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Updated: Jun 5, 2026
A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
Continuous local antibiotic perfusion for orthopaedic infections: A systematic review and pooled individual
Patrick Ze-En Ng1, Norio Yamamoto2,3, Mari Yamamoto2,4
1School of Medicine, IMU University, Kuala Lumpur, Malaysia.
Abstract:
BackgroundOrthopaedic infections are difficult to eradicate because biofilm and poor local vascularity limit antibiotic exposure. Continuous local antibiotic perfusion (CLAP) delivers sustained, titratable antibiotics directly into infected compartments. We used harmonised individual participant data (IPD) to quantify early effectiveness, longer-term control, safety, and patient-level modifiers.MethodsWe performed an IPD review of observational reports using CLAP as primary or adjunctive therapy (January-May 2025). The primary outcome was 30-days early response (C-reactive protein ≤3 mg/L or earliest sustained clinical/wound improvement). Secondary outcomes were durable infection control at ≥6 and ≥12 months using evaluable denominators with best-worst bounds, infection-free days) and safety. One-stage analyses used mixed-effects logistic regression; Restricted Mean Survival Time (RMST) was preferred when proportional hazards were violated. Multiple imputation supported inferences.ResultsEighty-one studies (n = 256) were included; 164 patients had observed time-to-response. Fifty-nine percent achieved a 30-days response; median time-to-response was 26 days. Implant involvement was associated with lower odds of 30-days response; trajectories were slower with implants and higher organism burden (polymicrobial ≥3), while osteomyelitis responded faster than fracture-related infection. RMST (30) showed delays with implants (+4.43 days) and polymicrobial infection (+6.74 days), and faster response for osteomyelitis versus fracture-related infection (-9.06 days). Durable control among evaluable patients was 88.4% at ≥6 months and 90.2% at ≥12 months, with best-worst bounds of 89.2-82.2% and 90.9-83.5%, respectively. Infection-free-day RMST supported substantial time free of recurrent infection within the first year. Adverse events were uncommon; renal events were generally reversible.ConclusionsCLAP achieved encouraging early response and high durability among evaluable patients, with slower trajectories when implants were retained or pathogen burden was high and faster responses in osteomyelitis. Safety appeared acceptable with monitoring. Prospective comparative studies using standardised endpoints, with RMST for non-proportional hazards, are warranted.
Insights
Continuous local antibiotic perfusion (CLAP) effectively treats orthopaedic infections, showing a 59% early response rate and high long-term durability. Factors like implants and polymicrobial infections slow response, but safety remains acceptable.
Area of Science:
- Orthopaedic Surgery
- Infectious Diseases
- Pharmacology
Background:
- Orthopaedic infections pose challenges due to biofilms and poor vascularity limiting antibiotic delivery.
- Continuous Local Antibiotic Perfusion (CLAP) offers a solution by delivering sustained, titratable antibiotics directly to infected sites.
- Harmonised individual participant data (IPD) is crucial for evaluating CLAP's effectiveness and safety.
Purpose of the Study:
- To quantify the early effectiveness of CLAP in treating orthopaedic infections.
- To assess the longer-term infection control and safety profile of CLAP.
- To identify patient-level factors influencing CLAP treatment outcomes.
Main Methods:
- An IPD review of 81 observational studies (n=256) using CLAP from January to May 2025.
- Primary outcome: 30-day early response (CRP ≤3 mg/L or clinical improvement).
- Secondary outcomes: Durable infection control (≥6 and ≥12 months), infection-free days, and safety, analyzed using mixed-effects logistic regression and Restricted Mean Survival Time (RMST).
Main Results:
- 59% of patients achieved a 30-day response, with a median time-to-response of 26 days.
- Implant involvement and polymicrobial infections were associated with slower response trajectories.
- Durable infection control was high (88.4% at ≥6 months, 90.2% at ≥12 months), with generally reversible adverse events.
Conclusions:
- CLAP demonstrates promising early effectiveness and high durability for orthopaedic infections.
- Treatment trajectories are influenced by implant retention and pathogen burden, with faster responses in osteomyelitis.
- Acceptable safety with monitoring supports further investigation through prospective comparative studies using standardized endpoints.
