Molecular Characterization of Carbapenem-Nonsusceptible Enterobacterial Isolates Collected during a Prospective Interregional Survey in France and Susceptibility to the Novel Ceftazidime-Avibactam and Aztreonam-Avibactam Combinations.

An interregional surveillance program was conducted in the northwestern part of France to determine the prevalence of carbapenem-nonsusceptible Enterobacteriaceae (CNSE) isolates and their susceptibility to ceftazidime-avibactam and aztreonam-avibactam combinations. Nonduplicate CNSE clinical isolates were prospectively collected from six hospitals between June 2012 and November 2013. MICs of ceftazidime and aztreonam, alone or combined with a fixed concentration of avibactam (4 µg/ml), and those of carbapenems (comparator agents) were determined. MICs of ertapenem in combination with phenylalanine arginine-naphthylamide dihydrochloride (PAßN) were also determined to assess active efflux. Genes encoding carbapenemases, plasmid-mediated AmpC enzymes, extended-spectrum ß-lactamases (ESBLs), and major outer membrane proteins (OMPs) were amplified and sequenced. OMPs were also extracted for SDS-PAGE analysis. Among the 139 CNSE isolates, mainly Enterobacter spp. and Klebsiella pneumoniae, 123 (88.4%) were ertapenem nonsusceptible, 12 (8.6%) exhibited reduced susceptibility to all carbapenems, and 4 Proteeae isolates (2.9%) were resistant to imipenem. Carbapenemase production was detected in only two isolates (producing OXA-48 and IMI-3). In contrast, OMP deficiency, in association with AmpCs and/or ESBLs (mainly CTX-M-9, SHV-12, and CTX-M-15), was largely identified among CNSE isolates. The ceftazidime-avibactam and aztreonam-avibactam combinations exhibited potent activity against CNSE isolates (MIC50/MIC90, 1/1 µg/ml and 0.5/0.5 µg/ml, respectively) compared to that of ceftazidime and aztreonam alone (MIC50/MIC90, 512/512 µg/ml and 128/512 µg/ml, respectively). This study reveals the in vitro activity of ceftazidime-avibactam and aztreonam-avibactam combinations against a large collection of porin-deficient enterobacterial isolates that are representative of the CNSE recovered in the northern part of France.

[Drug interactions with colchicine, are the contraindications well respected? A descriptive study of prescriptions in Brittany based on data from the French National Health Data System]. / Interactions médicamenteuses avec la colchicine, les contre-indications sont-elles bien respectées ? Étude descriptive des prescriptions en Bretagne à partir des données de l'Assurance maladie.

Although the French Health Authority "ANSM" widely informed healthcare professionals about the risk factors for colchicine overdose, its impact and suitable dosages, cases of potentially fatal preventable overdose continue to be reported in France. Using the French National Health Insurance of the Brittany area, we quantified the proportion of prescriptions presenting an absolute drug contraindication (CI) to colchicine (according to the ANSM Drug Interactions "Thesaurus") and its impact in terms of hospitalisation. Between 2013 and 2016, nearly 77,000 patients (mean age, 66±15 years) were reimbursed for at least one colchicine-based drug (Colchimax®, Colchicine Opocalcium®), representing nearly 205,000 prescriptions. General practitioners were the main prescribers (93%). Among the prescriptions, 0.5% had absolute IC with colchicine: in 51% of cases with pristinamycin, followed by azithromycin (15.6%), clarithromycin (15.2%) and roxithromycin (11.9%). In the 15 days following the simultaneous prescription of colchicine and a contraindicated drug, 53 hospital stays were recorded. However, using only the primary diagnosis of hospitalization was not sufficiently relevant to conclude that there was no potential overdose of colchicine. Over the study period, the Thesaurus contained inconsistencies that confused clinicians: mention of absolute IC with colchicine in the "macrolide" and "pristinamycin" sections but not in the sections of 'potent CYP inhibitors' or macrolide class molecules. Overall, very few prescriptions included absolute IC with colchicine. Regular training and information of healthcare professionals remains essential to limit the risk of colchicine overdose and to remind them of the potentially fatal consequences.