Trial evaluates antibiotic combination for MRSA bacteremia, endocarditis
A randomized phase 3 trial found that the combination of daptomycin and fosfomycin provided higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis, but the difference did not reach statistical significance, Spanish researchers reported yesterday in Clinical Infectious Diseases.
The open-label superiority trial was conducted in 18 Spanish hospitals, with patients randomly assigned to receive either 10 milligrams (mg) of intravenous daptomycin per kilogram daily plus 2 grams of intravenous fosfomycin every 6 hours or 10 mg of daptomycin per kilogram daily. The primary endpoint was treatment success 6 weeks after the end of therapy. Secondary endpoints included microbiological failure, complicated bacteremia, and adverse events leading to treatment discontinuation.
Of the 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. The results showed that treatment success was achieved in 40 of 74 patients (54.1%) who received daptomycin plus fosfomycin and 34 of 81 patients (42.0%) who received fosfomycin alone (relative risk, 1.29; 95% confidence interval [CI], 0.93 to 1.8; P = 0.135). The final microbiologic evaluation found that daptomycin plus fosfomycin was associated with lower microbiologic failure than fosfomycin alone (0 vs 9 patients; P = 0.003) and lower complicated bacteremia (16.2% vs 32.1%; P = 0.022).
Adverse events leading to treatment discontinuation occurred in 13 of 74 (17.6%) of patients treated with daptomycin plus fosfomycin, compared with 4 of 81 patients (4.9%) treated with daptomycin alone (P = 0.018). The most frequent serious events were cardiac failure (4 cases) and hypokalemia (2 cases).
"In conclusion, daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance," the authors wrote. "Our results suggest that this antibiotic combination could be more effective in younger patients and those with more severe disease."
Jul 29 Clin Infect Dis abstract
COVID-19 study identifies phases of antibiotic prescribing
An analysis of patients admitted to a Spanish hospital for COVID-19 has identified two specific phases of antibiotic use, Spanish researchers reported today in Infection Control & Hospital Epidemiology.
The before-and-after cross-sectional study compared antibiotic prescribing data at the hospital from two periods: Jan 1 to Apr 30, 2019 (pre-COVID) and Jan 1 to Apr 30, 2020 (COVID). The COVID period saw more than 1,293 admissions for COVID-19 and 317% increase in critical care bed usage.
The analysis found that antibiotic use was similar in January and February 2019 and 2020 but increased significantly in March and April 2020 compared with the pre-COVID period, rising from 73.3 defined daily doses (DDDs) per 100 patient-days in March 2019 to 87.8 DDDs/100 patient-days in March 2020 and from 69.8 DDDs/100 patient-days in April 2019 to 93.2 DDDs/100 patient-days in April 2020.
The researchers also observed that during the first COVID-19 peak in March, use of amoxicillin/clavulanate trended upward rapidly, consistent with the hospital's recommendations for empiric antibiotic prescribing in COVID-19 patients. But during the second peak, there was increased use of broader-spectrum antibiotics and reduced use of amoxicillin-clavulanate. This corresponded with increased admission to critical care for patients with severe illness, "probably corresponding with an increase in nosocomial infection," the authors wrote.
The authors said the findings suggest antimicrobial stewardship principles should be standardized to provide the safest antibiotic therapy for COVID-19—a recommendation that has also been made by the World Health Organization (WHO) to ensure that antibiotics aren't being used inappropriately during the pandemic.
"In conclusion, our data supports the WHO concern about inappropriate use of antibiotics during the pandemic, and the recent change in its guidelines discouraging empirical antibiotics in COVID-19," they wrote. "Long-term studies are needed to assess the impact of the increase in antibiotic usage during COVID-19 pandemic on the hospital flora, and in turn, how this might affect future nosocomial infection and antimicrobial resistance trends worldwide."
Jul 30 Infect Control Hosp Epidemiol abstract
New community-acquired pneumonia antibiotic approved in Europe
Nabriva Therapeutics, of Dublin, announced this week that the European Commission has approved lefamulin for the treatment of community-acquired pneumonia (CAP) following a review by the European Medicines Agency (EMA).
The approval of lefamulin, which is sold under the brand name Xenleta, was based on efficacy data from two phase 3 trials—LEAP 1 and LEAP 2—that found the antibiotic was non-inferior to standard-of-care moxifloxacin in the treatment of adults with CAP and was generally well-tolerated. The drug has a novel mechanism of action that company officials say has a low propensity for the development of resistance.
"The marketing authorization of Xenleta provides an important step forward for patients with CAP, offering the first new antibiotic class approved by the EMA in decades," Nabriva CEO Ted Schroeder said in a company press release. "We believe the approval of Xenleta is a significant improvement in the fight against antimicrobial resistance and we are excited to bring this critically needed medicine to patients throughout Europe."
Approximately 3 or 4 million cases of pneumonia occur in the European Union annually.
Lefamulin was approved by the US Food and Drug Administration for treatment of adult CAP patients in August 2019.
Jul 28 Nabriva press release