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

More than 1 in 3 urinary infections in nursing homes caused by resistant bacteria

An analysis of urinary tract infections (UTIs) in US nursing homes found that more than one in three were caused by antibiotic-resistant pathogens, researchers reported in Infection Control & Hospital Epidemiology.

In the study, researchers from the Centers for Disease Control and Prevention (CDC) Division of Healthcare Quality and Promotion analyzed data on UTI-causative pathogens and antibiotic susceptibility testing results reported to the National Healthcare Safety Network (NHSN) by US nursing homes. All nursing homes that reported at least 1 complete month of UTI surveillance data were included. The data have been reported to NHSN since 2012, but this is the first time they have been analyzed.

Overall, 243 nursing homes from 46 states reported at least 1 month of UTI surveillance data from January 2013 through December 2017. In total, 6,157 pathogens were reported from 5,485 UTIs, with 9 pathogens accounting for 90% of all UTIs.

The three most frequently identified pathogens were Escherichia coli (41%), Proteus species (14%), and Klebsiella pneumoniae/oxytoca (13%). Among E coli, fluoroquinolone resistance (49.9%) and extended-spectrum cephalosporin resistance were the most prevalent. Staphylococcus aureus (67.1% resistant to methicillin) and Enterococcus faecium (59.5% resistant to vancomycin) had the highest levels of resistance but accounted for less than 5% of pathogens reported.

Of the 5,485 UTIs reported, 36% were associated with a resistant pathogen.

"The levels of antibiotic resistance observed demonstrate the importance of monitoring nursing homes and implementing nursing-home specific antibiotic stewardship activities," the authors wrote.
Aug 12 Infect Control Hosp Epidemiol abstract

Israeli study finds high antibiotic use for asymptomatic bacteriuria

In another study in Infection Control & Hospital Epidemiology, Israel researchers reported a high rate of improper antibiotic use and a high rate of multidrug-resistant organisms (MDROs) in patients with asymptomatic bacteriuria (ASB), along with significantly worse outcomes in patients who received antibiotics.

The retrospective case-control and cohort analysis looked at adults patients at an Israeli tertiary medical center with a positive urine culture, defined as the growth of one or two pathogens in a single sample. Pregnant women, kidney transplant recipients, and patients who underwent urologic procedures were excluded.

The researchers constructed multivariable logistics regression models to analyze predictors and outcomes associated with antibiotic use in ASB patients. Despite efforts to reduce the practice, treatment of ASB—defined as the isolation of bacteria in an uncontaminated urine specimen in the absence of UTI symptoms—is prevalent across healthcare settings and frequently leads to inappropriate antibiotic prescribing.

Of the 1,530 patient-unique cultures collected in 2017, 610 (40%) had ASB, and antibiotic therapy was administered to 178 (29.2%) of those patients. Among the 696 pathogens isolated from the patients, 36% had at least one MDRO, most commonly extended-spectrum beta-lactamase–producing Enterobacteriaceae (23%) or Pseudomonas aeruginosa (5.4%).

Independent predictors of improper administration of antibiotics were dependent functional status (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.4 to 3.6) and male sex (aOR, 2.0; 95% CI, 1.25 to 2.6). Use of antibiotics was independently associated with re-hospitalization (aOR, 1.7; 95% CI, 1.1 to 2.6) and acute Clostridioides difficile infections in the following days (aOR, 4.5; 95% CI, 2 to 10.6).

"These findings should prompt practitioners and administrators to invest efforts in reducing antibiotic administration for ASB and to discourage the practice of obtaining urine cultures from certain high-risk groups with no signs or symptoms of UTI," the authors concluded.
Aug 13 Infect Control Hosp Epidemiol abstract

Unnecessary prescribing by Canadian physicians linked to antibiotic volume

Total antibiotic use among a cohort of family physicians in Ontario, Canada, was strongly correlated with unnecessary antibiotic prescribing, Canadian researchers reported earlier this week in Clinical Infectious Diseases.

To study the association between total and unnecessary antibiotic use among family physicians in Ontario, the researchers looked at 5 years of electronic medical records from a database that collects data from a sample of Ontario physicians.

They used predefined expected antibiotic prescribing rates for 23 common primary care conditions to calculate unnecessary prescribing rates and multilevel Poisson regression models to evaluate the association between total antibiotic volume, adjusted for multiple practice- and physician-level covariates, and unnecessary prescribing.

Over the study period, there were 499,570 patient encounters and 152,853 encounters that resulted in one or two antibiotic prescriptions. Substantial inter-physician variability in unnecessary prescribing was observed, but in the fully adjusted model, the only covariate that could explain the inter-physician variability was total antibiotic volume (adjusted rate ratio, 2.11; 95% CI, 2.05 to 2.17). No other practice- or physician-level variables were associated with unnecessary prescribing.

The authors of the study say the results strongly support community antibiotic stewardship teams using total antibiotic volume as a surrogate for unnecessary prescribing and a basis for providing feedback to family physicians.
Aug 12 Clin Infect Dis abstract

UK, South African scientists to collaborate on antibiotic discovery

Scientists in the United Kingdom and South Africa yesterday announced a collaborative effort to establish a hub for new antibiotic discovery.

The three-year, £1.9 million (US $2.5 million) project, led by the University of Plymouth in the United Kingdom and Rhodes University in South Africa, aims to discover novel compounds from natural sources that could be developed into new antibiotics. The focus of the effort will be on unexplored, biodiverse habitats, including deep sea and polar environments.

Among the initial projects will be an exploration of the diversity of antimicrobial peptides in South Africa.

"Natural products and their synthetic analogues are the basis for the majority of antibiotics in clinical use today, and the hope is that this collaboration will go some way towards unlocking the potential resources contained in marine and terrestrial biota in South Africa, one of the world's most biodiverse places," Mat Upton, PhD, a professor in medical microbiology at the University of Plymouth and project leader, said in a university press release.
Aug 13 University of Plymouth press release 

MDR-TB cases at Ohio food processing facility investigated

Originally published by CIDRAP News Aug 13

A case report today in the Centers for Disease Control and Prevention's (CDC's) Morbidity and Mortality Weekly Report describes three cases of multidrug-resistant tuberculosis (MDR-TB) among workers at an Ohio food-processing facility.

Investigation into the three cases by the CDC and Ohio Department of Health (ODH) began in February 2019 after whole-genome sequencing revealed that MDR-TB isolates from the three patients were genetically identical. The index patient was born in one of the 30 countries identified by the World Health Organization as having a high prevalence of MDR-TB. According to the available work schedules, the second and third patients had worked for at least 54 days and 7 days, respectively, on the same food production line as the index patient. The third patient also worked in a second facility, but that facility had closed by the time of the investigation.

All three patients recovered, and no other cases of MDR-TB related to the patients were identified, but testing of 160 high-priority workplace contacts (out of 448) found that 59 (37%) had positive results on tuberculin skin tests or interferon-y release assay tests, both of which test for TB infection. That's higher than the estimated percentage of non–US-born people in the United States who have a positive tuberculin skin test (21%) or a positive interferon-y assay result (16%) and is an indication of workplace transmission, the investigators concluded. Among those with positive results, 19 (32%) began latent TB treatment.

The authors say the low level of TB testing and treatment for infection among contacts is a concern, and is likely related to difficulties in communication, perceived barriers to care, and mistrust of government authorities.

They write, "Public health agencies need to facilitate engagement with communities with higher rates of TB to build trust, which is important for successful disease investigations. Activities might include communicating in a culturally sensitive manner with community members, offering patients incentives for getting tested or treated, providing transportation to clinics, using mobile clinics, and conducting communitywide education efforts."

ODH is continuing to work with local partners to facilitate TB testing and latent TB treatment for contacts and monitor for new cases.
Aug 13 MMWR Notes from the Field

CARB-X to fund development of new class of broad-spectrum antibiotics

Originally published by CIDRAP News Aug 12

CARB-X announced today that it is awarding $2.91 million to German drug developer Evotec SE to develop a new class of antibiotics to treat infections caused by multidrug-resistant bacteria.

Under the terms of the agreement, Evotec will in-license an antibiotics development program from US biotechnology company Resolute Therapeutics, and continue preclinical development using its proprietary drug discovery and development programs. The goal of the partnership is to develop a novel class of broad-spectrum antibiotics that cover gram-negative and gram-positive pathogens.

Evotec will be eligible for an additional $5.5 million in funding from CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) if certain project milestones are met.

"New antibiotics are urgently needed, particularly those that hold significant promise to overcome antimicrobial resistance," Evotec chief scientific officer Cord Dohrmann said in a CARB-X press release.

Since its launch in 2016, CARB-X has awarded $250 million to 67 projects targeting drug-resistant bacteria.
Aug 11 CARB-X press release

Study: High antibiotic prescribing linked to patients' future receipt of antibiotics

Originally published by CIDRAP News Aug 12

Patients who were treated by a high–antibiotic prescribing physician for an acute respiratory infection (ARI) were more likely to receive antibiotics for an ARI in the subsequent year, according to the results of a study published yesterday in Clinical Infectious Diseases.

In the study, a team led by researchers from Harvard Medical School examined encounter data from a US health insurer, looking specifically for patients under the age of 65 with a visit to an urgent care center for an ARI from January 2013 through Jun 10, 2016 and a prescription for an antibiotic filled the day before, the day of, or the 2 days after the visit. They then categorized clinicians within each urgent care center into quartiles based on their antibiotic prescribing rate and examined the association between the clinicians' antibiotic rate during the index visit and the patients' rate of ARI antibiotic receipt in the subsequent year. They also examined subsequent ARI antibiotic receipt among patients' spouses.

The hypothesis was that patients who saw high-prescribing doctors might be more likely to seek care for ARIs and receive an antibiotic in the subsequent year and that their spouses might be as well.

Across 232,256 visits at 736 urgent care centers, ARI antibiotic prescribing rates were 42.1% in the lowest quartile of clinicians and 80.2% in the highest quartile of clinicians. In the year after the index ARI visit, patients who saw the highest-prescribing clinicians received 3 more antibiotic fills per 100 people, or 14.6% more antibiotic fills, over the subsequent year compared with those who saw the lowest prescribers. The increase was also observed among the patients' spouses. The increase was largely driven by the increased number of ARI visits (+ 5.6 ARI visits per 100 patients) among patients who saw high-prescribing clinicians, rather than a higher prescribing rate during those subsequent visits.

"Our results emphasize the importance of how care in one encounter drives a patient to seek care for subsequent ARIs," the authors of the study wrote. "A reduction in antibiotic prescribing may create a feedback loop such that more judicious antibiotic use in one encounter may result in fewer future antibiotics. Thus, an additional benefit of greater antibiotic stewardship is the establishment of new norms for patients on when antibiotics are needed."
Aug 10 Clin Infect Dis abstract

ICD-10 codes for common COVID-19 symptoms inaccurate, study finds

Standard, symptom-specific international disease codes lack sensitivity and have poor negative predictive value (NPV) for characteristic COVID-19 symptoms, which could skew conclusions derived from them, a cohort study published today in JAMA Network Open shows.

Researchers compared the performance of International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for fever, cough, and shortness of breath with the electronic medical records (EMRs) of 2,201 patients tested for COVID-19 infection at University of Utah Health from Mar 10 to Apr 6. ICD-10 codes are often used for data aggregation and analysis.

Medical records showed that 1,444 of the 2,201 patients (66%) had fever, while 1,930 (88%) had cough, and 1,399 (64%) had shortness of breath.

The sensitivity (ability to identify those with a condition) of ICD-10 codes for fever was 26%, specificity (ability to identify those without a condition) was 98%, positive predictive value (PPV) (likelihood that those who test positive for a disease truly have it) was 96%, and NPV (likelihood that those who test negatively truly don't have a disease) was 41%. In general, the higher the percentage for these tests, the more reliable they are, with 90% or higher considered a good score.

Sensitivity for cough was 44%, specificity was 88%, PPV was 96%, and NPV was 18%. For shortness of breath, sensitivity was 24%, specificity was 97%, PPV was 93%, and NPV was 42%. ICD-10 performance was better for hospitalized patients than for those in the outpatient setting for fever and shortness of breath but not cough.

The authors called for "meticulous data validation to feed multicenter registries built from EMRs" to generate accurate, reliable research results.

"Our findings highlight the importance of quality control in COVID-19 data aggregation, which has become increasingly important with recent high-profile journal retractions," they wrote. "As with many aspects of this pandemic, we must pay careful attention to socioeconomically vulnerable populations, including racial minorities, rural patients, and low-income patients, for whom the gap between ICD-10 coding and clinical reality could be greater."
Aug 14 JAMA Netw Open study

Review of 11,000 COVID-19 pregnancies shows generally good outcomes

A study reviewing 11,308 published cases of COVID-19 in pregnancy showed that outcomes were generally favorable, though 21% of cases that included such information showed severe or critical outcomes. The study was published yesterday in Open Forum Infectious Diseases.

Overall, mortality rates were reassuring, and neonatal disease was rare: Only 41 possible cases of neonatal infection were reported in the literature, the authors said. Ninety-eight percent of women (10,437 of 10,597) survived to delivery or hospital discharge, and 33 maternal deaths were noted.

The authors found that pregnant women were also routinely excluded from ongoing clinical trials of COVID-19 treatments. Pregnancy was an exclusion criterion for 69% (75/109) of chloroquine/hydroxychloroquine studies, 80% (28/35) of lopinavir/ritonavir trials, and 48% (44/91) of convalescent plasma studies.

"The large number of clinical trials excluding pregnant persons, despite interventions with safety data in pregnancy, is concerning," the authors concluded. "In addition to observational cohort studies, pregnancy specific adaptive clinical trials could be designed to identify safe and effective treatments."
Aug 13 Open Forum Infect Dis study

China's top COVID-19 vaccine safe, triggers antibodies in phase 1/2 trials

Early data from phase 1 and 2 clinical trials of China's leading COVID-19 vaccine candidate suggest that it is safe and triggers development of antibodies against the novel coronavirus, according to a study published yesterday in JAMA.

In the phase 1 trial, 96 healthy adults 18 to 59 years old in Henan province, China, received either a 2.5-, 5-, or 10-microgram (µg) dose of the inactivated vaccine, which contains the immune-boosting adjuvant alum, or adjuvant only on days 0, 28, and 56. In the phase 2 trial, 224 participants received either 5 µg of the vaccine or adjuvant only on either days 0 and 14 or 0 and 21.

The vaccine triggered production of neutralizing antibodies 14 days after booster vaccination. In the phase 1 trial, adverse reactions in the first 7 days after vaccination in 3 participants (12.5%)  in the adjuvant-only group, 5 (20.8%) in the low-dose vaccine group, 4 (16.7%) in the medium-dose vaccine group, and 6 (25.0%) in the high-dose vaccine group.

In the phase 2 trial, among participants in the group vaccinated on days 0 and 14, 5 participants (6.0%) experienced adverse effects, while 4 (14.3%) in the group that received adjuvant only did so. Among of the group vaccinated at 0 and 21 days, 16 (19%) had adverse effects, while 5 (17%) in the adjuvant-only group did so. The most common adverse events were mild pain at the injection site and fever. No serious adverse events were observed.

Final results from the ongoing trials and a planned phase 3 trial are needed to interpret the magnitude of antibody response and determine the durability of immune response response, long-term safety profile, and whether it can protect against COVID-19, the authors noted.

The vaccine was developed by the China National Biotec Group and the Wuhan Institute of Biological Products, which also sponsored the study.
Aug 13 JAMA study

With 2 new cases, DRC Ebola outbreak grows to 86, with 36 deaths

Tests confirmed 2 more Ebola infections in the Democratic Republic of the Congo (DRC) Equateur province outbreak, raising the total to 86, the World Health Organization (WHO) African regional office said today on Twitter.

No new deaths were reported, keeping the total at 36.

At a WHO media briefing on COVID-19 yesterday, WHO Director-General Tedros Adhanom Ghebreyesus, PhD, said the DRC and its partners face significant logistical challenges in investigating and establishing response capacities in extremely remote and hard-to-access areas. The outbreak's geographic spread is vast, and some areas can be accessed only by helicopter or boat.

Tedros added that the WHO has about 100 staff on the ground who are working with the DRC health ministry, other United Nations agencies, and other groups. So far, the WHO has released $2.5 million from its contingency fund, but it needs more funding to bring the outbreak under control and end it.

The outbreak began in early June, marking the DRC's 11th involving Ebola. It is occurring in the same region as a short-lived outbreak in 2018 that affected at least 54 people, 33 of them fatally.
Aug 14 WHO African regional office tweet

Polio reemerges in Sudan, affects 5 other countries

Sudan has reported an outbreak involving circulating vaccine-derived poliovirus type 2 (cVDPV2), the first confirmed polio cases there since 2009, and five other countries reported more cVDPV2 cases, according to the Global Polio Eradication Initiative (GPEI) and the United Nations Office for the Coordination of Humanitarian Affairs (OCHA).

In Sudan, the health ministry declared an outbreak on Aug 9 after confirming two cases in South Darfur and Gedaref states. Environmental samples have also tested positive in seven other states, suggesting wide circulation in the country, OCHA said, noting that urgent vaccination is needed to target 5.2 million children in affected areas.

The GPEI report said paralysis onsets for the cases occurred on Mar 7 and Apr 1 and that a genetic analysis suggests the virus is similar to the strain circulating in Chad.

Elsewhere, Afghanistan reported 14 more cVDPV2 cases, 1 in Kabul, 5 in Laghman, and 8 in Nangahar, raising the country's total for the year to 25.

In addition to Sudan, four pther African countries reported more cVDPV2 cases. Chad confirmed 5 new cases in four provinces, raising its total for 2020 to 56 from two different outbreaks. Ivory Coast reported 6 more cases in four different provinces, putting its total at 25. The DRC noted 1 more case, involving a patient from Kwilu province, raising its 2020 number to 23. And Ethiopia reported 2 more, both in Oromiya province, putting its total for the year at 14.
Aug 13 OCHA update
Aug 13 GPEI weekly report