Fluoroquinolones are widely used globally and there is a growing trend of resistance to these agents. However, there is scanty information in Ethiopia and this study aimed to assess the level of bacterial resistance to fluoroquinolones and identify contributing factors in Addis Ababa, Ethiopia. Concurrent mixed methods study design was used. Records (January 2013 to December 2016) of the Microbiology Laboratory of International Clinical Laboratories were retrospectively reviewed. In addition, qualitative interviews were conducted with purposively selected 20 prescribers’ and dispensers’ to explore perceived contributing factors to resistance. Descriptive statistics was used to summarize the data and possible association was explored using multivariable logistic regression. Qualitative data was analyzed using thematic analysis. A total of 7,889 bacterial isolates were identified from 4,310 patients. The overall resistance of bacterial isolates to fluoroquinolones was 42.5% and the highest resistance was to nalidixic acid (63.3%). Enterococci and Escherichia coli developed high level of resistance to ciprofloxacin and norfloxacin; while Enterococci had higher resistant to nalidixic acid (77.8%). Resistance to fluoroquinolones was 5-times more likely in patients aged ≥ 60 years than those < 15 years old (AOR = 5.63, 95% CI: 4.71, 6.73). Resistance to fluoroquinolones increased from 40.4% in 2013 to 49.0% in 2015 but declined to 46.3% in 2016. Respondents of the qualitative interviews suggested that injudicious prescribing due to lack of institutional antibiogram and inadequate knowledge, nonprescription sales of antibiotics and/or patient hording and sharing practices contributed for the high level of fluoroquinolone resistance. The study showed a high level of bacterial resistance to fluoroquinolones. Patients’ age and year of testing were significantly associated with resistance. Moreover, inappropriate prescribing practice, illegal over-the-counter sales as well as their unreasonable use by patients were key drivers to the problem. This calls for the strict regulation of non-prescription sales of antibiotics, public awareness creation and development of local antibiogram to guide prescribing. Keywords: fluoroquinolones, bacterial resistance, qualitative interview, enterococci, Escherichia coli
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