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

Telemedicine linked to more appropriate antibiotic prescribing for UTIs

Telemedicine visits for urinary tract infections (UTIs) were associated with more appropriate antibiotic prescribing and decreased use of diagnostic and follow-up resources than virtual visits, according to the results of a primary care network study published yesterday in Infection Control and Hospital Epidemiology.

The retrospective cohort study, conducted at Mercy Health Physician Partners, a primary care network in western Michigan with 44 outpatient sites and one virtual visit platform, compared guideline-concordant antibiotic prescribing among adult women diagnosed as having an uncomplicated UTI during an office visit or a virtual visit in 2018. The researchers looked at antibiotics prescribed, duration of therapy, and patient outcomes. Guideline-concordant therapy was assessed based on the network's antimicrobial stewardship program guidelines.

A total of 350 women were included in the study, with 175 in each group. There was no difference in the rate of antibiotic prescribing between the two groups, but a guideline-concordant antibiotic was more commonly prescribed during virtual visits compared with office visits (74.9% vs 59.4%; P = .002). Guideline-concordant duration of therapy was also more common in the virtual-visit group (100% vs 53.1%; P < .001).

Patients treated through virtual visits were also less likely to have a urinalysis (0% vs 97.1%; P < .001) or urine culture ordered (0% vs 73.1%; P < .001) and were less likely to have an unplanned revisit within 7 days (5.1% vs 18.9%; P < .001).

The authors of the study attribute the more appropriate prescribing in part to a fixed drop-down menu of antibiotic choices for virtual visits, which is based on national guidelines and includes a corresponding fixed dose and duration for each antibiotic. "These results add further support to the growing evidence surrounding virtual visits as a tool to improve antibiotic prescribing in the outpatient setting," they wrote. 
Oct 29 Infect Control Hosp Epidemiol abstract

Promising phase 3 data for oral carbapenem presented at IDWeek

Originally published by CIDRAP News Oct 29

Data from a phase 3 trial presented last week at IDWeek 2020 by researchers from Spero Therapeutics show that oral tebipenem was comparable in safety and efficacy to intravenous (IV) ertapenem for treating complicated urinary tract infections (cUTIs) and acute pyelonephritis (AP).

In the double-blind phase 3 study, which was conducted at more than 100 hospitals in 15 countries, 1,372 hospitalized patients who had cUTIs or AP were randomized to receive either oral tebipenem pivoxil hydrobromide (TBP-PI-HBr) or IV ertapenem for 7 to 10 days. The primary end point was overall response (composite clinical cure and microbiologic eradication) at the test-of-cure visit on Day 19. The non-inferiority margin was -12.5%.

The results showed that oral TBP-PI-HBr met the primary objective of non-inferiority compared with IV ertapenem, with an overall response rate of 58.8% (264 of 449 patients) versus 61.6% (258/419) for IV ertapenem (treatment difference, -3.3%; 95% confidence interval [CI], -9.7% to 3.2%). Clinical cure rates were greater than 93% in both treatment groups, and microbiologic response rates for target uropathogens were comparable.

Treatment-emergent adverse events were observed in 25.7% of TBP-PI-HBr patients and 25.6% of IV ertapenem patients, and most were mild. Serious adverse events were infrequent in both groups (1.3% for TBP-PI-HBr patients vs 1.7% for IV ertapenem patients).

Spero Therapeutics said earlier this month that it plans to submit a new drug application for TBP-PI-HBr to the FDA in the second quarter of 2021. If approved, it would be the first oral carbapenem to receive approval in the United States.
Oct 24 IDWeek 2020 abstract
Oct 16 Spero Therapeutics press release

Panel issues C difficile guidance for low- and middle-income countries

Originally published by CIDRAP News Oct 27

A panel of experts convened by the International Society for Infectious Diseases (ISID) has released a set of recommendations for preventing Clostridioides difficile infections in hospitals in low- and middle-income countries (LMICs).

While epidemiologic studies suggest that the prevalence of C difficile in LMICs is similar to that in higher income countries and may be even higher, existing guidelines for control and prevention of the pathogen in healthcare settings do not specifically address LMICs and the challenges they might face due to insufficient testing capability and overcrowded healthcare facilities. The panel was convened by ISID to address some of these challenges and make evidence-based recommendations for infection prevention that are broadly applicable.

The recommendations, published yesterday in the International Journal of Infectious Diseases, acknowledge that resource-limited settings face distinct challenges in diagnosing and preventing C difficile. The panel recommends that diagnosis of C difficile only be pursued in symptomatic patients with clinical evidence of infection, that surveillance for C difficile infections be conducted to understand local burden and epidemiology, and that hand hygiene following the World Health Organization's 5 Moments of Hand Hygiene be performed.

Other core recommendations from the panel include isolation of patients who have C difficileinfection, use of gowns and gloves for care of infected patients, daily cleaning of high-touch hospital surfaces, cleaning of shared medical equipment after each use, terminal cleaning of patient rooms upon discharge, and implementation of antimicrobial stewardship programs to limit unnecessary use of antibiotics.

"The recommendations for C. difficile prevention outlined here support a tailored approach that acknowledges local resources and needs," the authors write. "Individual components of a C. difficile prevention bundle remain valuable in isolation, and should be pursued aggressively even if other components are not feasible to implement in a given setting."
Oct 26 Int J Infect Dis paper

Multispecialty clinical teams tied to less antibiotic use in COVID-19 patients

Originally published by CIDRAP News Oct 27

Implementation of a multispecialty COVID-19 clinical guidance team helped a Tennessee hospital reduce antibiotic use in COVID-19 patients following an initial increase, researchers reported yesterday in Infection Control and Hospital Epidemiology.

In an observational study conducted at Vanderbilt University Medical Center in Nashville, the researchers examined weekly antibiotic use among internal medicine (IM) and medical intensive care unit (MICU) teams treating COVID-19 patients at the hospital and those treating non-COVID-19 patients.

They looked at three different periods: a pre-COVID period (Dec 1, 2019, to Feb 29, 2020) and two post-COVID periods (Mar 1 to Mar 22 and Mar 22 to May 15). The initial post-COVID period started a week after the first confirmed COVID-19 patient in Tennessee, and the second started with the implementation of the COVID-19 clinical guidance team, which included infectious disease physicians with antibiotic stewardship experience who made case-by-case antibiotic recommendations.

When compared with the pre-COVID period, the IM COVID team had an initial increase in weekly antibiotic use of 145.3 days of therapy (DOT) per 1,000 days in the first post-COVID period, and the MICU COVID team had an increase of 204 DOT/1,000 days, compared with non-COVID IM and MICU teams. In the second post-COVID period, the IM and MICU COVID teams saw significant weekly decreases in antibiotic use of 362.3 DOT/1,000 days and 226.3 DOT/1,000 days, respectively. Of the 131 COVID-19 patients treated at the hospital from Mar 1 to May 15, 65.5% received antibiotics.

"This study is the first to describe significant reductions in team-based AU [antibiotic use] after COVID-19 in the context of an institutional systems-based approach, utilizing infectious diseases and stewardship guidance for COVID-19 providers," the authors wrote. "This may be a strategy to mitigate unnecessary AU and optimize COVID-19 patient care moving forward." 
Oct 26 Infect Control Hosp Epidemiol abstract

Survey: Few outpatient clinics have fully functional stewardship programs

Originally published by CIDRAP News Oct 26

A multicenter survey found that only 7% of ambulatory healthcare settings in the United States have fully functional antimicrobial stewardship programs (ASPs), researchers reported late last week in Open Forum Infectious Diseases.

The cross-sectional survey, sent to hospitals and healthcare systems in the Vizient network, asked respondents 51 questions about the presence of an outpatient ASP, the components of their ASP, compliance with the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antibiotic Stewardship, and ASP effectiveness. Respondents were asked to characterize ASPs as either fully functional, in development, no program but considering a small project, or no program with no plans to develop one.

ASP effectiveness was defined as self-reported achievement in at least one of the following areas within the past 2 years: cost savings or avoidance related to antibiotics, decreases in antibiotic use, decreased C difficile infection, or decreased rate of drug-resistant organisms. Survey respondents were also asked to compare their ambulatory ASPs to their inpatient ASPs, where applicable.

Overall, 129 survey responses were received from institutions across 44 states, with 9 of 129 respondents (7%) reporting a fully functional ASP in their ambulatory practice compared with 114 of 129 (88%) inpatient practices. Effectiveness in at least one antibiotic use-related outcome in the past 2 years was reported in 18 of 100 (18%) ambulatory ASPs compared with 103 of 123 (84%) inpatient ASPs. The characteristics most commonly reported in ambulatory ASPs that demonstrated effectiveness were use of institutional guidelines (89%), rapid diagnostic testing for respiratory viruses or group A Streptococcus (89%), and outpatient antibiograms (78%).

Ambulatory ASP effectiveness was shown to increase as programs met more of the CDC Core Elements of Outpatient Antibiotic Stewardship; zero reported effectiveness when meeting only one core element, compared with 59% of those that met all four core elements.

The authors say the findings should serve as a benchmark and provide areas of focus for ambulatory ASPs currently in development. 
Oct 24 Open Forum Infect Dis abstract

Roadblocks, priorities noted for sustainable ASPs in nursing homes

Originally published by CIDRAP News Oct 26

Interviews with staff at nine non-profit nursing homes with active ASPs identified three critical areas needed for sustainability, researchers reported today in Infection Control and Hospital Epidemiology.

The interviews were conducted by researchers with the University of Rochester 5 years after a collaborative project in which staff at nine nursing homes in Monroe County, New York, formed ASPs and implemented stewardship activities to optimize antibiotic use and reduce C difficile infection. The purpose of the interviews was to examine the experiences and perceptions of staff at the nursing homes and understand the factors that influence the sustainability of ASPs.

Interviews with 48 clinical and administrative staff members at the nursing home identified seven themes that threaten sustainability. These included the belief that ASPs are resource intensive for nursing homes with limited resources and high turnover rates, that a single champion cannot sustain an ASP even when fully committed, that an ASP requires access to and interpretation of data that are not readily available at nursing homes, and that ASPs require explicit support from nursing home leadership and partnerships with external consultants.

Staff members also reported that it was hard to make progress beyond ASP implementation because urgent resident care needs always take precedence over ASP tasks, that prescribing patterns of external providers (like emergency departments) often impede stewardship efforts, and that ongoing and consistent ASP education is necessary for sustainability.

Based on these interviews, the authors of the study recommend that nursing homes with ASPs prioritize three critical areas: (1) explicit, ongoing leadership support; (2) partnerships with external stewardship experts; and (3) consistent education and training for staff.

"We believe that sustainability cannot be an afterthought and needs to be integrated into the design of ASPs," the authors write. "Future research should target how ASPs in nursing homes with limited resources can be both implemented and sustained over time."
Oct 26 Infect Control Hosp Epidemiol abstract

CDC study finds household COVID-19 transmission common

New data released today in Morbidity and Mortality Weekly Report (MMWR) show that household transmission of SARS-CoV-2, the virus that causes COVID-19, is common, occurs early after illness onset, and can originate from both children and adults.

In a study conducted among households in Nashville, Tennessee, and Marshfield, Wisconsin, researchers from the Centers for Disease Control and Prevention and their partners enrolled 101 households (including 101 index patients and 191 household members) and asked participants to document their symptoms and obtain self-collected specimens for 14 days. The researchers then tested specimens from the first 7 days for SARS-CoV-2.

Index patients received SARS-CoV-2 testing a median of 1 day after illness onset and were enrolled in the study a median of 4 days after onset. Sixty-nine percent of index patients reported spending more than 4 hours in the same room with one or more household members the day before illness onset, and 40% the day after illness onset.

Overall, 102 household members tested positive during the first 7 days of follow-up, for a secondary infection rate of 53%. Excluding household members who had SARS-CoV-2 detected in specimens taken at enrollment, the secondary infection rate was 35%. Substantial secondary transmission occurred regardless of index patient age: 53% for index patients under 12, 38% for those aged 12 to 17 years, 55% for 18 to 49 year-olds, and 62% for those over 50.

Approximately 75% of infections were identified within 5 days of the index patient's illness onset. Forty percent of infected household members reported no symptoms at the time SARS-CoV-2 was detected, while 67% of household members reported symptoms over 7 days of follow-up. The rates of symptomatic and asymptomatic transmission were 36% and 18%, respectively.

"Persons who suspect that they might have COVID-19 should isolate, stay at home, and use a separate bedroom and bathroom if feasible," the authors wrote. "Isolation should begin before seeking testing and before test results become available because delaying isolation until confirmation of infection could miss an opportunity to reduce transmission to others."

The authors also suggest that all household members, including the index patient, start wearing a mask in shared spaces in the home during this period.
Oct 30 CDC MMWR study

Review suggests higher transmission in older schoolchildren

A literature review today in The Journal of Infectious Diseases found that SARS-CoV-2 appeared to have a more limited spread in primary schools compared with secondary/high schools, although mitigation measures and community case levels were also factors. The researchers also found that children under 10 years old appeared to be relatively less susceptible to SARS-CoV-2 infection and that serologic prevalence may be higher in younger adults under 35.

The authors, from Harvard University and the University of St. Andrews in Britain, included in their review 14 studies that looked at how susceptibility, infectivity, and seroprevalence differed across age-groups.

"Some uncertainty remains about the magnitude of the difference in susceptibility of children vs. adults due to presence of biases in several published studies," the researchers write. "On the other hand, comparisons between younger and older children are arguably more robust and—in the one study that reports them—reach the same conclusion."

Regarding school outbreaks, the researchers looked at papers published prior to Oct 6 on the Living Evidence on COVID-19 database and found that multiple outbreaks were linked to school transmission, not just community caseloads. Studies found that factors like limited mask use, normal/crowded class sizes, and limited testing and quarantine contributed to larger outbreaks.

In one outbreak in Baden-Würtemberg, Germany, officials were able to limit further infection despite not mandating face masks. Instead, the school followed other safety guidelines, such as halving group sizes, and the school had only 6 of 137 infected children spread COVID-19 to a total of 11 other school contacts. In a Salt Lake County, Utah, assessment, masks were mandated at schools, and the vast majority of outbreaks were under 15 cases, with the exception of a few larger outbreaks that were mostly centered around high schools.

To help prevent school outbreaks, the researchers recommend that schools adhere to World Health Organization guidelines for both students and staff and be particularly careful when opening secondary/high schools.
Oct 29 J Infect Dis study

Study notes 36% rate of COVID-19 in New York City emergency workers

From Mar 1 through May 31, 5,175 out of 14,290 (36.2%) firefighters and emergency medical workers with the Fire Department of the City of New York (FDNY) had confirmed or suspected COVID-19 infections, according to a study today in ERJ Open Research.

Compared with the general New York City population, which had a 2.4% infection rate during the same period, these frontline workers were 15 times more likely to be infected. Still, the number of severe cases in FDNY frontline workers was lower than the general population, possibly due to the "healthy worker effect": 62 cases (1.2%) were classified as severe and 4 (0.08%) were fatal.

FDNY emergency health workers were 26% more likely to have a confirmed COVID-19 case and a 4.23-fold increased likelihood of developing severe outcomes compared with firefighters, the study found. The researchers suggest this could be attributed to prolonged on-the-job contact with people (eg, sharing ambulance transportation, intubation procedures). Generally, the emergency medical workers were more likely to be younger than the firefighters (mean, 38.7 years vs 41.0), female (29.3% vs 1.1%), and of a non-white race or ethnicity (60.7% vs 22.9%).

Smoking habits did not seem to affect COVID-19 infections in this study, although deteriorating lung health (a decline in forced expiratory volume) increased the risk of severe COVID-19 infection by 71%. The data also revealed that minority race was strongly associated with COVID-19 hospitalizations, similar to other studies.

"These findings highlight the importance of protecting emergency workers in countries around the world and maintaining the capacity of our emergency services," said David Prezant, MD, senior author and FDNY chief medical officer, in a European Lung Foundation news release.
Oct 29 ERJ Open Res study
Oct 29 European Lung Foundation press release