News Scan for May 18, 2018

News brief

US flu levels continue late-season drop as 3 more kids' deaths reported

US flu levels fell sharply again last week with the approach of summer, but the Centers for Disease Control and Prevention (CDC) recorded three more pediatric flu deaths, according to the latest weekly update posted today.

Flu was reported as widespread in only two states: Massachusetts and New York.

Most flu markers are well below baselines, with clinic visits for flulike illness falling to 1.2%. The CDC said flu has now been below the national baseline for the sixth consecutive week. Of respiratory specimens tested at clinical labs last week, only 3.9% were positive for flu, and influenza B made up about 71% of the detections. At public health labs, of subtyped influenza A samples, half were H3N2 and half 2009 H1N1.

Of the three newly reported pediatric flu deaths, one occurred in April involving 2009 H1N1, another was from influenza B and occurred last week, and the other was unsubtyped in a child who was sick in April. So far this season the CDC has reported 168 pediatric flu deaths.

The overall hospitalization rate last week was 106.6 per 100,000 population, about the same as the previous week. The highest level is still in seniors: 460.3 per 100,000 population.

In a separate weekly summary, the CDC said localized or sporadic flu activity may continue for a number of weeks and that it recommends prompt antiviral treatment for those who are at high risk for flu complications.
May 18 CDC FluView report
May 18 CDC situation update

First human study of MERS monoclonal antibody treatment set to launch

Federal health officials today announced the start of enrollment for the first human clinical trial to test the safety of two monoclonal antibody (mAb) treatments for Middle East respiratory syndrome coronavirus (MERS-CoV) infections.

In a press release, the National Institute of Allergy and Infectious Diseases (NIAID), the trial's sponsor, said the mAbs—REGN3048 and REGN3051—were discovered and developed by scientists at Regeneron, a biotechnology company headquartered in Tarrytown, N.Y. The trial is partly funded the Department of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA). Earlier studies in mice at Regeneron and the University of Maryland suggested the mAbs can neutralize MERS-CoV.

Anthony Fauci, MD, NIAID's director, said in the statement that currently there are no specific treatments for MERS-CoV. First detected in humans in 2012, the disease so far has caused 2,206 cases, 787 of them fatal, in 27 countries, mostly in Saudi Arabia. "Having targeted therapeutics available to treat this unpredictable and frequently fatal respiratory disease would help us reduce MERS-associated deaths and control future outbreaks," Fauci said.

Investigators will enroll 48 healthy adults ages 18 to 45 divided into six groups that will receive placebo or both mAbs intravenously. The first group will receive the lowest dosage, with successive groups receiving successively higher dosages. Decisions to continue and give higher dosages will be made by an independent safety review committee that will monitor safety and tolerability data before clearing the next group to receive the higher dose. The group expects to complete the study by June 2019.
May 18 NIAID press release

Researchers report novel poxvirus in wild mice in Texas

Wild mice in Texas have been found infected with a new poxvirus, researchers reported this week in Emerging Infectious Diseases.

Investigators with Texas A&M and the CDC report on the capture of an adult northern pygmy mouse in August of 2014 that had large (4- to 8-millimeter [mm]) lesions on its hind paws and tail but otherwise appeared healthy. Two years and 8 months later researchers captured a second adult northern pygmy mouse 100 miles north of the first mouse that had similar but smaller lesions (1 to 2 mm) on one hind paw and its tail. Both mice were found in east-central Texas.

Polymerase chain reaction testing of DNA from lesions on both mice revealed a poxvirus not reported before. The phylogenetic position of the virus revealed that it belonged to the Chordopoxvirinae family but diverged from other Chordopoxvirinae poxviruses by an average of 35%.

The authors conclude that the poxvirus "is distinct from previously identified viruses, with genetic distances similar to those observed between genera . . . the genetic data strongly suggest this poxvirus does not belong to any recognized genus as of March 2018."

In 2014 US researchers reported a different novel poxvirus in a girl from Tennessee and a woman from Missouri.
May 15 Emerg Infect Dis report
Oct 10, 2014, CIDRAP News scan on human cases

H5N1 avian flu strikes layer farm in Nepal

Nepal today reported a highly pathogenic H5N1 avian flu outbreak at a layer farm, its first involving the strain since March of 2017, according to a notification from the World Organization for Animal Health (OIE).

The outbreak began on May 3 at a farm in Chitwan district in the south central part of the country.

Farmers noticed symptoms and sudden deaths in 72-week-old layers about 2 weeks after deaths were noted in free-range domestic ducks. The report suggests the virus killed 1,500 layers over a 2-week period, and culling is slated for the surviving poultry.
May 18 OIE report on H5N1 in Nepal

ASP Scan (Weekly) for May 18, 2018

News brief

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

Special journal issue focuses on resistance and ways to tackle it

Originally published by CIDRAP News May 17

In a special issue of Science published today, four reviews highlight the different ways that organisms develop resistance to the chemicals used to combat them, and how scientists might be able to counteract that resistance. Two of the articles focus on antimicrobial resistance (AMR) and antifungal resistance.

In the review on AMR, molecular microbiologist Stephen Baker, PhD, and colleagues provide an overview of how bacterial pathogens have developed resistance to antibiotics in humans and animals, with a focus on the key role that whole-genome sequencing (WGS) has played in helping scientists better understand resistance mechanisms, pathogen evolution, population dynamics, and genomic epidemiology. While we cannot stop bacterial evolution, they note, genomics has revealed several repeating patterns in the emergence and spread of AMR bacteria that could help clinicians develop new strategies for controlling them and use current and future antibiotics more effectively.

In the article on antifungal resistance, an international team, led by researchers from Imperial College of London and the University of Exeter, explain how the overuse of existing antifungal agents in human and animal medicine and plant agriculture has hastened the independent development of resistance in many environments. As a result, opportunistic fungal pathogens have emerged in the field and in the clinic, highlighted by the emergence of Candida auris, a multidrug-resistant fungus that is responsible for rapidly increasing invasive infections in intensive care units around the world. The authors argue that in addition to more research on new antifungals, more robust strategies to slow the development of antifungal resistance are needed, along with alternative antifungal strategies.

"To counter the escalating risks of fungal disease, we need to discover antifungal chemicals with new modes of action, hinder the emergence of resistance in extant chemicals by better stewardship, and develop new disease control strategies to avoid overreliance on fungicides," they write.
May 17 Science article on AMR
May 17 Science article on antifungal resistance

US kids and adolescents using fewer antibiotics, study finds

Originally published by CIDRAP News May 17

Prescription antibiotic use in US children and adolescents was nearly cut in half from 1999 to 2014, according to a new study in the Journal of the American Medical Association.

In a study to evaluate trends in use of all prescription medications among children ages 0 to 19 years, researchers from the Centers for Disease Control and Prevention (CDC) found an overall decrease in use of any medication between 1999-2002 and 2011-2014. The results were based on responses of more than 38,000 children to the National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey designed to monitor the health and nutritional status of Americans.

While use of asthma medication, ADHD medication, and contraceptives increased among certain groups during the study period, use of antibiotics, antihistamines, and upper respiratory combination medications decreased. Overall antibiotic use in children and adolescents decreased from 8.4% to 4.5%, with specific reductions in cephalosporins, amoxicillin, and amoxicillin-clavulanate. Decreases were significant in all age groups except children aged 2 to 5 years.

The authors say the study adds nationally age-specific trends for common individual antibiotic classes and will inform CDC efforts to promote awareness of antibiotic resistance and the importance of appropriate antibiotic prescribing.
May 15 JAMA abstract

Trial finds 7 days of antibiotics for kidney infections non-inferior to 14 days

Originally published by CIDRAP News May 17

Researchers in India report that stopping effective non-fluoroquinolone (FQ) antibiotic treatment at day 7 is non-inferior to continued treatment until day 14 in patients hospitalized with severe kidney infection, according to a study yesterday in PLoS One.

From March 2015 through August 2016, the researchers randomly allocated 54 patients with acute pyelonephritis (APN) on day 7 of effective treatment with non-FQ antibiotics; 27 patients were randomized to truncated treatment and 27 to continued treatment to day 14. In all, 41 patients (76%) received amikacin-based treatment. The primary outcome was retreatment for recurrent urinary tract infection (UTI) up to 6 weeks after completion of antibiotic treatment, with a pre-specified non-inferiority margin of 15%. Secondary outcomes included duration of hospital stay, antibiotic consumption per patient, and the presence of asymptomatic bacteriuria at week 1 and week 6 after treatment.

During the 6-week follow-up period, no patient in the truncated treatment arm required retreatment, while one patient in continued treatment arm was retreated for recurrent UTI. The difference (90% CI) in retreatment between the trial arms was -3.7%, and the upper bound of the difference (6.15%) was well below the pre-specified non-inferiority margin. In addition, patients in the truncated treatment arm had significantly shorter hospital stays (8 vs. 14 days) and consumed fewer antibiotics (8.4 vs. 17.4 defined daily doses). There was no significant difference in the presence of asymptomatic bacteriuria between the two arms at 6 weeks.

"We found that truncating the effective non-FQ antibiotic treatment at Day 7 is good enough for hospitalized patients without features of severe urosepsis and underlying urogenital tract abnormalities," the authors write. "Such a strategy could substantially cut down antibiotic consumption and shorten hospital stays in these patients."
May 16 PLoS One study

CARB-X to fund rapid diagnostic test for UTIs

Originally published by CIDRAP News May 15

CARB-X is adding another diagnostic system to its growing portfolio of products targeting drug-resistant bacteria.

The Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator announced today that it will award MicrobeDx of Los Angeles $900,000 to support development of the company's rapid diagnostic system for bacterial urinary tract infections (UTIs). The company could receive an additional $2.6 million based on achievement of certain project milestones.

The technology uses a ribosomal RNA-based assay and desktop-based system to identify bacterial infections from a urine sample in 30 minutes and produce antibiotic susceptibility results within 3 hours. Current methods of diagnosing UTIs and determining the most appropriate antibiotic take 2 to 3 days.

"MicrobeDx's technology addresses a critical unmet need: rapid, accurate and cost-effective near-to-care testing that enables correct antibiotic therapy from the patient's first dose," MicrobeDX Chairman and CEO Bernard Churchill, MD, said in a CARB-X press release.

Since 2016, CARB-X has awarded more than $87 million to companies in the early-stage of developing new antibiotics, diagnostics, and other therapeutics for treating the most serious drug-resistant pathogens.
May 15 CARB-X press release

FDA clears rapid diagnostic test for urinary tract infections

Originally published by CIDRAP News May 14

The US Food and Drug Administration (FDA) has given BacterioScan, Inc. of St. Louis clearance to market its rapid automated diagnostic system, 216Dx, for detection of bacterial urinary tract infections (UTIs).

The system uses an advanced laser sensor to rapidly detect the formation and growth of bacterial colonies in urine within 3 hours. Manual culturing of urine samples for detection of bacteria typically takes more than 2 days to yield a result. Company officials say the quick turnaround time could help promote more judicious use of antibiotics.

"Faster detection of infection means better patient outcomes and diminishes over-prescription of antibiotics," BacterioScan President and CEO Dana Marshall said today in a company press release today. "Inappropriate and excessive antibiotic use promotes drug resistance, a serious and growing global health crisis."

The FDA issued 510(k) Premarket Notification clearance for BacterioScan 216Dx based on clinical studies of more than 3,000 patients, in which the system was able to correctly identify patients with bacterial infections with 98.6% sensitivity and correctly identify patients without bacterial infections with 99.6% specificity. The company said that level of performance matches or exceeds the current standard of care in US hospitals.

Globally, over 150 million UTIs are estimated to occur annually. They are caused by a wide range of gram-negative and gram-positive bacteria and fungi, with uropathogenic Escherichia coli being the most common causative agent in complicated and uncomplicated infections.

The company said it's also working on antimicrobial susceptibility tests and infection detection tests for other human fluids.
May 14 BacterioScan press release

Antibiotics found to be most common cause of surgery-related anaphylaxis

Originally published by CIDRAP News May 14

In the largest prospective (longitudinal) study to date, UK anesthesiologists reported yesterday that antibiotics are the most common cause of life-threatening anaphylaxis related to anesthesia and surgery, with teicoplanin spotlighted as a drug of special concern.

Scientists with the Royal College of Anaesthetists (RCoA) published the sixth National Audit Project (NAP6) report, which includes 3 years of data and involved identifying and investigating every case of life-threatening anaphylaxis that occurred in National Health Service hospitals during 1 year, reported by 3 million anesthesiologists (anesthetists). Anaphylaxis is an especially serious allergic reaction.

Antibiotics were identified as an anaphylactic trigger in 47% of cases, followed by muscle relaxants (33%), chlorhexidine (9%), and patent blue dye (5%), used in some breast surgeries. Antibiotics were given to more than half of the surgical patients to prevent infection. The findings are a bit of a surprise, as previous studies found the main culprit to be muscle relaxants, according to an RCoA news release. The authors of the report suggest that anaphylaxis caused by antibiotics may be increasing because of wider use and sensitization in the population.

In addition, the authors indicate that some antibiotic anaphylactic reactions, including deaths, could have been prevented. Teicoplanin was found to be 17 times more likely to cause anaphylaxis than other antibiotics. Teicoplanin, which is not approved for US use but is frequently prescribed throughout Europe, is regularly used for UK patients who report an allergy to penicillin. But 90% of patients who report penicillin allergy are in fact not allergic, the authors noted.

While 96% of patients survived their anaphylactic reactions, 40 had a cardiac arrest and 10 died. Report author Professor Tim Cook said, "More than 95 per cent of patients survive life-threatening anaphylaxis because of timely detection and prompt action by their anaesthetist and the wider medical team. However, our research highlights the importance of this topic and shows evidence of new and growing risk factors."
May 13 RCoA news release
May 13 full NAP6 report

Treating methicillin-susceptible Staph aureus may cost more than MRSA

Originally published by CIDRAP News May 14

A new study in Clinical Infectious Diseases has attributed a higher healthcare cost to methicillin-susceptible Staphylococcus aureus (MSSA) than to methicillin-resistant S aureus (MRSA).

Researchers led by experts from the Center for Disease Dynamics, Economics & Policy in Washington, D.C., analyzed data from 2010 through 2014 from the National Inpatient Sample from the US Agency for Healthcare Research and Quality.

They found that, in 2014, adjusted costs were significantly higher for MSSA-related pneumonia than for MRSA-related pneumonia ($40,725 average vs. $38,561) and for other MSSA-related hospitalizations compared with MRSA-related hospitalizations ($15,578 vs. $14,792). "Similar patterns were observed from 2010 to 2013," the investigators wrote, "though crude cost differences between MSSA- and MRSA-related pneumonia hospitalizations rose from 25.8% in 2010 to 31.0% in 2014." MRSA-related hospitalizations, however, had a higher adjusted death rate.

The authors conclude, "Though MRSA infections had been previously associated with higher hospitalization costs, our results suggest that in recent years, costs associated with MSSA-related infections have converged with and may surpass costs of similar MRSA-related hospitalizations."
May 12 Clin Infect Dis abstract