Antitumor activity of trovafloxacin in an animal model.

Quinolone antibiotics come close to being ideal chemotherapeutic agents in that they are administered orally, are concentrated in cells and tissue, are readily available, relatively safe and exhibit increased activity against both bacteria and tumor cells both in vitro and in vivo. Our objective was to evaluate the in vivo activity of trovafloxacin and ciprofloxacin against murine leukemic cells in neutropenic mice with lung infection due to Klebsiella pneumoniae. The results showed that both trovafloxacin and ciprofloxacin were effective in clearing lung infection. However, trovafloxacin, but not ciprofloxacin, was effective in preventing metastasis of leukemia cells to the lungs and other tissue and in prolonging the survival of mice.

Thoracoabdominal injuries in the elderly: 25 years of experience.

BACKGROUND: The present study was conducted to determine the clinical characteristics and outcome of hospitalized elderly patients with thoracic and thoracoabdominal injuries. METHOD: This is a longitudinal, nonblinded study using established standard of care of patients with penetrating and blunt chest trauma. From April 1972 to August 1997, 5,702 patients were hospitalized for chest injuries. Out of these patients, 171 (3%) were aged 65 or above. Of these patients, 96 (56%) had blunt trauma (group 1)--motor vehicle accident in 83 (86%) and falls in 13 (14%). The remaining 75 (44%) patients had penetrating injuries (group 2)--gunshot wounds in 47 (63%) and stab wounds in 28 (37%). RESULTS: Of the blunt trauma patients, 45% (43/96), and 15% (11/75) of the penetrating trauma patients were managed by observation alone; the remainder required surgical procedures. The overall mortality was 10% (17/171), of which mortality among penetrating and blunt trauma to the chest were 12% (9/75) and 8% (8/96), respectively. Of eight deaths due to blunt trauma, six had multiple (four or more) rib fractures. There were no deaths among the 54 patients who were simply observed, and none of them required surgery at a later date. Complication rate among the survivors was 12.3%, with only 0.4% being infectious. CONCLUSIONS: Mortality was highest among the elderly with penetrating chest trauma. Mortality was high because of cardiac and great vessel injuries in group 2, whereas multiple rib fractures and brain injuries were the higher cause of mortality in group-1 patients. Infectious complications were low among the survivors.

Therapeutic efficacy of moxifloxacin, a new quinolone, in the treatment of experimental intra-abdominal abscesses induced by Bacteroides fragilis in mice.

Moxifloxacin, a new quinolone, is effective in vitro against several anaerobic bacteria including Bacteroides fragilis, but its in vivo activity against anaerobic infections is not known. In this study, we evaluated the in vivo activity of moxifloxacin in the treatment of experimentally induced intra-abdominal abscesses (IAA) caused by B. fragilis. For comparison, clindamycin, metronidazole, and levofloxacin were used, and saline for control. Absence of bacteria (sterile) in the abscess pus was required to call it a cure. Mice were intraperitoneally injected with B. fragilis plus sterile rat feces and barium sulfate. Animals were treated with moxifloxacin (40 mg/kg/b.i.d.), clindamycin (75 mg/kg/b.i.d.), levofloxacin (40 mg/kg/b.i.d.) or metronidazole (75 mg/kg/b.i.d.) for 10 days. The cure rate was 12% in controls on saline therapy, 57% on metronidazole, 67% on levofloxacin, 73% on moxifloxacin and 79% on clindamycin. The therapeutic efficacy of moxifloxacin in this B. fragilis infection was not significantly different from that observed with clindamycin. By virtue of its established efficacy on gram-negative aerobic bacteria and the observed in vivo efficacy on B. fragilis, moxifloxacin can be evaluated in the treatment of clinical anaerobic infections.

Comparison of telithromycin, a new ketolide, with erythromycin and clarithromycin for the treatment of Haemophilus influenzae pneumonia in suckling, middle aged and senescent mice.

We studied the efficacy of telithromycin in Haemophilus influenzae pneumoniae in three different age groups of mice. Pneumonia was produced by endotracheal instillation of 1 x 10(4) CFU/ml of bacteria and treatment was initiated with saline for control and compared with two different doses, 50 and 100 mg/kg per BID telithromycin twice a day for 1 week. For comparison, we used erythromycin (ERY) and clarithromycin (CLA), both given twice a day at 50 mg/kg per BID. Some animals were euthanized on the third or 7th day of therapy and their lung tissue was cultured for bacteria. Presence of bacteria was considered a failure and a sterile lung was considered cured. As expected, about one half of middle-aged animals (8-10 months) were cured on saline. In contrast, almost none of the young (2-3 weeks) and old animals (18-20 months) were cured without antibiotic therapy. Among the young, the cure rates with telithromycin, ERY and CLA were 81, 50 and 33%, respectively. Of the senescent mice, the cure rate with ERY was 50% whereas the rates with CLA and telithromycin (50 mg/kg) were 62 and 75%, respectively. In conclusion, telithromycin is effective against H. influenzae at both extremes of life.