French national cohort of first use of dalbavancin: A high proportion of off-label use.

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft-tissue infections (SSTIs), but its real-life use is not well known. The aim of this study was to describe all first prescriptions in France over an 16-month period. A retrospective study on all adult patients receiving at least one dose of dalbavancin from 1 June 2017 to 31 September 2018 was performed (75 patients from 29 French hospitals). Data were collected via a standard questionnaire. Failure was defined as persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment, and/or death from infection. The main indications were bone and joint infection (BJI) (64.0%), endocarditis (25.3%), and SSTI (17.3%). The main bacteria involved were Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%), and coagulase-negative staphylococci (44.4%). Median minimum inhibitory concentrations (MICs) for staphylococci to vancomycin and dalbavancin ranged from 0.875-2.0 mg/L and 0.032-0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. The main treatment regimens for dalbavancin were a two-dose regimen (1500 mg each) in 38 cases (50.7%) and a single-dose regimen (1500 mg) in 13 cases (17.3%). Overall, at the patient's last visit, clinical cure was observed in 54/68 patients, whilst failure was observed in 14/68 patients. First use of dalbavancin in France was mostly off-label. Most were due to BJI, often as rescue therapy for severe infections. Even in off-label situations, dalbavancin appears safe and effective.

Aminoglycosides use in patients over 75 years old.

OBJECTIVE: to describe aminoglycoside use and nephrotoxicity in patients older than 75 years. DESIGN: retrospective multicenter study. SETTING: hospital department, rehabilitation, long-term care center. POPULATION: patients ≥75 years old treated by aminoglycosides. RESULTS: 184 patients, mean age: 84.4 years (range: 75-101). One hundred and twenty-seven patients received other nephrotoxic drug(s). Gentamicin (70%) and amikacin (30%) were used and the once-daily dosing was preferred (92%). Average treatment period was 2.75 (1-10) days for amikacin and 4.4 (1-30) for gentamicin with average dosage 13.5 and 3.5 mg/kg/day, respectively. The monitoring of maximal plasmatic concentration (Cmax) was done in 37 patients, 9 of them had probabilistic treatment. Only one had a Cmax fulfilling the objective of French recommendations (gentamicin >30 mg/l, amikacin >60 mg/l). When infection was documented, the objective of Cmax >10 × minimal inhibitory concentration of the strain was reached for 27%. Minimal plasmatic concentration was checked in 38% of cases, with adequate value (gentamicin <0.5 mg/l, amikacin <2.5 mg/l) for 37%. At the end of aminoglycoside course, 40 patients increased their serum creatinine >25% of the baseline value. In multivariate analysis, this was associated with treatment length ≥3 days and concomitant use of nephrotoxic drugs. CONCLUSION: aminoglycosides dosing used in elderly patients probably need therapeutic drug monitoring and dose adjustment. Aminoglycosides are used to treat severe infections. One of the most important side effects is nephrotoxicity in oldest patients. To minimise nephrotoxicity, short treatments are necessary and avoiding others nephrotoxic drugs could be relevant.