In a multicentre non-randomized open prospective study, 124 patients hospitalized in medical infectious disease or intensive care units, with severe community and hospital-acquired bacterial infections were treated with 15 mg/kg body weight amikacin in a once-daily dose given as a 30 min iv infusion, combined with other antibiotics. Infections were bacteriologically proven in 101 patients. The clinical responses showed 83.1% primary success and 83.9% definitive cure predominantly in intensive care patients with hospital-acquired infections and pneumonia. Bacteriological eradication was achieved in 67.3%. Bacteria associated with true failures and colonizations were predominantly Pseudomonas, Acinetobacter and Staphylococcus spp. The risk of nephrotoxicity may be decreased with such a regimen of amikacin, but no conclusions could be drawn with regard to ototoxicity. In summary, a once-daily dosing regimen of amikacin 15 mg/kg is practical and probably efficacious and safe in severely infected patients.

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A clinical isolate of Pseudomonas aeruginosa resistant to pefloxacin (Pef) but susceptible to ciprofloxacin (Cip) was studied to compare the in vitro and in vivo activities of Pef, ofloxacin (Ofl), and Cip. The time-kill curve method showed no bactericidal activity for Pef and Ofl, but a reduction of 4 log 10 CFU/ml was achieved with Cip at 1 h. A model of experimental P. aeruginosa pneumonia was used to evaluate in vivo the relevance of the difference in susceptibility observed in vitro. At 36 h, a 100% cumulative survival rate was observed in Cip-treated rats, which was far higher than the survival rate obtained with Pef (53%) or Ofl (46%) (P < 0.001). At 4 h, no bacteremia was observed in Cip-treated rats, whereas 93% of the Pef-treated rats and 80% of the Ofl-treated rats were bacteremic (P < 0.001). The best pulmonary bacterial clearance was observed with Cip. Interestingly, Pef and Ofl, to which the strain was resistant in vitro, showed a fairly good in vivo activity despite sub-MIC concentrations. Cip was more effective than Pef and Ofl in terms of pulmonary and systemic bactericidal activity and provided the best survival rate in animals. We conclude that differences between the different quinolones in terms of the organism's sensitivity assessed in vitro may be relevant and that it might be useful to reconsider the use of a quinolone to which P. aeruginosa shows resistance if the organism shows sensitivity to no other agent.

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