Is Routine Measurement of the Serum C-Reactive Protein Level Helpful During Antibiotic Therapy for Diabetic Foot Infection?

SLR - December 2020 - Zachary A. Cohen

Reference: Pham TT, Wetzel O, Gariani K, Kressmann B, Jornayvaz FR, Lipsky BA, Uckay I. Is Routine Measurement of the Serum C-Reactive Protein Level Helpful During Antibiotic Therapy for Diabetic Foot Infection? Diabetes Obes Metab. 2020 Oct 7.

Level of Evidence: Level II

Scientific Literature Review

Reviewed By: Zachary A. Cohen, DPM
Residency Program: John Peter Smith Hospital – Fort Worth, TX

Podiatric Relevance: During the treatment of diabetic foot infections (DFI), clinicians frequently monitor serum (C-Reactive Protein) CRP levels serially to assess the evolution of infection. Evidence for monitoring CRP in DFI patients remains unclear, especially since the CRP can lag behind the clinical evolution by about two days. Failure of CRP levels to fall may trigger unnecessary diagnostic studies or therapeutic interventions even in the absence of clinical indications. This study correlated the CRP level at the enrollment and end of treatment periods to predict future treatment failure based on CRP levels alone.

Methods: Enrollment of 159 DFI patients in two separate prospective-comparative trials consisting of a short duration antibiotic group (80) and a long duration antibiotic group (79). Of the 159 patients, 66 were soft tissue infections only and 93 were soft tissue infections with osteomyelitis. The short duration arm therapy consisted of 10 days for soft tissue infection and 3 weeks for osteomyelitis, and the long duration arm therapy consisted of 20 days for soft tissue infection and six weeks for osteomyelitis. CRP levels were drawn on enrollment (day one), day 10, day 20, day 42, and end of treatment (day 60).

Results: Overall, 122 DFI episodes (77 percent) were clinically cured and 37 DFI episodes (23 percent) were failures after a median 53-day post-treatment. The osteomyelitis group remission rate was 84 percent in the short arm and 73 percent in the long arm antibiotic groups. The soft tissue only group remission rate was 77 percent in the short arm and 71 percent in the long arm antibiotic groups. Although the CRP levels in the failed episodes were slightly higher at both enrollment and end of treatment, the median CRP values at both time points were not statistically significant between groups. Also, the proportion of patients achieving normalization of their CRP and the relative CRP drop was the same in both groups. 

Conclusions: Using the data from two randomized trials with fixed antibiotic therapies for DFI’s, there was no association between the enrollment and end of treatment CRP between the cured and failed groups. Collecting CRP samples at different time points during ongoing therapy for DFI failed to predict the clinical outcomes. The authors recommend abandoning routine ordering of CRP. CRP levels are clinically unhelpful, waste money, lead to patient discomfort, increased time, and often leads to unneeded and excessive diagnostic evaluations.