CRITICAL INFLUENCE OF TIMING OF ADMINISTRATION OF GRANULOCYTE-COLONY-STIMULATING FACTOR ON ANTIBACTERIAL EFFECT IN EXPERIMENTAL ENDOCARDITIS DUE TO PSEUDOMONAS-AERUGINOSA

The effect of human recombinant granulocyte colony-stimulating factor (hrG-CSF) in rabbits with aortic endocarditis due to Pseudomonas aerug inosa was investigated, hrG-CSF significantly increased the number of polymorphonuclear neutrophils in blood and in cardiac vegetations and the expression of the adhesin molecule CD11b on the surface of polymor phonuclear neutrophils compared with those of animals that had not rec eived hrG-CSF, When treatment was started 72 h after bacterial challen ge, hrG-CSF alone had no antibacterial effect and did not enhance the efficacy of ciprofloxacin when used in combination, even with the high er dosing regimen used (50 mu g/kg of body weight subcutaneously every 12 h for 4 days), in terms of number of positive blood cultures, bact erial counts in vegetations, and survival, In contrast, when treatment was started 30 min prior to bacterial challenge, hrG-CSF (50 mu g/kg injected every 12 h) decreased bacterial titers in vegetations 72 h la ter (6.5 +/- 0.9 versus 7.9 +/- 0.9 log(10) CFU/g of vegetation for hr G-CSF and controls, respectively; P = 0.0175). However, this antibacte rial effect was no longer detected after a 7-day treatment with hrG-CS F, and prophylactic administration of hrG-CSF did not increase the ant ibacterial effect of ciprofloxacin. We concluded that the antibacteria l effect of hrG-CSF in experimental endocarditis was related to the ti ming of its administration since hrG-CSF demonstrated a significant bu t transient antimicrobial effect only when treatment was initiated bef ore bacterial challenge.