# Antibiotic therapy as a risk factor for chronic residual and phantom limb pain after combat-related amputation: a 212-patient cohort study

**Authors:** Kateryna Ksenchyna, Oleh Ksenchyn, Oleksandr Nazarchuk, Dmytro Dmytriiev

PMC · DOI: 10.3389/fpain.2026.1715446 · Frontiers in Pain Research · 2026-03-18

## TL;DR

This study finds that prolonged or combined antibiotic use after combat-related amputations increases the risk of chronic residual and phantom limb pain.

## Contribution

The study identifies antibiotic therapy duration and combination as novel risk factors for chronic post-amputation pain in military patients.

## Key findings

- 94 out of 212 patients (44.3%) developed chronic residual or phantom limb pain.
- Prolonged antibiotic use (>21 days) and combined regimens increased chronic pain risk.
- Neuropathic pain was more common in patients exposed to fluoroquinolones or metronidazole.

## Abstract

Antibiotic (AB) therapy is standard in managing combat-related infections, particularly after traumatic limb amputations. However, prolonged or combined antibiotic regimens may contribute to neuroinflammatory processes that predispose patients to chronic post-amputation pain (ChPAP), which combines the consepts of chronic residual limb pain (RLP) and phantom limb pain (PLP).

To investigate associations between antibiotic use (duration, type, and combination) and the development of RLP and PLP in post-amputation military patients.

This retrospective cohort study evaluated 212 military personnel treated between 2022 and 2024 for traumatic amputations. Antibiotic regimens, pain intensity, type, and chronicity were analyzed.

Chronic RLP/PLP developed in 94 patients (44.3%). Prolonged antibiotic use (>21 days) and combined regimens (≥2 antibiotics) were) were related with increased ChPAP risk in limbs Neuropathic pain was predominant in patients exposed to fluoroquinolones or metronidazole.

Extended and multi-agent antibiotic therapy was associated with ChPAP after combat-related limb amputation. Personalized antimicrobial stewardship and early pain screening are recommended in this high-risk population.

## Linked entities

- **Chemicals:** metronidazole (PubChem CID 4173)

## Full-text entities

- **Diseases:** Neuropathic pain (MESH:D009437), infections (MESH:D007239), RLP (MESH:D018365), PLP (MESH:D010591), ChPAP (MESH:D059350), neuroinflammatory (MESH:D000090862), pain (MESH:D010146)
- **Chemicals:** fluoroquinolones (MESH:D024841), metronidazole (MESH:D008795)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13039098/full.md

## References

24 references — full list in the complete paper: https://tomesphere.com/paper/PMC13039098/full.md

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Source: https://tomesphere.com/paper/PMC13039098