Stewardship / Resistance Scan for Jul 19, 2018

News brief

VRE outbreak identified in Swiss hospitals

Swiss researchers have identified a large outbreak of vancomycin-resistant enterococci (VRE) clone ST796 across multiple hospitals in Switzerland, according to a report today in Eurosurveillance.

The outbreak began on Dec 30, 2017, when two cases of vancomycin-resistant Enterococcus faecium bloodstream infection were reported in the hemato-oncology ward of Bern University Hospital. By April 30, 2018, screening of 3,096 samples from contact patients found that 89 patients in four hospitals were colonized or infected by VRE. Whole-genome sequencing (WGS) found that 77 of the 89 isolates (86.5%) were virtually indistinguishable, and core genome multilocus sequence typing (cgMLST) identified them as ST796, which was first recognized at an Australian hospital in 2011 and spread rapidly throughout Australia and New Zealand in the following years.

WGS analysis revealed a clear genomic relationship between isolates from the outbreak and those from Australia.

All 77 of the isolates carried the vanB resistance gene, and antimicrobial susceptibility profiles of 68 of the isolates showed resistance to ampicillin and levofloxacin and high-level resistance to gentamycin. Forty-six isolates were resistant to vancomycin, 21 were intermediate, and 1 was susceptible.

The authors conclude that the rapid spread of this VRE clone, and its history of rapid spread across hospitals, could seriously endanger healthcare facilities and warrants strengthening and synchronization of national infection control practices. The World Health Organization has listed VRE, which can be transmitted via the environment or healthcare workers, as a high priority for antibiotic development.
Jul 19 Eurosurveill rapid communication

Study shows benefits of targeted CRE screening on admission

A study today in Infection Control and Hospital Epidemiology suggests active screening to identify patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) is feasible, especially if targeted toward high-risk admissions and units.

In the study, researchers from Rush University Medical Center in Chicago retrospectively analyzed the implementation and outcomes of CRE admission screening from 2013 to 2016 during two study periods. In period 1, the hospital implemented active CRE rectal culture screening for all adults admitted to an intensive care unit (ICU) and for those transferred from outside facilities to general wards. In period 2, the screening policy in the ICU was modified so that only patients transferred from outside facilities were screened.

Overall, 11,757 patients qualified for screening, and rectal cultures were performed for 8,569 (73%). Overall adherence to screening in the ICU was higher in period 1 than in period (83.4% vs. 67.3%). The CRE culture positivity rate (positive CRE screening cultures divided by the total number of screening cultures collected) was highest in the medical and surgical ICUs during period 2 (3.3% combined rate); this rate was higher than the aggregated rate in the medical and surgical ICUs in period 1 (0.7% combined rate) and higher than the rate in general wards for period 2 (0.6%).

Although moving from a universal to a targeted screening resulted in more efficient screening, the analysis of the two periods also showed that nearly half of the 21 CRE screen-positive patients identified during period 1 (47.6%) were not directly transferred from other institutions, and therefore would have been missed by targeted screening.

Analysis of a subset of CRE screen-positive patients identified during period 2 found that, of 13 patients previously identified by outside facilities as CRE-positive, only 4 had documentation of CRE in their medical records, a finding the authors suggest bolsters the case for admission screening.
Jul 19 Infect Control Hosp Epidemiol abstract

Study indicates common yeast, pathogenic yeast are same species

A type of yeast that's commonly used in the food production industry is the same species as a pathogenic, drug-resistant yeast that's one of the five most prevalent causes of yeast infections, according to a study today in PLoS Pathogens.

In the study, researchers at University College Dublin examined the genomes of 20 clinical isolates of Candida krusei, which causes 2% of all yeast infections and has innate resistance to the widely used antifungal drug fluconazol, with 12 environmental isolates of Pichia kudriavzevii, a yeast regarded as safe by the US Food and Drug Administration because it's been used for centuries to make fermented food products. P kudriavzevii also has biotechnology applications, having been used for producing ethanol and other chemicals.

The results showed that the genomes of the isolates were 99.6% identical in their DNA sequence, indicating they belong to the same species. In addition, the researchers found that the P kudriavzevii isolates had levels of drug resistance similar to those of the C krusei isolates.

The authors of the study say the findings suggest P kudriavzevii could cause disease in humans, and that there should be limits on the levels of drug resistance in P kudriavzevii strains used in industry, particularly in food production.
Jul 19 PLos Pathog study

News Scan for Jul 19, 2018

News brief

UK study finds no flu vaccine protection against H3N2 last season

Public Health England (PHE) yesterday released its provisional seasonal flu vaccine effectiveness (VE) estimates for the 2017-18 flu season, which revealed low overall effectiveness and no protection against H3N2, but variable findings in different age-groups.

Based on test-negative case-control studies at five surveillance sites, the overall adjusted VE was 15% (95% confidence interval [CI], -6.3% to 32%), a finding that did not reach statistical significance. VE was higher for children ages 2 to 17 who received the nasal spray vaccine (26.9%) and lower those ages 10 to 64 who are at risk for flu complications (12.2%). In seniors age 65 and older, VE was 10.1%. But, again, none of these levels reached statistical significance.

Researchers found no significant effectiveness against H3N2, consistent with a drop in protection against that strain that other countries such as Canada and the United States have reported. They saw higher levels of protection against influenza B and 2009 H1N1 subtypes, especially in children in whom the vaccine was 60.8% effective against influenza B and 90.3% effective against 2009 H1N1, but confidence intervals were broad, indicated less robust data.

Paul Cosford, MBBS, PHE's director for health protection and medical director, said in a statement that the vaccine offered lower protection against H3N2 due to several factors, including a suboptimal match between the main circulating strain and the vaccine.

He also said for the upcoming season, health officials recommend the quadrivalent vaccine for all those under age 65. He also said an adjuvanted vaccine will be available for seniors to improve immune response.
Jul 18 PHE statement

FDA to explore drug imports to boost supply of certain sole-source drugs

US Food and Drug Administration (FDA) Commissioner Scott Gottlieb, MD, today announced the formation of a new work group to explore policy options to address shortages of certain medications that only have one US-based source.

In a statement, Gottlieb said the work group will focus on a narrow subset of mainly generic drugs that don't have blocking patents or market exclusivities, such as when there's only one US-approved version of an old drug that's not commonly used but is still medically important. He said some conditions develop with the drugs that can threaten patient access, such as disruptions in the supply chain or sudden, significant price increases.

The work group will assess if additional market competition from short-term imports of foreign versions of the drugs would help meet US needs until new competition enters the domestic market.

Gottlieb emphasized that any resulting policy would be narrowly tailored to avoid the risk of counterfeit or unsafe drugs entering the US supply chain.

"Americans greatly benefit from our vibrant, competitive market for medicines. Patients shouldn't face inordinate challenges in getting necessary access to needed drugs," he said. "The FDA's mission is to support the long-term availability of safe and effective versions of medically important medicines."

Today's move follows a Jul 12 FDA announcement of a new task force to address other drug shortages and long-term strategies for preventing them.
Jul 19 FDA statement
Jul 12 CIDRAP News scan "FDA announces efforts to tackle supply problems causing drug shortages"

Use of vaccine may have shortened DRC's Ebola outbreak, experts say

The Ebola outbreak in the Democratic Republic of the Congo (DRC) is most likely almost officially over, and an article in Science suggests the use of the experimental Ebola vaccine may have led to its short duration.

Health officials began administering Merck's vaccine on May 21, and approximately 3,300 people were vaccinated in a ring campaign. Of the 53 confirmed cases in the outbreak, none occurred in a person who had received the vaccine.

But it may have been the enhanced surveillance (ring vaccination campaigns require a detailed record of patient contacts) that went with administering the vaccine—-and not the vaccine itself—that proved the most useful in containing the outbreak, experts quoted in the story said.

Another benefit of the vaccine was that it was offered to healthcare workers. Jean-Jacques Muyembe-Tamfum, director of the National Institute of Biomedical Research in Kinshasa told Science, "At the beginning, there was a kind of a panic among the health care workers. With the arrival of the vaccine, the health care workers had more confidence that they could stay and work in the hospitals."

Experts agreed there were no adverse events seen during the ring vaccination campaign, and 1,000 recipients will provide blood samples regularly throughout the next year to measure immune response to the vaccine.

A total of 29 people died during this latest outbreak, the DRC’s eighth since 1976. The last known person infected with Ebola recovered on Jun 12. The outbreak is expected to be declared over on Jul 24, after 42 days (two transmission cycles) of no new confirmed cases.
Jul 18 Science article

Experts suggest next steps for Ebola treatment studies

In related news, Ebola experts agree that a randomized, controlled clinical trial based on a combination strategy of a monoclonal antibody and a direct-acting antiviral would be the most useful to conduct during the next Ebola outbreak, but they cautioned that achieving the desired sample size would be challenging.

Their opinions were gathered by researchers from the National Institute of Allergy and Infectious Diseases and published yesterday in the Journal of Infectious Diseases.

Because of a number of factors, including logistical challenges and lack of controls, onlyone clinical trial of an Ebola treatment was conducted during the 2013-2016 West African Ebola outbreak. That trial, PREVAIL II, compared treatment with ZMapp (an experimental monoclonal antibody) to standard of care, but the trial ended prematurely and suffered low enrollment.

According to leading pharmaceutical experts, academics, and government officials, monoclonal antibodies should be the backbone of future Ebola treatment studies, and could be combined with direct-acting antivirals in any study conducted during a future outbreak.

"There is a clear scientific and moral imperative to develop consensus on the most appropriate clinical research strategies to be undertaken in advance of the next outbreak," the authors concluded. "Having this consensus clearly articulated in advance might lead to earlier and more-effective introduction of clinical research initiatives in areas of disease outbreak and more-rapid acceptance both internationally and by the affected communities."
Jul 18 J Infect Dis study

HPV vaccine protective in young males, meta-analysis finds

A new meta-analysis of seven studies finds that, in boys and men, the human papillomavirus (HPV) vaccine is protective against anogenital and oral infections. The results were published yesterday in BMC Medicine.

Though the HPV vaccine has been proved safe and effective for widespread use in young girls and women, fewer studies have been conducted on male patients. And only a handful of countries (including the United States) recommend the routine use of HPV vaccine in pre-sexual boys, despite the fact that 33% of penile cancers and up to 90% of anal cancers are attributed to high-risk HPV infections, primarily with HPV type 16.

Four randomized controlled trials and three non-randomized studies were included in this analysis. The results showed the vaccine was 46.9% effective against persisting anogenital HPV 16 infections, 88.0% effective against persisting oral infections, and 61.9% and 46.8% (the latter not statistically significant) against anal intraepithelial neoplasia grade 2 and grade 3 lesions, respectively.

No data were identified in the analysis for anal, penile, or head and neck squamous cell cancer.

"This supports a recommendation for vaccination of boys before the onset of sexual activity with the goal of establishing optimal vaccine-induced protection," the authors said.
Jul 18 BMC Med study