# Incidence and risk factors for musculoskeletal adverse effects associated with daptomycin in patients receiving outpatient parenteral antimicrobial therapy

**Authors:** Meaghen B. Wiley, Kiya K. Bennett, Emily A. Siegrist, Stephen B. Neely, Joseph Sassine, Bryan P. White

PMC · DOI: 10.1017/ash.2025.10087 · 2025-07-31

## TL;DR

This study examines how often daptomycin causes muscle-related side effects in outpatient patients and identifies risk factors like male sex and cerebrovascular disease.

## Contribution

The study identifies specific risk factors for daptomycin-induced CPK elevation in outpatient settings, including male sex and cerebrovascular disease.

## Key findings

- 11.8% of patients experienced CPK levels above 500 U/L within 9–16 days of daptomycin therapy.
- Male sex and cerebrovascular disease were independent predictors of elevated CPK.
- Five patients (3.9%) developed rhabdomyolysis.

## Abstract

Daptomycin is preferred in outpatient parenteral antimicrobial therapy (OPAT) due to daily dosing. Elevations in creatine phosphokinase (CPK) of 3%–10% and musculoskeletal adverse events have been described with daptomycin, but data regarding risk factors and frequency of monitoring in the OPAT setting is limited. We evaluated the incidence and risk factors for CPK elevation and musculoskeletal adverse effects in patients receiving daptomycin OPAT.

This was a single-center, retrospective cohort study of adults on OPAT with daptomycin and at least two CPK values. The primary outcome was the incidence of CPK values greater than 500 U/L.

We included 127 patients. Most patients were male (55.1%), and the median age was 56 years (IQR 46–63). The most common indication was bone/joint infections (73.2%, n = 93). The median daptomycin dose was 7.4 mg/kg/day (IQR 6.1–8.1) and duration of therapy was 37 days (IQR 21–44). Fifteen patients (11.8%) experienced a CPK greater than 500 U/L within a median 13 days (IQR 9–16). Five patients (3.9%) developed rhabdomyolysis. Independent predictors of CPK>500 U/L included male sex (OR, 4.2 [95% CI, 1.05–16.61]; P = .0424) and cerebrovascular disease (OR, 11 [95% CI, 1.21–99.86]; P = .0332).

The incidence of CPK elevation was similar previously reported rates. This expands the literature to patients with daptomycin doses>6 mg/kg and prolonged durations of therapy. The incidence of CPK elevation and time to onset of 9–16 days supports the current recommendations for weekly lab monitoring.

## Linked entities

- **Chemicals:** daptomycin (PubChem CID 21585658)
- **Diseases:** cerebrovascular disease (MONDO:0011057), rhabdomyolysis (MONDO:0005290)

## Full-text entities

- **Genes:** PIK3C2A (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha) [NCBI Gene 5286] {aka CPK, OCSKD, PI3-K-C2(ALPHA), PI3-K-C2A, PI3K-C2-alpha, PI3K-C2alpha}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CMPK1 (cytidine/uridine monophosphate kinase 1) [NCBI Gene 51727] {aka CK, CMK, CMPK, UMK, UMP-CMPK, UMPK}
- **Diseases:** skin and skin structure infections (MESH:D012871), cerebrovascular accident (MESH:D020521), osteomyelitis (MESH:D010019), Infection (MESH:D007239), cancer (MESH:D009369), Endocarditis (MESH:D004696), Congenital immunodeficiency (MESH:D000081207), Infectious Diseases (MESH:D003141), ID (MESH:C537985), cerebrovascular disease (MESH:D002561), myalgia (MESH:D063806), OPAT (MESH:D015819), Myopathy (MESH:D009135), impaired renal function (MESH:D007674), GVHD (MESH:D006086), hypothyroidism (MESH:D007037), diabetes mellitus (MESH:D003920), rhabdomyolysis (MESH:D012206), Musculoskeletal (MESH:D009140), bone/joint infections (MESH:D001847), musculoskeletal adverse events (MESH:D064420), Bacteremia (MESH:D016470), obesity (MESH:D009765)
- **Chemicals:** Methicillin (MESH:D008712), Daptomycin (MESH:D017576), CMP (MESH:D003568), lipopeptide (MESH:D055666), steroids (MESH:D013256), vancomycin (MESH:D014640), atorvastatin (MESH:D000069059), alcohol (MESH:D000438), CrCl (-), Creatinine (MESH:D003404), prednisone (MESH:D011241)
- **Species:** Enterococcus faecalis (species) [taxon 1351], Staphylococcus aureus (species) [taxon 1280], Homo sapiens (human, species) [taxon 9606], Staphylococcus epidermidis (species) [taxon 1282], Human immunodeficiency virus (species) [taxon 12721], Human immunodeficiency virus 1 (no rank) [taxon 11676]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12322776/full.md

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Source: https://tomesphere.com/paper/PMC12322776