Protecting the tuberculosis drug pipeline: stating the case for the rational use of fluoroquinolones

The use of fluoroquinolones (FQs) to treat lower respiratory tract infections (LTRI) other than tuberculosis (TB) allows selection of Fa-resistant TB when TB is misdiagnosed. This study maps national guidelines on the use of FQs for LRTI in Europe and determines the risk of Fa-resistant TB upon FQ treatment before TB diagnosis. A questionnaire was developed to map existing national LRTI and community-acquired pneumonia (CAP) guidelines. A systematic review and meta-analysis were performed to determine the risk of Fa-resistant TB if prescribed FQs prior to TB diagnosis. 15 (80%) out of 24 responding European Respiratory Society national delegates reported having national LRTI management guidelines, seven including recommendations on FQ use and one recommending FQs as the first-choice drug. 18 out of 24 countries had national CAP management guidelines, two recommending FQ as the drug of choice. Six studies investigating FQ exposure and the risk of FQ-resistant TB were analysed. TB patients had a three-fold higher risk of having Fa-resistant TB when prescribed FQs before TB diagnosis, compared to non FQ-exposed patients (OR 2.81, 95% CI 1.47-5.39). Although the majority of European countries hold national LRTI/CAP guidelines, our results suggest that a risk of developing FQ resistance exists. Further strengthening of, and adherence to, guidelines is needed to ensure rational use of FQs.