Yoshiki Obana

Pathogenic Significance of Acinetobacter calcoaceticus: Analysis of Experimental Infection in Mice

The phenomenon that mixed infection with certain species of bacteria and Acinetobacter calcoaceticus is more virulent than single infection was analyzed experimentally. In mixed infections with A. calcoaceticus paired with either Escherichia coli, Serratia marcescens, or Pseudomonas aeruginosa, the virulence of the latter three organisms was markedly increased over that of single infections only by slime‐producing strains of A. calcoaceticus. Of the 100 strains of A. calcoaceticus tested, 14 had slime‐producing ability. There was scarcely any difference in the chemical components of the slimes of the two strains tested, but the components of the slime of P. aeruginosa were different from those of these strains. The slime of these two strains exhibited lethal activity in mice, but no correlation was found between the amount of slime produced and the virulence. The slime enhanced the virulence of E. coli, S. marcescens, and P. aeruginosa when it was inoculated along with their viable cells. Furthermore, the slime exhibited potent cell‐impairing activity against mouse neutrophils both in vitro and in vivo. This activity was considered to be mainly responsible for the enhancement of virulence in mixed infections.

Therapeutic Efficacy of Intravenous and Oral Ciprofloxacin in Experimental Murine Infections

The therapeutic efficacy of intravenous ciprofloxacin against experimentally induced systemic, respiratory tract and urinary tract infections was investigated in mice. The 50% effective dose (ED50) of intravenous ciprofloxacin against experimental systemic infections with Staphylococcus aureus Smith, Escherichia coli 444, Klebsiella pneumoniae KC-1, Serratia marcescens T-55 and Pseudomonas aeruginosa 15846 in mice, were 0.538, 0.0625, 0.0941, 0.294 and 7.76 mg/kg, respectively. These excellent results are equal to 6- to 17-fold the potency following oral administration. In murine respiratory tract infections with K. pneumoniae DT-S, the ED50 of intravenous ciprofloxacin was 20.1 mg/kg, and 26.2 mg/kg after oral administration. A marked decrease of viable bacteria count in lung was noted at doses above 7.4 mg/kg with intravenous administration. On the other hand, after oral dosing, although a marked decrease in viable bacteria count was observed with doses above 29 mg/kg, no decrease in counts was seen at 118 mg/kg and only a bacteriostatic effect could be noted. The therapeutic efficacy of intravenous ciprofloxacin against experimentally induced urinary tract infections in mice was compared to that after oral dosing by determining viable bacteria count in kidney 24h after inoculation. A dose-proportional decrease in counts was observed with both routes of administration at doses of 1.7, 5.6, 17 and 56 mg/kg. Based on these results, intravenous ciprofloxacin was found to have effects superior to those after oral administration in all infection models studied.

The therapeutic efficacy of AC-1370 against experimental infections in mice

The therapeutic efficacy of AC-1370, a new cephalosporin, was compared with that of cefoperazone in experimental infections in mice. For intraperitoneal infections caused by Escherichia coli and Klebsiella pneumoniae, the efficacy of AC-1370 was inferior to that of cefoperazone. On the other hand, AC-1370 was more potent than cefoperazone against pseudomonal infections. The MICs of AC-1370 against the test strains, however, were inferior or equivalent to those of cefoperazone. Serum and peritoneal exudate levels of AC-1370 in infected mice were more durable than those of cefoperazone. The relationship between AC-1370 and neutrophils was investigated. The efficacy of AC-1370 was more dependent on neutrophils than that of cefoperazone. AC-1370 did not enhance the neutrophil functions of migration and phagocytosis to any significant extent.