Evaluation of trovafloxacin in the treatment of Klebsiella pneumoniae lung infection in tumour-bearing mice.
Trovafloxacin, a new trifluoroquinolone, was evaluated for its therapeutic efficacy against Klebsiella pneumoniae lung infection in tumour (P388 murine leukaemia cells)-bearing mice, treated with or without a chemotherapeutic agent, daunorubicin (DNR) and in mice without tumour. Its activity was compared with ciprofloxacin and cephazolin. The effect on therapeutic efficacy of the addition of recombinant granulocyte colony stimulating factor (rGCSF) was also examined. Our study showed that both quinolones successfully cured pneumonia owing to infection with K. pneumoniae in mice without tumours but that all antibiotics failed in tumour-bearing mice if DNR was withheld. Substantial differences were noted in DNR-treated tumour-bearing mice with infection-the cure rate with trovafloxacin was 91% whereas the cure rate with ciprofloxacin or cephazolin was 57%. Addition of rGCSF to ciprofloxacin did not substantially improve its efficacy (when assessed by protection against death owing to infection; the survival rate was 41%). Trovafloxacin cure rates ranged from 80 to 90% whether or not rGCSF was added to the treatment regimen. Our results suggest that prior cancer chemotherapy had no adverse effect on the therapeutic efficacy of trovafloxacin, and that trovafloxacin may be a promising therapeutic agent for treatment of bacterial infections in the presence of leucopenia.
Thadepalli
H
H
Department of Medicine and Pathology, Charles R. Drew University of Medicine and Sciences, 1731 East 120th Street, Los Angeles, CA 90059, USA. geriatrics@pol.net
Reddy
U
U
Chuah
S K
SK
Hanna
N
N
Rana
G
G
Gollapudi
S
S
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D007710:Klebsiella Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000378:metabolism; D007941:Leukemia P388 / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009287:Naphthyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D018410:Pneumonia, Bacterial / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011994:Recombinant Proteins
D000890:Anti-Infective Agents; D000903:Antibiotics, Antineoplastic; D024841:Fluoroquinolones; D009287:Naphthyridines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D002939:Ciprofloxacin; C080163:trovafloxacin; D003630:Daunorubicin