Stewardship / Resistance Scan for May 07, 2018

News brief

CARB-X to fund development of new class of antibiotics

CARB-X announced today that it's awarding more than $2 million to Melinta Therapeutics to help the company advance a new class of antibiotics into clinical development.

According to a CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) press release, Melinta's novel pyrrolocytosine compounds have been designed de novo, from the ground up, in a site not previously exploited by other successful classes of antibiotics that target the ribosome. They are being developed to optimize properties that allow then to get in and stay in bacterial cells. In preclinical studies, pyrrolocytosines have shown activity against all ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter).

"Our structure-based design efforts to create and optimize the pyrrolocytosine class of antibiotics have shown exciting promise, with several compounds demonstrating comprehensive activity and preclinical effect across the full set of bacterial 'superbugs,' " Melinta Chief Scientific Officer Erin Duffy, PhD, said in the press release. "We believe this new class of antibiotics could be transformational in the fight against these urgent threats."

Under the terms of the agreement, Melinta will receive an initial award of up to $2.3 million from CARB-X, with the possibility of an additional $3.9 million based on achievement of certain project milestones.

Since it was established in 2016, CARB-X has awarded more than $82 million to 32 projects in seven countries.
May 7 CARB-X press release

German GP survey finds strong awareness of antimicrobial resistance

A survey of general practitioners (GPs) in Germany found a strong awareness of antimicrobial resistance but also identified barriers to rational antibiotic use in primary care, according to a study in BMC Infectious Diseases.

The survey, designed by a multidisciplinary team as part of a broader intervention study promoting rational antibiotic use, comprised 32 questions grouped around four issues: awareness of antimicrobial resistance, use of antibiotics, guidelines/sources of information, and socio-demographic factors. The questionnaire was mailed to 987 GPs with registered practices in eastern Germany in May 2015.

Overall, 34% (340/987) of the GPs responded to the survey. Most of the participants assumed that multidrug-resistant infections were a result of multiple factors, with 80.9% (275/34) identifying infection control in hospitals, 80.3% (273/340) the use of antibiotics by GPs, and 79.1% (261/340) the use of antibiotics in livestock as the main drivers for drug resistance. In addition, 70.2% (239/340) believed that their own prescribing behavior influenced the drug-resistance situation in their area. GPs with longer work experience (more than 25 years) assumed less individual influence on drug resistance than colleagues with less than 7 years of experience as practicing physicians.

However, only 39.1% (133/340) of the GPs indicated they frequently use guidelines for antibiotic therapy, and only 21.8% (74/340) answered that they "often" or "very often" apply a delayed prescribing strategy for dealing with uncomplicated respiratory tract infection, even though 99.1% (337/340) were familiar with the strategy. Also, 36.2% (123/340) responded that an acute infection with yellow or green sputum is an indication for an antibiotic prescription, a belief the authors argue has questionable diagnostic value in the case of an acute respiratory infection.

"This survey shows clear targets for further approaches to reduce the prevalence of drug-resistant organisms," the authors conclude.
May 4 BMC Infect Dis study

News Scan for May 07, 2018

News brief

WHO launches cholera vaccine drive to reach 2 million in Africa

In response to cholera outbreaks in several African countries over the past several months, the World Health Organization (WHO) today announced the largest cholera vaccination drive in history, with a goal of reaching 2 million people.

The oral cholera vaccine will come from the global stockpile and is funded by Gavi, the Vaccine Alliance. Campaigns will take place in Zambia, Uganda, Malawi, South Sudan, and Nigeria. Country health ministries, supported by the WHO and partners of the Global Task Force on Cholera Control, will complete the campaigns, which include a second round of vaccinations, by the middle of June.

Seth Berkley, MD, Gavi's chief executive officer, said the response is unprecedented. "We have worked hard to ensure there is now enough vaccine supply to keep the global stockpile topped up and ready for most eventualities." He added, however, that the need for improved water and sanitation—the only long-term sustainable solution to the outbreaks—has never been more obvious.

Use of cholera vaccines has expanded considerably since 1997 to 2012, when just 1.5 million doses were available. With steady growth in the global stockpile, nearly 11 million doses were deployed in 2017, and the WHO said that in the first 4 months of 2018, more than 15 million disease have already been approved for use. The vaccine is recommended to be given in two doses, with the first providing protection for 6 months and the second for 3 to 5 years.

As of yesterday, at least 12 areas or countries are reporting active cholera transmission in sub-Saharan Africa. The five vaccine campaigns involve:

Nigeria, 1.2 million doses to curb an emerging outbreak in Bauchi state
Malawi, 1 million doses to protect people in Lilongwe, the country's capital
Uganda, 360,000 doses to protect people in Hoima district, following an outbreak at a refugee camp, and long-term plan to reach more than 1.7 million people
Zambia, 667,100 doses, part a second round targeting the Lusaka slums following a major outbreak
South Sudan, 113,800 doses as a preventive measure ahead of the country's rainy season

Matshidiso Moeti, MD, the WHO's regional director for Africa, said in the press release that during every rainy season cholera returns and devastates communities across Africa. "With this historic cholera vaccination drive, countries in the region are demonstrating their commitment to stopping cholera from claiming more lives. We need to build on this momentum through a multisectoral approach and ensure that everyone has access to clean water and sanitation, no matter where they are located."
May 7 WHO press release

Food Safety News survey finds 1,200 US hepatitis A cases, 40 deaths

At least 1,200 cases of hepatitis A infection and 40 related deaths have been reported by state public health officials since the US Centers for Disease Control and Prevention (CDC) declared a multistate outbreak in March of last year, Food Safety News (FSN) reported today in two stories.

In the main hepatitis A story, FSN says the CDC no longer posts regular case count updates, so it contacted officials in all 50 states for outbreak totals. The story highlights California, which had 919 cases in 2017; Indiana, with 20 cases in 2017 and 71 so far this year; Kentucky, with 448 cases since August 2017; Michigan, with 828 cases, 665 hospitalizations, and 26 deaths since August 2016; and Utah, which reported 149 cases in 2017 and 82 thus far in 2018.

FSN reported that officials still say cases in homeless people and substance abusers account for the lion's share, but the totals in other populations are rising, including in foodservice workers. Food handlers can transmit the disease by not washing their hands or by otherwise contaminating food, as person-to-person spread occurs via the fecal-oral route. The story emphasizes the importance of vaccination, even though at this point the CDC does not recommend hepatitis A vaccine for foodservice employees.

The second story details cases by state for 2017 and 2018 and includes a US map.
May7 FSN main story
May 7 FSN state-by-state data

Study: HPV vaccination coverage low amid promising signs in males

An analysis of insurance company claims from 2007 through 2014 found low uptake of human papillomavirus (HPV) vaccine in both girls and boys, despite a federal recommendation that has been in place for girls since 2006 and for boys since 2011. CDC researchers reported their findings May 4 in Vaccine.

The team said that studying claims data is useful, because unlike national surveys, it isn't affected by problems with participation or recall and can evaluate broader age ranges. They said an earlier claims-based study examined only HPV vaccine uptake in girls and women. The data used in the new study came from the MarketScan Commercial Claims and Encounters database, a nationwide medical billing database that includes information on inpatient and outpatient healthcare encounters.

The researchers looked at participants who were ages 11 to 18 in 2006 and were continuously enrolled from 2006 through 2014, which included 916,513 females and 951,082 males. They looked at coverage of one or more HPV vaccine dose by sex, birth cohort, and calendar year.

For females, the proportion beginning vaccination at age 11 to 12 years old was low in 2008 and 2010 (12.6% and 11.1%, respectively), rising to 15.7% in 2012 and 19.5% in 2014. In comparison, for same-aged males, vaccination initiation was 0.9% in 2010, rising to 8.3% in 2012 and 15.1% in 2014. In females who became eligible for the vaccine, coverage by 2014 was higher in older cohorts (middle to late teens). For boys, cumulative coverage by 2014 was similar for boys in their mid to late teens, but lower in younger and older age-groups.

Overall, the investigators said the proportion starting vaccination at the recommended ages was low. And although more females than males were vaccinated in all age-groups, the male-female differences were smaller in younger cohorts. "The trajectory of male vaccination uptake could signal higher acceptability in males," they wrote.
May 4 Vaccine abstract