Stewardship / Resistance Scan for Sep 23, 2021

News brief

Study: COVID had mixed impact on US outpatient antibiotic use

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

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% confidence interval [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

News Scan for Sep 23, 2021

News brief

COVID-related syndrome in adults severe, hard to diagnose, study finds

Multisystem inflammatory syndrome in adults (MIS-A) is a rare but severe hyperinflammatory condition that begins roughly 4 weeks after COVID-19 symptom onset and likely results from an outsized immune response, concludes a systematic review yesterday in JAMA Network Open.

Researchers from the US Centers for Disease Control and Prevention conducted a literature review from May 1, 2020, to May 25, 2021, identifying 221 patients around the world diagnosed as having MIS-A. First identified in children (MIS-C) in April 2020, the syndrome has since also been recognized in adults.

MIS-A typically emerges about 4 weeks after COVID-19 symptoms began, producing inflammation and involving a median of five nonpulmonary organs, the authors report. Clinical presentations vary, but the organ systems most often affected were hematologic (92%), cardiovascular (87%), gastrointestinal (83%), and respiratory (74%).

Thirty percent of 205 patients had myocarditis, or inflammation of the heart muscle, and 25% of 175 had pericardial effusion, or fluid buildup around the heart.

Eleven percent of 94 patients were diagnosed as having Kawasaki disease. Of 195 patients, 90% had higher-than-normal concentrations of coagulation and/or inflammation markers, and 5% had arterial or venous thrombosis (blood clots), while 72% of 194 patients had SARS-CoV-2 antibodies.

Median hospital stay was 8 days, and 57% of patients required intensive care, 47% received respiratory support, and 7% died. Sixty-eight percent of 149 patients reported having a symptomatic coronavirus-like illness a median of 28 days earlier.

Common symptoms included fever (96%), low blood pressure (60%), cardiac dysfunction (54%), shortness of breath (52%), and diarrhea (52%). Median patient age was 21 years, 70% were men, 36% were Black, and 58% had no underlying illness.

The authors noted that it can be difficult to distinguish biphasic COVID-19 from MIS-A because MIS-A is complicated by the occurrence of other types of coronavirus-related inflammation, and much more research is needed. "It is important for the clinical and public health community to suspect and identify MIS-A…by exercising clinical acumen and considering empirical treatment to reduce related morbidity and mortality," they wrote.
Sep 22 JAMA Netw Open study

Study estimates Israeli COVID vaccination averted thousands of deaths

Writing in The Lancet Infectious Diseases yesterday, Israeli scientists estimate that, without the national vaccination campaign, Israel would have had triple the number of hospitalizations and deaths compared with what actually occurred during its latest and largest wave of COVID-19, which could have overwhelmed its healthcare system.

From Dec 20, 2020, to Apr 10, 2021, Israel launched a massive national COVID-19 vaccination campaign with the two-dose mRNA vaccine made by Pfizer-BioNTech. Approximately 74% of the country's population aged 16 and older were fully vaccinated by Apr 10, making Israel's the fastest and most comprehensive vaccination campaign in the world.

Even in the face of rising breakthrough cases caused by the Delta (B1617.2) variant and evidence of some waning protection against mild infections, the study authors estimate the vaccination campaign averted 158,665 SARS-CoV infections (95% confidence interval, 144,640 to 172,690), 24,597 hospitalizations (18,942 to 30,252), 17,432 severe or critical hospitalizations (12,770 to 22,094), and 5,532 deaths (3,085 to 7,982) during the study period.

During that period, Israel reported 13,338 hospitalization (8,429 of which were severe or critical), and 2,859 deaths from COVID-19.

In a commentary on the study, Frank Sandmann, PhD, and Mark Jit, PhD, MPH, said the research, "documents the immense success that rapid COVID-19 vaccine roll-out had in terms of reducing COVID-19-related morbidity and mortality at the population level."
Sep 22 Lancet Infect Dis study
Sep 22 Lancet Infect Dis commentary