Stewardship / Resistance Scan for Apr 24, 2019

News brief

Study finds FMT significantly reduces hospital costs for recurrent C diff

Researchers in Denmark report that the use of fecal microbiota transplantation (FMT) reduced hospital costs in patients with recurrent Clostridioides difficile infection (rCDI) by 42%, according to a study in Therapeutic Advances in Gastroenterology.

The single-center study, conducted at a public hospital in Denmark, included all adult patients who were referred for FMT from January 2014 through December 2015 and costs related to donor screening, laboratory processing, and clinical FMT application. The researchers calculated both the costs of FMT and the patient-related hospital costs 1 year before FMT and 1 year after FMT. Cost drivers included hospital admission days, intensive care unit (ICU) admission days, antibiotics use, outpatient visits, telephone consultations, and costs related to the FMT procedure.

Analysis of 50 consecutive adult patients with rCDI who were referred for FMT showed that the weighted average cost of an outpatient FMT procedure (applied by colonoscopy or nasojejunal tube) was €3,095 ($3,463). Total annual costs per rCDI patient dropped from €56,415 pre-FMT to €32,816 post-FMT ($63,132 to $36,723), with cost reductions driven by reductions in both the number of hospital admissions and the length of stay for each admission. The median number of days of hospital admission, including ICU days, fell 45%, from 37 days to 20 days. Sensitivity analyses demonstrated cost reductions in all scenarios.

The researchers say the study is the first to provide direct costs of FMT and to calculate derived hospital cost savings from the procedure, which has shown success in resolving rCDI in 70% to 90% of patients in observational and randomized trials.

"The introduction of new treatments is usually very expensive, but here we have a form of treatment that on top of everything also saves society millions of Euro every month. If we can establish a system that safeguards both patients and donors, then it'll be of huge benefit for everyone," lead study author Christian Lodberg Hvas, PhD, a consultant in the department of hepatology and gastroenterology at Aarhus University Hospital, said in a university press release.
Apr 10 Therap Adv Gastroenterol study
Apr 23 Aarhus University press release

Delayed antibiotics therapy tied to worse outcomes for Enterobacteriaceae

A study yesterday in Open Forum Infectious Diseases indicates that, in patients with Enterobacteriaceae infections, delayed antibiotic therapy had a stronger impact on outcomes and costs than carbapenem resistance did, though the effects of the two characteristics are synergistic.

For the study, researchers with Allergan, medical research firm Evidera, and the Albany College of Pharmacy and Health Sciences identified all admissions with evidence of a serious Enterobacteriaceae infection from a large US hospital database from July 2011 through September 2014. They were looking to determine the independent and combined impact of carbapenem-resistant Enterobacteriaceae (CRE) and delayed appropriate antibiotic therapy—defined as receipt of an antibiotic with activity against all index pathogens more than 2 days after the index date—on clinical and economic outcomes among patients hospitalized with Enterobacteriaceae infections.

Although both factors have been associated with worse outcomes, and patients with CRE infections often receive inappropriate or delayed antibiotic therapy, few studies have attempted to simultaneously weigh the contribution of each factor. Outcomes included duration of antibiotic therapy, hospital length of stay (LOS), in-hospital costs, discharge destination, and composite mortality (in-hospital death or discharge to hospice).

Among the 50,069 patients who met all selection criteria, 514 patients (1.0%) had infections caused by CRE, and the rest had carbapenem-susceptible Enterobacteriaceae (CSE). Overall, 55.4% of CRE patients received delayed appropriate antibiotic therapy versus 32.5% of CSE patients.

Multivariate-adjusted analysis revealed that, irrespective of CRE status, delayed appropriate antibiotic therapy was associated with longer durations of antibiotic therapy and LOS, lower likelihood of discharge to home, and greater likelihood of the composite mortality outcome. The worst outcomes were observed in patients with CRE who received delayed appropriate therapy.

"Our findings have important implications for clinical practice, as they suggest that the worse outcomes typically associated with Enterobacteriaceae infection, regardless of carbapenem susceptibility status, can potentially be mitigated by timely appropriate antimicrobial therapy," the authors of the study write. They add that the findings highlight the need for rapid diagnostics for earlier detection of drug-resistant gram-negative pathogens and decision-support system tools to identify patients at high risk of infections caused by these pathogens.
Apr 23 Open Forum Infect Dis abstract

Antibiotic development collaboration involving 2 drug firms announced

San Diego-based Forge Therapeutics announced today that it has entered into a partnership with Swiss drug maker Basilea Pharmaceutica to discover, develop, and commercialize novel antibiotics.

According to a company press release, Basilea will pay Forge to access its Blacksmith chemistry platform, a drug-discovery platform that identifies small molecule inhibitors of metalloenzymes, which support a variety of biological functions in bacteria. Basilea will apply the Blacksmith platform to develop inhibitors against two well-characterized metalloenzyme targets.

"We are excited to partner with Basilea, a global leader in anti-infective research and development, to pursue novel metalloenzyme targets that have significant promise in this challenging therapeutic area," said Forge CEO Zachary A. Zimmerman, PhD. "Linking our novel chemistry with Basilea's deep drug development and commercial expertise will be a powerful combination in addressing the global threat of antibacterial resistance."

Under the collaboration, Forge is eligible to receive potential development and sales milestone payments of up $167 million per target and tiered royalties upon commercialization of each antibiotic.
Apr 24 Forge Therapeutics press release

News Scan for Apr 24, 2019

News brief

WHO offers new details on hospital-related Saudi MERS outbreak

The World Health Organization (WHO) released new details today about a MERS-CoV outbreak in Wadi ad-Dawasir, Saudi Arabia. Since January, officials have identified 61 cases in the city, of which 14 were in health workers, and 37 were thought to involve healthcare exposure.

Eight patients died from their MERS-CoV (Middle East respiratory syndrome coronavirus) infections, resulting in a case-fatality rate of 13.1% for this outbreak. The median age of patients was 46, and 65% of them were men.

"Investigations into the source of infection of the 61 cases found that 37 were health-care acquired infections, 14 were primary cases presumed to be infected from contact with dromedary camels and the remaining (10) infections occurred among close contacts outside of health care settings," the WHO said. "As previously reported, two human to human transmission amplification events took place at a hospital during this outbreak."

The amplification events took place in an emergency department and a cardiac unit, the WHO said.

The last identified case from Wadi ad-Dawasir was reported on Mar 12, and as of Mar 31, officials have followed up with 380 case contacts for 14 days.
Apr 24 WHO statement

Study finds repeat flu infections most common in younger children

A study of Austrian children and adolescents over four flu seasons found that repeat infections in consecutive seasons occurred frequently, mostly involving children between ages 3 and 8 years old.

The retrospective analysis is based on results of 2,308 positive flu cases identified by a lab in Innsbruck from the 2014-15 season to the 2017-18 season. Researchers reported their findings yesterday in Open Forum Infectious Diseases.

They found that in 2015-16, nearly 12% of patients diagnosed with flu had also been sick with the virus during the previous season, and in 2016-17, more than 14% had been sick with flu at least once during the previous two seasons, and in 2017-18, more than 18% had one or more infections during the earlier three seasons. Most of the repeated illnesses occurred in kids ages 3 to 8 years old.

Of the group, 29 patients had three or four infections during the four flu seasons, and 38 children had two flu episodes within the same season. Circulating strains changed yearly over the study period, and the study wasn't set up to differentiate between different influenza A subtypes. However, their observations about repeated influenza B infections yielded some key findings.

Several children had influenza B infections in 2014-15 (when the Yamagata lineage circulated) and 2015-2016 (when the Victoria lineage circulated), hinting that there is no or only limited cross-protection between the two types of viruses. The investigators also found five kids who had influenza B infections when the Yamagata lineage was almost exclusively circulating in Austria, which the authors said could suggest there is no long-lasting protection after infection with a specific B strain.

Consecutive and subsequent infections in kids occur mainly during the first decade, peaking at a time when long-lasting immune memory is most likely to be developed, they wrote, adding that the findings raise questions about how often people can get sick with flu after experiencing illness in the first decade. They said further studies are needed to analyze the influenza A subtypes to assess efficacy and duration of immune protection after earlier infection with the same strain.
Apr 23 Open Forum Infect Dis abstract