Bacterial antibiotic resistance development and mutagenesis following exposure to subminimal inhibitory concentrations of fluoroquinolones in vitro: a systematic literature review protocol

INTRODUCTION: Antibiotic resistance (AR) is among the most pressing global health challenges. Fluoroquinolones are a clinically important group of antibiotics that have wide applicability in both humans and animals. While many drivers of AR are known, the impact of medicine quality on AR remains largely unknown. The aim of this review is to systematically evaluate the evidence of the impact of in vitro subinhibitory antibiotic exposure, a major tenet of substandard antibiotics, on the development of AR and mutagenesis, using fluoroquinolones as a case study. METHODS AND ANALYSIS: EMBASE, Web of Science and PubMed will be systematically searched for primary experimental in vitro studies, from earliest available dates within each database (1947, 1965 and 1966, respectively) through 2018, related to subinhibitory fluoroquinolone exposure and AR. A specifically developed non-weighted tool will be used to critically assess the evidence. Subgroup analyses will be performed for different variables and outcomes. ETHICS AND DISSEMINATION: Ethical approval is not required as no primary data are to be collected. The completed systematic review will be disseminated through conference meeting presentations and a peer-reviewed publication.