Frequent and diverse use of antibiotics linked to severe Covid-19 side effects

7th July 2023

Patients with higher prior antibiotic use are more likely to experience severe Covid-19 outcomes after infection, including hospitalisation and death, a new study led by the University of Manchester has shown.

When infected with Covid-19, the chances of dying from complications due to Covid-19 is 1.34 times higher in patients with the most exposure to antibiotics than those without antibiotic exposure.

The research, published in The Lancet‘s eClinicalMedicine, is the first to explore how the severity of Covid-19 is affected by prior antibiotic use.

The UK team of scientists behind the work say the findings should act as a warning against the overuse of antibiotics.

Primary and secondary care data

Using the NHS OpenSAFELY platform, which enabled the researchers to look at electronic health records across primary and secondary care, the team examined data from 670,000 patients infected with Covid-19 between February 2020 and December 2021. The patients were reviewed for Covid-19 outcomes and divided into five groups based on the frequency with which they had taken antibiotics three years prior to infection.

Each group was further split based on the number of different antibiotics a patient used, giving the researchers an understanding of how the frequency and diversity of antibiotic use affect the body’s response to a Covid-19 infection. Of the sample, 98,420 patients were admitted to hospitals, 22,660 died, and 55 unique antibiotics were prescribed.

Patients with more frequent antibiotic exposure in the past three years were more likely to experience severe Covid-19 outcomes, including admission to hospital and death within 30 days.

The odds of being hospitalised due to a Covid-19 infection were 1.8 times higher for those with the highest history of antibiotic use and the most diversity of antibiotic use. Using a range of antibiotics was more likely to be associated with Covid-19 hospital admission, and using a larger range of antibiotic types was associated with more severe consequences of Covid-19 upon hospital admission.

Antibiotics and gut resilience

Professor Tjeerd van Staa, a principal investigator from the University of Manchester, said: ‘Our study has provided evidence that patients with high prior antibiotic use were more likely to experience severe Covid-19 outcomes. In addition, we also found an association between the number of different prior antibiotic types and Covid-19 related hospital admission.’

The researchers suggest this may be because frequent antibiotic use can increase the likelihood of patients being infected with viruses or bacteria, leading to an increased susceptibility to adverse consequences of infection.

Professor Van Staa added: ‘The literature shows that antibiotic treatment might alter gut microbiota, which can impact metabolic and immune function. While in most situations gut microbiota will recover after stopping an antibiotic course, frequent antibiotic use may affect the resilience of gut microbiomes more seriously.’

The researchers suggest that antibiotic guidelines should outline the possible adverse consequences of the overuse of antibiotics, and personalised patient leaflets could highlight these risks and the risks of the patient’s bacteria developing resistance to antibiotics.

Co-principal investigator Dr Victoria Palin from the University of Manchester said: ‘Common infection guidelines in England, as developed by the National Institute for Health and Care Excellence, focus on the treatment of the first infection episode. They do not provide guidance around repeated antibiotic use and a patient’s risk of developing resistance.’

She added: ‘There needs to be more awareness of the impact of long-term antibiotic exposure and its adverse outcomes. We would discourage regular and indiscriminate prescribing of these drugs for self-limiting infections.’

This article was originally published by our sister publication Nursing in Practice.

Antibiotic use in midlife women for at least two months associated with small decrease in cognition scores

8th April 2022

Antibiotic use among midlife women for two months and longer is linked to lower cognition scores when assessed approximately 7 years later

Antibiotic use for at least two months among midlife women has been found to be associated with a minor, but significant reduction in overall cognition scores when re-assessed approximately 7 years later. This was the conclusion of an analysis of women in the Nurses’ Health Study II by researchers from the Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, US.

Research has increasingly pointed to a connection between the gut-brain axis, linking emotional and cognitive centres of the brain with intestinal functions and especially the influence of the gut microbiota in these interactions. In fact, it is already established that there are microbiome composition links with mental health including quality of life and depression.

Antibiotic use negatively affect the balance of the gut microbiota and in fact, some evidence suggests that in women, use of antibiotics (for ≥ 2 months) in late adulthood is associated with a significant increased risk of cardiovascular disease.

Nevertheless, whether antibiotic use, which affects microbiome diversity, might also have a detrimental impact upon cognition is unclear although early exposure to antibiotics in the first 24 months of life may be associated with detrimental neuro-developmental outcomes, 11 years later. There is also some data showing how gut microbial alterations may also be associated with Alzheimer’s disease.

For the present study, the US team examined midlife antibiotic use among women and subsequent cognitive function which was assessed 7 years later. They used data from the Nurses’ Health Study II, which is an on-going prospective cohort study and in which participants complete detailed lifestyle, medication and health-related questionnaires every 2 years. In 2009, participants were asked to report on their total duration of antibiotic use into 7 categories, ranging from none to > 3 years, over the preceding 4 years. Since at the time, the mean age of participants was 54.7 years, this was called midlife antibiotic use. Approximately 7 years after 2009, the researchers administered the CogState battery which assesses global cognition, psychomotor function, learning and working memory. Antibiotic use was categorised as none, 1 – 14 days, 15 days to 2 months and 2 months+.

Regression analysis was undertaken to assess the relationship between the use of antibiotics and cognitive decline, adjusting for several factors including body mass index, smoking status, educational attainment.

Antibiotic use and cognition scores

A total of 14,542 women with a mean age of 61.7 years completed the cognitive testing and were included in the analysis.

Compared to non-antibiotic users, women using antibiotics for at least 2 months or longer, had mean global cognition scores that were lower by -0.08 standard units (95% CI -0.12 to – 0.073 p for trend = 0.002) in fully adjusted models. Similarly, for psychomotor speed and attention, the mean scores were -0.10 (95% CI -0.16 to -0.04, p = 0.004) and -0.06 (95% CI -0.11 to – 0.01, p = 0.03) for learning and working memory.

The authors concluded that chronic antibiotic use in midlife were associated with minor decreases in cognitive scores when assessed approximately 7 years later.

Citation
Mehta RS et al. Association of midlife antibiotic use with subsequent cognitive function in women PLoS One 2022