Randomized Prospective Controlled Trial of Recombinant Granulocyte Colony-Stimulating Factor as Adjunctive Therapy for Limb-Threatening Diabetic Foot Infection

Abstract

limb-threatening foot infection were consecutively enrolled in a prospective, randomized, controlled clinical study aimed at assessing the safety and efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) (lenograstim) as an adjunctive therapy for the standard treatment of diabetic foot infection. Forty patients, all of whom displayed evidence of osteomyelitis and long-standing ulcer infection, were randomized 1:1 to receive either conventional treatment (i.e., antimicrobial therapy plus local treatment) or conventional therapy plus 263 g of G-CSF subcutaneously daily for 21 days. The empiric antibiotic treatment (a combination of ciprofloxacin plus clindamycin) was further adjusted, when necessary, according to the results of cultures and sensitivity testing. Microbiologic assessment of foot ulcers was performed by both deep-tissue biopsy and swab cultures, performed at enrollment and on days 7 and 21 thereafter. Patients were monitored for 6 months; the major endpoints (i.e., cure, improvement, failure, and amputation) were blindly assessed at weeks 3 and 9. At enrollment, both patient groups were comparable in terms of both demographic and clinical data. None of the G-CSF-treated patients experienced either local or systemic adverse effects. At the 3-and 9-week assessments, no significant differences between the two groups could be observed concerning the number of patients either cured or improved, the number of patients displaying therapeutic failure, or the species and number of microorganisms previously yielded from cultures at day 7 and day 21. Conversely, among this small series of patients the cumulative number of amputations observed after 9 weeks of treatment appeared to be lower in the G-CSF arm; in fact, only three patients (15%) in this group had required amputation, whereas nine patients (45%) in the other group had required amputation (P ‫؍‬ 0.038). In conclusion, the administration of G-CSF for 3 weeks as an adjunctive therapy for limb-threatening diabetic foot infection was associated with a lower rate of amputation within 9 weeks after the commencement of standard treatment. Further clinical studies aimed at precisely defining the role of this approach to this serious complication of diabetes mellitus appear to be justified.

Melioidosis: Epidemiology, Pathophysiology, and Management

“…Multiple studies of G-CSF in nonneutropenic animal models have demonstrated improvements in outcome (172,276,312,322,433). In human studies, improvements in laboratory markers are seen following G-CSF use (186,242,360), and patients with diabetic foot infection may benefit from the use of G-CSF (134,175). However, large multicenter clinical trials have failed to demonstrate benefits in pneumonia and severe sepsis, possibly due to late administration of G-CSF in the course of the illness (85,310,311,361).…”

Autologous Transplantation of Granulocyte Colony–Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cells Improves Critical Limb Ischemia in Diabetes

“…However, some investigations reported that treatment by G-CSF improves symptoms but not signs of myocardial ischemia in patients with severe ischemic heart disease (25). The adjunctive treatment with G-CSF for 3 weeks was well tolerated but could not significantly affect the clinical and biological parameters of the healing process in diabetic patients with severe limbthreatening infection (26). We have also treated two patients with diabetic CLI G-CSF alone and have not observed obvious improvement of the main clinical manifestations at 12 weeks (data not shown).…”

Diagnosis and Treatment of Diabetic Foot Infections

“…Two adjunctive modalities do deserve brief comments. First, granulocyte colony-stimulating factors (G-CSFs) have now been investigated in 5 randomized trials involving diabetic foot infections [223][224][225][226][227]. A preliminary meta-analysis of these trials suggests that G-CSF does not accelerate resolution of infection but may significantly reduce the need for operative procedures (B-I) [228].…”