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

Front Pain Res (Lausanne). 2026 Mar 18;7:1715446. doi: 10.3389/fpain.2026.1715446. eCollection 2026.

ABSTRACT

BACKGROUND: 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).

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

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

PMID:41930232 | PMC:PMC13039098 | DOI:10.3389/fpain.2026.1715446