JAC Advance Access published online on May 5, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh237
© 2004 by The British Society for Antimicrobial Chemotherapy
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1 Center for Anti-Infective
Research and Development , Hartford Hospital,
80 Seymour Street, Hartford, CT 06102, USA
* To whom correspondence should be addressed. E-mail: dnicola{at}harthosp.org.
Objectives: 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 Results: Treatment with G-CSF showed a dose-dependent
increase in survival from 50 to 300 µg/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.
Revised February 12, 2004
Accepted March 15, 2004
Brief report
Adjunctive efficacy of granulocyte colony-stimulating
factor on treatment of Pseudomonas aeruginosa pneumonia
in neutropenic and non-neutropenic hosts
2 Center for Anti-Infective
Research and Development, and Division
of Infectious Diseases, Hartford Hospital,
80 Seymour Street, Hartford, CT 06102, USA
Abstract 
5 x 107 cfu/mL
and 5 x 109 cfu/mL
(LD100) 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 µg/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.
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