Effects of adjunctive treatment with combined cytokines in a neutropenic mouse model of multidrug-resistant Enterococcus faecalis septicemia.
OBJECTIVE
To examine whether the antienterococcal efficacy of a regimen of gentamicin plus vancomycin combined with granulocyte colony-stimulating factor (G-CSF) is enhanced by concurrent therapy with interferon-gamma (IFN-gamma).


METHODS
Hospital laboratory.


METHODS
Mice rendered neutropenic by cyclophosphamide were intraperitoneally inoculated with a gentamicin- and vancomycin-resistant Enterococcus faecalis isolate.


RESULTS
Infected animals were randomized into treatment groups that received G-CSF alone or in combination with various dosages of IFN-gamma. Additional groups of animals received vancomycin; G-CSF, G-CSF plus vancomycin, IFN-gamma, and G-CSF; or vancomycin with both cytokines. Addition of IFN-gamma to G-CSF regimen resulted in no significant change (p>0.05) in survival, compared with treatment with G-CSF alone. Also, the antienterococcal efficacy of antibiotic plus G-CSF was not modified by coadministration of IFN-gamma.


CONCLUSIONS
This study suggests that adjunctive application of combined cytokines may not be more beneficial than only G-CSF in combination with an antibiotic to treat multidrug-resistant enterococcal infection.
Department of Pharmacy, Hartford Hospital, Connecticut, USA.
D P
DP
Nicolau
C O
CO
Onyeji
M A
MA
Banevicius
J
J
Li
C H
CH
Nightingale
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination; D013293:Enterococcus faecalis; D005260:Female; D005839:Gentamicins / Q000494:pharmacology / Q000627:therapeutic use; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D051379:Mice; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy*; D011994:Recombinant Proteins; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D016207:Cytokines; D005839:Gentamicins; D011994:Recombinant Proteins; D014640:Vancomycin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor