Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

WHO panel offers list of drug-resistant priority pathogens

A World Health Organization (WHO) working group has created a list of priority pathogens for developing new antibiotics, with multidrug-resistant tuberculosis (MDR-TB) and resistant gram-negative bacteria at the top, as well as certain species of Salmonella and Campylobacter, Neisseria gonorrheae (which causes gonorrhea), and Helicobacter pylori.

Detailing its findings in The Lancet Infectious Diseases yesterday, the WHO Pathogens Priority List Working Group used a multicriteria decision analysis method to select 20 antimicrobial-resistant bacteria. The experts then applied 10 criteria to assess priority: mortality, healthcare burden, community burden, prevalence of resistance, 10-year resistance trends, transmissibility, preventability in the community, preventability in healthcare settings, treatability, and drug pipeline. They categorized the bacteria into critical-, high-, and medium-priority groups.

The experts listed as a top priority in their own category MDR-TB and extensively drug-resistant TB. Critical-priority bacteria were carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae.

Vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus (MRSA) were the highest-ranked gram-positive bacteria. Among bacteria typically responsible for community-acquired infections, the group also included in the high-priority list clarithromycin-resistant H pylori and fluoroquinolone-resistant Campylobacter, N gonorrheae, and Salmonella.

In a commentary in the same issue, Glenn Tillotson, senior vice president of medical affairs with Cempra Pharmaceuticals in Chapel Hill, N.C., said, "The statistical approach used by Tacconelli and colleagues to establish the list of antibiotic-resistant bacteria was of the highest standard, with multiple experts enlisted to provide input into a complex process. A factor that stood out was the use of six WHO regions to support the overall process."

He notes that this is the fourth such list produced in the past 5 years, with previous efforts from the US Centers for Disease Control and Prevention, the Longitude Prize team, and the government of Canada.
Dec 21 Lancet Infect Dis report
Dec 21 Lancet Infect Dis commentary

Study finds long-term success for fecal transplant to treat C difficile

Originally published by CIDRAP News Dec 20

A study yesterday in Clinical Infectious Diseases reports high long-term success rates of fecal microbiota transplant (FMT) against recurrent Clostridium difficile infection (CDI).

Emory University researchers contacted all eligible patients who received FMT for recurrent CDI from Jul 1, 2012, to Dec 31, 2016. Of 190 eligible patients, 137 (72%) completed the telephone survey.

The survey found that 113 of 137 patients (82%) had no C difficile recurrence after a median follow-up of 22 months. Almost all patients (122 of 128, or 95%) said they would undergo FMT again, and 70% of those 122 said they would prefer FMT to antibiotics as initial treatment if they were to have a CDI recurrence.
Dec 19 Clin Infect Dis study

Pulsed-dose fidaxomicin determined superior to vancomycin for C diff

Originally published by CIDRAP News Dec 20

A multicenter European study has found extended pulsed dosing of fidaxomicin to be superior to standard-dose vancomycin for the sustained cure of CDI, according the a report yesterday in The Lancet Infectious Diseases.

In the trial, known by the acronym EXTEND, researchers enrolled 364 patients from 96 European hospitals, half of whom received extended-pulse fidaxomicin (200-milligram [mg] oral tablets twice daily for 5 days, then once every other day on days 7 through 25) and half of whom were prescribed vancomycin (125-mg oral capsules four times daily for 10 days).

In the fidaxomicin group, 124 of 177 patients (70%) were still cured 30 days after their treatment ended, compared with 106 of 179 patients (59%) who received vancomycin. The rate of adverse events did not differ between the two groups.

In a commentary on the study in the same issue, US medical researcher Dale N. Gerding, MD, said the study holds promise but requires "more sophistication" in its application. He says the exact dosing of fidaxomicin for CDI still needs fine-tuning, and its cost is steep. In addition, he writes, "Adjunctive measures such as monoclonal antibodies and faecal microbiota transplants are also available to reduce the incidence of recurrent C difficile infection."

The study was funded by Astellas Pharma, Inc, of Japan, which is licensed to develop and market fidaxomicin in various parts of the world, including Europe.
Dec 19 Lancet Infect Dis study
Dec 19 Lancet Infect Dis commentary

Study shows direct sexual transmission of drug-resistant gonorrhea

Originally published by CIDRAP News Dec 19

Australian researchers have found that transmission of antibiotic-resistant strains between sexual partners is a key driver of resistance rates in gonorrhea among men who have sex with men (MSM), according to a new study in Sexually Transmitted Infections.

Increasing resistance to the last remaining treatment for Neisseria gonorrhea has become a major global health problem, and transmission of drug-resistant gonorrhea strains has repeatedly been linked to MSM. But direct evidence of such transmission is limited. To investigate the role of direct transmission in MSM, investigators with the University of Melbourne used whole-genome sequencing (WGS) to compare isolates and their resistance to antibiotics at a genome level.

The study included 458 male couples who were tested for gonorrhea at the Melbourne Sexual Health Centre on the same day from September 2005 to September 2014. WGS was conducted on all isolates (94) from 34 couples (68 men) where both men had N gonorrhea cultured from at least one site. All but two isolates (98%) were resistant to penicillin, six (7%) showed decreased susceptibility to ceftriaxone, 41 (45%) were resistant to ciprofloxacin, and 7 (8%) were tetracycline resistant.

WGS showed that the resistance-determining genes and mutations were identical in isolates from each partner in 33 out of 34 couples (97%). In addition, resistance determinants in isolates from 23 of 23 men (100%) with multisite infections were identical within an individual. Other molecular typing methods also indicated that the partner and within-host isolates were indistinguishable.

"To our knowledge, our study is the first to provide detailed genomic evidence for direct transmission of the genetic determinants for N. gonorrhoeae resistance between men across multiple antibiotic classes at a person-to-person level," the authors write, adding that the improved understanding of transmission dynamics will inform treatment and prevention guidelines. They note that the findings may not extend to gonorrhea in heterosexuals.
Dec 15 Sex Transm Infect study

More Candida auris infections recorded in US

Originally published by CIDRAP News Dec 18

According to an updated case count from the Centers for Disease Control and Prevention (CDC), there are now 174 cases of Candida auris infections in the United States, 17 more than the CDC reported last month.

As of Nov 30, the multidrug-resistant (MDR) fungus has been identified in healthcare facilities in 10 states, with New York (110), New Jersey (38), and Illinois (12) all reporting new cases since the last update. Cases have also been reported in California (1), Connecticut (1), Florida (2), Indiana (1), Maryland (2), Massachusetts (6), and Oklahoma (1).

"U.S. C. auris cases are a result of inadvertent introduction into the United States from a patient who recently received healthcare in a country where C. auris has been reported or a result of local spread after such an introduction," the CDC explained.

All cases represent laboratory-confirmed C auris infections, and the CDC said 257 other patients have been colonized with C auris detected through targeted screening in four states with clinical cases.

In patients with compromised immune systems, C auris can cause serious invasive infections affecting the bloodstream, heart, brain, ear, and bones.
Dec 15 CDC update

Wendy's to reduce antibiotic use in beef supply

Originally published by CIDRAP News Dec 18

Fast-food chain Wendy's says it will take steps to reduce the use of antibiotics in its beef supply, according to a company press release.

In its annual update on corporate social responsibility initiatives, Wendy's said that starting in 2018, it will source about 15% of its beef from a group of producers that have each committed to a 20% reduction in the amount of the one medically important antibiotic routinely fed to their cattle. According to Reuters, that antibiotic is Tylosin, a broad-spectrum macrolide. The company said it's committed to increasing the amount of beef purchased from these producers.

The company also announced that it has eliminated all medically important antibiotics from chicken production, fulfilling a pledge it made last year, and that it plans to decrease the use of antibiotics in its pork supply.

Wendy's is one of several major fast-food and fast-casual restaurant chains that have committed to removing medically important antibiotics from their poultry supply in recent years, in response to growing consumer demand for antibiotic-free chicken. The movement to reduce the use of medically important antibiotics in the beef and pork supplied to these chains has been slower to develop.

Earlier this month, data released by the US Food and Drug Administration showed that the amount of medically important antibiotics sold for use in livestock and poultry fell by 14% from 2015 to 2016, the first decline since the agency began collecting the data in 2009.
Dec 15 Wendy's press release
Dec 15 Reuters story

Study finds high rate of hospital readmission for MDRO-infected patients

Originally published by CIDRAP News Dec 18

A single-center study published yesterday in Infection Control and Hospital Epidemiology found that over a 10-year period, more than 60% of patients with multidrug-resistant organisms (MDROs) were readmitted to the hospital within a year of the initial infection.

The purpose of the retrospective study, conducted at a 1,250-bed academic tertiary referral center in St. Louis, MO, was to determine incidence of and risk factors for readmission with MDROs among patients with previous MDRO infection. Investigators from Washington University School of Medicine identified patients with MDROs obtained from the bloodstream, bronchoalalveolar lavage (BAL)/bronchial wash, or other sterile sites from January 2006 to October 2015. They then evaluated all readmissions less than a year from the index hospitalization for bloodstream, BAL/bronchial wash, or other sterile sites positive for the same or different MDROs.

Of the 4,429 patients with a positive culture for an MDRO, 2,127 (61.6%) were readmitted more than once within a year, and 512 patients (24.1%) had the same or a different MDRO isolated from blood, BAL/bronchial wash, or another sterile site during readmission. Bone marrow transplant, end-stage renal disease, lymphoma, methicillin-resistant Staphylococcus aureus, or carbapenem-resistant Pseudomonas aeruginosa during index hospitalization were factors associated with increased risk of an MDRO isolated during a readmission. MDROs isolated during readmissions were in the same class of MDRO as the index hospitalization 9% to 78% of the time, with variation by index pathogen.
Dec 17 Infect Control Hosp Epidemiol abstract

Romaine-linked E coli outbreak sickens 10 more in eastern Canada

The Public Health Agency of Canada (PHAC) is advising people in five eastern provinces to avoid eating romaine lettuce because of an ongoing Escherichia coli outbreak associated with that type of salad greens. In a statement yesterday, the PHAC said continued reports of illnesses suggest that contaminated romaine lettuce may still be on the market.

Since the PHAC's previous update on Dec 14, 10 more illness have been reported, raising the outbreak total to 40. Illnesses have been reported in Ontario, Quebec, New Brunswick, Nova Scotia, and Newfoundland and Labrador. Sixteen people have been hospitalized, and one death has been reported

Most of the sick people reported eating romaine lettuce before their symptoms began, at home, in prepared salads from grocery stores, and in restaurants, including fast-food chains. The Canadian Food Inspection Agency is working with public health officials to determine the source of the outbreak, and so far there's no evidence that western Canada is affected.
Dec 21 PHAC update

WHO warns of Salmonella threat from globally distributed baby formula

A Salmonella Agona outbreak that has sickened 35 infants in France has prompted a French infant formula maker to a recall of products exported to 48 countries, including some in Africa, Asia, the Middle East, and the French overseas territories, the World Health Organization (WHO) announced today.

In France, 16 infants have been hospitalized but all have fully recovered. No deaths have been reported.

Earlier this month, the company, Lactalis Nutrition Sante, recalled 600 batches of four different brands, but yesterday it expanded the recall to include all infant and nutritional produces made or packaged at its Craon plant since Feb 15, 2017.

The WHO said affected products pose a serious illness risk to infants, and French authorities are investigating the outbreak source. It said an international food safety network is coordinating the alert to countries outside of the European Union.

The WHO warned that similar outbreaks have occurred before and that powdered infant formulas are not sterile products, given that Salmonella is prevalent in raw ingredients and can survive under harsh, dry conditions for a lengthy period. Preparing formula with tepid water can allow rapid growth from initially low levels of Salmonella contamination. French authorities have posted information on formula substitutions and how to prepare formula in a way that inactivates Salmonella.
Dec 22 WHO statement