Stewardship / Resistance Scan for Dec 11, 2019

News brief

Study probes increasing use of cefdinir in Kentucky children

A review of Medicaid claims in Kentucky from 2012 through 2016 found that cefdinir prescriptions for treating outpatient pediatric infections has increased over the study period, researchers based at the University of Kentucky reported today in the Journal of the Pediatric Infectious Diseases Society.

Cefdinir is an oral third-generation cephalosporin that, despite its ease of prescribing in children, isn't recommended as first-line therapy because of pharmacokinetics concerns and unnecessarily broad and mismatched coverage. The authors looked at cefdinir prescribing patterns as part of an effort to understand why Kentucky has the highest rate of antibiotic prescribing for children. The researchers had previously found an overall decrease in antibiotic use in Kentucky; however, the number of cefdinir prescriptions rose over that period.

In the current study, the researchers linked pharmacy claims to medical claims to better understand diagnoses related to cefdinir use. Of 3.6 million antibiotic prescriptions filled over the 5-year study period, 10% were for cefdinir, which led to a cost of $18 million—22% of all Medicaid antibiotic spending. Rates of use rose from 140 per 1,000 children in 2012 to 209 per 1,000 in 2016. During the same timeframe, amoxicillin use was stable and rates of azithromycin and amoxicillin-clavulanate declined.

Upper respiratory infections accounted for most cefdinir use, and the team saw a shift toward higher prescribing in young children and provider type from physicians to nurse practitioners, consistent with overall antibiotic prescribing in Kentucky's Medicaid recipients.

Given that much of the use was probably inappropriate and that the drug is costly, the authors wrote, "Cefdinir is the ideal target for outpatient stewardship; it is both inappropriately prescribed and also expensive, so reducing use may lead to better patient care as well as substantial cost savings.
Dec 11 J Pediatric Infect Dis Soc abstract

Colistin resistance MCR genes found in Ecuador, China clusters

In the latest in colistin resistance genes, Ecuadorian researchers yesterday reported a household animal-human cluster of MCR-1, and Chinese investigators today report a cluster of colistin- and carbapenem-resistant Klebsiella pneumoniae carrying both NDM-1 and MCR-8 resistance genes.

In the first study, published in the Journal of Global Antimicrobial Resistance, the scientists attempted to detect possible sources of colistin-resistant Escherichia coli after a boy was determined to have Ecuador's first case of MCR-1–containing E coli carriage. They collected fecal swabs and soil fecal samples from domestic animals in the boy's home.

The researchers found MCR-1.1 in three isolates, from two dogs and a chicken. The three isolates were on three different E coli sequence types, and the human isolate was found on a fourth sequence type.

The authors conclude, "Our results indicate a polyclonal dissemination of mcr-1.1 in the environment surrounding the first MCR-producing E. coli strain reported in Ecuador."
Dec 10 J Glob Antimicrob Resist study

In the second study, researchers in Chengdu, the capital of Sichuan province, detail a cluster of five carbapenem-resistant K pneumoniae strains from patients in two hospitals, four of which were also resistant to colistin. The findings appear in the Journal of Infectious Diseases.

Whole-genome sequencing identified NDM-1 (New Delhi metal-beta-lactamase), which confers resistance to carbapenem antibiotics. The four colistin-resistant strains harbored a new variant of MCR-8, called MCR-8.2, which differs from MCR-8.1 by four amino acid substitutions. The authors say the findings represent an emerging threat for clinical management.
Dec 11 J Infect Dis abstract

News Scan for Dec 11, 2019

News brief

Study finds combination of antivirals may aid in recovery from severe flu

Patients with severe flu treated with a combination of the antiviral drugs favipiravir and oseltamivir compared with oseltamivir (Tamiflu) alone had faster recoveries, according to findings published today in The Journal of Infectious Diseases.

The retrospective study offers the first data on combination therapy for severe flu, and was conducted by Chinese and British researchers, who compared 40 patients given combination therapy and 128 patients treated with oseltamivir alone. All patients had severe lab-confirmed influenza, were hospitalized, and were symptomatic for less than 10 days.

The combination therapy group exhibited higher rates of clinical improvement by day 14 than the monotherapy group (62.5% vs 42.2%, P = 0.0247). The proportion of undetectable viral RNA at day 10 was higher in the combination group than in the oseltamivir group (67.5% vs 21.9%, P < 0.01), the authors said, and there were no significant differences in mortality rates in the two groups.

Oseltamivir is the most widely used neuraminidase inhibitor in flu patients, while favipiravir is a novel inhibitor of influenza RNA.

"To date, no antiviral randomized controlled trials (RCTs) have established a treatment regimen superior to oseltamivir monotherapy in hospitalized patients with influenza due to susceptible strains," the authors concluded. "Of concern is the relatively high frequency of emergence of oseltamivir-resistant variants in critically ill patients and their association with poor outcomes."

The authors said their findings should prompt an RCT of favipiravir-oseltamivir treatment for severe flu.
Dec 11 J of Infect Dis study

Flu markers on the rise in Northern Hemisphere, WHO reports

Flu activity is risking in most Northern Hemisphere countries, with all subtypes circulating in North America and influenza A strains predominant in Europe, except for its eastern region where influenza B is more common, the World Health Organization (WHO) said on Dec 9 in its global flu update, which covers the middle part of November.

In the Middle East, flu increased in Bahrain, Kuwait, and Saudi Arabia, mainly involving 2009 H1N1. Also, Iran reported an increase in flu, mainly involving the 2009 H1N1 virus.

In Asia, Laos and Vietnam continue to report flu activity. In eastern Asia flu increased in most countries, with levels rising above the seasonal threshold in South Korea, where 2009 H1N1 is the dominant strain.

Globally, of the most recent flu viruses tested, 71.1% were influenza A and 28.9% were influenza B. Of the subtyped influenza A viruses, 71.5% were H3N2 and 28.5% were 2009 H1N1. Of the characterized influenza B viruses, nearly all (96.8%) belonged to the Victoria lineage.
Dec 9 WHO global flu update

Low-path H5 avian flu strikes UK poultry farm

Animal health officials in the United Kingdom yesterday announced that a low-pathogenic H5 avian flu outbreak has been detected at a large commercial poultry arm in Suffolk County in eastern England.

In a statement from the UK's Department for Environment, Food, and Rural Affairs (DEFRA), Christine Middlemiss, BVMS, MBA, chief veterinary officer, said 27,000 birds on the chicken farm will be culled and that immediate steps have been taken to limit the spread. A 1-kilometer restriction zone has been placed around the farm, and health officials are looking for the source of the virus and any other spread.

Farmers have been urged to be alert for any disease signs, including mild breathing problems, though affected birds may not show any symptoms.

The UK's last low-pathogenic avian flu outbreak occurred in January 2016 in Dunfermline, Scotland. Public Health England said the public health risk from the virus is very low, though as a precaution, health officials are offering health advice and antivirals to those who had contact with the birds, according to standard practice.
Dec 10 DEFRA statement

In other avian flu developments, two countries—South Africa and Taiwan—reported more highly pathogenic outbreaks, according to notifications from the World Organization for Animal Health (OIE).

South Africa reported two H5N8 outbreaks, both affecting commercial ostrich farms in Western Cape province. The events began in the middle of September and the middle of October, sickening 8 of 787 birds combined at the two locations. The birds were slated for culling. The country has reported sporadic H5N8 outbreaks since 2017.

Taiwan, meanwhile, reported six more outbreaks involving H5N2, part of ongoing activity involving the strain since 2015. The affected commercial farms housed meat ducks or native chickens, and the start dates for the events ranged from Nov 7 to Nov 27. Taken together, the virus killed 1,256 of 45,341 susceptible birds, and all of the surviving birds were culled to control the spread of the virus.
Dec 10 OIE report on H5N8 in South Africa
Dec 10 OIE report on H5N2 in Taiwan