Stewardship / Resistance Scan for Jan 02, 2018

News brief

Experts issue call for action on antimicrobial resistance in ICU patients

Intensive care and infectious disease experts from the Antimicrobial Resistance in Critical Care (ANTARCTICA) coalition have released a statement in Intensive Care Medicine calling for increased awareness and action to reduce antimicrobial resistance (AMR) in intensive care units (ICUs).

The statement comes out of discussions held at a 2016 meeting in Milan on AMR in the ICU organized by the European Society of Intensive Care Medicine, the European Society of Clinical Microbiology and Infectious Diseases, and the World Alliance Against Antimicrobial Resistance. Recognizing that ICU patients are particularly at risk of acquiring AMR infections, that action is urgently required, and that multiple aspects of the problem need to be covered, the members of the coalition released a set of recommendations for investigating AMR in critically ill patients and developing guidance for treating these patients, along with priorities for improved management of multidrug-resistant (MDR) infections in different domains.

Recommendations from the coalition include committing to making AMR a priority in guideline development and research activities, documenting the global prevalence of gram-negative AMR infection and colonization, developing clinical guidance on specific topics such as antibiotic dosing and duration in the ICU and optimization of empiric treatment, collecting data on treatment and outcomes for extensively- and pan-drug-resistant infections, and assembling a consortium for collaborative research on AMR in the ICU.

Priorities were categorized into four domains (risk stratification, diagnosis, therapy, and prevention) and include identifying MDR pathogen-specific risk factors, developing tools for early diagnosis of sepsis and rapid identification of pathogens and resistance patterns, elucidating the role of combination therapy in MDR infections, and defining optimal use of barrier precautions.

The coalition also proposed a number of immediate interventions that can be taken to reduce AMR in the ICU, including enforcing infection control practices, developing an antimicrobial stewardship team, applying smart antibiotic dosing, and reviewing antibiotics daily.
Dec 29 Intensive Care Med paper

New candidate for multidrug-resistant UTIs shows promise in human trial

Biopharmaceutical company Achaogen today announced positive top-line results from a phase 1 clinical trial of C-Scape, an oral antibacterial candidate being developed for treatment of MDR gram-negative infections.

C-Scape is a combination of two previously approved drugs, the third-generation cephalosporin ceftibuten and the beta-lactamase inhibitor clavulanate. Achaogen is developing the combination therapy as a potential oral treatment for patients who have complicated urinary tract infections (cUTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, which are often resistant to currently available oral antibiotics and require intravenous carbapenem therapy. In preliminary non-clinical studies, C-Scape showed potent in vitro activity against ESBL-producing Enterobacteriaceae and rapid bactericidal activity.

The phase 1 trial was a double-blind, randomized, placebo-controlled, parallel group study to assess the safety, tolerability, and clinical pharmacology of C-Scape in 41 healthy subjects. According to a company press release, the results showed that the combination of ceftibuten and clavulanate was well tolerated when administered for 14 days and did not demonstrate any drug-drug interactions or serious side effects. The most commonly reported adverse events included vascular access site bruising, headache, diarrhea, gastroenteritis, and nausea.

"The positive top-line results from this first-in-human clinical trial for C-Scape are supportive of further evaluation and we continue to plan for Phase 3 in 2018," Kenneth Hillan, MBChB, Achaogen's president of research and development, said in the press release.

In January 2017 the US Food and Drug Administration awarded C-Scape Qualified Infectious Disease Product (QIDP) status for the treatment of cUTI. The QIDP designation, created to provide incentives for new antibiotic treatments, includes priority review and an additional 5 years of marketing exclusivity.
Jan 2 Achaogen press release

News Scan for Jan 02, 2018

News brief

Malaysian man diagnosed with MERS after travel to Saudi Arabia

A Malaysian man who recently returned from a religious pilgrimage to Saudi Arabia has been diagnosed as having MERS-CoV.

The 55-year-old man traveled to Mecca and returned to Malaysia on Dec 23, according to a Bernama story yesterday. He was admitted to a local hospital on Dec 28 and diagnosed as having a MERS-CoV (Middle East respiratory syndrome coronavirus) infection on Dec 31. Malaysian officials said he is in stable condition.

According to a translated statement from the Malaysian Ministry of Health posted on the infectious disease blog Avian Flu Diary, the man visited a camel farm during his pilgrimage and drank raw camel's milk. Direct contact with camels has been linked to transmission of MERS-CoV.

Saudi Arabia first reported MERS in 2012.
Jan 1 Bernama story
Jan 1 Avian Flu Diary post

More avian flu outbreak reported in 4 countries

More avian flu outbreaks continued in four countries that reported earlier outbreaks, all involving different H5 subtypes, according to reports from the World Organization for Animal Health (OIE) and governments.

In Saudi Arabia, which reported its first highly pathogenic H5N8 outbreak in the middle of December, three more outbreaks were detected in poultry all in the Riyadh region in the central part of the country, the OIE said in a notification today. The outbreaks all began on Dec 21, affecting backyard birds. Between the three locations, the virus killed 1,351 of 8,806 birds, and authorities culled the remaining ones to control the spread of the virus.

Over the past few days, Avian Flu Diary translated and posted Saudi agriculture ministry reports of several other H5N8 outbreaks from the Riyadh region, as well as Al Qassim region. An earlier outbreak had been reported in the Eastern region, bringing the total number of regions experiencing outbreaks to three.

In other highly pathogenic H5 developments, South Korea reported two more H5N6 outbreaks, both at commercial duck farms in already-affected South Jeolla province. The new outbreaks began on Dec 28, with the virus killing 12 of 58,000 susceptible birds. The remaining ones were destroyed as part of the outbreak response. It's not clear if the strain is the new reassortant recently reported for the first time in South Korea, which has also been reported from a handful of other countries.

Also, Cambodia reported another H5N1 outbreak in village birds in Kampong Cham province. The event began on Dec 15 when the village's poultry owners started noticing high numbers of illnesses and deaths. The virus killed 189 of 342 birds, and the remaining ones were destroyed.
Jan 2 OIE report on H5N8 in Saudi Arabia
Dec 29 Avian Flu Diary post on H5N8 in Saudi Arabia
Dec 30 Avian Flu Diary post on H5N8 in Saudi Arabia
Dec 30 OIE report on H5N6 in South Korea
Dec 30 OIE report on H5N1 in Cambodia

In low-pathogenic avian flu developments, routine screening of ducks that were being readied for transport as part of the foie gras production process tested positive for low pathogenic H5N2, a strain that has been cropping up in the poultry production region since 2015.

In the latest outbreak, the virus was detected on Dec 19 at a farm in Landes department in the country's southwest. About 1,300 birds were destroyed to control the spread of the virus.
Dec 29 OIE report on low-path H5N2 in France

Study: Flu vaccine showed mixed protection during multi-strain season

Canada's 2011-12 flu season—mild with all strains circulating—offered researchers a unique opportunity to study the impact of the flu vaccine on severe illness in adults, and the findings revealed that it was highly effective against A strains and moderately effective against influenza B. A group of Canadian and GSK scientists, using a test-negative study design that examined adults ages 16 and older from a surveillance network who were hospitalized for possible flu infections, reported their findings in the Dec 29 issue of BMC Infectious Diseases.

During that flu season, a little more than half of all flu detections were influenza B, and about half of those were the lineage not included in the trivalent vaccine.

Overall, unadjusted and adjusted vaccine effectiveness (VE) against flu hospitalization was 41.8% and 42.8%, respectively. In younger adults, those ages 16 to 64, unadjusted and adjusted VE were lower at 35.8% and 33.2%. For all adults, adjusted VE against 2009 H1N1 was 72.5%, H3N2 was 86.1%, influenza B Victoria was 40.5%, and influenza B Yamagata was 32.3%. The adjusted early season VE was higher than the late-season estimate: 54.4%, compared to 29.7%, which they said could reflect higher influenza B activity typically seen later in the season.

The authors wrote that the findings highlight the need to look at VE by subtype in lineage, as well by timing during the season to more accurately gauge performance and guide public health decision-making.
Dec 29 BMC Infect Dis abstract