In vivo efficacy and pharmacokinetics of biapenem in a murine model of ventilator-associated pneumonia with Pseudomonas aeruginosa.
Biapenem (BIPM) has high bactericidal activity against Pseudomonas aeruginosa and similar activity in vitro as meropenem (MEPM). We used a murine model to examine the efficacy of biapenem against ventilator-associated pneumonia (VAP) caused by P. aeruginosa. Mice were treated by intraperitoneal injection with 100 mg/kg BIPM or MEPM every 12 h beginning 12 h after inoculation with P. aeruginosa. Survival was evaluated for 7 days, and 24 h after infection, lung histopathology was analyzed and the number of viable bacteria in the lungs and blood was counted. In addition, the pharmacokinetics of BIPM and MEPM were analyzed after the initial treatment. BIPM and MEPM significantly prolonged survival compared to control (P < 0.05). The lungs of mice treated with BIPM or MEPM had significantly fewer viable bacteria (3.54 ± 0.28 vs. 3.77 ± 0.14 log(10) CFU/ml) than in the lungs of control mice (6.65 ± 0.57 log(10) CFU/ml) (P < 0.05). Furthermore, viable bacteria were not detected in the blood of mice treated with BIPM or MEPM (control 2.85 ± 0.85 log(10) CFU/ml) (P < 0.05). Histopathological examination of lung specimens indicated that BIPM and MEPM prevent the progression of lung inflammation, including alveolar neutrophil infiltration and hemorrhage. The % time above MIC for BIPM and MEPM was 15.4% and 18.3% in plasma and 19.8% and 19.8% in lungs, respectively. These results show that BIPM and MEPM significantly prolongs survival and reduces the number of viable bacteria in a murine model of VAP caused by P. aeruginosa. Therefore, BIPM might be a potent and effective treatment for VAP caused by this bacterium.
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Koichi
K
Yamada
Yoshihiro
Y
Yamamoto
Katsunori
K
Yanagihara
Nobuko
N
Araki
Yosuke
Y
Harada
Yoshitomo
Y
Morinaga
Koichi
K
Izumikawa
Hiroshi
H
Kakeya
Hiroo
H
Hasegawa
Shigeru
S
Kohno
Shimeru
S
Kamihira
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D016022:Case-Control Studies; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D006651:Histocytochemistry; D008168:Lung / Q000382:microbiology; D008297:Male; D000077731:Meropenem; D051379:Mice; D008826:Microbial Sensitivity Tests; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric; D013845:Thienamycins / Q000493:pharmacokinetics / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem; C065257:biapenem