High rates of off-label use in antibiotic prescriptions in a context of dramatic resistance increase: a prospective study in a tertiary hospital

• Off-label prescriptions of antibiotics are frequent (47.5%) in our hospital.
• Most off-label uses (including indications and doses) are supported by guidelines (78.9%).
• Marketing authorisation cannot replace a referent in antimicrobial therapy.
• A high amount of off-label use was not associated with an increased rate of adverse events (P = 0.35).

The use of antibiotics, as any other drug, is regulated by the terms of its marketing authorisation, notified in the Summary of Product Characteristics (SPC). If a prescription is not in accordance with the SPC, the physician prescribes off-label. There is very little literature regarding off-label use of antibiotics in adult healthcare facilities. A prospective monocentric study was conducted during 11 days from February to June 2015 in hospitalised patients from a tertiary teaching hospital with a high prevalence of multidrug-resistant organism colonisation to evaluate off-label use of antibiotics. Two independent experts assessed whether prescriptions complied with the latest guidelines in infectious diseases and whether off-label use of antibiotics was associated with an increased risk of adverse events. In total, 160 antibiotic prescriptions were analysed, of which 76 (47.5%) were off-label. Of the 76 off-label prescriptions, 50 (65.8%) were off-label regarding indications and 26 (34.2%) regarding doses. Nevertheless, 46/50 off-label indications (92.0%) and only 14/26 off-label doses (53.8%) were approved by experts, especially because of dose adjustment requirements. During follow-up, the rate of reported adverse events was not statistically different between patients with (n = 76) and without (n = 84) off-label prescriptions (P = 0.35). In a context of multidrug resistance and a lack of new drugs, high rates (47.5%) of antibiotic off-label use were observed in our hospital, but without an increased rate of adverse events. Moreover, 78.9% of off-label uses were in accordance with guidelines. Therefore, the SPC is not the warrant of an appropriate use of antibiotics.