ArticleAntimicrobial agents and chemotherapy2013
Evaluation of reduced susceptibility to quaternary ammonium compounds and bisbiguanides in clinical isolates and laboratory-generated mutants of Staphylococcus aureus.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Bacterial sensitivity to chlorhexidine and povidone-iodine antiseptics over time: a systematic review and meta-analysis of human-derived data.Scientific reports · 2023Pooled it
- Combating Antimicrobial Resistance with Hydrophilic and Eco-Friendly Membrane-Active Antibiotics Derived from Biological Nanoparticles.ACS nanoscience Au · 2026Article
- Mechanism and Molecular Design Principles of Cationic Surfactants: From Charge-Driven Membrane Interactions to Next-Generation Quaternary Ammonium Compounds.ChemMedChem · 2026Review
- Occurrence, variability and evolutionary relations of efflux pump determinants across five pathogenicFrontiers in pharmacology · 2026Article
- NorA and Tet38 efflux pumps enableAntimicrobial agents and chemotherapy · 2025Article
- Skin Infections Caused by Panton-Valentine Leukocidin and Methicillin-Susceptible Staphylococcus aureus in Child, Japan.Emerging infectious diseases · 2025Article
- Genomic analysis of theFrontiers in microbiology · 2025Article
- Review
- Functional promiscuity of small multidrug resistance transporters from Staphylococcus aureus, Pseudomonas aeruginosa, and Francisella tularensis.Molecular microbiology · 2024Article
- Quaternary ammonium compounds of emerging concern: Classification, occurrence, fate, toxicity and antimicrobial resistance.Journal of hazardous materials · 2023Review
- Screening ofMicroorganisms · 2023Article
- Environmental Persistence of Staphylococcus capitis NRCS-A in Neonatal Intensive Care Units: Role of Biofilm Formation, Desiccation, and Disinfectant Tolerance.Microbiology spectrum · 2022Article
- Occurrence and Variability of the Efflux Pump GeneInternational journal of molecular sciences · 2022Article
- Impact of benzalkonium chloride, benzethonium chloride and chloroxylenol on bacterial antimicrobial resistance.Journal of applied microbiology · 2022Review
- Virulence Potential of Biofilm-ProducingAntibiotics (Basel, Switzerland) · 2022Article
- In-Membrane Nanostructuring of Cationic Amphiphiles Affects Their Antimicrobial Efficacy and Cytotoxicity: A Comparison Study between a De Novo Antimicrobial Lipopeptide and Traditional Biocides.Langmuir : the ACS journal of surfaces and colloids · 2022Article
- Increasing usage of chlorhexidine in health care settings: blessing or curse? A narrative review of the risk of chlorhexidine resistance and the implications for infection prevention and control.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2022Review
- Antimicrobial, Cytotoxic and Mutagenic Activity of Gemini QAS Derivatives of 1,4:3,6-Dianhydro-l-iditol.Molecules (Basel, Switzerland) · 2022Article
- Assessing the risk of resistance to cationic biocides incorporating realism-based and biophysical approaches.Journal of industrial microbiology & biotechnology · 2022Review
- Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures.Nature communications · 2022Article
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MICs and minimum bactericidal concentrations (MBCs) for the biocides benzalkonium chloride and chlorhexidine were determined against 1,602 clinical isolates of Staphylococcus aureus. Both compounds showed unimodal MIC and MBC distributions (2 and 4 or 8 mg/liter, respectively) with no apparent subpopulation with reduced susceptibility. To investigate further, all isolates were screened for qac genes, and 39 of these also had the promoter region of the NorA multidrug-resistant (MDR) efflux pump sequenced. The presence of qacA, qacB, qacC, and qacG genes increased the mode MIC, but not MBC, to benzalkonium chloride, while only qacA and qacB increased the chlorhexidine mode MIC. Isolates with a wild-type norA promoter or mutations in the norA promoter had similar biocide MIC distributions; notably, not all clinical isolates with norA mutations were resistant to fluoroquinolones. In vitro efflux mutants could be readily selected with ethidium bromide and acriflavine. Multiple passages were necessary to select mutants with biocides, but these mutants showed phenotypes comparable to those of mutants selected by dyes. All mutants showed changes in the promoter region of norA, but these were distinct from this region of the clinical isolates. Still, none of the in vitro mutants displayed fitness defects in a killing assay in Galleria mellonella larvae. In conclusion, our data provide an in-depth comparative overview on efflux in S. aureus mutants and clinical isolates, showing also that plasmid-encoded efflux pumps did not affect bactericidal activity of biocides. In addition, current in vitro tests appear not to be suitable for predicting levels of resistance that are clinically relevant.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.