title: High rates of off-label use in antibiotic prescriptions in a context of dramatic resistance increase: a prospective study in a tertiary hospital.
abstract: 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.
authors.affiliation: Maladies infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches 92380, France. Electronic address: benjamin.davido@aphp.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Davido
authors.affiliation: Pharmacie hospitalière, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Bouchand
authors.affiliation: Maladies infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches 92380, France.
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Calin
authors.affiliation: Maladies infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches 92380, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Makhloufi
authors.affiliation: Maladies infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches 92380, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Lagrange
authors.affiliation: Maladies infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches 92380, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Senard
authors.affiliation: Maladies infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches 92380, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Perronne
authors.affiliation: Pharmacie hospitalière, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches, France.
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Villart
authors.affiliation: Maladies infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches 92380, France.
authors.forename: Jérome
authors.initials: J
authors.lastname: Salomon
authors.affiliation: Maladies infectieuses, Hôpital Universitaire Raymond-Poincaré, AP-HP, Garches 92380, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Dinh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003141:Communicable Diseases / Q000188:drug therapy*; D024881:Drug Resistance, Bacterial; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use; D011446:Prospective Studies; D062606:Tertiary Care Centers
chemical_list: D000900:Anti-Bacterial Agents
keywords: Antibiotics; Hospital; Marketing authorisation; Off-label