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ASP Scan (Weekly) for Feb 05, 2021

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

Stewardship intervention linked to more appropriate ER prescribing

A multifaceted intervention implemented in a Japanese emergency department was associated with reduced antibiotic prescribing at discharge and an increase in appropriate prescribing, Japanese researchers reported today in Infection Control and Hospital Epidemiology.

In a before-and-after study conducted at a tertiary-care center in Tokyo, hospital researchers compared the average monthly proportion of appropriate antimicrobial prescriptions at discharge (APD), and the average rate of monthly APD per 1,000 visits, in the year prior to the intervention (January 2016 to December 2016) and the year following the implementation of intervention (October 2018 to September 2019).

The intervention included an educational session about common infectious diseases encountered in the emergency department, an evidence-base pocket treatment guide, antimicrobial order sets, monthly reports on the proportion of appropriate APD, and post-prescription review and feedback by an infectious diseases (ID) physician.

A total of 70,093 patients visited the emergency department during the study period‚ÄĒ36,308 during the preintervention period and 33,785 during the intervention period. The average monthly proportion of appropriate APD increased from 47.2% in the preintervention period to 79.5% in the intervention period. The analysis also found that the number of monthly APD fell by 11.7% overall in the intervention period, despite an increasing trend in the average monthly APD. The number of fluoroquinolones prescribed fell from 5.8 to 2.0 per 1,000 visits, while macrolides fell from 2.3 to 0.9 per 1,000 visits.

The authors say the educational sessions led by an ID physician and the pocket guide on common infectious diseases provided clinicians with a better understanding of antimicrobial stewardship goals, clarified the appropriate indications for antimicrobial use for each type of infectious disease, and likely contributed to a change in prescribing behaviors.
Feb 5 Infect Control Hosp Epidemiol abstract


Poll finds older US adults often use leftover antibiotics

A new poll of US adults aged 50 to 80 years indicates that taking leftover antibiotics without consulting a healthcare professional is a common practice, University of Michigan researchers reported today in Infection Control and Hospital Epidemiology.

Among 2,256 respondents to the University of Michigan National Poll on Healthy Aging, 47.7% reported receiving an antibiotic prescription in the previous 2 years. The most common indications were respiratory (49.7%), dental (17.6%), urinary tract (16.6%), and skin (11.7%) infections.

Among those who filled a prescription, 139 of 1,091 (12.7%) had leftover medication, and 65% of those with leftovers said they kept the medication. Among all respondents, 422 of 2,256 (18.7%) reported ever taking leftover antibiotics without talking to a healthcare professional (16.8% took their own medication and 3.4% took someone else’s).

Of the respondents who had leftover antibiotics in the previous 2 years, 71 of 141 (50.7%) had ever taken antibiotics without talking to a healthcare professional. For those who had a prescription for antibiotics but did not have leftover medication in the previous 2 years, 215 of 948 (22.7%) reported taking antibiotics without talking to a healthcare professional. Respondents aged 50 to 64 were more likely to have taken antibiotics without talking to a provider than respondents aged 65 to 80 (21.0% versus 15.0%), and women were more likely than men to have taken leftover antibiotics (20.7% vs 16.5%).

“The use of leftover antibiotics without supervision could result in serious drug interactions, cause other side effects, and contribute to resistance,” the authors wrote. “In addition to counseling patients to take all antibiotics as prescribed, prescribers should consider the number of pills dispensed and follow guidance supporting shorter treatment durations for common infections.”

The survey also found that many patients still ask for and expect antibiotics when they know they are unlikely to be helpful. While 91.5% agreed that they are cautious about the use of antibiotics and 88.6% agreed that overuse can lead to antibiotics not working the next time they are needed, 41.3% said they expect antibiotic when they have a cold that lasts long enough for them to visit a doctor, and 34% said they believed antibiotics will help them get better sooner if they get a cold or the flu. 
Feb 5 Infect Control Hosp Epidemiol abstract


CARB-X funds work on novel antibiotic for carbapenem-resistant pathogens

Originally published by CIDRAP News Feb 3

CARB-X announced today that it is awarding up to $6.4 million to French biopharmaceutical firm Mutabilis to develop a new class of antibiotics to treat infections caused by carbapenem-resistant Enterobacterales (CRE) bacteria.

The award from CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) will help fund the preclinical development of EBL-1463, a potential first in-class representative of the dabocin family. The compound is a non-beta-lactam inhibitor of penicillin-binding proteins that kills bacteria by interfering with cell wall synthesis. Lab testing has shown it to be impervious to any beta-lactamase-based resistance tested, which suggests it could be effective against CRE and other carbapenem-resistant bacteria.

“New treatments are urgently needed to address serious life-threatening antibiotic-resistant bacterial infections, like those caused by CRE and other Gram-negative bacteria for which there are few treatment options,” CARB-X chief of research and development Erin Duffy, PhD, said in a CARB-X press release. “The novel inhibitor of penicillin-binding proteins designed and optimized by Mutabilis is an achievement in this area of antibacterial drug discovery.”

Mutabilis, of Romainville, France, will be eligible for an additional $5.8 million if it meets certain project milestonest.
Feb 3 CARB-X press release


UK trials finds no benefit from azithromycin in hospital COVID-19 patients

Originally published by CIDRAP News Feb 3

New data from the United Kingdom’s RECOVERY trial shows that azithromycin did not improve survival or other prespecified clinical outcomes in hospitalized COVID-19 patients, according to results published yesterday in The Lancet.

In the azithromycin arm of the randomized, controlled trial, which is being conducted in 176 UK hospitals to identify effective treatments for hospitalized COVID-19 patients, eligible patients were randomly allocated to receive either standard of care alone or standard of care plus 500 milligrams of oral or intravenous azithromycin for 10 days or until discharge. The primary outcome was 28-day all-cause mortality.

A total of 7,763 patients were included in the study from Apr 7 through Nov 27, 2020, with 2,582 in the azithromycin group and 5,181 receiving standard of care. Overall, 561 (22%) of patients treated with azithromycin and 1,162 (22%) of patients in the standard-of-care group died within 28 days (rate ratio [RR], 0.97; 95% confidence interval [CI], 0.87 to 1.07). Similar results were observed among prespecified subgroups. In addition, no significant difference was seen in the length of hospital stay (10 days versus 11 days) or the proportion of patients discharged from the hospital alive within 28 days (69% vs 68%, RR, 1.04; 95% CI, 0.98 to 1.10).

Among those not on ventilators at baseline, there was no significant difference in the proportion of patients meeting the composite end point of invasive mechanical ventilation or death (25% vs 26%, RR, 0.95; 95% CI, 0.87 to 1.03).

Although azithromycin has not been recommended for routine use in COVID-19 patients unless there is evidence of a bacterial superinfection, macrolide antibiotics like azithromycin have been proposed as a possible treatment for COVID-19 because of their immunomodulatory activity. Azithromycin has widely been used in hospitalized COVID-19 patients during the pandemic, particularly in combination with the antimalaria drug hydroxychloroquine. But this and other trials have indicated that neither drug provides a benefit.

“Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication,” the investigators wrote.
Feb 2 Lancet study

VHA hospital study shows benefits of carbapenem-specific stewardship

Originally published by CIDRAP News Feb 2

An assessment of 90 Veterans Health Administration (VHA) hospitals found that carbapenem-specific stewardship strategies were associated with a lower volume of carbapenem use and more appropriate carbapenem prescribing, researchers reported yesterday in the Journal of Antimicrobial Chemotherapy.

In the study, researchers from the University of Iowa Carver College of Medicine and the Iowa City Veterans Affairs Health Care System analyzed all acute care admissions at VHA hospitals in 2016 and used a national VHA survey to categorize each hospital’s carbapenem-specific antibiotic stewardship strategy into one of three types: no strategy (NS), prospective audit and feedback (PAF), and restrictive policies (RP).

They then calculated overall carbapenem use and days of therapy (DOT) per 1,000 days present and compared strategy effectiveness using risk-adjusted generalized estimating questions that accounted for clustering within hospitals. Auditors assessed carbapenem appropriateness with an assessment score on day 4 of therapy.

Overall, there were 429,062 patient admissions across 90 hospitals in 2016, and at least one inpatient carbapenem dose was administered during 8,566 patient admissions (20.0%). Median carbapenem use across hospitals was 17.4 DOT/1,000 days present. In the adjusted analysis, carbapenem use was lower at PAF than NS sites (RR, 0.6; 95% CI, 0.4 to 0.9) but similar between RP and NS sites (RR, 0.8; 95% CI, 0.5 to 0.12).

Carbapenem prescribing was considered appropriate in 215 (50.6%) of the reviewed cases. Assessment scores were significantly lower (ie, better) in hospitals with an RP strategy compared with NS hospitals (mean 2.3 versus 2.7) but did not differ significantly between PAF and NS sites (mean 2.5 vs 2.7). Across all three strategies, infectious disease (ID) consultations‚ÄĒwhich were more common at PAF/RP than NS sites‚ÄĒwere associated with better assessment scores.

The authors concluded that antibiotic stewardship strategies and ID consultations appear to be complementary and that hospitals should leverage both to optimize carbapenem use. 
Feb 1 J Antimicrob Chemother abstract


Antibiotic use declined during Spain’s COVID-19 lockdown

Originally published by CIDRAP News Feb 2

Data from Andalusia, Spain, show antibiotic use in the community declined during the pandemic compared with the pre-COVID period, according to a study yesterday in Clinical Microbiology and Infection.

To assess the impact of the pandemic on community antibiotic use in a region with an existing antibiotic stewardship program (ASP) for hospitals and primary care clinics, a team of Spanish researchers conducted a before and after cross-sectional study comparing outpatient antibiotic prescribing in Andalusia in the first two quarters of 2019 and the same quarters in 2020, when a regional lockdown was in force. Data were collected from a pharmacy database containing records of reimbursed and dispensed drugs.

The analysis found that overall community antibiotic consumption in Andalusia fell by 7.6% between the first quarter of 2019 and the first quarter of 2020, and by 36.8% between the second quarters of 2019 and 2020. Larger reductions were found between the second quarters for most antibiotic classes studied as well as four antibiotics used for respiratory infections (amoxicillin, amoxicillin-clavulanate, cefuroxime, and levofloxacin).

The analysis also revealed a concomitant reduction in primary care consultations in the region.

The authors say the question is how much the reduction in community antibiotic use was linked to the lockdown, limited access to the healthcare system and antibiotic prescriptions, and how much can be attributed to Andalusia’s ASP. 

“Gaining access to that information may be useful to improve ASPs in primary care,” they wrote. “If these results are confirmed in other health systems, further studies are needed to determine whether this reduction in antibiotic use in the community during the pandemic has resulted in a favourable ecological impact.”
Feb 1 Clin Microbiol Infect study


CARB-X to fund development of electronic antibiotic susceptibility test

Originally published by CIDRAP News Feb 1

CARB-X announced today that it is awarding up to $2.5 million to Avails Medical of Menlo Park, California, to develop an electronic antibiotic susceptibility test (eAST).

The Avails eAST has 96 integrated electronic biosensors in a disposable lid that would fit onto widely available susceptibility testing panels and rapidly detect bacterial growth when immersed in positive blood culture samples. Company officials say the aim of the technology is to provide phenotypic results that can guide antibiotic therapy decisions within 4 hours. Current susceptibility testing methods take days to identify the most effective antibiotic treatments.

“Speed is a critical component of effectively diagnosing and treating serious antibiotic-resistant bacterial infections, including bloodstream infections,” Erin Duffy, PhD, chief of research and development at CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), said in a CARB-X press release. “Every hour of delay in effective treatment increases the risk of complications and septic shock.”

Avails Medical could receive up to $14.7 million in additional CARB-X funding if the project, which is currently in the feasibility development phase, successfully progresses to later phases.

Since its launch in 2016, CARB-X has awarded more than $278.5 million for projects focused exclusively on drug-resistant bacteria. There are currently 51 active projects in the CARB-X portfolio.
Feb 1 CARB-X press release


UK study: Flu vaccine linked to fewer amoxicillin prescriptions in seniors

Originally published by CIDRAP News Feb 1

Influenza vaccination was associated with reduced amoxicillin prescribing in a large cohort of UK seniors, according to a study published late last week in PLOS One.

To estimate the effects of the flu vaccine on amoxicillin prescribing in UK adults age 65 and over, researchers analyzed electronic health record data on 88,158 who turned 65 and received the vaccine in the year 2000 but had not received the vaccine the 2 previous years. They then matched the vaccinated patients 1:1 with unvaccinated patients based on a propensity score model.

The time to prescription of amoxicillin, which is frequently prescribed for respiratory illness and may serve as a proxy for flu diagnosis, in the year before and the year after vaccination was analyzed using the Prior Event Rate Ratio (PERR) Pairwise method to address bias from measured and unmeasured confounders.

Compared to the unvaccinated patients, those from the vaccinated group were more likely to be prescribed amoxicillin in the year prior to vaccination (hazard ratio [HR], 1.90; 95% CI, 1.83 to 1.98) and the year following vaccination (HR, 1.64; 95% CI, 1.58 to 1.71). But after adjusting for prior differences in the two groups using the PERR Pairwise method, the vaccinated group had a 14% lower risk of receiving amoxicillin (HR, 0.86; 95% CI, 0.81 to 0.92) after vaccination.

Subgroup analysis showed similar results for vaccinated adults 65 to 75 (HR, 0.87; 95% CI, 0.82 to 0.93) and those age 75 and over (HR, 0.84; 95% CI, 0.76 to 0.94).

“Antibiotic resistance is a growing healthcare problem, the consequences of which include longer healthcare stays and more expensive healthcare costs,” the study authors wrote. “Our findings suggest that improving uptake of influenza vaccination in older patients can contribute to strategies to reduce antibiotic resistance.”
Jan 29 PLOS One study


Review finds high mortality from ICU infections in lower-income countries

Originally published by CIDRAP News Feb 1

A review of literature on intensive care unit (ICU)-acquired infections suggests mortality is much higher in ICUs in low- and middle-income countries (LMICs) compared with higher-income countries, as is the level of antibiotic resistance, Dutch and Indonesian researchers reported late last week in Antimicrobial Resistance and Infection Control.

The scoping review of 51 articles on ICU-acquired infections in LMICs from 2005 to 2018 found average point-prevalence rate of 22.4 infected patients per 100 present, which is comparable to the 19.5% rate recorded in Western European countries in 2011 and 2012. But the overall ICU mortality in LMICs was 33.6% (varying from 14% to 70% across studies), compared with a 15.3% ICU mortality rate found in a European Union study conducted from 2008 through 2012 and a 18.2% ICU mortality rate found in a 2009 study of ICUs in 75 countries.

The reviewers also found that multidrug-resistant gram-negative species were the most prevalent group of pathogens in ICUs in LMICs, with Acinetobacter baumannii (24%), Pseudomonas aeruginosa (16%), and Klebsiella pneumoniae (15%) causing more than 50% of infections. By comparison, these three pathogens caused less than 25% of ICU infections in Western Europe in the same period.

The authors note that the findings are limited by the relatively few high-quality studies, most of them conducted in only a handful of countries.

“Many gaps in knowledge remain since most LMICs have not produced high quality reports,” they wrote. “However, from the reported evidence it is clear that the rate of ICU-acquired infections is likely to be somewhat higher in LMICs compared to high income countries and that the ICU mortality rate is much higher.”
Jan 29 Antimicrob Resist Infect Control study

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