Stewardship / Resistance Scan for Apr 26, 2018

News brief

Study: Mass distribution of azithromycin reduces childhood mortality in Africa

A study today in the New England Journal of Medicine reports that childhood mortality in sub-Saharan African communities randomly assigned to mass distribution of azithromycin was lower than in those assigned a placebo. But the authors warn that resistance emerging from mass distribution of the antibiotic could curb or reverse any potential benefit.

In a cluster-randomized trial conducted by an international team of researchers, communities in Malawi, Niger, and Tanzania were assigned to four biannual mass distributions of either oral azithromycin or placebo to children ages 1 to 59 months. Because azithromycin has been shown to reduce rates of infectious diseases like malaria, trachoma, and pneumonia in poor rural communities, and a case-control study in Ethiopia suggested mass distribution of the drug might reduce childhood mortality, the investigators wanted to see if mass distribution in three geographically distinct areas in Africa could have an impact on childhood mortality.

A total of 1,533 communities underwent randomization, with 97,047 children in the azithromycin group and 93,191 in the placebo group. Over five census visits, 323,302 person-years were monitored. At the end of the trial, the annual mortality rate for eligible children in the three countries was 14.6 deaths per 1,000 person-years in the communities that received azithromycin and 16.5 deaths per 1,000 person-years in the communities that received placebo. Mortality was 13.5% lower overall in the communities that received azithromycin, with a larger impact seen in Niger (18.1% lower) than in Malawi (5.7% lower) and Tanzania (3.4% lower). Children in the ages 1 to 5 months who received azithromycin saw the greatest benefit, with 24.9% lower mortality compared with those who received placebo.

The trial did not investigate how azithromycin prevented death, but the authors of the study say research into that question is already underway. In addition, they say further follow-up is warranted to determine whether the mortality effect observed in the trial changes with subsequent rounds of treatment. That could provide insight into the potential impact of side effects and emerging resistance.

They conclude, "Any policy that recommends mass distribution of oral azithromycin to address childhood mortality would need to consider not only cost but also the risk of side effects, especially the potential for the induction or amplification of antibiotic resistance."
Apr 26 N Engl J Med study

Studies assess effect of probiotics in C difficile infection

Two studies today in Infection Control and Hospital Epidemiology suggest that probiotics may be a prevention tool for Clostridium difficile infection (CDI).

In the first study, an international group of researchers analyzed 18 randomized controlled trials with data on 6,851 patients that compared probiotic prophylaxis to placebo or to no treatment and that reported CDI as an outcome. They found that probiotics reduced CDI odds by nearly two-thirds in both the unadjusted model (odds ratio [OR] 0.37) and the adjusted model (OR 0.35). In addition, a subgroup analysis suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single species probiotics, as was using probiotics in clinical settings where the CDI risk was greater than 5%. Odds for serious adverse events were similar in both groups.

The authors of the study concluded that the results provide moderate quality evidence for probiotic prophylaxis may be a useful and safe CDI prevention strategy. "While it's not a perfect solution for a bacterium that has proven very difficult to prevent and treat, probiotics could offer patients another line of defense," lead author Bradley Johnson, PhD, of Dalhousie University said in a press release from journal publisher the Society for Healthcare Epidemiology of America (SHEA).

In the second study, a separate team of researchers evaluated a before-and-after quality improvement intervention program in which all eligible antibiotic recipients at a tertiary care hospital received capsules containing a three-probiotic mixture, to be taken within 12 hours of their initial dose of antibiotics. Comparing the hospital-onset CDI incidence during the 12-month baseline and intervention periods, the researchers found that the incidence rate was similar—6.9 per 10,000 patient days in the baseline period vs. 7.0 per 10,000 patient days in the intervention period. But they also detected a significant decrease in CDI during the final 6 months of the intervention compared with the first 6 months. Overall adherence to the protocol was low, with only 26% of eligible patients receiving a probiotic.

The authors say the delayed effect may have been related to poor adherence to the protocol for probiotic administration and a delayed gradual reduction in environmental contamination.
Apr 26 Infect Control Hosp Epidemiol study #1
Apr 26 Infect Control Hosp Epidemiol study #2
Apr 26 SHEA press release

CARB-X to fund development of next-generation aminoglycoside

CARB-X today announced an initial award of up to $2.4 million to biopharmaceutical company Achaogen for the development of a next-generation aminoglycoside antibiotic.

According to a press release from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), the funding will help Achaogen further develop an aminoglycoside that has been engineered to overcome resistance mechanisms. The hope is that this next-generation aminoglycoside will be able to treat drug-resistant pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii.

"We are honored to have CARB-X's support in advancing our novel aminoglycoside program, which we believe has significant potential to address the growing multi-drug resistance problem in gram-negative bacteria," Achaogen chief scientific officer Lee Swem, PhD, said in the press release.

Achaogen could receive up to $9.6 million more in two additional stages based on the achievement of certain project milestones.

Since it was established in 2016, CARB-X has awarded nearly $80 million to accelerate the development of new antibiotics, diagnostics, and other products to address antibiotic resistance.
Apr 26 CARB-X press release

News Scan for Apr 26, 2018

News brief

USDA clears way for work on modified FMD on US mainland

The US Department of Agriculture (USDA) today announced that Secretary Sonny Perdue has authorized the movement of a modified, noninfectious version of the foot and mouth disease (FMD) virus from the Plum Island Animal Disease Center, off the coast of New York, to the US mainland for vaccine development and research purposes.

Though the modified FMD virus can't cause disease and doesn't pose a transmission risk, it is still a live virus, and federal law requires USDA approval for its movement, the USDA's Animal and Plant Health Inspection Service (APHIS) said today in a statement.

Because the disease could devastate the livestock industry, developing a vaccine using a modified virus will help the USDA more quickly order and acquire an FMD vaccine in the event of an outbreak. The USDA added that the move allows vaccine companies to apply for USDA permits to continue their work with the modified virus in the United States, which when granted requires appropriate biocontainment and use restrictions.

Handling unmodified live FMD viruses has been illegal in the United States, except for at the USDA's Plum Island research facility, where work has been done on the virus under very strict biocontainment procedures. The United States has not had an FMD outbreak since 1929.
Apr 26 APHIS press release

New Saudi MERS case linked to direct camel contact

The Saudi Arabian Ministry of Health (MOH) confirmed one new case of MERS-CoV related to camel contact. This is the MOH's first update in 10 days.

Officials said in an Apr 22 report posted yesterday that a 72-year-old Saudi man from Al Qunfudhah has been diagnosed as having MERS-CoV (Middle East respiratory syndrome coronavirus). The man is in critical condition, and the source of his infection is primary direct contact with camels, a known risk factor for the virus.

On Apr 15 the Saudi MOH reported a MERS-CoV case in a 93-year-old man in Al Qunfudhah, and it had confirmed one earlier in that city, in late January. The new case brings Saudi Arabia's MERS totals since 2012 to 1,836, including 742 deaths. Five people are still being treated for their infections.
Apr 22 MOH report

Second measles outbreak reported in KC area; alerts issued elsewhere

Ten illnesses have been reported in a second measles outbreak in the Kansas City, Mo., area, and an infected traveler from Missouri has prompted warnings about possible exposure in Iowa, Minnesota, and Wisconsin.

The latest measles activity in the Kansas City area mainly involves people infected in the Missouri side of the metro area, including three students who attend Liberty Public Schools, the Kansas City Star reported yesterday, citing a spokesman with the Kansas City Health Department. The Missouri Department of Health & Senior Services (MDHSS) today detailed possible exposure locations and times.

A separate outbreak that began in March at a Johnson County daycare center in the Kansas part of the metro has grown to 18 cases, according to an Apr 20 update from the Kansas Department of Health and Environment (KDHE). That total includes 14 Johnson County residents, plus 3 from Linn County, and 1 from Miami County. According to the Star, that outbreak is Kansas's largest involving measles since 1990.

Meanwhile, the same infected Missouri traveler has triggered warnings in Iowa, Minnesota, and Wisconsin, Kerri Tesreau, with the MDHSS, told the Star. On Apr 23, the Iowa Department of Public Health (IDPH) warned of exposure at a fast food outlet in Des Moines on Apr 13 and at a restaurant in Ankeny on Apr 16. The Minnesota Department of Health (MDH) yesterday warned of exposures at a fast food restaurant in Winona on Apr 13 and a gas station in Albert Lea on Apr 16. In western Wisconsin, the La Crosse and Trempealeau county health departments on Apr 23 warned of exposures at seven locations, mainly hotels and restaurants, between Apr 13 and Apr 16.
Apr 25 Star story
Apr 26 MDHSS press release
Apr 20 KDHE news release
Apr 23 IDPH news release
Apr 25 MDH news release
Apr 23 La Crosse County Health Department home page

Report profiles rotavirus outbreaks following vaccine introduction

Though the rollout of rotavirus vaccination in 2006 has substantially cut severe diarrhea infections in US kids, seasonal outbreaks causing mainly mild-to-moderate illness continue to occur, and researchers today described three 2017 outbreaks in California that illustrate current patterns in the postvaccine era.

A team from California and the US Centers for Disease Control and Prevention (CDC) profiled the events, two of which were first thought to involve norovirus, in the latest issue of Morbidity and Mortality Weekly Report (MMWR).

One of the outbreaks, first suspected as norovirus, struck a child care center in Long Beach in April, which led to 27 cases of acute gastroenteritis in children and 4 in staff members. Five secondary infections in household members were also reported. No hospitalizations or deaths were reported, and 6 of the 27 children had been vaccinated.

The same month another outbreak occurred at an adult assisted living and memory care facility in San Mateo, sickening 4 residents and 5 staff members. Health officials initially suspected norovirus, but tests on two ill people confirmed rotavirus as the cause. No hospitalizations or deaths were reported, and none of the patients were vaccinated, with the authors noting that the patients weren't eligible to be immunized.

A third outbreak struck a subacute care facility for children in Santa Clara County in May, sickening 24 of 25 patients, along with 3 of 115 staff members. A 22-month-old child who had preexisting respiratory failure died from rotavirus-related dehydration. That child and 16 others had not been vaccinated for various reasons, including being on a delayed vaccination schedule that may have made them ineligible to be immunized.

The authors said the outbreaks show that rotavirus disease continues to occur, even in vaccinated people, and that outbreaks can affect adults, especially those in congregate living situations. They also said the outbreaks are a reminder that although the vaccine is highly effective against severe disease, it doesn't always prevent infection and mild disease. "Thus, rotavirus disease and outbreaks can occur even in populations where vaccination coverage is high," they wrote.
Apr 27 MMWR report

Report: Listeria outbreaks associated with soft cheese on the rise in the US

Listeriosis infections connected to eating soft cheeses are on the rise in the United States, according to a report today in Emerging Infectious Diseases. The report tracked illnesses caused by Listeria monocytogenes from 1998 to 2014 in the United States, noting a rise in cases since 2006.

Using data from the Foodborne Disease Outbreak Surveillance System, CDC scientists recorded 58 listeriosis outbreaks, 30% of which were related to soft cheeses (most were "Latin-style" soft cheeses like queso fresco). The outbreaks linked to soft cheese included 180 illnesses, 14 fetal losses, and 17 deaths. The vast majority of patients (88%) were hospitalized for their infections. Of 116 patients with known ethnicity, 38 (33%) were Hispanic.

According to the report, the proportion of listeriosis outbreaks linked to soft cheese made from pasteurized milk was significantly higher from 2007 to 2014 (12 outbreaks, 33%) than from 1998 to 2006 (1 outbreak, 5%). The authors said the increase could be due to a number of factors, including "the growing US Hispanic population (which increased from 11% in 1998 to 17% in 2014 ); a 2.5-fold increase in per capita consumption of cheese from 1980–2013; consumer demand for certain types of cheeses; and an increase in the number of small producers, some of which had sanitary deficiencies."

Listeriosis outbreaks are most commonly associated with refrigerated ready-to-eat foods, including deli meats, hot dogs, soft cheeses, and other dairy products, the authors note.
Apr 26 Emerg Infect Dis study

Chronic wasting disease not transferred to monkeys in NIH-led study

Chronic wasting disease (CWD), a prion disease affecting cervids such as deer, did not cross the species barrier to infect monkeys in a National Institutes of Health–funded study published yesterday in the Journal of Virology.

Since the late 1960s, scientists have tracked CWD in elk, deer, and moose, but the risk to humans who consume infected animal meat remains unknown. Though prion diseases do not normally cross species, the "mad cow" (bovine spongiform encephalopathy) outbreak of the 1980s demonstrated the possibility.

In the study, seven monkeys were inoculated with CWD via intracerebral or oral routes and followed for 11 to 13 years to see if prion disease developed. In humans, prion diseases usually develop over the course of a decade. Scientists used RT-QuIC (real-time quaking-induced conversion) tests on the monkeys and found no clinical or pathological signs of CWD in the animals.
Apr 25 J Virol study