Stewardship / Resistance Scan for Nov 15, 2018

News brief

Scottish officials report human antibiotic use down slightly

Health Protection Scotland (HPS) this week released its One Health antimicrobial resistance (AMR) report, which found decreases in antibiotic use overall and in primary care but increases in acute care, with AMR levels in animals remaining fairly steady.

The report said the total use of antibiotics in people was 25.5 defined daily doses per day in 2017, a 3.0% decline since 2013. Antibiotic use in primary care declined 7.8% since 2013, but in acute hospitals it increased 18.0% in the same period.

Other findings in humans:

As part of Scotland's shift in healthcare roles, nurses are now responsible for the second-highest proportion of antibiotic prescribing in the community: 8.4%, up from 3.9% in 2013.
The proportion of Escherichia coli bacteremia isolates non-susceptible to commonly used antibiotics was generally stable in the last 5 years, but resistance to some antibiotics stayed high.
Officials reported 108 carbapenemase-producing organisms in 2017, a 39% increase since 2013.
The HPS recorded 2,610 gonorrhea cases in 2017. None were ceftriaxone non-susceptible, but high levels of azithromycin resistance were noted in 1.6%.

Professor Alistair Leanord, Director of Scottish Microbiology Reference Laboratories, said in an HPS news release, "It is reassuring that we have not seen any significant changes in resistance to antibiotics in the common organisms that cause the majority of infections."

In animals, data from veterinary clinics show that levels of non-susceptibility to antibiotics have remained stable from 2013 to 2017, though levels of non-susceptibility in E coli from poultry and pigs were greater than those from cattle and sheep.

Extended-spectrum beta-lactamases (ESBLs) were detected in an E coli isolate from a fecal sample from a single pig and also in the urine of a dog in 2017. That compares with five ESBLs detected from animal samples in 2016.

The report did not include antibiotic use data for animals.
Nov 13 HPS news release
Nov 13 HPS full report

Study shows evidence of artemisinin resistance in East India

A study today in the New England Journal of Medicine provides evidence of artemisinin-resistant Plasmodium falciparum malaria in Eastern India that may be spurred by a novel mutation.

The study was conducted in West Bengal, India, in 2013 and 2014, and involved 136 patients with uncomplicated malaria treated with artesunate-sulfadoxine-pyrimethamine. Therapeutic efficacy was monitored from day 1 to day 42, using thick blood smears that analyzed the clearance of the malaria parasite from the blood.

The authors followed World Health Organization (WHO) guidelines to define artemisinin resistance, which included the presence of parasitemia at 72 hours after treatment (with a parasite-clearance half-life of more than 5 hours), the persistence of a parasite survival rate greater than 10%, and the presence of a mutation in kelch13 distal to codon 440.

Increased parasite clearance half-lives longer than 5 hours were observed in 14% of the patients.

"Among the 5 patients who were positive for parasites at day 3, the isolates from 4 patients had the kelch13 G625R mutation, and the isolate from the other patient had the R539T mutation. In accordance with the WHO criteria, these 5 isolates were thus identified as being artemisinin-resistant," the authors said. "We identified G625R as a potential novel mutation that, along with R539T, is associated with artemisinin resistance."

The authors concluded the study by calling for increased surveillance of drug resistance.
Nov 15 N Engl J Med study

News Scan for Nov 15, 2018

News brief

Three more Ebola cases, 1 death recorded in DRC

The Democratic Republic of the Congo's (DRC's) health ministry revised its tally of the ongoing Ebola outbreak today, noting three more cases and one additional fatality. Officials have now reported 344 cases and 202 deaths in an outbreak that begin in North Kivu and Ituri provinces in August.

The fatality number is lower than yesterday, because duplicates and listing errors were corrected, the DRC said. The revisions also added 2 more probable cases, bringing the total to 40. The three new cases are from Beni, Katwa and Kalunguta, a violence-prone "red zone," and the new confirmed death is from Katwa. The ministry said 45 suspected Ebola cases are still under investigation.

Ring vaccination campaigns with Merck's unlicensed Ebola vaccine are still under way. As of today, a total of 30,563 case contacts and contacts of contacts have been vaccinated, including 15,573 in Beni.
Nov 15 DRC update

Study: Novel antiviral pimodivir cuts viral load in patients with influenza A

A phase 2 trial of the novel antiviral drug pimodivir found reductions in viral load when given alone or with oseltamivir (Tamiflu) for patients with influenza A infections and was well tolerated. An international research team reported its findings yesterday in the Journal of Infectious Diseases.

Pimodivir, developed by Janssen Pharmaceuticals, is a polymerase inhibitor that blocks the PB2 subunit of influenza A viruses. Polymerase inhibitors signify a new antiviral class that also includes favipiravir and baloxavir. In 2017, pimodivir received US Food and Drug Administration fast-track designation.

In the double-blind phase 2b study, 223 adults with uncomplicated influenza A were randomized to receive one of four treatments twice a day for 5 days: placebo, pimodivir 300 milligrams (mg) or 600 mg, or 600 mg pimodivir with 75 mg oseltamivir.

Patients who received the pimodivir-oseltamivir combination had significantly lower viral loads than those who received 600 mg pimodivir alone. Though the finding was not statistically significant, the researchers saw a trend of greater clinical improvement in patients who received the 600 mg of pimodivir alone or with oseltamivir. Mild and transient diarrhea was the most common adverse effect.

The authors concluded that the promising virologic findings, with or without oseltamivir, support further development of the pimodivir given at the 600 mg dose.

In a commentary on the study in the same issue, two infectious disease experts wrote that the results of the trial are promising and show possible synergistic effects with oseltamivir, but future studies will need to confirm if this translates into a clinical benefit. The authors are Nelson Lee, MD, MBBS, professor in the division of infectious diseases at the University of Alberta, and Michael Ison, MD, with Northwestern University's Feinberg School of Medicine.

The experts added, however, that researchers should keep a close eye on the emergence of genetic variants when patients are treated with polymerase inhibitors. Lee and Ison concluded that the new antiviral class may prove to have important roles for treating severe flu, as well as infections caused by viruses resistant to neuraminidase inhibitors like oseltamivir.
Nov 14 J Infect Dis abstract
Nov 14 J Infect Dis commentary

Restaurant inspection grades tied to reduced Salmonella rates in New York

Posting health inspection letter grades at restaurants was associated with a lower incidence of Salmonella in New York City, according to a new study in Emerging Infectious Diseases.

Researchers compared Salmonella rates in New York City (NYC) and the rest of the state (ROS) after health department letter grading was put into place (from 2011 to 2016), to rates of the infectious foodborne pathogen from before the letter system was used (2006 to 2010), noting a 5.3% drop per year in the city following the implementation of the letter grading system.

"The period-to-period percent change after letter grading implementation was a decline of 32.6% in NYC, compared with a decline of 14.1% in the ROS," the authors said. In the period after letter grading was implemented, the mean rate of Salmonella infection was no longer significantly different (P = 0.37) in NYC (mean 12.6 cases/100,000 persons; 95% confidence interval [CI], 10.9–14.4) compared with the ROS (mean 12.0 cases/100,000 persons; 95% CI, 11.4–12.6), because the rate in NYC was higher than the ROS initially.

"NYC's experience provides a useful case study of the beneficial effect of letter grading programs," concluded the authors, Melanie J. Firestone and Craig Hedberg, PhD, of the University of Minnesota. "Although the relationship between restaurant inspections and risk for foodborne illness is not well understood and inspections represent a snapshot in time that may not represent the overall sanitary conditions in restaurants, factors related to food handling and preparation practices and food worker health and hygiene are frequent contributors to outbreaks in restaurants."
Nov 13 Emerg Infect Dis study