Antibiotics can influence varicella zoster virus reactivation


Tetracyclines have been shown to provide some degree of immune protection leading to mucosal scarring, and in this study they had one of the smallest associations with shingles.

New research has found a potential association between earlier antibiotics and varicella zoster virus reactivation, and this effect may be relatively long-term.

The effect of antibiotics on the human microbiome is well established, but their direct impacts on the associated immune response are less clear. Likewise, existing risk factors and studies have shown a clear link between shingles and cell-mediated immunity, but what triggers this immune response is unclear. One possibility is disruption of the patient’s microbiome.

Researchers know that antibiotics create some degree of dysbiosis in the microbiome, which may play a role in susceptibility to varicella zoster virus reactivation. There is also evidence that alterations in the gut microbiome can cause dysregulated mucosal immune responses leading, for example, to the onset of inflammatory bowel disease. Therefore, to understand the effects of antibiotics on varicella zoster virus reactivation, investigators conducted a case-control study comparing antibiotic prescriptions of patients with a diagnosis of shingles and those without.

Study researchers identified 163,754 patients with shingles and 331,559 age- and sex-matched controls. The analysis revealed that the risk of shingles is partly related to the number of antibiotics prescribed in the previous 10 years, although beyond the first 1 or 2 prescriptions the risk did not increase markedly . Sensitivity analyzes that included prescriptions issued during the one-year protopathic exclusion period showed similar results and the association of antibiotic prescription with shingles increased the earlier the first prescription was recorded.

The study could not examine the biological mechanisms that might underlie the association between shingles and antibiotics. However, the authors noted the growing body of evidence that the increased risk could be caused by microbiome dysbiosis and its subsequent effect on the immune response.

The gut microbiome has been shown to be associated with immune cell dynamics in humans and immune-mediated adverse reactions are a known short-term reaction to antibiotics. Animal studies have also suggested that the microbiome regulates virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection.

When examining the associations by age group, the largest associations were observed in the youngest group of patients aged 18-50 years. The smallest association was observed in subjects over 65 years of age.

There is also a significant amount of evidence that the immune response declines with age, which contradicts the study’s findings that younger patients are at greatest risk. Although shingles is more common in older patients, the authors said these findings suggest that younger patients may be more susceptible to damage from antibiotics despite having a stronger immune system. If this strength stems from immune plasticity, it could increase susceptibility to microbiome damage by antibiotics.

The association between antibiotic type and shingles showed some variability between tetracyclines with an adjusted odds ratio (aOR) of 1.30 and penicillins with an aOR of 1.87. Different antibiotics are known to affect the bacterial microbiome differently, but researchers don’t fully understand if this extends to the immune response.

Notably, however, tetracyclines have been shown to provide some degree of immune protection leading to mucosal scarring, and in this study they had one of the smallest associations with shingles.

Given the alteration of the immune response that allows the herpes zoster virus to reactivate, the researchers showed by an association between shingles and previous prescriptions of antibiotics that the latter could be involved in this reactivation. Perhaps most notably, this effect may be relatively long term. Any indirect effect of antibiotics on the immune response may be particularly important given the varying responses of individuals to viral infection.


Armstrong D, Dregan A, Ashworth M, White P. Earlier antibiotics and later shingles risk: a population-based case-control study. PLOS One; October 27, 2022. Accessed November 1, 2022.


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