# The role of oral amoxicillin/clavulanic acid in the treatment of osteomyelitis: a systematic review

**Authors:** Elena Sofia Giovanna Ercolin, Holger Bäthis, Benedikt Marche, Bertil Bouillon, Robin Otchwemah

PMC · DOI: 10.1007/s00068-025-03028-w · European Journal of Trauma and Emergency Surgery · 2026-01-22

## TL;DR

This paper reviews whether oral amoxicillin/clavulanic acid is an effective treatment for osteomyelitis, finding it to be a viable option with mild side effects.

## Contribution

The study systematically evaluates the effectiveness of oral amoxicillin/clavulanic acid for osteomyelitis in the absence of universal treatment guidelines.

## Key findings

- Amoxicillin/clavulanic acid shows non-inferiority to standard antibiotics for osteomyelitis.
- Pharmacokinetic data suggest AMC can effectively reach bone tissue with prolonged dosing.
- Adverse effects of AMC are mild compared to alternative antibiotics.

## Abstract

Osteomyelitis continues to pose significant challenges in clinical management, with no universally accepted treatment guidelines at either national or international level as of 2025. Amoxicillin/clavulanic acid (AMC) is a widely used β-lactam antibiotic known for its safety, tolerability, and broad-spectrum activity against common osteomyelitis pathogens. This work seeks to determine whether oral AMC could serve as a viable and effective option in the management of osteomyelitis based on the current treatment landscape of osteomyelitis.

Preferred Reporting Items for Systematic Reviews (PRISMA) were applied during the preparation of the article. For the structured search in PubMed®, The Cochrane Library, and UpToDate®, key research questions were defined and translated into specific search terms. Inclusion and exclusion criteria were defined using the population-intervention-comparison-outcome-study design strategy. All relevant publications available from 1981 to March 2025 were considered.

A total of 1,321 publications were identified. After applying in- and exclusion criteria - supported by automation tools − 104 publications were analysed. The number of primary studies specifically investigating AMC for osteomyelitis is limited. However, available data suggest that AMC is effective and demonstrates non-inferiority compared to standard reference antibiotics. Pharmacokinetic data indicate that prolonged and repeated dosing may enhance distribution into deeper compartments, including bone tissue. Reported adverse effects of AMC are generally mild to moderate, in contrast to alternative agents.

The analysis of the included publications and theoretical considerations on the treatment of osteomyelitis show that surgical debridement followed by long-term administration of AMC can be an effective option for empirical therapy.

## Linked entities

- **Chemicals:** amoxicillin/clavulanic acid (PubChem CID 6435924)
- **Diseases:** osteomyelitis (MONDO:0005246)

## Full-text entities

- **Genes:** HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}
- **Diseases:** penicillin allergy (MESH:D008586), cholestatic (MESH:D002779), lower back pain (MESH:D017116), gastrointestinal side effects (MESH:D064420), Kounis syndrome (MESH:D000074962), MRSA (MESH:D013203), Major Extremity Trauma (MESH:D004830), fatigue (MESH:D005221), sepsis (MESH:D018805), nausea and vomiting (MESH:D020250), aseptic meningitis (MESH:D008582), urinary tract infections (MESH:D014552), Infectious Diseases (MESH:D003141), adenopathy (MESH:D000072281), vomiting (MESH:D014839), jaundice (MESH:D007565), liver failure (MESH:D017093), gastrointestinal symptoms (MESH:D012817), diabetic foot infections (MESH:D017719), Neuropsychiatric disorders (MESH:D001523), decreased appetite (MESH:D001068), Steven-Johnson syndrome (MESH:D013262), bacterial infections (MESH:D001424), Native Vertebral Osteomyelitis (MESH:D010019), AKI (MESH:D058186), urticarial rash (MESH:D005076), drug-induced enterocolitis syndrome (MESH:D000081015), AGEP (MESH:D056150), Clostridioides difficile infection (MESH:D003015), type 4 hypersensitivity (MESH:D006969), foot infections (MESH:D007239), neuropsychiatric (MESH:C000631768), nephropathy (MESH:D007674), fractures (MESH:D050723), mesenteric (MESH:D008639), pruritus (MESH:D011537), congenital malformations (OMIM:163000), Cardiac arrhythmia (MESH:D001145), diarrhea (MESH:D003967), pseudomembranous colitis (MESH:D004761), allergic (MESH:D004342), tendon ruptures (MESH:D012421), purpura (MESH:D011693), QT prolongation (MESH:D008133), necrotic bone (MESH:D010020), cardiovascular death (MESH:D002318), pelvic infections (MESH:D034161), death (MESH:D003643), phototoxicity (MESH:D017484), AMC (MESH:D011015), DILI (MESH:D056486), Gastrointestinal complaints (MESH:D005767), Diabetic (MESH:D003920), AICN (MESH:D000092162), anaphylactic shock (MESH:D000707), nausea (MESH:D009325), dizziness (MESH:D004244), headaches (MESH:D006261), bone and joint infections (MESH:D001847)
- **Chemicals:** Vancomycin (MESH:D014640), Clindamycin (MESH:D002981), clavulanic acid (MESH:D019818), AMC (MESH:D019980), Cotrimoxazole (MESH:D015662), AICN (-), ciprofloxacin (MESH:D002939), macrolides (MESH:D018942), Quinolone (MESH:D015363), hydroxyapatite (MESH:D017886), beta-lactam antibiotic (MESH:D008997), beta-lactam (MESH:D047090), Piperacillin-tazobactam (MESH:D000077725), Ceftriaxone (MESH:D002443), Metronidazole (MESH:D008795), Amoxicillin (MESH:D000658), Fluoroquinolones (MESH:D024841), moxifloxacin (MESH:D000077266), glycopeptides (MESH:D006020), flucloxacillin (MESH:D005436), Cefuroxime (MESH:D002444), Doxycycline (MESH:D004318), Fusidic acid (MESH:D005672), Rifampicin (MESH:D012293), Methicillin (MESH:D008712), ofloxacin (MESH:D015242), Imipenem/cilastatin (MESH:D000077728), gentamicin (MESH:D005839), azithromycin (MESH:D017963)
- **Species:** Staphylococcus aureus (species) [taxon 1280], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Staphylococcus epidermidis (species) [taxon 1282], Bacteroides sp. (species) [taxon 29523], Enterobacterales (order) [taxon 91347], Streptococcus pyogenes (species) [taxon 1314], Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

20 references — full list in the complete paper: https://tomesphere.com/paper/PMC12827303/full.md

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Source: https://tomesphere.com/paper/PMC12827303