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Observational Study
. 2025 Feb;53(1):359-372.
doi: 10.1007/s15010-024-02379-7. Epub 2024 Sep 9.

Efficacy and safety of colistin plus beta-lactams for bone and joint infection caused by fluoroquinolone-resistant gram-negative bacilli: a prospective multicenter study

Mikel Mancheño-Losa  1   2 , Oscar Murillo  3   4   5 , Eva Benavent  2   6 , Luisa Sorlí  2   7   8 , Melchor Riera  2   7   9 , Javier Cobo  2   7   10 , Natividad Benito  2   7   11   12 , Laura Morata  2   13 , Alba Ribera  2   14 , Beatriz Sobrino  2   15 , Marta Fernández-Sampedro  2   7   16 , Elena Múñez  2   17 , Alberto Bahamonde  2   18 , José María Barbero  2   19 , Mª Dolores Del Toro  2   7   20 , Jenifer Villa  21 , Raül Rigo-Bonnin  22 , Sonia Luque  7   23 , Isabel García-Luque  24 , Antonio Oliver  7   25 , Jaime Esteban  2   7   26 , Jaime Lora-Tamayo  1   2   7
Affiliations
Observational Study

Efficacy and safety of colistin plus beta-lactams for bone and joint infection caused by fluoroquinolone-resistant gram-negative bacilli: a prospective multicenter study

Mikel Mancheño-Losa et al. Infection. 2025 Feb.

Abstract

Objectives: The prognosis of bone and joint infections (BJI) caused by Gram-negative bacilli (GNB) worsens significantly in the face of fluoroquinolone-resistance. In this setting, scarce pre-clinical and clinical reports suggest that intravenous beta-lactams plus colistin may improve outcome. Our aim was to assess the efficacy and safety of this treatment in a well-characterized prospective cohort.

Methods: Observational, prospective, non-comparative, multicenter (14 hospitals) study of adults with BJI caused by fluoroquinolone-resistant GNB treated with surgery and intravenous beta-lactams plus colistin for ≥ 21 days. The primary endpoint was the cure rate.

Results: Of the 44 cases included (median age 72 years [IQR 50-81], 22 [50%] women), 32 (73%) had an orthopedic device-related infection, including 17 (39%) prosthetic joints. Enterobacterales were responsible for 27 (61%) episodes, and Pseudomonas spp for 17 (39%), with an overall rate of MDR/XDR GNB infections of 27/44 (61%). Patients were treated with colistin plus intravenous beta-lactam for 28 days (IQR 22-37), followed by intravenous beta-lactam alone for 19 days (IQR 5-35). The cure rate (intention-to-treat analysis; median follow-up = 24 months, IQR 19-30) was 82% (95% CI 68%-90%) and particularly, 80% (95% CI 55%-93%) among patients managed with implant retention. Adverse events (AEs) leading to antimicrobial withdrawal occurred in 10 (23%) cases, all of which were reversible. Colistin AEs were associated with higher plasma drug concentrations (2.8 mg/L vs. 0.9 mg/L, p = 0.0001).

Conclusions: Combination therapy with intravenous beta-lactams plus colistin is an effective regimen for BJI caused by fluoroquinolone-resistant GNB. AEs were reversible and potentially preventable by close therapeutic drug monitoring.

Keywords: Multidrug-resistant; Osteoarticular infection; Osteomyelitis; Polymyxins; Prosthetic joint infection.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose.

References

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