A comparison of safety and outcomes with cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bloodstream infections.

BACKGROUND: Methicillin-susceptible Staphylococcus aureus (MSSA) is a frequent cause of bloodstream infections (BSI). Treatment with nafcillin (NAF) has been preferred to cefazolin (CFZ). However, comparable outcomes have been found with CFZ with possibly lower risk for side-effects. This study compared safety and effectiveness of NAF versus CFZ for MSSA BSI. METHODS: This single center retrospective study evaluated adults admitted with MSSA BSI who received NAF or CFZ. Patients receiving ≥24 h of antibiotics were included for safety analyses. Patients receiving NAF or CFZ for ≥75% of a 14 day minimum treatment course were assessed for clinical effectiveness. The primary safety outcome was incidence of renal toxicity with multiple secondary safety endpoints. Clinical success was defined as symptom resolution, repeat negative cultures, lack of additional therapy for presumed failure, and lack of recurrence within 30 days. RESULTS: A total of 130 patients receiving NAF (n = 79) or CFZ (n = 51) were included for safety analysis. Of those, 90 met criteria for effectiveness assessment (NAF n = 40, CFZ n = 50). Baseline characteristics were well matched. NAF was associated with a higher incidence of nephrotoxicity compared to CFZ (25% vs. 2%, RR 1.31, 95% CI 1.15-1.5, p < 0.001), allergic reactions (p = 0.01) and a trend for hepatotoxicity (p = 0.08). Clinical success was achieved in 82% NAF and 94% CFZ treated patients (p = 0.1). CONCLUSION: CFZ was associated with less nephrotoxicity and no difference in clinical success compared to NAF for MSSA BSI. A prospective study comparing NAF to CFZ for MSSA BSI should be conducted to elucidate differences in therapies.

Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data.

BACKGROUND: Protective mechanical ventilation strategies using low tidal volume or high levels of positive end-expiratory pressure (PEEP) improve outcomes for patients who have had surgery. The role of the driving pressure, which is the difference between the plateau pressure and the level of positive end-expiratory pressure is not known. We investigated the association of tidal volume, the level of PEEP, and driving pressure during intraoperative ventilation with the development of postoperative pulmonary complications. METHODS: We did a meta-analysis of individual patient data from randomised controlled trials of protective ventilation during general anesthaesia for surgery published up to July 30, 2015. The main outcome was development of postoperative pulmonary complications (postoperative lung injury, pulmonary infection, or barotrauma). FINDINGS: We included data from 17 randomised controlled trials, including 2250 patients. Multivariate analysis suggested that driving pressure was associated with the development of postoperative pulmonary complications (odds ratio [OR] for one unit increase of driving pressure 1·16, 95% CI 1·13-1·19; p<0·0001), whereas we detected no association for tidal volume (1·05, 0·98-1·13; p=0·179). PEEP did not have a large enough effect in univariate analysis to warrant inclusion in the multivariate analysis. In a mediator analysis, driving pressure was the only significant mediator of the effects of protective ventilation on development of pulmonary complications (p=0·027). In two studies that compared low with high PEEP during low tidal volume ventilation, an increase in the level of PEEP that resulted in an increase in driving pressure was associated with more postoperative pulmonary complications (OR 3·11, 95% CI 1·39-6·96; p=0·006). INTERPRETATION: In patients having surgery, intraoperative high driving pressure and changes in the level of PEEP that result in an increase of driving pressure are associated with more postoperative pulmonary complications. However, a randomised controlled trial comparing ventilation based on driving pressure with usual care is needed to confirm these findings. FUNDING: None.