Stewardship / Resistance Scan for Mar 15, 2018

News brief

Study: MCR-4 and MCR-5 genes prevalent in China's pigs, poultry

A research team based in China yesterday reported that the newly identified colistin-resistance genes MCR-4 and MCR-5 occur widely in the country's pigs and poultry, according to a study in PLoS One.

They used a polymerase chain reaction (PCR) test to directly detect the genes in anal and nasal swabs from 1,454 apparently healthy pigs in nine of China's provinces and cloacal and oropharyngeal samples from 1,836 poultry from live-bird markets in 24 provinces.

For both of the genes, prevalence was significantly higher in swine than in poultry swabs. MCR-4 was found in 41.4% of pigs and 11.5% of poultry, and MCR-5 was present in 31.1% of pigs and 5.6% of poultry. Poultry species that harbored the gene included geese, chickens, pigeons, and ducks. In both animal types, MCR-4 and MCR-5 prevalence was higher in the nasal and oropharyngeal swabs than in anal and cloacal swabs.

Researchers found both of the genes in swabs from 2.6% of poultry and 18.3% of pigs.

The authors noted that the levels of genes detected using PCR of swabs is considerably higher than those obtained with studies on bacterial isolates and may more accurately reflect the true prevalence of the genes. "However, the data did not enable us to determine the bacterial species that carried the resistance genes, or the location of the mcr in plasmids or in the bacterial chromosomes," they wrote.

The high levels of MCR-4 and MCR-5 in pigs and poultry from a large part of China is probably linked to prolonged and widespread use of colistin—a last-resort antibiotic—as a growth promoter, but the two genes might also be prevalent in other countries, as well, the team wrote. They also said the higher levels of the genes in nasal and oropharyngeal swabs suggests that bacteria in saliva or respiratory secretions might play key roles in maintaining and transmitting colistin-resistance genes in pigs and poultry.
Mar 14 PLoS One report

CARB-X funds new test to diagnose whole-blood infections

CARB-X, the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, announced an award of $1 million to HelixBind, a Massachusetts-based company producing a new diagnostic test for whole-blood samples. The test will provide resistance information for invasive bloodstream infections, and HelixBind will have the opportunity to receive another $1 million in funding based on project achievements.

"The world urgently needs new diagnostics, antibiotics, vaccines and other products to protect us from current and emerging drug-resistant bacteria. All the projects in the Powered by CARB-X are in the early stages of development, but if successful, they offer great potential in the fight against life-threatening drug-resistant bacteria," said Kevin Outterson, JD, executive director of CARB-X, in a press release.

HelixBind's test eschews blood cultures, potentially saving time and money for clinicians. This means patients with sepsis, a life-threatening blood infection, can be treated with appropriate antibiotics sooner.

The test is the third diagnostic assay funded by CARB-X since 2016. CARB-X's portfolio includes 27 novel antibiotics, diagnostics, and other product that address drug resistance.

Earlier this week, CARB-X hosted a webinar and addressed frequently asked questions about its funding rounds for 2018.
Mar 15 CARB-X press release
Mar 15 CARB-X webinar and FAQs

Only 2 single antibiotics shown effective against Staphylococcus biofilms

A lab-based study of commonly used antibiotic combinations effective against Staphylococcus biofilms in periprosthetic joint infections (PJIs) found that gentamicin and daptomycin were the only effective single-agent treatments. Researchers from Scotland reported their findings yesterday in the Journal of Antimicrobial Chemotherapy.

Locally delivered antibiotics play a key role alongside surgical debridement in managing PJI, but there is little evidence on whether a single agent or combination of drugs is better. Commercial bone cements for PJI typically include gentamicin, either with clindamycin or vancomycin.

The investigators used the dissolvable bead microfilm assay to determine the minimum biofilm eradication concentration (MBEC) for the different medications and drug combinations against staphylococcal PJIs. Then they modified the tractional inhibitory concentration index to craft a fractional biofilm eradication concentration index to evaluate synergism or antagonism among the antibiotics.

Only gentamicin (MBED 64 milligrams per liter [mg/L]) and daptomycin (MBEC 64 mg/L) were effective at clinically achievable concentrations. The researchers also observed that other antibiotics alone or in combination were ineffective. Also, they noted that combining bactericidal antibiotics (except for daptomycin) with gentamicin showed a synergistic effect, though bacteriostatic antibiotics had an antagonistic effect when combined with gentamicin.

Though gentamicin and daptomycin have different mechanisms of action, both affect membrane integrity, which might provide an antistaphylococcal effect, including against methicillin-resistant Staphylococcus aureus, the authors wrote. "Further investigation of these findings may be useful in evaluating optimal use of antibiotic combinations in the management of PJI," they concluded.
Mar 14 J Antimicrob Chemother abstract

News Scan for Mar 15, 2018

News brief

Two-year follow-up study on cholera vaccine shows good efficacy

A 2-year follow-up study of the single-dose oral cholera vaccine (OCV) showed it was effective in adults and children over the age of 5 years. Consistent with results from the 6-month follow-up, the vaccine failed to protect children under the age of 5 from the disease.

The study was published yesterday in The Lancet Infectious Diseases and is based on a 2014 Bangladeshi trial that randomly assigned participants to either a placebo or the vaccine. The overall incidence rates of initial cholera episodes during the 2 years were 0.22 (95% confidence interval [CI], 0.18 to 0.27) per 100,000 person-days in vaccine recipients versus 0.36 (95% CI, 0.31 to 0.42) per 100,000 person-days in placebo recipients (adjusted protective efficacy 39%; 95% CI, 23% to 52%).

For recipients ages 5 to 15, the vaccine was 52% effective in protecting against all cholera and 71% effective in protecting against severe episodes. For adults, the vaccine protective efficacy was 59% against all cholera episodes.

"The lower protective efficacy in young children might be explained by their lower prevaccination exposure to and immunological priming by natural cholera infections, as well as the nature of the protective antigen in the OCV, which might require immunological priming," the authors said.

The authors warn that the lack of efficacy should not deter countries from using the vaccine for older children and adults during an outbreak, and said further investigation into OCV and young immune systems is needed.
Mar 14 Lancet Infect Dis study
Mar 14 Lancet Infect Dis commentary

H5N6 strikes Dutch poultry farm, wild bird in Sweden

The Netherlands has reported its second highly pathogenic H5N6 avian flu outbreak in poultry, and Sweden has detected the virus again in a wild bird, according to separate report from the World Organization for Animal Health (OIE).

The Dutch outbreak began on Mar 12 at a commercial poultry farm in Overijssel province in the east central part of the country, killing 100 of 28,886 birds. The rest were culled to curb the spread of the virus. Health officials have also established surveillance and protection zones around the facility, and so far all farms within 3 kilometers of the affected location have tested negative for the virus, which is a reassortant related to the H5N8 virus.

The Netherlands' first H5N6 outbreak in poultry occurred in February in Groningen province, north of where the newly reported outbreak.

In Sweden, H5N6 was detected in a buzzard found dead on Feb 24 in Blekinge County in the south. The event marks the country's second detection of H5N6 in a wild bird.

In other avian flu outbreak developments, Taiwan reported seven more highly pathogenic H5N2 outbreaks at commercial poultry farms. The events began from Feb 22 to Mar 5, affecting meat ducks, layer ducks, and native chickens. Six of the farms are in Yunlin County, and one is in Pingtung County. Taken together, the virus killed 810 of 54,403 susceptible birds, and the rest were destroyed as part of the outbreak response.
Mar 15 OIE report on H5N6 in the Netherlands
Mar 14 OIE report on H5N6 in Sweden
Mar 15 OIE report on H5N2 in Taiwan

Health officials take steps to address Africa's rise in monkeypox cases

An increase in monkeypox cases across Africa and lack of strong surveillance in the affected areas has raised the level of global concern over the zoonotic disease, experts from the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) reported today in the latest issue of Morbidity and Mortality Weekly Report (MMWR).

They wrote that the WHO and CDC hosted an informal consultation on monkeypox in November 2017 that brought together researchers, global health partners, health ministers, and orthopoxvirus experts to review recent human cases and discuss surveillance and response areas that need improvement.

Six African countries have confirmed human cases since 2016, many of which had not reported a case in decades. They are Central African Republic, Democratic Republic of the Congo, Liberia, Nigeria, Republic of Congo, and Sierra Leone. The virus has also been detected in captive chimpanzees in Cameroon. Most recently, an outbreak in Nigeria resulted in 80 confirmed cases, the largest outbreak of its kind to occur in West Africa. "The emergence of cases is a concern for global health security," the group wrote.

Though overall surveillance has improved in West Africa, health providers in many countries lack the knowledge to recognize and treat the infections or how to curb the spread of monkeypox. Also, the group wrote that outbreaks often occur in forested areas that have limited access to health services.

To address some of the gaps, the WHO and CDC are prioritizing several work areas, such as developing updated guidance and regional training and improving capacity for lab surveillance, disease detection, patient care, and outbreak response.
Mar 16 MMWR report