Molgramostim (GM-CSF) Associated With Antibiotic Treatment in Nontraumatic Abdominal Sepsis

Abstract

The addition of molgramostim (recombinant human granulocyte-macrophage colony-stimulating factor) to antibiotic therapy for nontraumatic and generalized abdominal sepsis is effective and has a significant impact on length of hospitalization, direct medical costs, and mortality. Design: Randomized, double-blind, placebo-controlled clinical trial. Setting: Tertiary referral center. Patients: Fifty-eight patients with abdominal sepsis. Interventions: Patients were allocated to receive, in addition to ceftriaxone sodium, amikacin sulfate, and metronidazole, molgramostim in a daily dosage of 3 µg/kg for 4 days (group 1) or placebo (group 2). Antibiotics were administered for at least 5 days and discontinued after clinical improvement had occurred and white blood cell count had been normal for 48 hours. Main Outcome Measures: Time to improvement, duration of antibiotic therapy, hospital stay, complications, mortality, and adverse reactions to drugs. Results: Median time to improvement was 2 days in group 1 and 4 days in group 2 (PϽ.005). Median length of hospitalization was 9 and 13 days, respectively (PϽ.001), and median duration of antibiotic therapy was 9 and 13 days, respectively (PϽ.001). Numbers of infectious complications in the 2 groups were, respectively, 6 and 16 (P=.02); of residual abscesses, 3 and 5; and of deaths, 2 and 2. Costs per patient were $12 333 and $16 081 (US dollars), respectively. Conclusion: Addition of molgramostim to antibiotic therapy reduces the rate of infectious complications, the length of hospitalization, and costs in patients with nontraumatic abdominal sepsis.

Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) for sepsis: a meta-analysis

“…Among the selected trials, three trials were conducted in North America [40,44,45], two in Europe [43,48], two in Asia [39,46] and two in Australia [41,47]. Five trials were multicenter studies [37,38,40,42,48].…”

“…Randomized allocation sequence was adequately generated in six trials [41-43,46-48], for the other six trials it was judged to be unclear based on the available documents [37-40,44,45]. Allocation sequences concealment was adequately reported in six trials [41,43,44,46-48] and was judged to be unclear in the other six trials [37-40,42,45].…”

A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury*

“…These trials have varied significantly in the clinical characteristics of the patients enrolled, the dose and duration of GM-CSF treatment, and the endpoints measured. Separately, they have demonstrated reduced evidence of leukocyte deactivation and more rapid resolution of sepsis (30), more rapid clinical improvement in abdominal sepsis (31), and improved leukocyte function and pulmonary gas exchange in patients with severe sepsis and respiratory dysfunction (32-33). Although the doses, site of administration, and duration of GM-CSF administration have varied, these studies together indicate that treatment with GM-CSF is well tolerated in patients with severe sepsis and suggest trends toward improvements in secondary endpoints.…”

Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies

“…Therapeutic protocols with GM-CSF, G-CSF and IFNγ have been conducted in sepsis with the aims to stimulate innate immune function, improve myelopoiesis and limit lymphocyte apoptosis. Small clinical studies in ICU patients with sepsis or trauma showed no effect to decrease mortality but there was a beneficial effect on illness severity and rate of pathogen clearance [38–42]. Interestingly, no study detected any adverse events.…”