Adjunctive efficacy of granulocyte colony-stimulating factor on treatment of Pseudomonas aeruginosa pneumonia in neutropenic and non-neutropenic hosts.
OBJECTIVE
Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation of neutrophils and enhances their phagocytic and microcidal activity. Increasing resistance to existing antibacterials and the dearth of new alternatives have complicated the treatment of Gram-negative infections. The aim of this study was to evaluate the efficacy of G-CSF in the treatment of Pseudomonas aeruginosa pneumonia when administered in combination with ceftazidime in both neutropenic and non-neutropenic hosts.


METHODS
A group of mice were rendered neutropenic with cyclophosphamide. Pneumonia was induced by intratracheal instillation of approximately 5 x 10(7) cfu/mL and approximately 5 x 10(9) cfu/mL (LD(100)) of the organism to neutropenic and non-neutropenic mice, respectively. Two hours after inoculation, the mice received normal saline and 5% dextrose, G-CSF (300 micro g/kg per day x 3 days), ceftazidime (2000 mg/kg x 2 doses) or a combination of G-CSF and ceftazidime. Survival was monitored at different time points for 5 days.


RESULTS
Treatment with G-CSF showed a dose-dependent increase in survival from 50 to 300 micro g/kg. In neutropenic mice, survival was markedly better in the G-CSF + ceftazidime group compared with controls (P = 0.0001), G-CSF (P = 0.0002) or ceftazidime (P = 0.0172). In non-neutropenic mice, survival in the G-CSF + ceftazidime group (20%) was significantly higher than in the control and G-CSF groups (P = 0.0001) but not significantly higher than ceftazidime alone (9%) (P > 0.05).


CONCLUSIONS
G-CSF administered in combination with antibiotic after onset of severe P. aeruginosa pneumonia may improve therapeutic outcome and this suggests a new treatment option in the management of pneumonia especially in neutropenic patients.
Babalola
Chinedum P
CP
Center for Anti-Infective Research and Development and Division of Infectious Diseases, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA.
Nightingale
Charles H
CH
Nicolau
David P
DP
D000477:Alkylating Agents; D000818:Animals; D002442:Ceftazidime / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D003520:Cyclophosphamide; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D016019:Survival Analysis
D000477:Alkylating Agents; D002511:Cephalosporins; D004338:Drug Combinations; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D002442:Ceftazidime