Stewardship / Resistance Scan for Jul 10, 2019

News brief

Study shows decline in antibiotic prescribing in English primary care

The rate of antibiotic prescribing and the proportion of patients receiving antibiotics in primary care settings in England declined consistently from 2014 through 2017, researchers from King's College London reported yesterday in BMJ Open.

Analyzing data from 102 general practices in England, the researchers found that total antibiotic prescribing declined from 608 prescriptions per 1,000 person-years in 2014 to 489 per 1,000 person-years in 2017, with an estimated relative rate reduction (RRR) of 6.9% per year. And broad-spectrum beta-lactam antibiotic prescribing decreased from 221 prescriptions per 1,000 person-years to 163 (RRR, 9.3% per year).

The proportion of registered patients prescribed antibiotics in each year declined from just over 1 in 4 (25.3%) to just over 1 in 5 (21.1%). Declines in prescribing were similar for men and women and were seen in all age-groups, but the rate of decline was lower for patients over the age of 55 years than for younger patients.

When broken down by indication, antibiotic prescribing declined by 9.8% per year for respiratory infections, 5.7% for genitourinary infections, and 3.8% for no recorded indication. Overall, 38.8% of antibiotic prescriptions were associated with codes that did not suggest specific clinical conditions, and 15.3% of antibiotic prescriptions had no medical codes recorded.

The authors say the results show that declines in antibiotic prescribing in English primary care are broad-based, but they note that the slowest decline was seen in antibiotic prescriptions associated with no medical codes, and suggest this might be a target for future stewardship efforts.
Jul 9 BMJ Open study


MCR-1−carrying E coli identified in 4 Michigan patients

A colistin resistance surveillance program in a Michigan health system has identified four patients carrying the mobile colistin-resistance gene MCR-1, researchers reported today in Infection Control and Hospital Epidemiology.

From January 2016 through April 2017, the Michigan Medicine Clinical Microbiology Laboratory tested more than 15,000 clinical Enterobacteriaceae isolates and found that 95 patients had colistin-resistant isolates. Of the 36 isolates tested for the presence of MCR-1 gene, four (all Escherichia coli) were positive. Two isolates belonged to the same sequence type (ST 263), and two carried additional antibiotic-resistance genes.

Colistin is considered a last-resort antibiotic for treating multidrug-resistant infections.

The four patients included a 70-year-old woman with diabetes mellitus and nonalcoholic steatohepatitis, a 19-year-old man with spina bifida and recurrent urinary tract infections (UTIs), a 22-year-old healthy woman with a UTI, and a 77-year-old man with a history of cystectomy and ileal conduit for bladder cancer who was being treated for a complicated UTI. Transmission of MCR-1 between the patients was not identified. Epidemiologic investigation found that all four had travelled internationally and had antibiotic exposure within 6 months prior to MCR-1 identification.

"Further study is required to define mcr-1 prevalence in community and healthcare settings, to identify risk factors for mcr gene acquisition, and to describe the natural history of mcr-1 gene carriage," the authors write.

As of November 2018, 53 human cases of MCR-1−producing Enterobacteriaceae have been reported in 19 US states, including Michigan.
Jul 10 Infect Control Hosp Epidemiol abstract

Study: Malaria vaccine effectiveness holds up longer than previously shown

The efficacy of malaria vaccine RTS,S/AS01 in infants and children is sustained for up to 7 years after vaccination, according to an extension study published Jul 9 in The Lancet Infectious Diseases following a previous phase 3 study.

The original study followed children in two age-groups at vaccination—6 to 12 weeks and 5 to 17 months—at 11 sites in Africa. The children were randomly assigned to 4-dose, 3-dose, or control groups. The vaccine was shown to be moderately effective over the 3- to 4-year follow-up period.

In the extension study, children from three of the African sites were followed for 3 additional years. The incidence of severe malaria remained moderate, varying somewhat by site and drug regimen but, according to the authors, declining over the total 6- or 7-year follow-up after vaccination regardless of treatment assignment.

Moreover, there was no significant change in vaccine efficacy against severe malaria over the additional 3 years of follow-up, nor was there any evidence of increased susceptibility in the vaccinated children compared with controls (i.e., rebound effect). No vaccine-related severe adverse events and no potential immune-mediated diseases (pIMDs) were reported.

A letter in The Lancet, meanwhile, notes that although the the vaccine has shown only partial efficacy, in areas with high disease burden, it "could potentially result in substantial public health benefits and could help protect children when they are most vulnerable to malaria and its serious consequences."

The world's first malaria vaccine program was launched in Malawi in April.
Jul 9 Lancet Infect Dis abstract
Jul 9 Lancet Infect Dis
 commentary introduction
Jul 9 Lancet letter
Apr 23 CIDRAP News article on vaccine program launch


DoD awards contract for smallpox postexposure prophylaxis

SIGA Technologies, maker of TPOXX (tecovirimat), a novel small-molecule drug approved last year by the US Food and Drug Administration for treating smallpox, has been awarded a multiyear contract of up to $19.5 million by the Department of Defense to do work potentially leading to the drug's approval for postexposure prophylaxis (PEP) as well.

Smallpox, while eradicated, remains a bioterrorism threat, because stockpiles of the virus still exist. According to the company's press release, "TPOXX for PEP could provide significant potential benefit in the event of a smallpox outbreak."

Smallpox vaccine would be useful to contain disease spread in an outbreak or bioterror attack but is effective only if administered before or within 4 days after exposure. Smallpox symptoms do not typically appear until about 14 days after exposure, and diagnosis presently is not possible until symptoms appear.

"Given the uncertainty of an individual's infection status in that two-week period, and the highly contagious nature of smallpox, the administration of vaccine in combination with TPOXX could potentially be an important strategy for reducing morbidity and mortality in a smallpox outbreak," says the release.
Jul 8 SIGA press release
Jul 13, 2018, CIDRAP News scan on TPOXX approval as smallpox therapy


CEPI funds new Rift Valley fever vaccine candidate

CEPI, the Coalition for Epidemic Preparedness Innovations, has granted a consortium led by Wageningen Bioveterinary Research up to $12.5 million to support phase 1 trails of the group's single-dose vaccine candidate (RVFV-4s) against Rift Valley fever (RVF).

"This emerging virus has shown its ability to expand its habitat and cause public health emergencies. We can and must develop a safe and effective human vaccine against this deadly virus to protect those people who are most at-risk and to improve global epidemic preparedness. We hope to achieve this goal through our partnership with Wageningen Bioveterinary Research," said Richard Hatchett, MD, the CEO of CEPI, in a press release today.

RVF is mostly found in livestock throughout Africa and on the Arabian peninsula. RVF vaccines have already been used successfully to protect animals, but none have been tested in humans.

Most humans contract the virus from the blood or organs of infected animals, but the possibility that human-to-human transmission could be established through the Aedes aegypti mosquito has led CEPI and the World Health Organization to designate RVF a priority pathogen.

Though rare, RVF has as high as a 50% case-fatality rate in humans once it reaches the hemorrhagic stage, CEPI said.
Jul 10 CEPI
press release


Study: Flu fact sheet leads to more pediatric influenza vaccinations

A randomized control trial conducted in Manhattan pediatric offices shows that providing parents with a simple influenza fact sheet during regular office visits led to higher rates of seasonal flu vaccinations. The study was published today in Pediatrics.

"We found that a low-cost handout that can be easily implemented in any pediatrics practice had a significant and meaningful impact on influenza vaccination in children," said Melissa Stockwell, MD, MPH, associate professor at Columbia University Vagelos College of Physicians and Surgeons and senior author on the paper, in a press release.

The intervention could be a way to combat rising rates of vaccine hesitancy among American parents, the authors said.

The study was conducted at two pediatric clinics in New York City in 2016 and 2017, where 400 parent-child pairs were given regular care or provided handouts on influenza in the waiting room.

"Parents who received an intervention (versus usual care) had greater odds of child influenza vaccine receipt by the end of the season (74.9% vs 65.4%; adjusted odds ratio 1.68; 95% confidence interval: 1.06–2.67)," the authors wrote.
Jul 10 Pediatrics study

Jul 10 Columbia University press release

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