Stewardship / Resistance Scan for Sep 19, 2017

News brief

FDA approves new 1-dose antibiotic for treating bacterial vaginosis

Symbiomix Therapeutics announced yesterday that the US Food and Drug Administration (FDA) on Sep 15 approved its antibiotic Solosec (secnidazole) for treating bacterial vaginosis (BV) in adults, the first single-dose option for the condition.

The Newark, N.J.–based company said in a news release, "The FDA approval was supported by a comprehensive set of studies, including two pivotal trials in BV and an open label safety study, which found efficacy for single-dose secnidazole 2g. All treatment-emergent adverse events were mild or moderate in intensity; no serious adverse events were reported, and no patients discontinued treatment due to adverse events."

The FDA awarded the company fast-track designation, which made Solosec eligible for priority review and at least 10 years of US market exclusivity. BV is the most common gynecologic infection in the United States, affecting 21 million girls and women aged 14 to 49 each year, Symbiomix said. The most commonly prescribed antibiotics for the condition require twice-a-day pills for 7 days.

Solosec granules are designed to be sprinkled onto applesauce, yogurt, or pudding and consumed within 30 minutes without chewing the granules.

David L. Stern, CEO of Symbiomix, said in the news release, "Solosec is the first new oral antibiotic to treat BV in more than a decade and will provide women with a new treatment option. We look forward to making this treatment available to patients in the first quarter of 2018."
Sep 18 Symbiomix news release

Whole-genome sequencing effective in tracing spread of resistant bacteria

Phylogenetic analysis based on whole-genome sequencing (WGS) was superior to conventional epidemiologic methods for reconstructing transmission pathways in an outbreak of carbapenem-resistant Klebsiella pneumoniae at a Leipzig hospital, German scientists reported yesterday.

From July 2010 to April 2013, Leipzig University Hospital experienced its largest-ever outbreak of carbapenem-resistant K pneumoniae infections. The researchers, writing in the American Journal of Infection Control, aimed to reconstruct transmission pathways after the outbreak ended.

The investigators performed WGS on 117 isolates from 89 outbreak patients, 5 matching environmental strains, and 24 K pneumoniae strains not linked to the outbreak. They confirmed a patient from Greece as the source of the outbreak. By applying strict definitions in an epidemiologic investigation, they were able to explain transmission pathways for 11 (12.4%) of the 89 patients. Using phylogenetics, in contrast, they were able to confirm 5 of these plus an additional 15 pathways—for a total of 20 (22.5%).

The authors conclude, "Effective phylogenetic identification of transmissions requires systematic microbiologic screening. Extensive screening and phylogenetic analysis based on WGS should be started as soon as possible in a bacterial outbreak situation."
Sep 18 Am J Infect Control study

Review: Tetracyclines pose lower risk of C difficile

A new meta-analysis conducted by researchers at the Mayo Clinic suggests tetracyclines offer a lower risk of Clostridium difficile infection than other antimicrobials. The findings were published yesterday in Clinical Infectious Diseases.

Researchers analyzed six studies collected from several databases. The studies included hospital patients recruited between 1993 and 2012. They found that use of tetracyclines was negatively associated with C difficile, at an odds ratio of 0.62.

The authors conclude that tetracyclines may be used as a first line treatment when prescribers are concerned about C difficile infection, a life threatening condition most commonly associated with healthcare settings. The bacteria, which flourishes after treatment and overuse of antibiotics, inflames the colon, leading to colitis.
Sep 18 Clin Infect Dis study

News Scan for Sep 19, 2017

News brief

NIH awards $5.8 million for development of next-generation H7N9 vaccine

EpiVax, Inc., a vaccine development and immune engineering company based in Providence, R.I., yesterday announced it is part of collaboration supported by a $5.8 million award from the National Institutes of Health (NIH) to develop a new type of vaccine against H7N9 avian influenza.

Scientists using bioinformatics and molecular modeling techniques will engineer the H7N9 hemagglutinin (HA) to resemble seasonal flu, which could help trigger immune memory and help conventional HA-oriented flu vaccine protect against H7N9, the company said in a press release.

The 5-year program will also include scientists from the University of Massachusetts Medical School, Protein Sciences, and the University of Georgia.

EpiVax's first-generation H7N9 vaccine is currently in clinical trials in Australia.
Sep 18 EpiVax press release

Multistate Cyclospora outbreak approaches 1,000 cases

In its latest update on an ongoing multistate Cyclospora outbreak, the US Centers for Disease Control and Prevention (CDC) reported 31 more cases, including 20 in people with no recent history of international travel.

As of Sep 13, the CDC said it has received reports of 988 lab-confirmed cases. At least 553 people (56%) did not report international travel and were sick on or after May 1. Texas is the hardest-hit state, accounting for 163 of the case-patients who reported no travel history. The latest illness onset among the locally acquired cases was Aug 18.

Investigators so far haven't identified a food vehicle, but previous outbreaks have involved imported produce such as basil, cilantro, mesclun lettuce, raspberries, and snow peas. On Aug 7 the CDC sent a Health Alert Network Advisory notice to health providers that said health departments were probing an increase in cases that had already passed the number for the same period in 2016.

Cyclosporiasis is caused by the Cyclospora cayentanensis parasite. Symptoms, which include prolonged watery diarrhea, appetite loss, nausea, and fatigue, typically begin about 7 days after a person ingests sporulated oocysts, according to the CDC.
Sep 15 CDC Cyclospora outbreak update

Phase 1 MERS vaccine trial cleared in South Korea

The South Korean Ministry of Food and Drug Safety (KMFDS) granted GeneOne Life Science approval for a phase 1/2a trial of GLS-5300, a vaccine that protects against Middle East respiratory syndrome coronavirus (MERS-CoV). This is the second clinical trial for the vaccine, which was proved to be immunogenic during trials at Walter Reed Army Institute of Research in the United States.

GLS-5300 has previously been shown to be fully protective in non-human primates. The new trial in Korea will assess the responses of injected GLS-5300 followed by electroporation (EP) using the CELLECTRA device at doses of 0.3 and 0.6 mg.

MERS-CoV has an overall mortality rate of 35%; since 2012, more than 2,000 cases of MERS-CoV have been reported from 27 countries, the majority in Saudi Arabia. In 2015, South Korea experienced a MERS-CoV outbreak when a traveler infected 186 people, as the virus spread in several hospitals. Almost 20% (19.4%) of patients died during that outbreak.

"GeneOne has been honored to have participated in the response to this deadly viral illness," said Young K. Park, CEO of GeneOne, in a press release. "Regulatory approval for this Phase 1/2a clinical trial will enable GeneOne to bring the GLS-5300 MERS-CoV vaccine into Korea, a country whose citizens suffered significantly from this highly fatal infection in 2015."
Sep 17 GeneOne press release

Modeling studies identify Zika hot spots for vaccine research

To help select research sites for candidate Zika vaccine trials in 2017 amid declining disease levels, a comparison of three different modeling estimates in eight priority countries suggests that incidence rates are low but pockets of increased risk remain in some countries in the Americas.

Vaccine researchers from the NIH and the CDC asked three academic groups to use existing mathematical models to help identify areas that may have an increased probability of Zika transmission in 2017. The group published its findings yesterday on bioRxiv, a prepublication Web portal for scientific studies.

Only three provinces or departments in two countries had Zika infection rates projected to be above 5% and ranked in the top quartile for their country by two or more of the models. They are Sucumbios province in Ecuador and Tumbres and Piura departments in Peru.

A modeling system that allowed analysis at the city or urban level found 21 with a probability greater than 5% of having a Zika infection rate of at least 10% in 2017, of which 9 were in regions identified by two or more models:

Colombia: Tumaco in Narino state
Ecuador: Lago Agria/Nueva Loja in Sucumbios province
Mexico: Los Mochis and Culiacan in Sinaloa state and Tampico in Tamaulipas state
Peru: Piura in Piura department, Tumbes in Tumbes department, Tarapoto in San Martin department, and Pacallpa in Ucayli department

The models suggest that vaccine studies may need to increase the number of participants, study sites, or duration of follow-up to meet the efficacy end points. The group wrote, "The findings also support initiating a high number of study sites in multiple geographic areas to maximize the likelihood of having study capacity in one or more areas that experience Zika virus infections in 2017 and provide flexibility to responsively increase enrollment in areas with the highest incidence of infection."
Sep 18 bioRxiv abstract

Cholera vaccine campaign launches in Nigeria

Gavi, the Vaccine Alliance, and the World Health Organization (WHO) yesterday announced a cholera vaccination campaign in Nigeria's Borno state. The partners delivered 915,005 doses of oral cholera vaccine late last week in an effort to beat back an outbreak in the northern region of Nigeria.

The outbreak began last month after heavy rainfall contaminated several water sources in Borno, an area plagued by civil unrest and the terrorist organization Boko Haram. As of Sep 16 there have been 2,600 suspected cholera cases reported, including 40 deaths.

Most cases have been reported in the Muna internally displaced persons (IDPs) camp, which houses 20,000 people who have fled the Boko Haram conflict. According to Gavi, "The number of suspected cholera cases has also increased dramatically in Dikwa and Monguno areas in the past few weeks. The campaign will take place in Muna internally displaced persons (IDPs) camp in Maiduguri as well as Jere, Monguno and Dikwa local government areas. The goal is to vaccinate everyone over the age of 1 in the next few days."

The decision to launch a mass vaccination campaign was made on Sep 7.
Sep 18 WHO announcement