Sara Tedeschi, Maddalena Giannella, Michele Bartoletti, Filippo Trapani, Marina Tadolini, Claudio Borghi, Pierluigi Viale; Clinical impact of renin-angiotensin

A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC_24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration–time data. Creatinine clearance (CL_CR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.

OBJECTIVE: To assess the impact of an antimicrobial stewardship program (ASP) on antibiotic consumption, Clostridium difficile infections (CDI), and antimicrobial resistance patterns in a rehabilitation hospital.DESIGN: Quasi-experimental study of the periods before (from January 2011 to June 2012) and after (from July 2012 to December 2014) ASP implementation.SETTING: 150-bed rehabilitation hospital dedicated to patients with spinal-cord injuries.INTERVENTION: Beginning in July 2012, an ASP was implemented based on systematic bedside infectious disease (ID) consultation and structural interventions (ie, revision of protocols for antibiotic prophylaxis and education focused on the appropriateness of antibiotic prescriptions). Antibiotic consumption, occurrence of CDI, and antimicrobial resistance patterns of selected microorganisms were compared between periods before and after the ASP implementation.RESULTS: Antibiotic consumption decreased from 42 to 22 defined daily dose (DDD) per 100 patient days (P<.001). The main reductions involved carbapenems (from 13 to 0.4 DDD per 100 patient days; P=.01) and fluoroquinolones (from 11.8 to 0.99 DDD per 100 patient days; P=.006), with no increases in mortality or length of stay. The incidence of CDI decreased from 3.6 to 1.2 cases per 10,000 patient days (P=.001). Between 2011 and 2014, the prevalence of extensively drug-resistant (XDR) strains decreased from 55% to 12% in P. aeruginosa (P<.001) and from 96% to 73% in A. baumannii (P=.03). The prevalence of ESBL-producing strains decreased from 42% to 17% in E. coli (P=.0007) and from 62% to 15% in P. mirabilis (P=.0001). In K. pneumoniae, the prevalence of carbapenem-resistant strains decreased from 42% to 17% (P=.005), and the prevalence of in methicillin-resistant S. aureus strains decreased from 77% to 40% (P<.0008).CONCLUSIONS: An ASP based on ID consultation was effective in reducing antibiotic consumption without affecting patient outcomes and in improving antimicrobial resistance patterns in a rehabilitation hospital.Infect Control Hosp Epidemiol. 2016;1–7

Introduction Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. Methods A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. Results One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m² and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. Conclusions TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. Trial registration This study is registered at clinicaltrials.gov, registration no. NCT03826108. Graphical abstract