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.