Stewardship / Resistance Scan for Feb 24, 2020

News brief

Analysis links outpatient penicillin prescribing with sepsis mortality rates

A new study by researchers from Harvard TH Chan School of Public Health suggests that outpatient prescribing of penicillins is associated with rates of mortality with sepsis in older US adults.

The study, published in BMC Infectious Diseases, used a multivariable mixed-effects model to relate state-specific rates of outpatient prescribing for oral fluoroquinolones, penicillins, macrolides, and cephalosporins in 2014 and 2015 to state-specific rates of mortality with sepsis in different age-groups of US adults in the same years, adjusting for additional covariates and random effects associated with 10 US Department of Health and Human Services regions. The aim was to see whether use of different antibiotics in the community might be linked to rising rates of hospitalization with sepsis and associated mortality.

The results of the analysis suggest a positive association between rates of outpatient prescribing of oral penicillins and rates of mortality with sepsis in individuals aged 75 to 84 years and those 85 and older.

An increase in the rate of prescribing of oral penicillins by 1 annual dose per 1,000 state residents was associated with increases in annual rates of mortality with sepsis of 0.95 (95% confidence interval [CI], 0.02 to 1.88) per 1,000 persons aged 75 to 84 years, and 2.97 (95% CI, 0.72 to 5.22) per 1,000 persons over 85. Additionally, the percent of individuals among those aged 50 to 64 who lacked health insurance and the percent of individuals aged 65 to 84 who were African-American were both associated with higher rates of mortality with sepsis in the corresponding age-groups.

The authors of the study note that the findings support the results of a previous analysis that showed an association between the use of penicillins and rates of septicemia hospitalization in older US adults, and are also in agreement with the fact that prevalence of resistance to penicillins, particularly in older adults, is high for a variety of gram-negative and gram-positive infections.

They conclude, "While these findings support the potential utility of replacement of penicillins by other antibiotics with the goal of reducing the rates of sepsis and associated mortality, further studies, including individual-level analyses are needed to better understand the effect of replacement of certain antibiotics, particularly penicillins by other antibiotics in the treatment of different syndromes, well as the effect of reduction in antibiotic prescribing in the treatment of certain conditions on the rates of severe outcomes associated with bacterial infections."
Feb 22 BMC Infect Dis study

Rapid test for tigecycline resistance genes performs well in lab study

A simple, rapid, and cost-effective assay for detecting genes that confer high-level resistance to tigecycline showed high sensitivity and specificity in lab tests, Chinese researchers reported today in the Journal of Antimicrobial Chemotherapy.

The assay, called the tetracycline inactivation method (TIM), was developed to detect the tet(X3/X4) genes, which are present on mobile plasmids and can directly inactivate tetracycline antibiotics, including the newly approved eravacycline and omadacycline. The test uses Bacillus stearothermophilus as the indicator strain, coupled with a pH-sensitive dye (bromecresol purple), to determine the production of tet(X3/X4) in bacterial strains. If the test strain carries the plasmid-encoded tet(X3/X4) genes, eravacycline will be degraded, allowing the growth of the susceptible indicator strain, and a yellow colorimetric zone will develop; otherwise, the color will be purple.

To evaluate the TIM assay, researchers from South China Agricultural University tested it on 118 isolates obtained from feces, soil, dust, sewage, and vegetable samples, including 30 tet(X4)-positive Escherichia coli, 30 tet(X3)-positive Acinetobacter spp., and 58 tet-negative E coli and Acinetobacter spp. The results showed the sensitivity and specificity for E coli carrying tet(X4) was 96.7% and 100%, respectively, while sensitivity and susceptibility for Acinetobacter spp. carrying tet(X3) were both 100%. The assay can be completed in 6.5 hours.

"Overall, the high sensitivity and specificity of TIM combined with its rapid readout make it a useful tool in clinical microbiology laboratories for the detection of plasmid-mediated high-level tigecycline resistance in E. coli and Acinetobacter spp.," the authors of the study write. They add that evaluation off the assay in clinical samples is worth further study.
Feb 24 J Antimicrob Chemother study

FDA grants breakthrough status to lysin therapy for MRSA bloodstream infections

Biotechnology company ContraFect Corporation, of Yonkers, New York, announced today that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to execabase, a recombinantly produced lysin, for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections.

According to a company press release, the designation was based on results of a phase 2 superiority trial that evaluated whether the addition of execabase to standard-of-care (SOC) antibiotic therapy in patients with S aureus bloodstream infections improved clinical response rates compared with SOC antibiotic therapy alone. In a pre-specified analysis of the subgroup with MRSA infections, the clinical responder rate at day 14 among exebacase-treated patients was 42.8 percentage points higher than the responder rate among patients treated with SOC antibiotics alone (74.1% vs 31.3%, respectively, P = 0.010).

Treatment with exebacase was also associated with a 21-percentage-point reduction in the 30-day all-cause mortality (P = 0.056), a 4-day reduction in length of hospital stay, and meaningful reductions in 30-day hospital readmission rates in MRSA-infected patients.

"The decision by the FDA to grant Breakthrough Therapy designation to exebacase recognizes the urgent need for new therapies that can impact the lives of patients with these MRSA infections," ContraFect President and CEO Roger Pomerantz, MD, said. "Based on the Phase 2 data, we believe exebacase could be the first anti-infective agent to demonstrate superior outcomes for these patients."

Execebase is the first lysin to enter human clinical trials in the United States. It works by targeting the peptidoglycan cell wall, which is vital to S aureus bacteria.

Breakthrough Therapy designation expedites development and review of drugs for serious or life-threatening diseases that have provided preliminary clinical evidence that they may demonstrate substantial improvement over available therapies on at least one clinically significant end point.
Feb 24 ContraFect press release

News Scan for Feb 24, 2020

News brief

Ebola cases hit 3,444 in DRC; study shows vaccine reduces viral load

After additions of what might be retrospective cases, the World Health Organization's (WHO's) online Ebola dashboard shows a case count of 3,444 today, which represents 11 more cases than the total reported at the end of last week. The death toll now stands at 2,264 in an outbreak that has lasted 18 months in the eastern region of the Democratic Republic of the Congo (DRC).

The DRC's Ebola technical committee (CMRE) said the 11 cases are probable and not confirmed, and the confirmed total is 3,433. Six of the probable cases are in North Kivu province, and five are in Ituri province.

The CMRE also updated vaccination information; 15,337 people have been vaccinated with Johnson & Johnson's vaccine, and 297,122 have received Merck's rVSV-ZEBOV.

In a new study published in Vaccine, researchers found that Ebola patients in the DRC who had received rVSV-ZEBOV prior to their infections had lower viral loads and better outcomes than unvaccinated Ebola patients. The study compared 44 patients vaccinated prior to admission to Ebola treatment centers in Butembo and Katwa from January through March of 2019 with 213 unvaccinated patients.

Ten (23%) of 44 vaccinated patients died, compared with 117 (55%) of 213 unvaccinated patients (odd ratio, 0.24, 95% confidence interval, 0.11 to 0.51, P < 0.001), the study found. The vaccinated patients were also less likely to suffer kidney damage.
WHO Ebola dashboard
Feb 22 CMRE report
Feb 21 Vaccine study

Two new cases of MERS reported in Saudi Arabia

Saudi Arabia's Ministry of Health (MOH) reported two new MERS-CoV cases yesterday and today. This raises the number of MERS cases recorded this month to 10.

The first case involved an 81-year-old man from Riyadh whose exposure to MERS-CoV (Middle East respiratory syndrome coronavirus) is listed as primary, meaning it is unlikely he contracted the virus from another person. The MOH said the man had camel contact, a known risk factor for MERS.

The second case was detected in a 67-year-old man from Najran. His case is also listed as primary, but he did not have camel contact. Neither patient is a health worker.

The WHO said in its latest monthly update that, since 2012, it has received reports of 2,499 MERS-CoV cases, at least 861 of them fatal. The vast majority of these cases have been in Saudi Arabia.
Feb 24 MOH report

High-path H5N1 avian flu kills 1,300 poultry on farm in India

A poultry breeding farm in India has been hit by highly pathogenic H5N1 avian flu, according to a report late last week from the World Organization for Animal Health (OIE).

The virus infected all 2,146 birds on the farm and 226 outside the farm but within 1 kilometer of it, killing 1,348, the OIE said in a Feb 21 report. The surviving poultry were culled to prevent further spread of the disease.

The outbreak began on Jan 20 at the farm, located in Odisha province in eastern India, on the Bay of Bengal. Authorities are disinfecting the farm, prohibiting the movement of poultry, and instituting other control measures.
Feb 21 OIE report