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ASP Scan (Weekly) for Sep 24, 2021

ASP Scan (Weekly) for Sep 24, 2021

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

Nursing home trial ties CRP testing to safe antibiotic reduction

Point-of-care testing for C-reactive protein (CRP) in nursing home residents with suspected lower respiratory tract infections resulted in a large reduction in antibiotic prescribing at initial consultation, according to the results of a cluster-randomized trial published this week in BMJ.

The trial, conducted in the Netherlands, involved 11 nursing homes and 241 participants with suspected lower respiratory tract infections. The nursing homes were allocated to either an intervention group that had access to CRP point-of-care testing (CRP POCT), which measures the level of a protein produced by the liver in response to inflammation, or to a control group that provided usual care without CRP POCT.

The primary outcome was antibiotic prescribing at initial consultation. Secondary outcomes included full recovery at 3 weeks, changes in antibiotic management during follow-up, hospital admission, and all-cause mortality at any point.

Antibiotics were prescribed at initial consultation at for 84 patients (53.5%) in the intervention group and 65 patients (82.3%) in the control group. The between-group difference in initial antibiotic prescribing at any point from initial consultation to follow-up was 23.6%. Patients in the intervention group had 4.93 higher odds (95% confidence interval [CI], 1.91 to 12.73) of not being prescribed antibiotics at initial consultation, compared with patients in the control group, irrespective of patient characteristics or treating physician.

Differences in secondary outcomes between the intervention and control groups were 4.4% for full recovery at 3 weeks (86.4% vs 90.8%), 2.2% for all-cause mortality (3.5% vs 1.3%), and 0.7% for hospital admission (7.2% vs 6.5%), though mortality and hospital admission were low in both groups. The odds of full recovery at 3 weeks, and the odds of hospital admission and mortality at any point, did not significantly differ between the two groups.

“The high full recovery rate in both groups, the low occurrence of hospital admissions and mortality, and the non-significant difference in odds of these secondary outcomes between groups suggest that CRP POCT can be safely used in nursing homes,” the study authors wrote. “Because of the pragmatic trial design, we believe that the results can be generalised to other nursing homes and other countries with similar long term care facilities.” 
Sep 21 BMJ study

Acid suppressants, MDR bacteria carriage not linked, study finds

Analysis of data from a subcohort of a nationwide Dutch seroprevalence study found that use of acid suppressants was not associated with intestinal carriage of multidrug-resistant (MDR) Enterobacterales, Dutch researchers reported this week in The Journal of Antimicrobial Chemotherapy.

The subcohort included healthy individuals 18 years and older who had provided fecal specimens from February 2016 through June 2017. The primary outcome was carriage of extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacterales (ESBL-E). To determine whether acid-suppressing medications are a risk factor for ESBL-E, the researchers assessed data from self-administered questionnaires and conducted multivariable analysis that controlled for confounding factors.

Among the 2,746 participants, the prevalence of ESBL-E carriage was 7.4%, and 11.5% used acid suppressants. In the primary analysis, current use of acid suppressants was not associated with ESBL-E carriage (adjusted odds ratio [aOR], 1.05; 95% CI, 0.64 to 1.74), and lifestyle and comorbidity did not modify the association. But in a secondary analysis, a higher BMI (aOR, 1.42; 95% CI, 1.02 to 1.98), non-Western ethnic origin (aOR, 1.96; 95% CI 1.34 to 2.87), travel to Eastern-Mediterranean, Western-Pacific, or South East Asia regions (aOR, 3.16; 95% CI, 1.71 to 5.83) were associated with ESBL-E carriage.

The study authors note that the findings are inconsistent with a previous meta-analysis of Dutch hospital patients that had found the use of proton pump inhibitors nearly doubled the risk of ESBL-E carriage. They suggest that finding could be explained by the fact that hospital patients are more likely to be exposed to a resistant organism and may have other risk factors that predispose them to enteric bacterial colonization when using acid suppressants.

While several of the observed risk factors associated with ESBL-E carriage have been previously documented, the association with higher BMI is a novel finding, according to the authors.

“The latter may play a role via alterations in gut microbiota composition and merits further study,” they wrote.
Sep 22 J Antimicrob Chemother study

Black fungus cases exemplify a need for in-house pharma, letter says

India’s black fungus (mucormycosis) surge and subsequent treatment shortages highlight a need for the country to on-shore pharmaceutical supply chains, according to a letter by six authors from St. Joseph’s College and other higher education institutes in India. The World Health Organization has noted that mucormycosis, which has an overall 50% case fatality rate, has an 80-fold higher prevalence in India than in developed countries (up to 140 infections per million people vs 1.7). It is commonly treated with the antifungal amphotericin B.

The letter, published yesterday in Infection Control & Hospital Epidemiology, says that despite the Indian government’s efforts to increase amphotericin B by exempting custom duties on imports, reallocating the drug, and creating new facilities for treatment, there was very little improvement to treatment access. The in-country manufacturers, Bharat Serums & Vaccines, BDR Pharmaceuticals, Sun Pharma, Cipla, and Life Care Innovations, didn’t have sufficient supplies on their own.

The authors add that on top of the black fungus cases, some cases of white fungus have been identified, which is of particular concern because of its association with multidrug-resistant nosocomial infections as well as its own frequent fluconazole and amphotericin B resistance.

“With the pandemic still looming over the country’s heads, it is imperative that efforts are made to invest in local pharma as a means of meeting the demand of the nation, and simultaneously reduce dependency and expenses on import,” they write. “Apart from all this, the ancient field of herbal and indigenous medicine in India, through the likes of Ayurveda and Unani should be re-examined and probed in the hopes of finding replacement options or cheaper, safe treatment options.”

International headlines have largely moved on from the black fungus surge in India, and a Hindustan Times article from Sep 3 says that the head of the ENT department at Delhi’s Sir Ganga Hospital was not seeing any active cases from patients coming in. Still, as of Jul 21, the BBC reported 45,374 cases and more than 4,300 deaths in India.
Sep 23 Infect Control Hosp Epidemiol letter


Study: COVID had mixed impact on US outpatient antibiotic use

Originally published by CIDRAP News Sep 23

A review of national prescription drug data finds a mixed picture on US outpatient antibiotic use in 2020, researchers reported yesterday in JAMA Network Open.

Using IQVIA National Prescription Audit data, researchers with the University of Pittsburgh and the VA Pittsburgh Healthcare System analyzed monthly prescription fills for commonly used outpatient antibiotics, including amoxicillin, azithromycin, amoxicillin-clavulanate, doxycycline, cephalexin, nitrofurantoin, ciprofloxacin, and levofloxacin.

Their analysis found that during the first quarter of 2020 (January through March), prior to the COVID-19 pandemic, mean monthly fills of each agent did not differ from anticipated values, which were based on prescription fill volumes from 2015 through 2019.

But in quarters 2 (April through June), 3 (July through September), and 4 (October through December), the mean monthly fills of amoxicillin, amoxicillin-clavulanate, and doxycycline were significantly lower than anticipated (amoxicillin, 25.3% to 44.1% decrease; amoxicillin-clavulanate, 30.1% to 40%; doxycycline, 17.8% to 20.7%).

Azithromycin fills were 35.4% lower in quarter 2 and 31.8% lower in quarter 4. Mean monthly cephalexin fills were 10.1% lower in quarter 4, and clindamycin fills were 4.8% lower than anticipated in quarter 3.

Mean monthly ciprofloxacin fills were 12.2% and 14.3% higher in quarters 3 and 4, respectively, reversing a 5-year trend of reductions in ciprofloxacin use.

The study authors say the reasons for the prescription patterns are unclear but suggest that widespread masking and other COVID-19 preventive measures may have curbed the type of bacterial respiratory infections that amoxicillin, azithromycin, amoxicillin-clavulanate, and doxycycline are used to treat. The lack of sustained reductions in cephalexin and clindamycin use and the increase in ciprofloxacin use may reflect their primary use against urinary tract and skin infections.

“We cannot exclude an association of factors unrelated to COVID-19, such as greater attention to antibiotic stewardship,” they wrote. “Further studies of antibiotic consumption during the COVID-19 pandemic are needed, with particular attention to drivers and appropriateness of use, regional differences, and antibiotic resistance.”
Sep 22 JAMA Netw Open study


Trial: Kids with chest infections don’t benefit from antibiotics

Originally published by CIDRAP News Sep 23

A randomized trial involving children with uncomplicated chest infections found that amoxicillin did not reduce the duration or severity of symptoms compared with placebo, British researchers reported yesterday in The Lancet.

The ARTIC (Antibiotics for lower Respiratory Tract Infection in Children) PC trial randomly assigned children 6 months to 12 years who had acute uncomplicated lower respiratory tract infections (LRTIs) to receive either 50 milligrams per kilogram (mg/kg) amoxicillin or placebo in three daily doses for 7 days. Both patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse for up to 28 days or until symptoms resolved.

A total of 432 children were enrolled in the study from November 2019 to March 2020, with 221 assigned to the antibiotics group and 211 to the placebo group. Key baseline characteristics were similar across the treatment groups. Complete data on symptom duration was available for 317 children. The median duration of moderately bad or worse symptoms was similar in the antibiotics group (5 days), compared with the placebo group (6 days), for a hazard ratio of 1.13 (95% CI, 0.90 to 1.42).

No differences between the treatment groups were observed in any of the five prespecified subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and shortness of breath), although the effect of antibiotics was slightly, but not significantly, greater in those with fever or who were unwell. There was no evidence of additional complications in children in the placebo group.

The study authors note that this is one of the few studies to examine effectiveness of antibiotics in young children with chest infections. Recent UK data shows at least 40% of children with chest infections receive antibiotics.

“Our results suggest that antibiotics do not provide a clinically important benefit on average for symptom reduction nor symptom severity,” they wrote. “Unless pneumonia is suspected, clinicians should provide so-called safety-netting advice (ie, explain what illness course to expect and when it would be necessary to reattend) but not prescribe antibiotics for most children presenting with chest infections.”
Sep 22 Lancet study


Fluoroquinolones tied to increased risk of acute liver injuries

Originally published by CIDRAP News Sep 22

A nationwide cohort study in Sweden found a twofold increased risk of acute liver injuries (ALIs) associated with oral fluoroquinolones in the first 2 months after starting treatment, researchers reported this week in Clinical Infectious Diseases.

Using individual data from national healthcare and drug registries, researchers investigated the risk of ALI in Swedish adults ages 40 to 85 who were prescribed oral fluoroquinolones or amoxicillin from July 2006 to January 2014. To reduce the influence of confounding from baseline health factors, they used propensity score matching. The main analysis and follow-up interval was 1 to 60 days after filling a prescription.

Comparing 419,930 courses of oral fluoroquinolones and amoxicillin, respectively, over the study period, the researchers found 18 events in the oral fluoroquinolones group and 8 in the amoxicillin group. There was an increased risk of ALI associated with oral fluoroquinolones, with a hazard ratio (HR) of 2.32 (95% CI, 1.01 to 5.35). The adjusted absolute risk difference for use of fluoroquinolones compared with amoxicillin in the 60-day period was 4.94 (95% CI, 0.04 to 16.3) per 1 million episodes. There were no observed differences in any subgroups.

The results align with previous studies that have found an increased risk of ALI associated with oral fluoroquinolones, which are one of the most widely used antibiotic classes and have also been linked with tendon injuries and heart-rhythm issues. While the absolute risk of ALI is low, the study authors note that the extensive use of fluoroquinolones needs to be considered.

“Naturally, the low absolute risk needs to be taken into consideration when weighing cost vs. benefit of initiating treatment with these drugs,” they wrote. “Nevertheless, the scope of the worldwide and extensive use of fluoroquinolones is substantial and also has to be factored into the overall picture.”
Sep 19 Clin Infect Dis abstract

Canadian study finds high antimicrobial use in preterm infants

Originally published by CIDRAP News Sep 21

A study of preterm newborns in Canada found high rates of antimicrobial use in the first 7 days after birth, researchers reported last week in Infection Control & Hospital Epidemiology.

Using data from the Canadian Neonatal Network, which covers 90% of neonatal intensive care unit (NICU) admissions in Canada, the researchers analyzed antimicrobial use in infants born earlier than 33 weeks gestational age (GA) to determine the proportion of preterm infants without culture-proven early-onset sepsis (EOS) or necrotizing enterocolitis (NEC) who received one or more antimicrobials during the first 7 days after birth. They also explored the variability in antimicrobial use between sites in different GA subgroups.

Out of 31,295 infants from 30 sites, 27,163 (85%) did not develop EOS or NEC ≥ stage 2 during their hospitalization and were included in the analysis. Among those infants, 44% born at 26 weeks or earlier, 21% born from 27 to 29 weeks, and 10% born from 30 to 32 weeks GA received an antimicrobial on day 7 of life. Those proportions dropped to 29%, 10%, and 4%, respectively, by day 14.

The site-level median antibiotic use rate values for those without EOS and/or NEC ≥ stage 2 were 0.15 for infants born at 26 weeks or earlier, 0.11 for infants born from 27 to 29 weeks, and 0.12 for infants born from 30 to 32 weeks GA, with significant variability across the individual sites in each GA group. This intersite variability persisted for infants in all three GA groups after adjusting for confounding variables.

The study authors note that although antimicrobials are the most commonly prescribed medication in NICUs and are administered shortly after birth to most preterm infants due to increased risk of infection, excessive antimicrobial exposure in newborns without EOS is associated with increased morbidity, mortality, and/or neurodevelopmental impairment. They say the findings suggest that decreasing antimicrobial exposure in preterm infants without infections could be an important antimicrobial stewardship program (ASP) target.

“Reduction of high rates of antimicrobial use at early postnatal age, particularly among lower GA infants at very low risk of developing EOS by applying 36- or 48-hour automatic stop order and regular audit and feedback can be important ASP strategies,” they wrote. “Standardizing and auditing the practice by developing nationwide NICU-specific ASP may help reduce interfacility variability in the long run.” 
Sep 17 Infect Control Hosp Epidemiol abstract


Trial: Probiotic doesn’t prevent ventilator-associated pneumonia

Originally published by CIDRAP News Sep 21

A randomized trial conducted among critically ill patients found that the probiotic Lactobacillus rhamnosus GG did not prevent ventilator-associated pneumonia (VAP) or other infections, researchers reported today in JAMA.

Conducted in 44 intensive care units (ICUs) in the United States, Canada, and Saudi Arabia, the trial enrolled critically ill adults predicted to require mechanical ventilation and randomly assigned them to receive L rhamnosus GG or a placebo twice daily.

Previous randomized trials have indicated that probiotics can reduce infection rates in critically ill patients by 20% and may decrease the risk of VAP by 25% to 30%, perhaps through enhanced gut barrier function, competitive inhibition of pathogenic bacteria, and modulation of the host inflammatory response. Investigators wanted to see if this particular strain might have a similar benefit.

The primary outcome was VAP. Secondary outcomes included other ICU-acquired infections (including Clostridioides difficile infection), diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality.

Of the patients included in the analysis, 1,318 received L rhamnosus GG, and 1,332 received a placebo for a median of 9 days. VAP developed in 289 of the 1,318 patients (21.9%) who received probiotics, compared with 284 of 1,332 (21.3%) in the placebo group (HR, 1.03; 95% CI, 0.87 to 1.22; absolute difference, 0.6%).

No significant differences were found between the two groups for any of the secondary outcomes. Fifteen patients who received probiotics (1.1%) experienced an adverse event, compared with only 1 (0.1%) in the placebo group (odds ratio, 14.02; 95% CI, 1.79 to 109.6).    

“These findings do not support the use of L rhamnosus GG for prevention of ventilator-associated pneumonia or other clinically important outcomes in critically ill patients,” the study authors concluded.
Sep 21 JAMA abstract


Antibiotic use in British poultry has declined dramatically, report shows

Originally published by CIDRAP News Sep 20

Antibiotic use by poultry farmers in the United Kingdom has declined by nearly 75% since 2012, according to a report last week by the British Poultry Council (BPC).

The BPC 2021 antibiotic stewardship report shows that UK farmers raising chickens, turkeys, and ducks used 21 tonnes of antibiotics in 2020, down from 81.7 tonnes in 2012, a decline of 74.2%. Use of fluoroquinolones and critically important antibiotics declined by 97.2% a 95.5%, respectively. Antibiotic use in chickens and turkeys is below the government-approved sector targets set by the Responsible Use of Medicines in Agriculture Alliance, which sets standards for food safety, animal health, and animal welfare in the British livestock industry.

The decline follows the 2011 establishment of the BPC Antibiotic Stewardship Scheme, under which the UK poultry sector has ended preventive use of antibiotics, introduced a voluntary ban on the use of third- and fourth-generation cephalosporins, committed to reducing fluoroquinolone use, and stopped using the last-resort antibiotic colistin.

“As the sector producing half the meat this country eats, our Antibiotic Stewardship plays a crucial role in delivering good bird health and welfare, ensuring responsible use of antibiotics, safeguarding the efficacy of antibiotics, and helping produce food people can trust,” BPC Chief Executive Richard Griffiths said in a BPC press release.
Sep 15 BPC 2021 antibiotic stewardship report
Sep 15 BPC press release

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