Prevalence of ciprofloxacin resistance in multiresistant gram-negative intensive care unit isolates.

Of 107 gram-negative isolates obtained from intensive care units examined for patterns of multiresistance to 16 antimicrobial agents, 54.2% were multiresistant, defined as resistant to three or more test antimicrobials. Ciprofloxacin had excellent activity against all isolates with 93.4% susceptibility. Ciprofloxacin also performed well on multiresistant isolates with 89.7% susceptibility, which included 42.2% inducible Enterobacteriaceae. All six multiresistant ciprofloxacin-resistant isolates were resistant to five or more of the tested antimicrobials (mean 9.0), including a highly resistant Proteus mirabilis urine isolate resistant to 14 of 16 agents. The only antimicrobial to which all of the ciprofloxacin-multi-resistant isolates were resistant, was ampicillin, indicating an absence of cross resistance. In addition, ciprofloxacin had excellent activity (100% susceptibility) against Enterobacter spp. and Klebsiella pneumoniae, two organisms frequently associated with nosocomial infections.

Hydroxyurea and etoposide: in vitro synergy and phase I clinical trial.

L1210 murine leukemia cells were treated with hydroxyurea (10-200 microM) for 24 hours and/or etoposide (0.17-3.4 microM) for 2 hours. Combination treatments used a fixed molar hydroxyurea:etoposide ratio of 58.9:1, and drug-drug interactions were quantitated according to the median effect principle. Hydroxyurea and etoposide were antagonistic at low doses at which the survival fraction was greater than 0.5 and synergistic at higher doses at which the survival fraction was less than 0.25. In a phase I clinical trial, 19 patients were treated with the two drugs at one of three dose levels. The dose-limiting toxic effect was myelosuppression. Doses of 100 mg of etoposide/m2 per day by continuous infusion and 500 mg of hydroxyurea orally every 4 hours, both for 3 days, are recommended for phase II trials.