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

Stewardship initiative linked to lower outpatient prescribing in NYC clinics

An effort to reduce inappropriate antibiotic prescribing in New York City hospitals was associated with a modest decrease in prescribing for acute respiratory infections (ARIs), according to a study today in Infection Control and Hospital Epidemiology.

The intervention was the second stage of two-stage initiative from the United Hospital Fund to evaluate outpatient antibiotic stewardship in hospital-owned clinics in New York City. In stage 1, investigators found few clinics with outpatient stewardship activities, significant variation in prescribing practices, common prescribing of macrolides, and an interest among providers in learning more about appropriate prescribing. In stage 2, clinics implemented from 3 to 13 interventions based on the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antibiotic Stewardship recommendations, including augmented patient and provider education, clinical decision support, provider audit and feedback, and communication skills training.

The investigators reviewed 991 visits for ARI pre-intervention and 902 post-intervention. They found that antibiotic prescribing declined from 30.6% of ARI visits pre-intervention to 25.5% (P = .016) post-intervention. Prescribing for patients with "bronchitis, not specified" decreased from 62.0% to 43.4% (P = .01) and, although not statistically significant, prescribing for patients with acute sinusitis decreased from 77.6% to 68.0% (P = .27).

Declines in ARI prescribing were also observed among patients 40 to 59 years of age (31.8% to 22.7%, P = .007), Medicaid patients (30.3% to 14.1%, P < .0001), and Spanish-speaking patients (25.6% to 11.1%, P = .004). The proportion of macrolide and fluoroquinolone prescriptions decreased from 55.1% to 46.5% (P = .05) and from 12.2% to 7.0% (P = .038), respectively. But prescriptions of amoxicillin/clavulanic acid increased from 18.8% to 27% (P = .028), and substantial variation in system-level prescribing remained (10% to 65%, P <.0001).

The authors of the study note that although they were not able to ascertain which interventions were most effective, their observations suggest that targeting both providers and patients works best.
Jul 26 Infect Control Hosp Epidemiol abstract

BARDA to help fund new antibiotic for MDR pathogens, bioterror threats

The Department of Health and Human Services (HHS) announced this week that it will partner with the Department of Defense (DoD) and drug maker VenatoRx Pharmaceuticals on a novel combination antibiotic to treat multidrug-resistant gram-negative infections.

Under the partnership, VenatoRx, of Malvern, Pennsylvania, will receive up to $20.7 million over 2 years from the Biomedical Advanced Research and Development Authority (BARDA)—part of the HHS Office of the Assistant Secretary for Preparedness and Response—to develop cefepime/VRNX-5133, which combines a currently marketed fourth-generation cephalosporin with a novel beta-lactamase inhibitor. The drug, which has completed phase 1 clinical trials, has the potential to treat infections caused by carbapenem-resistant Enterobacteriaceae, as well as pathogens that can be engineered for bioterrorism, such as Burkholderia spp.

"Developing new antibiotics that represent an improvement over standard of care antibiotics is essential to national health security and global health efforts to combat antibiotic-resistant infections," BARDA Director Rick Bright, PhD, said in an HHS press release. "This unique public-private partnership will focus on adding a new tool to healthcare providers' toolkits and to help them save lives in an incident involving some of the serious bioterrorism threats our country faces."

BARDA and VenatoRx will share the costs of all studies needed to bring the drug to market. DoD's Threat Reduction Agency will provide up to $10 million to fund studies to test the efficacy of cefepime/VRNX-5133 against bioterror threats.
Jul 22 HHS press release

Study finds substantial costs, extended hospital stays from C diff

Originally published by CIDRAP News Jul 25

A population-based analysis indicates that hospital-acquired Clostridioides difficile infection (HA-CDI) is associated with millions of dollars in attributable costs and with extended hospital stays, Canadian researchers reported today in Infection Control and Hospital Epidemiology.

In a multicenter, propensity-score–matched cohort study, researchers from the University of Calgary and Alberta Health Services compared adult inpatients at 14 Alberta hospitals who had developed HA-CDI with adult inpatients who had not developed HA-CDI, using data available from April 2012 through March 2016. The outcomes were attributable costs and length of stay at the hospital where HA-CDI was identified.

The mean adjusted costs of HA-CDI cases was $83,155 (USD $64,178), compared with $12,465 (USD $9,620) for non-cases, with HA-CDI cases incurring more costs across all categories and having longer stays. Of the 2,916 HA-CDI cases at facilities with microcosting data available, 2,871 were matched to 13,024 non-cases. Adjusted outcomes after matching showed that the total adjusted cost among HA-CDI cases was 27% greater than non-cases (ratio, 1.27; 95% confidence interval [CI], 1.21 to 1.33). The mean attributable cost of a typical HA-CDI case was $18,386 (USD $14,190). The adjusted length of stay among HA-CDI cases was 13% longer than non-cases (ratio, 1.13; 95% CI 1.07 to 1.19), corresponding to an extra 5.6 days in the hospital.

Extrapolating those results to the entire cohort of HA-CDI cases that occurred in Alberta during the study period, the burden to the healthcare system was an additional 5,856 hospital days and an excess of $19,227,379 (USD $14,839,376) per year on average.

The authors of the study conclude, "Our estimates will assist decision makers, healthcare providers, and patients in understanding the healthcare system burden of disease, justifying expenditures in intervention efforts and policies related to infection prevention and control, evaluating program effectiveness, determining allocation of research funding, and assessing the potential cost savings or bed days saved due to prevented infections."
Jul 25 Infect Control Hosp Epidemiol abstract

MCR-1, MCR-3–carrying E coli reported in New Zealand

Originally published by CIDRAP News Jul 25

Researchers from New Zealand yesterday reported the identification of the colistin-resistance genes MCR-1 and MCR-3 in a clinical Escherichia coli isolate. The findings were published in the Journal of Antimicrobial Chemotherapy.

The isolate, one of 23 clinical randomly collected in New Zealand from 2015 through 2018 and tested for colistin susceptibility, was from a woman in her late 60s with a spinal cord injury who was being treated for a urinary tract infection (UTI). Antimicrobial susceptibility testing showed that the isolate was resistant to multiple classes of antibiotics, and multilocus sequence typing identified it as belonging to ST101, an E coli sequence type found infrequently in New Zealand. Whole-genome sequencing located the MCR-1 and MCR-3 genes on separate plasmids, along with other antibiotic resistance genes, including blaCTX-M-55. 

Further inquiry revealed the patient had traveled to Thailand 4 months prior to her UTI, and the researchers suspect that the MCR-1 and MCR-3–carrying E coli was likely acquired there, since MCR-3 and blaCTx-M-55 have links to Thailand.

To date, only two other clinical isolates carrying both MCR-1 and MCR-3—a Salmonella isolate and an E coli isolate—have been reported.
Jul 24 J Antimicrob Chemother abstract

Resistant Pseudomonas death in Utah linked to surgery in Mexico

Originally published by CIDRAP News Jul 25

A Utah resident who died after traveling to Tijuana, Mexico, for weight-loss surgery tested positive for a multidrug-resistant form of Pseudomonas aeruginosa, according to a news release from the Utah Department of Health (UDOH).

The patient was one of eight Utah residents who tested positive for Verona integron-encoded metallo-beta-lactamase–producing carbapenem-resistant P aeruginosa (VIM-CRPA) after getting weight-loss surgery in Tijuana. Interviews with patients or their family members revealed that seven of the eight patients had the same surgeon.

The Utah VIM-CRPA cases are linked to similar cases that have been reported to state health departments and the CDC since September 2018. On May 24, the CDC reported that 12 VIM-CRPA cases with links to surgical procedures in Mexico had been identified in seven states. Eleven of the 12 patients reported having bariatric surgery at five hospitals in Mexico. Six of the patients were subsequently hospitalized in the United States for their infection, and one died.

UDOH said individuals who had a surgical procedure in Tijuana during or after August 2018 and are experiencing signs of infection—including fever, redness, drainage from the surgical site, or swelling at the surgical site—should seek immediate medical care. The department is also recommending that residents not travel to Mexico for invasive surgical procedures.

"I cannot stress enough the safest course of action is not to travel to Mexico for these procedures," Allyn Nakashima, MD, manager of the UDOH Healthcare-Associated Infections/Antimicrobial Resistance Program, said. "Using an internationally accredited facility is not a guarantee that your medical care will be free of complications."
Jul 22 UDOH news release
May 23 CIDRAP News stewardship/resistance scan

Paper suggests climate change may have aided Candida auris emergence

Originally published by CIDRAP News Jul 24

Could climate change have played a role in the emergence of the multidrug-resistant fungus Candida auris?

That's the hypothesis presented in a paper yesterday in mBio by researchers from Johns Hopkins Bloomberg School of Public Health, University of Texas MD Anderson Cancer Center, and Westerdijk Fungal Biodiversity Institute in the Netherlands. The experts note that the sudden, independent emergence of C auris as a human pathogen on three continents simultaneously cannot be explained solely by widespread use of antifungal drugs or recent acquisition of virulence traits, and that fungal pathogens are rare in mammals because they can't grow at human body temperature.

Hence, the researchers suggest that C auris was until recently an environmental fungus that adapted to warmer ambient temperatures caused by climate change and was able to break the mammalian thermal barrier.

To evaluate the hypothesis, they compared the thermal susceptibility of C auris to those of some of its close phylogenetic relatives, including Candida haemulonii, and found that it is capable of growing at higher temperatures than other fungal species. They present a scenario in which C auris emerged in wetlands and gained tolerance for warmer temperatures, adapted to an intermediate host—birds—was transplanted by birds to areas where humans and birds are in contact, and then acquired genetic traits that enabled transmission to humans. They say the fact that C auris typically grows on cooler skin sites, rather than the warmer human gut, supports the notion that it was, until recently, an environmental pathogen.

Although they acknowledge that climate change does not explain the whole story of how C aurisemerged, the authors warn that a hotter climate could give rise to new fungal infections.

"Whether C. auris is the first example of new pathogenic fungi emerging from climate change or whether its origin into the realm of human-pathogenic fungi followed a different trajectory, its emanation stokes worries that humanity may face new diseases from fungal adaptation to hotter climates," they write.
Jul 23 mBio paper

Indian government prohibits use of colistin in food-producing animals

Originally published by CIDRAP News Jul 23

The Indian government has banned the use of the last-resort antibiotic colistin in food-producing animals, according to Indian media reports.

The Hindu reports that India's Ministry of Health and Family Welfare issued an order on Jul 19 directing manufacturers of colistin and its formulations to add a label to containers stating the drug should not be used in "food-producing animals, poultry, aqua farming, and animal feed supplements." The ministry said the ban was necessary because colistin use in animals poses a risk to humans.

The World Health Organization has classified colistin a "highest priority critically important antimicrobial." The antibiotic is used in human medicine to treat serious, multidrug-resistant infections that aren't responding to other antibiotics. Antimicrobial resistance and infectious disease experts are concerned that using the drug in food-producing animals promotes the emergence of colistin-resistant pathogens that can spread from animals to humans. The emergence of the colistin-resistance gene MCR-1, first identified in Chinese pigs and pork products in 2015, has been linked to widespread use of colistin on Chinese farms.

Banning colistin from being used in food-producing animals puts India in line with the European Union, United States, China, and Brazil, which have all stopped using colistin in animal agriculture in recent years.

"We welcome the health ministry's move to ban colistin use in food-producing animals," Chandra Bhushan deputy director general of India's Centre for Science and Environment (CSE), said in a press release yesterday. "It will help preserve this last-resort antibiotic for humans and save lives from deadly antibiotic-resistant infections. It will go a long way in fighting antibiotic resistance." 
Jul 20 The Hindu story
Jul 22 CSE press release

Survey: Antibiotic stewardship often lacking for end-of-life care

Originally published by CIDRAP News Jul 22

A survey of 36 hospitals discovered that about two-thirds had antimicrobial stewardship programs (ASPs) that monitored antimicrobial use in patients during end-of-life care, but only a third had ASPs that offered guidance for patients receiving comfort care only, according to a study today in Infection Control & Hospital Epidemiology.

Yale University investigators conducted an electronic survey of ASPs from the Society for Healthcare Epidemiology of America (SHEA) Research Network, a consortium of hospitals collaborating on multicenter projects in healthcare epidemiology. Members of 36 of the 94 hospitals completed the survey in May and June of 2018.

In addition to finding that 23 hospitals (64%) had ASPs that monitored antimicrobial use during end-of-life care and 13 (36%) had ASPs offering comfort-care antimicrobial use guidance for patients, the survey results showed that recommendations for intravenous antimicrobials were more common than recommendations for oral antimicrobials in 86% of programs.

The researchers also found that approval of antimicrobials in the ASPs was often influenced by patients' goals, with 15 ASPs (42%) having antimicrobials restrictions affected by comfort measures only, 9 (25%) having them affected by no-escalation-of-care status, and 4 (11%) affected by do-not-resuscitate/intubate orders.

Free-text responses indicated that ASPs should support end-of-life clinical decisions in four ways: (1) discerning adverse events, (2) supporting palliative care providers, (3) refining guidelines specific to end-of-care issues, and (4) educating physicians.
Jul 22 Infect Control Hosp Epidemiol study

Study: Molecular test for group A strep could lead to overprescribing

Originally published by CIDRAP News Jul 22

Researchers in Chicago report today that the illumigene test, a molecular-based assay for group A Streptococcus (GAS), is significantly more likely than throat culture to yield positive results in patients without GAS pharyngitis, a finding they say could have an impact on outpatient antimicrobial stewardship efforts.

In a study published in The Pediatric Infectious Disease Journal, researchers from Northwestern University Feinberg School of Medicine and Lurie Children's Hospital of Chicago enrolled children between the ages of 3 and 17 who visited the hospital's pediatric clinic for health supervision or follow-up of a non-infectious condition and had no signs or symptoms of pharyngitis. They then performed the illumigene test and blood agar plate throat cultures on duplicate throat swabs to compare the proportion of positive tests.

The illumigene test replaced throat cultures at the hospitals for diagnosis of GAS pharyngitis in 2014, and since then hospital records have detected an increase in positive GAS tests. The researchers hypothesized that asymptomatic carriers may be testing positive and receiving unnecessary antibiotics.

Among the 385 enrolled children, significantly more illumigene tests (78/385, 20.3%) than throat cultures (48/385, 12.5%) were positive. Three swabs yielded an "indeterminate" illumigene test result (all 3 paired swabs were culture-negative), leaving 382 pairs for analysis. Results were discordant for 32 of 382 pairs (8.4%), of which 31 of 32 (97%) were illumigene-positive/culture-negative. A positive result was significantly more likely with the swab chosen for the illumigene test than with the one used for culture. In a small subset of 13 illumigene-positive lysates tested by polymerase chain reaction, 4 (31%) were negative, and the paired cultures were negative in all four.

"The results of the present study are consistent with the hypothesis that the sensitivity of the illumigene test is such that it can identify GAS more readily than occurs with standard throat culture, especially in patients with very low streptococcal burden," the authors of the study write.

They conclude that additional studies of GAS molecular tests are needed, and that new clinical guidelines are needed to define the role of these tests in clinical care.
Jul 22 Pediatr Infect Dis J study