Effects of parenterally administered ciprofloxacin in a murine model of pulmonary Pseudomonas aeruginosa infection mimicking ventilator-associated pneumonia.
METHODS
We compared the bacteriological, pharmacological and histopathological effects of parenterally administered ciprofloxacin (CPFX) to those of imipenem/cilastatin (IMP/CS) and cefozopran (CZOP) in a murine model of mucoid Pseudomonas aeruginosa pneumonia mimicking ventilator-associated pneumonia.


RESULTS
The minimum inhibitory concentrations (MICs) of CPFX, IMP and CZOP were 1.0, 1.0 and 4.0 mg/l, respectively. Treatment with CPFX resulted in a significant decrease in the number of viable bacteria [control, IMP/CS, CZOP and CPFX (mean +/- SEM): 5.02 +/- 0.20, 4.96 +/- 0.38, 5.44 +/- 0.13 and 3.27 +/- 0.02 log(10) colony-forming units lung, respectively]. Histopathological examination revealed that inflammatory changes in the CPFX-treated group were less marked than in other groups. Of the drugs analyzed, the pharmacokinetic parameters of area under the time-concentration curve (AUC)/MIC, AUC exceeding MIC and the time that lung concentrations of drug remained above the MIC were highest for CPFX.


CONCLUSIONS
Our results suggest that parenterally administered ciprofloxacin is effective in ventilator-associated P. aeruginosa pneumonia.
Kaneko
Y
Y
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Yanagihara
K
K
Kuroki
M
M
Ohi
H
H
Kakeya
H
H
Miyazaki
Y
Y
Higashiyama
Y
Y
Hirakata
Y
Y
Tomono
K
K
Kadota
J I
JI
Kohno
S
S
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015377:Cilastatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000662:veterinary; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000662:veterinary; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D012121:Respiration, Artificial / Q000009:adverse effects*; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000097586:Cefozopran
D000890:Anti-Infective Agents; D002511:Cephalosporins; D015377:Cilastatin; D002939:Ciprofloxacin; D015378:Imipenem; D011480:Protease Inhibitors; D013845:Thienamycins; D000097586:Cefozopran