Stewardship / Resistance Scan for Jun 11, 2019

News brief

Study: Standard gonorrhea treatment superior to solithromycin

Solithromycin, a novel fourth-generation macrolide, isn't a suitable alternative to standard therapy of ceftriaxone plus azithromycin for treating gonorrhea, according to a study yesterday by researchers from Australia and the United States in The Lancet Infectious Diseases.

Given growing concerns about antibiotic-resistant Neisseria gonorrhoeae, scientists are looking for new therapies. The study took place at two sites in Australia and one in the United States from September 2014 through August 2015. Patients with gonorrhea ages 15 and older were randomly assigned to receive a single 1,000-milligram (mg) dose of solithromycin or a 500-mg intramuscular dose of ceftriaxone plus a 1,000-mg dose of azithromycin. Of 261 participants, 130 were in the solithromycin group and 131 were in the standard-treatment group. Researchers also obtained Neisseria gonorrhoeae cultures at baseline and test day of cure.

Of patients in the solithromycin group, 80% showed evidence of cure on follow-up testing, compared with 84% of the standard-treatment group, suggesting that solithromycin did not show non-inferiority at the preset -10% criterion.

A secondary analysis limited to patients who had follow-up testing found that the eradication rate for solithromycin was 92%, compared with 100% for standard therapy. Also, the team found that adverse events such as diarrhea and nausea were higher in the solithromycin group.

The authors concluded that the solithromycin dose tested isn't a suitable alternative first-line treatment, and further trials of longer dosing will need to consider potential side-effect risks.

In a related commentary in the same issue, two infectious disease specialists from Amsterdam said the ceftriaxone cure rate for gonorrhea is still about 95%, but the number of N gonorrhoeae with decreased susceptibility is increasing, and alternative antibiotics are urgently needed. The authors are Henry de Vries, MD, PhD, and Maarten Schim-van der Loeff, MD, PhD.

They note that the study found that solithromycin treatment failures weren't due to reinfection, hinting that a single dose might not be sufficient. They wrote that more study is needed on the pharmacodynamics of solithromycin. They add that the novel drug's use might be threatened by emerging azithromycin-resistant gonorrhea strains and that future trials involving the drug should include azithromycin-resistant gonorrhea strains.
Jun 10 Lancet Infect Dis abstract
Jun 10 Lancet Infect Dis commentary

Amoxicillin prescribing tied to amoxicillin and ciprofloxacin resistance

An analysis of UK national data has found that amoxicillin prescribing was not only associated with amoxicillin resistance but ciprofloxacin resistance, as well, whereas nitrofurantoin prescribing was associated with lower levels of resistance to amoxicillin, according to a study yesterday in PLOS One.

The authors used primary care prescribing data from the National Health Service and records of 888,207 urine samples collected from April 2014 through January 2016 that were positive for Escherichia coli.

The researchers determined that amoxicillin prescribing, measured in defined daily doses per 1,000 inhabitants per day, was positively associated with amoxicillin resistance (relative risk [RR], 1.03; 95% confidence interval [CI], 1.01-1.04) and ciprofloxacin (RR, 1.09; 95% CI 1.04-1.17) resistance. In contrast to those findings, nitrofurantoin prescribing was associated with lower levels of resistance to amoxicillin (RR, 0.92; 95% CI 0.84-0.97). Clinical practices with higher levels of trimethoprim prescribing also had higher levels of ciprofloxacin resistance (RR, 1.34; 95% CI, 1.10-1.59).

The authors conclude, "Amoxicillin, which is mainly (and often unnecessarily) prescribed for respiratory tract infections is associated with increased resistance against various antibiotics among E. coli causing urinary tract infections. Our findings suggest that when predicting the potential impact of interventions on antibiotic resistances it is important to account for use of other antibiotics, including those typically used for other indications."
Jun 10 PLOS One study

News Scan for Jun 11, 2019

News brief

Large study affirms inhaled flu vaccine safety in kids with asthma

A large study to assess if a new guideline recommending live attenuated influenza vaccine (LAIV, or FluMist) for children over age 2 years with asthma found no increase in lower respiratory events following vaccination. A research team from HealthPartners, a Minnesota-based healthcare and insurance provider, published its findings yesterday in Vaccine.

Little data are available on wheezing after LAIV in children with asthma, and the team's goal was to help fill the gap by studying kids ages 2 to 17 years who were vaccinated in two large medical groups from 2007 to 2016. In 2010, one of the groups implemented the new clinical guideline recommending LAIV for all children, including those with asthma. In comparing outcomes in the two groups, the researchers examined a cohort of 7,851 vaccinations in 4,771 children with asthma.

Of patients in the LAIV group, the proportion of kids receiving the formulation increased from 23% to 68% after guideline implementation, compared with a rise from 7% to 11% in the group that didn't implement the guideline.

After adjusting for age and baseline asthma severity, the researchers found no increase in lower respiratory events, including asthma exacerbations, within 21 days and 42 days of vaccination, even in the youngest subset of kids.

They concluded that the findings strengthen existing data that suggest LAIV is safe for children with asthma who are older than 2 years and that guidelines for flu vaccination in children with asthma over age 2 should allow use of either LAIV or inactivated vaccine (flu shots) and be based on vaccine effectiveness.
Jun 10 Vaccine abstract

Study shows increasing rates of Legionnaires' disease in New Zealand

Rates of Legionnaires' disease are increasing in New Zealand, with cases in 2015 and 2016 triple the average of the preceding 3 years, according to new data published in The Lancet Infectious Diseases.

The data come from the first nationwide study of routine systematic polymerase chain reaction (PCR) testing to assess the incidence of Legionnaires' disease in hospitals in New Zealand. From May 2015 through May 2016, 5,622 eligible respiratory specimens from 4,862 patients were tested for Legionnaires'. Through the specimens and notification systems, the authors detected 238 cases.

"The overall incidence of Legionnaires' disease cases in hospital in the study area was 5.4 per 100 000 people per year, and Legionella longbeachae was the predominant cause, found in 150 (63%) of 238 cases," the authors said.

The increase in incidence occurred because PCR testing found more cases than culture-based testing, the authors noted.

In a commentary on the study, Mathias Pletz, PhD, and colleagues from Jena University Hospital in Jena, Germany, said the research shows "that the real burden of Legionnaires' disease seems to have been underestimated. This finding might have implications for community-acquired pneumonia treatment guidelines."
Jun 10 Lancet Infect Dis study
Jun 10 Lancet Infect Dis commentary

Rotary pledges $100 million to support polio eradication

As Africa nears polio-free status, the Rotary organization has pledged $100 million US to address the final challenges to ending poliovirus transmission.

"We have the wild poliovirus cornered in the smallest geographic area in history, and now there are just two countries that continue to report cases of the wild virus," said Michael K. McGovern, chair of Rotary's International PolioPlus Committee in a press release. "Rotary is doubling down on our commitment to end polio for good."

Nigeria is approaching 3 years since the last detection of a wild poliovirus case, while Afghanistan and Pakistan are still detecting wild poliovirus cases.

Rotary funding will be split among Pakistan ($25.2 million), Afghanistan ($13.6 million), and Nigeria ($10.2 million). The remaining funds will be given to 10 countries that are polio-free but still vulnerable to the virus.

Last year saw 33 cases of wild poliovirus, Rotary said. So far in 2019 the Global Polio Eradication Initiative has tracked 29 wild poliovirus cases, 21 in Pakistan and 8 in Afghanistan.
Jun 10 Rotary press release