Are Granulocyte Colony–Stimulating Factors Beneficial in Treating Diabetic Foot Infections?

Abstract

OBJECTIVE -To assess the value of granulocyte colony-stimulating factor (G-CSF) as adjunctive therapy for diabetic foot infections.RESEARCH DESIGN AND METHODS -We systematically searched the medical literature (including Medline, Embase, LookSmart, and the Cochrane Library) for prospective randomized studies that used G-CSF as an adjunct to standard treatment for diabetic foot infections. Using a conventional meta-analysis, we pooled the relative risks (RRs) for outcomes of interest, including resolution of infection, wound healing, duration of antibiotic therapy, and need for various surgical interventions, using a fixed-effects model. RESULTS -Five randomized trials, with a total of 167 patients, met our inclusion criteria. The methodological quality of the studies was satisfactory. The investigators administered various G-CSF preparations parenterally for between 3 and 21 days. The meta-analysis revealed that adding G-CSF did not significantly affect the resolution of infection or the healing of the wounds but was associated with a significantly reduced likelihood of lower extremity surgical interventions ], number of patients who needed to be treated: 4.5), including amputation (0.41 [0.17-0.95], number of patients who needed to be treated: 8.6). There was no evidence of heterogeneity among the studies or of publication bias, suggesting that these conclusions are reasonably generalizable and robust.CONCLUSIONS -Adjunctive G-CSF treatment does not appear to hasten the clinical resolution of diabetic foot infection or ulceration but is associated with a reduced rate of amputation and other surgical procedures. The small number of patients who needed to be treated to gain these benefits suggests that using G-CSF should be considered, especially in patients with limb-threatening infections. Diabetes Care 28:454 -460, 2005F oot infections in patients with diabetes can be difficult to treat, and therapeutic failure often leads to a lower-extremity amputation (1,2). These infections may be refractory to treatment for several reasons, including inadequate surgical interventions, suboptimal wound care, or severe limb ischemia (3). All infected foot lesions require antibiotic therapy, but their penetration to infected soft tissue and bone may be inadequate, and the incidence of antibiotic resistance is increasing (4). Furthermore, diabetes may cause immunological deficiencies, including abnormal neutrophil chemotaxis, phagocytosis, and intracellular killing (5-7). These factors help explain reported clinical failure rates for diabetic foot infections of 20 -30% (3,5-7). Thus, several investigators have sought adjunctive therapies for treating these potentially severe infections.Granulocyte colony-stimulating factor (G-CSF) is an endogenous hematopoietic growth factor that induces terminal differentiation and release of neutrophils from the bone marrow (8). G-CSF stimulates the growth and improves the function of both normal and defective neutrophils (9), including in patients with diabetes (10). It appears to play a c...

Polymers in Wound Repair

“…Similarly, granulocyte macrophage colony stimulating factor (GM-CSF) has been also showed promising for wound treatment in vitro, mainly due to the stimulation of VEGF production [58]. Other studies have given encouraging results in clinical trials on patients with venous stasis ulcers [59] and diabetic-foot ulcers [60]. However, cytokines should not be considered individually, because in vivo they function in complex networks and cascades, frequently exhibiting antagonism (the effects of one cytokine may be inhibited by another cytokine).…”

Risk Factors for Foot Infections in Individuals With Diabetes

“…Foot ischemia certainly appears to be associated with an increased severity of an infection (36). Diabetic patients often have a diminished inflammatory response to injury or infection (37)(38)(39)(40)(41)(42)(43); this deficit could be further impaired by ischemia. Diminished blood flow could result in a lack of erythema or induration, visual cues of infection.…”

A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes

“…In contrast, the effect of G-CSF was studied primarily to determine whether its use may help eradicate infection, and published trials were of either too small or too short a term to demonstrate an effect on healing when it was included as a secondary endpoint. Nevertheless, a small meta-analysis suggested that G-CSF may lead to a reduced incidence of major amputation in limbthreatening infection [85].…”