Stewardship / Resistance Scan for Mar 14, 2018

News brief

Studies shed more light on managing VRE bacteremia in hospital patients

Vancomycin-resistant enterococci (VRE) have become an increasingly common cause of healthcare-related bacteremia, and two new studies published yesterday in the Journal of Antimicrobial Chemotherapy shed new light on managing the infections, one exploring treatment with high-dose daptomycin and another that found longer exposure to vancomycin, fluoroquinolone, or meropenem was associated with that type of infection.

In the first study, a team based at the University of Texas noted that recent literature suggests that daptomycin is the preferred treatment for VRE bacteremia, though it is often used off-label for that purpose. However, optimal dosing strategies haven't been determined, despite the need for high doses and worries about toxicity.

Their review of studies on the standard-dose and high-dose treatment for VRE bacteremia found that earlier studies didn't find differences in mortality, but newer larger studies suggest an association between high-dose (greater than or equal to 9 milligrams per kilogram [mg/kg]) daptomycin and reduced mortality, compared with the standard 6 mg/kg dose. They concluded that the high-dose regimens appear to be safe and may be linked to improved microbiological outcomes.

In the second study, researchers from the University of Cambridge and Public Health England examined risk factors for VRE bacteremia, focusing on the duration of antibiotic exposure in patients at Cambridge University Hospitals, which has in the past reported the highest numbers of VRE bacteremia in England. Over the study period, the hospital had an active antimicrobial stewardship program in place. And though infection control practices targeting VRE didn't change during that time period, in the early part of the study, the hospital implemented a line-care bundle and a deep-clean program.

The study took place January 2006 through December 2012, comparing 235 patients who had their first episode of VRE bacteremia with 220 matched controls. They found that longer exposure to parenteral vancomycin, fluoroquinolones, and meropenem was independently associated with VRE bacteremia.

They concluded that targeting the use of a single antibiotic in an endemic setting isn't likely to significantly affect VRE bacteremia rates, but a combination of steps including antimicrobial stewardship that limits the duration of high-risk antibiotics along with infection control interventions could help reduce rates of the disease.
Mar 13 J Antimicrob Chemother daptomycin dosing abstract
Mar 13 J Antimicrob Chemother multiple antibiotics and VRE risk abstract

Israeli study finds UTIs, antibiotic use tied to resistant bacteria in pregnancy

Israeli scientists have discovered that prior urinary tract infections (UTIs) and antibiotic exposure were significant risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) pathogens in the urine of pregnant women, but this finding was not associated with worse obstetric outcomes compared with non-ESBL-E pathogens, according to a matched case-control study yesterday in Epidemiology & Infection.

The study included 87 pregnant women whose urine tested positive for ESBL-E and 174 controls whose urine tested negative from 2004 through 2015.

The researchers determined that statistically significant risk factors of ESBL-E detection in urine were previous UTI or asymptomatic bacteriuria (50.6% vs. 26.3% incidence), previous isolation of ESBL-E in urine cultures (12.6% vs. 0.6%) and prior antibiotic exposure (71.3% vs. 54.0%).

They also found that previous hospitalization was not a risk factor. And they did not find a significant difference in adverse obstetric outcomes between the ESBL-E–positive group and the controls.
Mar 14 Epidemiol Infect abstract

News Scan for Mar 14, 2018

News brief

Nigeria's Lassa fever total grows, expands to another state

The number of suspected cases in Nigeria's Lassa fever outbreak has climbed to 1,386 over the past week, which includes 12 more confirmed cases and 4 more deaths, the country's Centre for Disease Control (NCDC) said in its latest report for the week ending Mar 11. So far 365 confirmed cases and 114 deaths have been reported.

Since the NCDC's last report, the first confirmed case has been reported in Kaduna state, raising the number of affected states to 19. However, 84% of all the infections are reported from just 3 states: Edo, Ondo, and Ebonyi. Thirty-six people are still being treated for their illnesses, and 1,150 contacts are under monitoring.

The NCDC said it has deployed teams to four states that border Benin as part of enhanced surveillance for the disease.

Lassa fever is primarily spread by rodents, but human transmission can occur by contact with an infected patient's body fluids. So far 16 healthcare workers have been sickened in the outbreak, 4 of them fatally.

In other Lassa developments, the NCDC said in a Mar 12 statement that early results of virus sequencing on the samples from seven lab-confirmed patients, compared with sequences from samples obtained in past years from different part of the country, suggest that no new virus lineages have appeared, that circulating viruses are similar to those from other years, and that the latest cases aren't epidemiologically linked.

"The most likely route of transmission continues to be spillover of viruses from the rodent reservoir to humans rather than extensive human-to-human transmission," the report said.
Mar 13 NCDC situation update
Mar 12 NCDC statement on early sequencing results

Study finds no link between increased teen suicide risk and Tamiflu

A large study based on a national claims database found no link between oseltamivir (Tamiflu), the most commonly used drug to treat flu, and an increase risk of suicide in children. A team from the University of Illinois at Chicago published its findings yesterday in Annals of Family Medicine.

In 2006, health officials in Japan raised concerns about psychiatric symptoms in teens who were treated with the drug, which prompted Tamiflu's maker to add a warning to its labeling about the potential for neuropsychiatric effects, such as hallucinations, delirium, self-harm, and suicide. However, clinical studies looking at the association have been inconclusive and fraught with methodology and confounding factors.

James Antoon, MD, PhD, the study's corresponding author and assistant professor of clinical pediatrics at the University of Illinois at Chicago College of Medicine, said in a press release from the school that the link between a drug and suicide is a difficult topic to study. "Many events, which can happen simultaneously or over time, can influence a person to attempt suicide, as can an illness itself—so it can be difficult to study scientifically," he said.

To help tease out the factors, the group used a novel method called a case-crossover design, Antoon said. "This analysis is different because it allowed us to use each individual subject as his or her own comparison—we retrospectively studied how patients behaved when on Tamiflu and compared it to their behavior when they were not taking the drug."

From the claims database, researchers identified 21,047 children ages 1 to 18 who attempted suicide during five recent flu seasons (from 2009 to 2013). Of the group, 251 children were exposed to Tamiflu, based on outpatient pharmacy dispensing data. The mean age was 15 years, 61% were female, and 65% had an underlying mental health diagnosis.

For each patient, the researchers assigned the 10-day period just before the suicide attempt as the case period and identified four earlier control periods during the same flu season, which Antoon said helped the group control for within-person confounders, such depression, mental health, trauma, or abuse. Then they repeated the analysis with flu diagnosis alone, without the use of Tamiflu, to explore if infection itself could have been a confounding factor associated with suicide risk.

The group found no association between exposure to Tamiflu and suicide in the pediatric patients. Antoon said the findings will help alleviate some healthcare provider fears, but they will probably continue prescribing the drug with caution, because there are still questions about other neuropsychiatric side effects, which he said his group will look at in future studies.
Mar/Apr Ann Fam Med study
Mar 13 University of Illinois news release

Valneva launches phase 1 trial of chikungunya vaccine

Valneva SE, a vaccine company based in France, announced yesterday the launch of a phase 1 trial to assess the safety and immunogenicity of VLA1553, its live attenuated vaccine against chikungunya.

The multicenter trial will take place in the United States and will evaluate three different dose levels in about 120 healthy adults who will receive one dose, the company said in a press release. To test antibody persistence, investigators will revaccinate participants at 6 and 12 months to assess if they are protected from vaccine-induced viremia.

First data are expected in early 2019, the company said. In preclinical studies in monkeys, VLA1553 prompted strong long-lasting neutralizing antibody response comparable to wild-type chikungunya infection.
Mar 13 Valneva press release