Treatment of Staphylococcus aureus skin infection in vivo using rifampicin loaded lipid nanoparticles.

We have previously reported on a novel nanoparticle formulation that was effective at killing Staphylococcus aureus in vitro. Here, we report for the first time, the antibacterial effects of a lipidic nano-carrier containing rifampicin (NanoRIF) which can be used to successfully treat Methicillin-Resistant S. aureus (MRSA) infection at a reduced antibiotic dosage compared to the free drug in a skin wound model in mice. The formulation used contains the lipid monoolein, a cationic lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP) and the antibiotic. We have shown that rifampicin-loaded nanoparticles are more effective at treating infection in the skin wound model than the antibiotic alone. Cryo-TEM was used to capture for the first time, interactions of the formed nanoparticles with the cell wall of an individual bacterium. Our data strongly indicate enhanced binding of these charged nanoparticles with the negatively charged bacterial membrane. The efficacy we have now observed in vivo is of significant importance for the continued development of nanomedicine-based strategies to combat antibiotic resistant bacterial skin infections.

The prevalence of complications associated with lumbar and thoracic spinal deformity surgery in the elderly population: a meta-analysis.

BACKGROUND: The prevalence of spinal deformities increases with age, affecting between 30% and 68% of the elderly population (ages ≥65). The reported prevalence of complications associated with surgery for spinal deformities in this population ranges between 37% and 71%. Given the wide range of reported complication rates, the decision to perform surgery remains controversial. METHODS: A comprehensive search was conducted using PubMed, Embase, and Cochrane to identify studies reporting complications for spinal deformity surgery in the elderly population. Pooled prevalence estimates for individual complication types were calculated using the random-effects model. RESULTS: Of 5,586 articles, 14 met inclusion criteria. Fourteen complication types were reported, with at least 2 studies for each complication with the following pooled prevalence: reoperation (prevalence 19%; 95% CI, 9-36%; 107 patients); hardware failure (11%; 95% CI, 5-25%; 52 patients); infection (7%; 95% CI, 4-12%; 262 patients); pseudarthrosis (6%; 95% CI, 3-12%; 149 patients); radiculopathy (6%; 95% CI, 1-33%; 116 patients); cardiovascular event (5%; 95% CI, 1-32%; 121 patients); neurological deficit (5%; 95% CI, 2-15%; 248 patients); deep vein thrombosis (3%; 95% CI, 1-7%; 230 patients); pulmonary embolism (3%; 95% CI, 1-7%; 210 patients); pneumonia (3%; 95% CI, 1-11%; 210 patients); cerebrovascular or stroke event (2%; 95% CI, 0-9%; 85 patients); death (2%; 95% CI, 1-9%; 113 patients); myocardial infarction (2%; 95% CI, 1-6%; 210 patients); and postoperative hemorrhage (1%; 95% CI, 0-10%; 85 patients). CONCLUSIONS: Most complication types following spinal deformity surgery in the elderly had prevalence point estimates of <6%, while all were at least ≤19%. Additional studies are needed to further explore composite prevalence estimates and prevalence associated with traditional surgical approaches as compared to minimally-invasive procedures in the elderly.

Efficacy and safety of argatroban and bivalirudine in patients with suspected heparin-induced thrombocytopenia.

BACKGROUND: Argatroban is the only commercially available Food and Drug Administration (FDA)-approved anticoagulant for managing heparin-induced thrombocytopenia (HIT). However, bivalirudin may be an attractive alternative. OBJECTIVE: To assess the efficacy and safety of argatroban and bivalirudin in patients with suspected HIT. METHODS: This single-center, retrospective analysis included patients who received argatroban or bivalirudin for at least 24 hours between January 1, 2000, and June 30, 2012. The primary end point assessed anticoagulation goals, specifically time to therapeutic activated partial thromboplastin time (aPTT) goal and percentage of aPTT values within therapeutic range. Secondary end points included new thromboembolic events, bleeding, and mortality. RESULTS: Of the 68 patients who met the inclusion criteria, 48 received argatroban and 20 received bivalirudin. Baseline characteristics were similar between the 2 groups except for age, percentage of patients with liver dysfunction, aPTT immediately prior to drug initiation, and the serotonin release assay results. The mean ± SD times to reach therapeutic aPTT goal for argatroban and bivalirudin were 14 ± 15 and 7 ± 8 hours, respectively (P = 0.024). The mean ± SD percentage of aPTT values within therapeutic aPTT goal was 69% ± 23% for argatroban and 84% ± 18% for bivalirudin (P = 0.005). Rates of thromboembolic events were similar between the 2 groups, as were the rates of bleeding and all-cause mortality. CONCLUSIONS: Bivalirudin appears to reach therapeutic aPTT goal faster with more aPTT values within therapeutic aPTT goal while achieving similar clinical outcomes. Although not approved by the FDA for managing HIT, bivalirudin may be an attractive alternative anticoagulant.