Stewardship / Resistance Scan for Jul 30, 2020

News brief

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

News Scan for Jul 30, 2020

News brief

Study shows higher COVID-19 exposure rates in pregnant black, Hispanic women

Pregnant black and Hispanic women at two Philadelphia hospitals were five times more likely than their white and Asian peers to have been exposed to COVID-19, according to a study published yesterday in Science Immunology.

Overall, 80 of 1,293 pregnant women (6.2%) who went into labor from Apr 4 to Jun 3 tested positive for coronavirus antibodies. But 9.7% of black women (95% confidence interval [CI], 7.3% to 12.5%) and 10.4% of Hispanic women (95% CI, 5.7% to 17.1%) tested positive, versus only 2.0% of white women (95% CI, 0.9% to 3.8%) and 0.9% of Asian women (95% CI, 0.0% to 5.1%).

As of June, 23,160 COVID-19 infections had been reported in Philadelphia, home to nearly 1.6 million people, suggesting an infection rate of about 1.4%—more than four times lower than the estimates generated in this study.

Of the 72 pregnant women with COVID-19 antibodies, 46 (64%) also tested positive for coronavirus on polymerase chain reaction (PCR), compared with 18 (1.7%) of 1,037 women with no antibodies against the virus. The researchers noted that the clinical significance of coronavirus antibodies in immunity remains unclear.

They also said that identification of the disparities in virus exposure could lead to a discovery of the causes of these differences, including systemic racism, and inform public health measures to limit future infections and adverse pregnancy outcomes.

"Pregnant women are fairly representative of community exposure, and these data provide more evidence, on top of what we already know with COVID-19, that health and socio-economic equity are inextricably linked," coauthor Scott Hensley, PhD, said in a University of Pennsylvania press release. "Hopefully, this will help lead to policies that address these inequities."
Jul 29 Sci Immunol study
Jul 29 University of Pennsylvania School of Medicine press release


Physical distancing in COVID-19 pandemic varies strongly by income, research finds

A modeling study published yesterday in Proceedings of the National Academy of Sciences (PNAS) has revealed another burden for low-income communities amid the COVID-19 pandemic: less ability to limit virus exposure by staying home and physical distancing.

Researchers at the University of California at Davis who analyzed mobile device location data from January to April of this year found that, in a complete reversal, wealthy communities went from being the most mobile before the coronavirus pandemic to the least, while residents of poorer neighborhoods went from least mobile to most mobile.

Wealthy communities saw a 25% jump in those staying home completely, versus only a 10% increase in lower-income areas. The study didn't determine the causes of this reversal, but the authors said that it could be because lower-income workers more often have essential jobs that require them to be onsite rather than work remotely from home.

Previous research has already shown that low-income people are more vulnerable to COVID-19 because they have higher rates of underlying medical conditions and less access to healthcare.

Coauthor Michael Springborn, PhD, MA, said in a University of California at Davis press release that the findings point out another way in which residents of low-income areas are especially vulnerable in the pandemic.

"As policymakers are thinking about emergency relief packages, this points to the need for lower-income regions to be an area of focus in order to build capacity for social distancing and other measures critical to reduce the spread of this disease," he said.
Jul 29 PNAS study
Jul 29 University of California at Davis press release


Another Ebola case reported in the DRC; 69 total with 32 deaths

The Democratic Republic of Congo (DRC) has confirmed one more Ebola case in its Equateur province outbreak in the northwest of the country, raising the overall total to 69 cases, the World Health Organization (WHO) African regional office said today on Twitter.

On more death was reported, and it's unclear if that involves the patient who was recently diagnosed. The death raises the outbreak's fatality count to 32.

The outbreak began in early June, and cases have been reported from 23 health areas from 7 health zones, with several cases reported from Mbandaka, the provincial capital. The event marks the DRC's 11th Ebola outbreak and is occurring in the same province where the country battled its ninth outbreak in 2018.
Jul 30 WHO African regional office tweet

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