Stewardship / Resistance Scan for May 17, 2018

News brief

Special journal issue focuses on resistance and ways to tackle it

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

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

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

News Scan for May 17, 2018

News brief

E coli outbreak grows to 172 cases but romaine OK to eat, US officials say

Federal officials have added 23 cases and three newly affected states to a multistate outbreak of Escherichia coli cases linked to romaine lettuce and gave what amounts to an all-clear to resume eating the lettuce, according to updates yesterday.

New outbreak totals are 172 cases in 32 states, 75 hospitalizations, and 1 death, the Centers for Disease Control and Prevention (CDC) said in an update. Twenty patients developed hemolytic uremic syndrome, a type of kidney failure, which is 3 more cases than reported in the CDC's previous update on May 9.

The newly affected states are Iowa, Nebraska, and Oregon. California has logged the most cases, at 39, followed by Pennsylvania (21), Minnesota (12), and Idaho (11).

Patients range in age from 1 to 88 years, with a median age of 29. Illness-onset dates range from Mar 13 to May 2. The implicated lettuce was grown in the Yuma, Ariz., growing region.

The Food and Drug Administration (FDA) said in its update, "The FDA has received confirmation from the Arizona Leafy Greens Marketing Agreement administered by the Arizona Department of Agriculture that romaine lettuce is no longer being produced and distributed from the Yuma growing region and that the last date of harvest was April 16, 2018. It is unlikely that any romaine lettuce from the Yuma growing region is still available in stores or restaurants due to its 21-day shelf life."

The CDC said, "This investigation is ongoing, and CDC will provide updates when more information is available."
May 16 CDC update
May 16 FDA update

FDA to exempt certain N95 respirators from premarket requirements

Effective today, the FDA is exempting certain N95 respirators—facemasks that are used in disease settings, including epidemics and pandemics, to protect both the patient and healthcare provider from airborne pathogens—from premarket requirements, the agency said in a statement yesterday.

The FDA and the CDC's National Institute for Occupational Safety and Health (NIOSH) share regulatory oversight of N95 respirators. In final order published today in the Federal Register, the FDA exempted the N95s from premarket notification (510[k]) requirements, and executed a Memorandum of Understanding (MOU) with NIOSH.

The FDA said, "The final order and MOU streamline the regulation of N95s to help manufacturers easily identify, understand, and work to meet marketing requirements, and help ensure the availability of safe and effective medical products, particularly during times of increased demand, such as a public health emergency. This final action will also decrease regulatory burden on the medical device industry and will eliminate costs required to comply with certain Federal regulations."

NIOSH will first evaluate manufacturers' applications to see if they pass the criteria for exemption. It will consider several factors, including whether a specific N95 has had a history of misleading claims or risks, characteristics that might make it unsafe, and any changes in the device that could affect safety or effectiveness.
May 16 FDA statement
May 17 Federal Register notice
FDA-NIOSH Memorandum of Understanding

CDC: Ball python Salmonella cluster sickened people in 4 states

Though the tame nature and smaller size of ball pythons make them popular pets, the snakes can harbor multiple Salmonella strains, the CDC warned today, based on a recent investigation into a cluster of five closely related isolates identified though PulseNet, the national subtyping network.

In July 2017, the network identified five matching Salmonella Paratyphi B variant L (+) tartrate + (Java) clinical isolates from four states, researchers noted in a report in Morbidity and Mortality Weekly Report (MMWR). Two unrelated patients were from Indiana, with Arizona, Oklahoma, and Oregon each reporting a single case. Investigations by state and local health department found that all five patients had been exposed to snakes, with four having ball pythons in their homes.

Sampling at the Arizona patient's house found the outbreak strain in a ball python bedding sample, along with another Salmonella strain from a feeder rodent and the snake. Environmental sampling in Oregon turned up yet another Salmonella strain, and testing at the National Veterinary Services Laboratory identified three Salmonella Paratyphi B variant L (+) tartrate + (Java) isolates from other pythons in 2017.

Whole-genome sequencing of the human isolates found that only the two Indiana patient samples were related, though ball python bedding samples matched the Arizona patient's samples and the Indiana ball python and environmental samples were closely related to both patient samples.

The CDC said that, as with other reptiles, ball pythons are known to carry Salmonella, a fact that has driven its warning that children younger than 5 should avoid contact with the animals. The report's authors noted, however, that the median age in the ball python cluster was 10 years, suggesting that older children are also at risk of illness.
May 18 MMWR report

Type 3 poliovirus samples detected in Mogadishu, Somalia

Health officials in Somalia confirmed the detection of vaccine-derived poliovirus type 3 in four environmental samples collected from two sites near Mogadishu, Somalia, in March. The World Health Organization (WHO) today released a notification on the detection, updating information on the Horn of Africa.

Earlier this year, Somalia reported the detection of vaccine-derived poliovirus type 2 in environmental samples from Mogadishu and Nairobi, Kenya, but no acute flaccid paralysis cases linked to these virus types have been reported.

The WHO said countries in the region are upping surveillance and vaccination efforts in the wake of the detections.

"In Somalia, three large-scale supplementary immunization activities (SIAs) have been implemented in Banadir, Lower Shabelle and Middle Shabelle regions; additional SIAs are planned other affected areas in the Horn of Africa in May," the WHO said. "Intensified surveillance activities are being undertaken to determine the origin of the viral circulation."
May 17 WHO notice