Stewardship / Resistance Scan for Nov 11, 2021

News brief

Study highlights non-medical factors behind irresponsible antibiotic use

Non-prescription and irresponsible antibiotic use are prevalent across the world and are largely influenced by non-biomedical factors, an international team of researchers reported this week in Clinical Microbiology and Infection.

The review and meta-analysis of 71 studies covering 52 countries, many of them low- and middle-income countries (LMICS), explored the non-biomedical factors that influence healthcare consumers' antibiotic use globally. The aim was to develop a better understanding of what drives community antibiotic use in different parts of the world, and how future mitigation policies could help improve antibiotic use practices.

The analysis revealed a wide range of irresponsible antibiotic use in all regions. Self-medication with antibiotics for therapeutic purposes was reported in 48 studies from 40 countries, with a prevalence ranging from 3.1% (in 19 European countries) to 82% (Qatar) among adults, and from 3.3% (the United States) to 62% (China) among children.

The prevalence of prophylactic self-medication with antibiotics ranged from 6.0% (Serbia) to 33.4% (China). Over-the-counter purchasing of antibiotics was reported in 34 studies from 35 countries and ranged from 5.2% (Lebanon) to 88.8% (Tanzania). The prevalence of household storage of antibiotics ranged from 6.5% (Hong Kong) to 80.5% (Pakistan).

Antibiotic use was found to be heavily influenced by individuals' sociodemographic variables, perceptions of vulnerability and susceptibility to infections, and access to drugs. In addition, social-contextual factors such as barriers to healthcare resulted in avoiding medical interactions, purchasing antibiotics over-the-counter, and self-medicating. The meta-analysis further identified older age, living in rural areas, storing antibiotics at home, having relatives with medical backgrounds, and bearing a positive attitude towards self-medication with antibiotics to be risk factors for self-medication with antibiotics.

"This study identified the non-biomedical factors that drive antibiotic use in the community within different cultural contexts, highlighting the complexity of the challenge," the study authors wrote. "Future AMR [antimicrobial resistance] strategies that aim to reduce antibiotic use without clinical indication should incorporate a multifaceted community-based design that addresses non-biomedical drivers tailored to local contexts."
Nov 9 Clin Microbiol Infect study

Beta-lactam plus doxycycline tied to better pneumonia outcomes in elderly

A retrospective study of elderly pneumonia patients treated at Department of Veterans Affairs (VA) hospitals found that use of doxycycline as part of guideline-concordant therapy was associated with lower mortality than regimens without doxycycline, researchers reported this week in Clinical Infectious Diseases.

Of the 70,533 patients 65 and older who were hospitalized with community-acquired pneumonia (CAP) at VA hospitals from 2002 through 2012, 5,282 (7.5%) received empiric therapy with a beta-lactam antibiotic plus doxycycline. That combination is an alternative regimen recommended for CAP under 2019 American Thoracic Society/Infectious Diseases Society of America guidelines, but prior to this study, there was limited evidence supporting its use.

To evaluate its efficacy, researchers compared 30- and 90-day mortality in patients who received a beta-lactam plus doxycycline with those who received other guideline-concordant regimens, using propensity score matching to balanced measured confounders between groups.

The unadjusted 30- and 90-day mortality rates were 6.4% and 13.8% for those who received a beta-lactam plus doxycycline, respectively, versus 9.1% and 16.8% in those who did not. In the propensity-score matched models, both 30-day (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.63 to 0.84) and 90-day (OR, 0.83; 95% CI, 0.74 to 0.92) mortality were significantly lower for those who receive doxycycline.

"With growing antibiotic resistance to frontline agents, there is an urgent need for exploring and promoting newer antibacterial regimens to address the escalating burden of CAP," the study authors wrote.

"Our study suggests that an empiric regimen of beta-lactam and doxycycline is associated with similar, or better, outcomes compared to other guideline concordant empiric therapies. Randomized control trials are needed to confirm this finding and to identify the best therapies for patients hospitalized with CAP."
Nov 9 Clin Infect Dis abstract

News Scan for Nov 11, 2021

News brief

Tests reveal much higher COVID rate in unvaccinated nursing home staff

Positive COVID-19 test results were more than 10 times more common among unvaccinated, asymptomatic healthcare professionals (HCP) in Veterans Health Administration (VHA) long-term care facilities than among their fully vaccinated counterparts, according to a research letter yesterday in JAMA Network Open.

Researchers at the VA Boston Healthcare System tracked mandatory weekly COVID-19 test results among 1,269 HCP and twice-weekly antigen testing among 704 more from Jan 15 to Jun 8, 2021.

Each month, lower rates of COVID-19 infection were identified in vaccinated versus unvaccinated asymptomatic HCP. Of 52,557 tests of 1,973 HCP, 25 (1.3%) tested positive for COVID-19 (0.3% vaccinated, 3.6% unvaccinated). Contact tracing linked one HCP infection with an asymptomatic, fully vaccinated resident.

By the end of the study period, 70.3% of HCP and 90% of residents were fully vaccinated. Infection rates began to decline in both groups along with a drop in community transmission.

"The yield of positive test results was much higher in HCP who were unvaccinated than those who were vaccinated, consistent with an evolving literature that suggests full vaccination status reduces asymptomatic SARS-CoV-2 infection in HCP," the study authors wrote.

"The observation that surveillance was primarily beneficial in HCP who were unvaccinated during periods of high community transmission is consistent with recent guidance from the Centers for Disease Control and Prevention and presents a quandary regarding how to identify and differentially test HCP who are unvaccinated in the absence of mandatory vaccination policy," they added.

The researchers noted that the proportion of false-positive COVID-19 tests will increase as infection rates fall, even among unvaccinated HCP, which will sometimes lead to unnecessary quarantine of essential HCP.

"Hence, the utility of frequent surveillance will vary as a function of the rate and trend of community transmission, vaccination status of HCP and residents, and the transmissibility of variant strains of SARS-CoV-2," they said.
Nov 10 JAMA Netw Open research letter

Study shows cancer patients can safely receive COVID-19 vaccines

A study yesterday in the Journal of Clinical Oncology shows COVID-19 vaccines are safe in people undergoing treatment for cancer and produce modestly impaired immune responses. Booster vaccine doses, however, enhance immunity.

The study was based on 762 active oncology patients at Massachusetts General Hospital, who were compared to 1,638 healthy controls. The patients were currently receiving cancer treatments, including chemotherapy, bone marrow transplants, corticosteroids, and radiation. All three vaccines currently used in the United States were included in the study.

The mRNA vaccines elicited a stronger immune response in cancer patients than the Johnson & Johnson adenovirus-based vaccine. But regardless of vaccine type, antibody titers and neutralization were quantitatively lower in cancer patients, the authors said. Prior COVID-19 infection (7.1% of the cohort) was associated with higher immune responses, and older patient age was associated with a diminished vaccine response.

Thirty-two cancer patients included in the study also had received a third booster dose of vaccine. In 30 of 32 study subjects, researchers recorded increased antibody titers (geometric mean concentration, 1.05 before the additional dose, 3.17 after). The Centers for Disease Control and Prevention now recommends all immunocompromised vaccine recipients, including cancer patients, receive a booster dose.

"Our data suggest that patients with cancer should receive mRNA vaccines," said co-lead investigator Justin Gainor, MD, director of the Center for Thoracic Cancers at Massachusetts General Hospital, in a press release. "In addition, patients who received the J&J [Johnson & Johnson] vaccine should be considered for additional vaccine doses."

Side effects were no worse in study subjects compared to controls.
Nov 10 J Clin Oncol study

Multivalent Ebola vaccine enters clinical trial

Oxford University today announced the launch of a multivalent (multi-strain) Ebola virus vaccine, which targets the two species likely to infect humans.

The small phase 1 trial is enrolling 26 healthy UK adults ages 18 to 55 with the goal of assessing immune response and safety, the university said in a statement. The vaccine targets the Zaire and Sudan strains and uses the same adenovirus vector as the AstraZeneca-Oxford COVID-19 vaccine.

Participants will receive one dose and be monitored over the next 6 months. Researchers expect results in the second quarter of 2022. Another phase of the trial is expected to launch in Tanzania by the end of 2021.

Daniel Jenkin, MBChB, MSc, principal investigator, said Ebola can be caused by different species, and each may require a targeted immune response to offer protection. He added that nearly all Ebola cases and deaths have been caused by the two species contained in the vaccine.

Also, Paola Cicconi, MD, the trial's chief investigator, said there's an unmet need for a multivalent vaccine, and experience with the AstraZeneca-Oxford COVID-19 vaccine shows that a product using the same adenovirus vector can be rapidly scaled up at a low cost and can be kept in storage conditions suited to developing countries.
Nov 11 Oxford University statement