A retrospective, multicentre evaluation of eravacycline utilisation in community and academic hospitals.

OBJECTIVES: Eravacycline is a novel, fully-synthetic tetracycline approved by the FDA for treatment of complicated intra-abdominal infections in August 2018. This study sought to characterise early clinical experience with this novel antibiotic. METHODS: Eravacycline utilisation for 66 patients was retrospectively evaluated. RESULTS: Eravacycline was used as monotherapy in 62.1% of cases. Mean duration of therapy was 13.1 ± 9.9 days. The majority (68.2%) of treatment was for off-label indications, including 34.8% for pulmonary and 28.8% for skin/soft tissue infections. A number of difficult-to-treat organisms were encountered: 50% of identified Gram-negative pathogens were resistant to carbapenems in vitro; and 48% of identified Gram-positive pathogens were resistant to vancomycin in vitro. The patient population had a high illness acuity, with 42.4% requiring ICU admission, 59.1% having ≥2 co-morbidities and 33.3% having ≥3 co-morbidities. Nevertheless, 95.5% experienced clinical improvement, with 86.4% achieving full infection resolution following eravacycline. Three patients who did not experience clinical improvement had an intra-abdominal source of infection without adequate source control. The remaining six who did not experience full infection resolution died from unrelated non-infectious causes during hospital admission. Adverse events were uncommon (4.5%), limited to nausea/vomiting, and not leading to eravacycline discontinuation. Although two patients had a history of Clostridioides difficile infection (CDI), no patients developed CDI while receiving eravacycline. CONCLUSION: These results illustrate the potential versatility of eravacycline with a broad activity spectrum, good safety and tolerability profile, flexibility for use in patients with renal injury or antibiotic allergies, and positive clinical outcomes in this real-world cohort.

A New Potential Strategy for Acute Non-Alcoholic Steatohepatitis (NASH).

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States, and 25% of patients with NAFLD progress to non-alcoholic steatohepatitis (NASH). NAFLD is predicted to be the most common indication for liver transplantation by 2030. Despite associated high morbidity and mortality, there is currently no approved therapy for NASH. PCSK9 inhibitors are approved for reducing LDL in patients who are statin-intolerant or need further LDL reduction. Increased LDL levels are independently associated with an elevated risk of NAFLD. CASE REPORT We present a case of a 39-year-old woman with acute NASH with familial hypercholesterolemia that was refractory to lifestyle modifications and HMG-CoA reductase inhibitors. An episode of rhabdomyolysis warranted a search for alternatives to statin therapy. Results of a liver biopsy showed microvesicular and macrovesicular steatosis with ballooning degeneration, indicating acute NASH. She was started on PCSK9 inhibitors as salvage therapy. Three monthly doses resulted in a more than an 80% reduction in ALT and AST and a 48% reduction in LDL levels. A liver biopsy done 8 months after the first biopsy showed normalization of liver histology. CONCLUSIONS The use of PCSK9 inhibitors showed a dramatic response in this patient who failed conventional therapies, and the encouraging results seen in this case merit further research into the use of PCSK9 inhibitors as first-line therapy for the acute phase of NASH.