Stewardship / Resistance Scan for Mar 23, 2021

News brief

Audit and feedback tied to improved antibiotic use in long-term care

Audit and feedback with peer comparison was associated with small reductions in prolonged antibiotic treatment in a study involving physicians and long-term care (LTC) facility residents in Ontario, Canadian researchers reported today in Clinical Infectious Diseases.

In the province-wide difference-in-differences study, researchers assessed antibiotic prescribing among 1,238 physicians caring for 96,185 resident. They compared the prescribing of 343 physicians who received a voluntary audit and feedback report and quarterly information on antibiotic prescribing in relation to their peers with 895 physicians who received no feedback. The report was launched in January 2019, and the study evaluated antibiotic prescribing in LTC facilities from 2018 through 2019.

The primary outcomes were the proportion of residents initiated on an antibiotic and the proportion of antibiotic prescriptions that lasted longer than 7 days in the year before and after the report was introduced. The researchers also embedded a pragmatic randomized controlled trial (RCT) within the study to compare a novel, dynamic feedback report with a static report.

The researchers observed a temporal decline in antibiotic initiation and duration between the first quarter of 2018 and the last quarter of 2019, with the proportion of residents initiated on an antibiotic dropping from 28.4% to 21.3%, and the proportion of treatments lasting longer than 7 days falling from 34.4% to 29%. Difference-in-differences analysis indicated that the audit and feedback report was associated with a greater decline in use of prolonged antibiotics (adjusted absolute difference, -2.65%; 95% confidence interval [CI], -4.93% to -0.28%), for an estimated total reduction of 335,912 days of antibiotic treatment after the intervention.

Audit and feedback not associated with a greater decline in antibiotic initiation (adjusted difference 0.10%; 95% CI, -0.51% to 0.61%), and the embedded RCT found no difference in outcomes between the dynamic and static reports.

"Audit and feedback is a pragmatic, scalable intervention to improve antibiotic use, and when coupled with evaluation systems using administrative databases it could generate sustainable and large reductions in antibiotic use," the study authors conclude.
Mar 23 Clin Infect Dis abstract

Trial finds no benefit from additional amoxicillin for acute sinusitis

The results of a randomized clinical trial indicate additional amoxicillin did not benefit adults receiving amoxicillin and clavulanate for acute sinusitis, researchers reported today in JAMA Network Open.

In the double-blind, comparative effectiveness trial, adult patients at Albany Medical Center in New York who had symptoms of acute sinusitis were randomly allocated to two treatment groups: the standard treatment of 875 milligrams (mg) of amoxicillin and 125 mg of clavulanate plus a placebo tablet, or a high-dose treatment of 875 mg of amoxicillin and 125 mg of clavulanate plus 875 mg of amoxicillin twice a day for 7 days. The purpose was to replicate a previous trial in which an unplanned subgroup analysis had found that higher-dose amoxicillin might provide a benefit.

The primary efficacy outcome was the percentage of patients who reported a Global Rating of Improvement (GRI) score of 5 or 6 ("a lot better" or "no symptoms") after 3 days of treatment. The primary safety outcome was a score of 3 ("severe") for diarrhea at day 3 or 10. A total of 157 patients, out of a projected 240, were enrolled in the study, with 79 receiving the standard dose and 78 the high dose; 9 and 12 patients, respectively, withdrew or were lost to follow-up before assessment of the primary outcome.

An unplanned interim analysis prompted by COVID-19 restrictions found that at day 3, a total of 31 of 70 patients in the standard-dose group (44.3%) reported a score of 5 or 6, compared with 24 of 66 (36.4%) in the high-dose group, for a difference of -7.9% (95% CI, -24.4% to 8.5%). At that point, the study was stopped for futility. Evaluation of safety data showed diarrhea was common in both groups at day 3, with 40.8% in the standard-dose group and 43.1% in the high-dose group reporting any diarrhea. Severe diarrhea was reported in 7.0% of the standard-dose patients and 7.7% of the high-dose group.

The study authors say the finding is disappointing, since the standard treatment has been found to provide only minimal benefits for acute sinusitis.
Mar 23 JAMA Netw Open study

News Scan for Mar 23, 2021

News brief

Infliximab associated with lower likelihood of COVID-19 antibodies

People with COVID-19 infections who also used the inflammatory bowel disease (IBD) drug infliximab had significantly fewer detectable antibodies than those who used vedolizumab, which treats IBD without the immune suppression, according to a study yesterday in Gut.

Dubbed CLARITY (ImpaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY), the study looked at 6,935 patients ages 5 and above with IBD from 92 UK hospitals from Sep 22 to Dec 23, 2020, and researchers plan to follow them up to 40 weeks thereafter. About two thirds (67.6%) of the cohort took infliximab, while the remainder took vedolizumab. Patients' median age was 39 years.

In both general seroprevalence surveys and seroconversion tests following laboratory-confirmed COVID-19 diagnoses, lower antibody presence was seen in those who took infliximab, raising the researchers' concerns about reinfection risk.

While 3.4% of the infliximab-treated group had SARS-CoV-2 seroprevalence, 6.0% of the vedolizumab-treated group did (seropositivity odds ratio [OR], 0.66; 95% confidence interval [CI], 0.51 to 0.87). Those who were on additional immunomodulators such as thiopurines and methotrexate compared with those who were not also had a reduced likelihood of being seropositive (OR, 0.70; 95% CI, 0.53 to 0.92).

Of people with confirmed COVID-19 infections, only 48.0% of the 81 treated with infliximab demonstrated seroconversion, compared with 83.3% of the 36 on vedolizumab. Additionally, the magnitude of anti-COVID reactivity was lower (median 0.8 cut-off index vs 37.0).

"The poor antibody responses observed in patients treated with infliximab raise the possibility that some patients may not develop protective immunity after COVID-19 infection, and might be at increased risk of reinfection," said study lead Tariq Ahmad, DPhil, MBChB, in a University of Exeter press release. "What we don't yet know is how use of anti-TNF drugs will impact antibody responses to vaccination." He is referring to anti-tumor necrosis factor drugs, which include infliximab and are effective treatments for immune-mediated inflammatory diseases.
Mar 22 Gut study
Mar 22 University of Exeter press release

COVID-19 pandemic linked with steady weight gain

After the United States' mid-March shelter-in-place began, a 269-person cohort gained on average 1.5 pounds every month, regardless of comorbidities or geographic location, according to a research letter published yesterday in JAMA Network Open.

While the study did not explore possible reasons, the researchers point to past articles that discuss a decrease in daily steps taken and self-reports of increased overeating and snacking during the initial shelter-in-place.

The researchers recorded an average of 28 weigh-ins per participant from Feb 1 to Jun 1, 2020. (Shelter-in-place orders occurred in 45 states from Mar 18 to Apr 6.) Almost half (48.3%) the participants were men, 77% were White, and average age was 52 years.

"Although this may not appear clinically important, prolonged effects as have occurred with the pandemic might lead to substantial weight gain," the researchers write. "The detrimental health outcomes suggested by these data demonstrate a need to identify concurrent strategies to mitigate weight gain, such as encouraging healthy diets and exploring ways to enhance physical activity, as local governments consider new constraints in response to SARS-CoV-2 and potential future pandemics."
Mar 22 JAMA Netw Open research letter

Countdown begins for end of DRC's Ebola outbreak

In the Democratic Republic of the Congo's (DRC's) latest Ebola outbreak, the last patient was discharged from a treatment center in Katwa yesterday, starting the 42-day countdown until the country is declared free of the virus again.

In an update on Twitter today, the World Health Organization (WHO) African regional office said the countdown began just 37 days after the virus reappeared in the country. The outbreak was declared on Feb 7. Early genetic analysis suggested that the virus resurgence was linked to contact with a survivor of the recent large outbreak centered in the DRC's North Kivu province.

So far, 12 cases, 1 of them listed as probable, have been reported in the DRC's 12th Ebola outbreak. Six people have died from their infections.

Elsewhere, Guinea's outbreak total remains at 18 cases, including 9 deaths, the WHO said in a separate Twitter update. So far, nearly 4,000 people have been vaccinated.
Mar 23 WHO African regional office tweet
Mar 23 WHO African regional office tweet on Guinea outbreak