June 10, 2021, 5:05 p.m. News Staff — Two CDC-funded studies published in recent months appear to shed light on certain antibiotic prescribing trends seen during the COVID-19 pandemic, finding that although some short-term increases were seen among antibiotics specifically investigated as potential COVID treatment options, overall prescribing of antimicrobials was down compared with previous years.
“Trends in U.S. outpatient antibiotic prescriptions during the COVID-19 pandemic,” published online first on Dec. 29, 2020, by Clinical Infectious Diseases, focused on antibiotic prescriptions dispensed among outpatients from January through May 2020, comparing those totals with prescribing figures from the same period in 2017, 2018 and 2019.
Methodology. The study was based on data from nearly 49,000 U.S. retail pharmacies that was used to generate national projections of numbers of unique patients receiving dispensed prescriptions.
Researchers categorized antibiotic prescriptions by active ingredient and therapeutic class. Patients were categorized by age into three main groups: 19 years and younger, 20 to 64, and 65 and older. The study authors were then able to estimate the number of patients dispensed antibiotic prescriptions each month by agent, therapeutic class and patient age group.
The number of patients dispensed antibiotic prescriptions for each month averaged across all three years was used as a baseline. Expected seasonal changes in prescribing patterns were calculated by contrasting the averaged January totals with those for May.
The researchers then determined the percentage change from the number of patients dispensed antibiotic prescriptions averaged by month in 2017-2019 to the number who were dispensed antibiotic prescriptions by corresponding month in 2020. They also were able to calculate the change from the number of patients dispensed antibiotic prescriptions for the January 2017-2019 average to the May 2017-2019 average, as well as the change from January to May 2020.
Findings. During that January to May 2020 period, the number of patients dispensed antibiotic prescriptions decreased from 20.3 million to 9.9 million. That figure is 6.6 million fewer than would be seasonally expected based on 2017-2019 totals, representing an additional decrease of 33 percentage points beyond the expected seasonal decline.
Interestingly, although monthly numbers of patients with antibiotic prescriptions in 2020 were only slightly lower than 2017-2019 averages for January through March (i.e., decreases of 4% in January and February and 9% in March), differences for April and May 2020 were much larger (i.e., decreases of 39% and 42%, respectively) than 2017-2019 averages for these months.
These larger than seasonally expected drops in antibiotic prescriptions dispensed between January and May 2020 were seen across microbial agents and classes, with the largest seen in the penicillin (2.3 million fewer patients), macrolide (1.5 million fewer patients) and cephalosporin (1.1 million fewer patients) classes. Looking at changes among specific agents, amoxicillin accounted for 2.2 million fewer patients than expected and 34% of the total beyond seasonally expected decline in patients who received antibiotic prescriptions, and azithromycin accounted for 1.4 million fewer patients and 21% of the total beyond expected decrease.
As for percentage changes among patients dispensed antibiotic prescriptions for January through May 2020 compared with January through May 2017-2019 averages, cefdinir saw a 46 percentage point reduction and amoxicillin dropped by 43 percentage points.
It’s worth noting that although the number of patients dispensed azithromycin prescriptions declined overall from January to May 2020, that number actually rose 5% between February and March, but then plummeted 71% from March to May.
Among other trends observed:
The study authors speculated that the decreases in outpatient antibiotic prescribing observed may have been “driven by declines in non-COVID-19 disease transmission and by changes in health care access and care-seeking,” noting that other research has documented reductions in U.S. outpatient visits during the pandemic that aligned temporally with the drops in antibiotic prescribing. In addition, daycare and school closures, as well as other COVID-19 mitigation efforts, may have reduced transmission of respiratory illness that would normally require antimicrobial therapy.
“Trends for azithromycin differed temporally and geographically from trends for other antibiotics, with implications for patient safety and antimicrobial resistance,” the authors noted, pointing out that azithromycin, especially in combination with hydroxychloroquine, “was suggested as a potential therapy for COVID-19 among hospitalized patients based on extrapolations from in vitro studies of other respiratory infections, medical reports, and widely reported press conferences.”
“Compared with historic levels, increases in patients dispensed azithromycin prescriptions in March and April were highest in New York and New Jersey, which experienced high COVID-19 case counts during these months,” they wrote, adding that the increases were concerning for the following reasons:
Conclusions. Ongoing surveillance of antibiotic prescribing and related events is needed to evaluate the long-term effects of these changes in outpatient antibiotic trends, the authors concluded. “Shifts in health care delivery, particularly the use of telehealth, are likely to be sustained and should prompt assessment of effective antibiotic stewardship interventions to optimize antibiotic prescribing practices and ensure patient safety,” they recommended.
The study “Trends in Prescribing of Antibiotics and Drugs Investigated for Coronavirus Disease 2019 (COVID-19) Treatment in US Nursing Home Residents During the COVID-19 Pandemic,” published online first on March 10, 2021, by the same journal, targeted a much more specific patient population and covered a period from January 2019 to October 2020.
Methodology. Utilizing data from 1,944 nursing homes across the country, researchers assessed two categories of drugs: antibiotics ― particularly those commonly prescribed in the nursing home setting ― and drugs that were investigated for COVID-19 treatment, including co-prescribed azithromycin and hydroxychloroquine.
After accounting for seasonal variability in antibiotic prescribing, as well as the decline in nursing home residency seen during the pandemic, they used regression modeling to estimate the prevalence ratios for each agent prescribed in 2020 compared with 2019. They were then able to calculate the monthly relative percentage change from 2019 to 2020 to evaluate the impacts of COVID-19 on drug use in the nursing homes included in the study.
Findings. Prescribing of hydroxychloroquine and azithromycin per 1,000 residents between March and October 2020 exceeded 2019 totals. In April 2020, prescribing was 563% higher for hydroxychloroquine and 150% higher for azithromycin. Of residents who received azithromycin that month, 23% were co-prescribed hydroxychloroquine. Prescribing of these drugs declined in May 2020 but from July to October 2020, levels were still higher than those seen in 2019.
Nonantimicrobial agents that were investigated for use as COVID-19 treatments also saw significant prescribing upticks among this population from 2019 to 2020. In April 2020, for example, prescribing was 59% higher for famotidine and 155% higher for zinc compared with 2019 figures.
Notably, prescribing was 34% lower for prednisone and 36% lower for dexamethasone in April 2020 compared to 2019. In June 2020, however, dexamethasone prescribing increased, and by July, it was 303% higher than in 2019.
Total antibiotic prescribing among nursing home residents dropped 16% from January to June 2020, exceeding the 9% seasonal decrease seen for that period in 2019. From May through October 2020, total antibiotic prescribing prevalence was lower than in 2019, with a 4% lower prevalence in October 2020 compared with 2019.
Although total antibiotic prescribing in the study population was similar from January to April in both 2019 and 2020, when azithromycin is excluded, the rate of antibiotic prescribing dropped 12% in April 2020 compared with April 2019. That change can be attributed to a 150% increase in azithromycin prescribing in April 2020 compared with April 2019. Ceftriaxone use also saw a boost of 43% for that month compared with 2019.
Meanwhile, prescribing prevalence declined for various other commonly used antibiotics between April and October 2020 compared with 2019, including amoxicillin, levofloxacin, cefuroxime, cephalexin and trimethoprim-sulfamethoxazole.
The authors noted that increases and subsequent decreases in prescribing of certain drug therapies thought to be potentially effective against COVID-19 (i.e., hydroxychloroquine, azithromycin, famotidine, and dexamethasone) coincided with the release of specific information about these agents.
For example, the March 28, 2020, FDA emergency use authorization for hydroxychloroquine for treatment of SARS-CoV-2 infection sparked the 563% jump in use of this agent in April. Similarly, the FDA’s April 24 Drug Safety Communication warning of heart rhythm irregularities in patients with COVID-19 who had been treated with hydroxychloroquine, often in combination with azithromycin, coincided with the declines in prescribing rates for these two agents that were seen in May.
The authors cited a greater than seasonally expected decrease in total antibiotic use in the study’s nursing homes during the COVID-19 pandemic, which they suggested might be attributed to changes in health care delivery among these residents, as well as to changes in the resident population during the pandemic. In addition, a pandemic-induced drop in elective procedures may also bear responsibility, because post-op, short-stay residents typically have higher antibiotic use rates.
Still, more residents overall received antibiotic agents that are commonly prescribed for respiratory infections, including azithromycin, ceftriaxone and doxycycline, during the pandemic than before. Residents receiving antibiotic therapy for respiratory illness require appropriate testing, monitoring and follow-up so therapy can be adjusted or stopped if SARS-CoV-2 infection is confirmed and no evidence of bacterial co-infection or sepsis is found.
Conclusions. Overall, appropriate antimicrobial prescribing is essential to reduce risk of complications of antibiotic use, including adverse drug events and infection with multidrug-resistant organisms and Clostridioides difficile, the authors noted. “COVID-19-specific testing and treatment protocols that incorporate antibiotic stewardship principles can improve the diagnosis and treatment of residents with suspected infection with SARS-CoV-2 and other respiratory illnesses,” they concluded.