci, enterococci, lactic acid bacteria, and fungi (2,(22)(23)(24)(25)(26)(27). In this context, the detailed characterization of biocide susceptibility phenotypes and genotypes is the first step of correlation of these data with antimicrobial resistance profiles.…”