Ceftolozane/Tazobactam vs Polymyxin or Aminoglycoside-based Regimens for the Treatment of Drug-resistant Pseudomonas aeruginosa.

BACKGROUND: Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination that often retains activity against resistant Pseudomonas aeruginosa. The comparative safety and efficacy vs polymyxins or aminoglycosides in this setting remains unknown. METHODS: A retrospective, multicenter, observational cohort study was performed. Patients who received ceftolozane/tazobactam were compared with those treated with either polymyxin or aminoglycoside-based regimens for infections due to drug-resistant P. aeruginosa. Multivariate logistic regression was performed controlling for factors associated with treatment to assess the independent impact of ceftolozane/tazobactam on clinical cure, acute kidney injury (AKI), and in-hospital mortality. RESULTS: A total of 200 patients were included (100 in each treatment arm). The cohort represented an ill population with 69% in the intensive care unit, 63% mechanically ventilated, and 42% in severe sepsis or septic shock at infection onset. The most common infection type was ventilator-associated pneumonia (52%); 7% of patients were bacteremic. Combination therapy was more commonly used in polymyxin/aminoglycoside patients than those who received ceftolozane/tazobactam (72% vs 15%, P < .001). After adjusting for differences between groups, receipt of ceftolozane/tazobactam was independently associated with clinical cure (adjusted odds ratio [aOR], 2.63; 95% confidence interval [CI], 1.31-5.30) and protective against AKI (aOR, 0.08; 95% CI, 0.03-0.22). There was no difference in in-hospital mortality. The number needed to treat for a clinical cure with ceftolozane/tazobactam was 5, and the number needed to harm with AKI with a polymyxin/aminoglycoside was 4. CONCLUSIONS: These data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.

An update on nutrition support in the critically ill.

Nutrition support in the critically ill patient has shifted from adjunctive toward fundamental therapy with the publication of high-grade evidence. Early enteral nutrition (EN) is recommended because it is associated with decreased infectious complications and use of EN is associated with decreased mortality and infections compared with parenteral nutrition (PN). EN is not without risks, such as diarrhea or aspiration, but use of prokinetic agents, head of bed elevation, and use of feeding protocols can maximize benefits and minimize risks. Although recently high-grade evidence on nutrition support in the critically ill population has been published, many controversies still exist. In obese patients, use of hypocaloric feedings with increased protein has been demonstrated to promote weight loss and improved glucose management. In nonobese patients, small studies have demonstrated that providing more than 70% or less than 30% of goal caloric intake may be associated with worse outcomes, but more studies are needed. Additional research is also needed to conclude whether withholding intravenous fat emulsions for the first 7 to 10 days of PN reduces infectious complications. Finally, more high-quality studies are needed to define the role of immune-enhancing nutrients such as arginine, glutamine, omega-3 fatty acids, zinc, and selenium.

Vitamin B6 deficiency: a potential cause of refractory seizures in adults.

OBJECTIVE: In children, vitamin B(6) (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B(6) deficiency) that resolved after pyridoxine treatment. DESIGN: Case series. SETTING: Tertiary care surgical intensive care unit. PATIENTS: In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an intraventricular bleed and developed new onset of refractory seizures. INTERVENTIONS: Intravenous pyridoxine followed by oral pyridoxine. MEASUREMENT AND MAIN RESULTS: In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5'-phosphate concentrations normalized with pyroxidine administration. CONCLUSIONS: Although refractory seizures caused by vitamin B(6) deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures.