Fluoroquinolones for the Treatment of Other Respiratory Tract Infections: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines [Internet]

Fluoroquinolones (FQs) are a common class of antibiotic used for the treatment of infections, including those of the respiratory tract. However, the use of FQs has been controversial as certain types are associated with antibiotic resistance and adverse events.

Antibiotic resistance is of significant concern due to the broad-spectrum nature and common use of FQs, and FQ resistance occurs through a number of potential individual or combined mechanisms. Recent global surveillance studies have found increasing rates of FQ resistance among almost all species of bacteria, and this has been demonstrated in urinary tract infection, respiratory tract infections, intraabdominal infections, skin and skin structure infections, and sexually transmitted infections.^, FQ resistance has likely been driven by the widespread use of the antibiotic, and adjustments clinical practice guidelines may be warranted to limit misuse of FQs.

Common adverse events include gastrointestinal and central nervous system toxicities, while other adverse events include rashes and other allergic reactions, tendinitis and tendon rupture, QT prolongation, hypoglycemia and hyperglycemia, and hematologic toxicity. Several FQs have been withdrawn from the market due to adverse events. In the United States, examples include the withdrawal of grepafloxacin in 1999 due to fatal cardiovascular events, temafloxacin in 1992 due to severe adverse reactions (e.g. hemolytic anemia, acute renal failure, hepatotoxicity, and death), and alatrofloxacin in 2006 due to liver toxicity and death.

The association of FQ use with serious adverse events has led to reevaluations of the use of FQs for uncomplicated infections in several jurisdictions. In 2016, the United Sates Food and Drug Administration (FDA) released a statement advising the restriction of FQ use in patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment options, because the risk of serious side effects generally outweighed the benefits. As a result, Health Canada undertook a review of FQs and associated adverse events, and posted the results in their Summary Safety Review in January 2017. The review concluded that adverse events associated with FQ use may be persistent and disabling in rare cases, and that Health Canada would collaborate with drug manufacturers to update product safety information to reflect this potential risk. There remains uncertainty in the use of FQs for the treatment of infections.

This report is an extension of a previous Rapid Response report, which identified evidence for the clinical effectiveness, cost-effectiveness, and guidelines for FQs in pneumonia and chronic obstructive pulmonary disease (COPD). The report found inconsistent results in the systematic reviews of the clinical effectiveness of FQ use in pneumonia, while there was a limited volume of evidence in the clinical effectiveness in COPD, and cost-effectiveness of FQ use in pneumonia. The current report aims to identify and synthesize the evidence describing the clinical effectiveness, cost-effectiveness and guidelines for the use of FQs in other respiratory tract infections (excluding COPD, pneumonia, cystic fibrosis and tuberculosis).