Study: Antibiotics May Influence Reactivation of Varicella Zoster Virus


Tetracyclines have been shown to offer some degree of immune protection resulting in mucosal healing, and in this study, they had one of the smaller associations with herpes zoster.

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

The effect of antibiotic medications on the human microbiome has been well established, but their direct impacts on the related immune response is less clear. Similarly, existing risk factors and studies have shown a clear link between herpes zoster and cell-mediated immunity, but what triggers that immune reaction is unclear. One possibility is a disturbance in the patient’s microbiome.

Researchers do 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 some evidence that alterations of the gut microbiome may cause dysregulated mucosal immune responses leading, for example, to the onset of inflammatory bowel diseases. Therefore, to understand the effects of antibiotics on reactivation of varicella zoster virus, investigators conducted a case control study comparing the antibiotic prescriptions of patients with a herpes zoster diagnosis and those without.

The study investigators identified 163,754 patients with herpes zoster and 331,559 age- and sex-matched controls. The analysis found that the risk of herpes zoster is partly related to the number of antibiotics prescribed over the previous 10 years, though beyond the first 1 or 2 prescriptions the risk did not increase markedly. Sensitivity analyses that included prescriptions issued during the 1-year protopathic exclusion period showed similar results and the association of antibiotic prescription with herpes zoster increased the earlier a first prescription was recorded.

The study could not examine biological mechanisms that might underpin the association between herpes zoster and antibiotics. However, the authors noted the growing body of evidence that the increased risk might 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 effects 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 to 50 years. The smallest association was seen 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 have the greater risk. Although herpes zoster is more common in older patients, the authors said these findings suggest that younger patients may be more susceptible to antibiotic damage despite stronger immune systems. If that strength derives from immune plasticity, this might increase vulnerability to microbiome damage by antibiotics.

The association between antibiotic type and herpes zoster showed some variability from tetracyclines with an adjusted odds ratio (aOR) of 1.30 to penicillins with an aOR of 1.87. Different antibiotics are known to affect the bacterial microbiome differently, but researchers do not fully understand whether this extends to the immune response.

Notably, however, tetracyclines have been shown to offer some degree of immune protection resulting in mucosal healing, and in this study, they had one of the smaller associations with herpes zoster.

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


Armstrong D, Dregan A, Ashworth M, White P. Prior antibiotics and risk of subsequent Herpes zoster: A population-based case control study. PLOS One; October 27, 2022. Accessed November 1, 2022.

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