Table 1.

Population Intervention Comparator Outcome Study design criteria

	Include	Exclude
Population	Bacteria (all isolates of Gram-negative and Gram-positive species)	Eukaryotes (all). Archaea.
Intervention (exposure)	Exposure to ranges of fluoroquinolone (second to fourth-generation) concentrations with levels below the defined MIC*, under controlled in vitro experimental conditions. * Defined as the concentration visibly inhibiting growth in the experimental set-up. Methods employed would include broth and agar dilution methods and commercially available MIC test strips.	Exposure to first-generation quinolone antibiotics, for example, nalidixic acid, or other classes of antibiotics. Exposure to sub-MIC fluoroquinolone concentrations in combination with another class of antibiotic or compound. Purely computational models. Studies involving animals.
Comparator	No treatment, MIC at 0% API of parental strain.
Outcomes	Quantitative experimental microbiological data related to: (1) resistance acquisition (to same or other antibiotic) and (2) mutagenesis rate. Examples of data include standard microbiological assays (ie, phenotypical tests, commercially available antibiotic susceptibility tests and molecular and PCR assays for identification of mutations). Whether any mention of substandard of medicine quality within the paper (yes/no).	Outcomes from studies that treat bacteria with subinhibitory levels but do not follow-up with results related to resistance acquisition or mutagenesis. Examples of results to exclude include community behaviour, such as surface cell adhesion and biofilm formation, virulence (persister formation, toxin/antitoxin systems) and plasmid curing.
Study design	Primary experimental studies (all languages) published from 1966 to 2018 on NCBI PubMed, from 1965 to 2018 on ISI Web of Science and from 1947 to 2018 on Elsevier Embase.	Conference abstracts. Review articles (no primary data). Observational studies.

API, active pharmaceutical ingredient;MIC, minimum inhibitory concentration.