In Vivo Efficacies and Pharmacokinetics of DX-619, a Novel Des-Fluoro(6) Quinolone, against
            <i>Streptococcus pneumoniae</i>
            in a Mouse Lung Infection Model

Fukuda, Yuichi; Yanagihara, Katsunori; Ohno, Hideaki; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Tsukamoto, Kazuhiro; Hirakata, Yoichi; Tomono, Kazunori; Mizuta, Yohei; Tashiro, Takayoshi; Kohno, Shigeru

doi:10.1128/aac.50.1.121-125.2006

Cited by 11 publications

(7 citation statements)

References 23 publications

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“…The CBA=J mouse model of pneumococcal pneumonia has been described elsewhere [10,11]. All mouse experiments were performed in accordance with the guidelines of the Laboratory Animal Center for Biomedical Research, Nagasaki University School of Medicine.…”

Section: Laboratory Animalsmentioning

confidence: 99%

“…Penicillin-sensitive S. pneumoniae-NU83127 serotype 4 (isolated at Nagasaki University, Nagasaki, Japan) was used [9][10][11]. Bacteria were incubated in brain=heart infusion broth overnight at 37 C, and were harvested by centrifugation for 10 minutes at 10,000 Â g. The harvested bacteria were suspended in phosphate-buffered saline (PBS; pH 7.2 to 7.4) at a concentration of 1 Â 10 5 colony-forming units (CFU)=mL, as determined by colony-forming assay on blood agar plates.…”

Section: Bacteria Preparationmentioning

confidence: 99%

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Effects of Specific Neutrophil Elastase Inhibitor, Sivelestat Sodium Hydrate, in Murine Model of Severe Pneumococcal Pneumonia

Yanagihara

Fukuda

Seki

et al. 2007

Experimental Lung Research

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An excessive amount of neutrophil elastase (NE) released from neutrophils accumulated in the lung can cause tissue damage, despite its importance to host defense against microbial pathogens in severe pneumonia. Therefore, NE inhibitors may reduce tissue damage in lungs with severe pneumonia. In this study, the efficacy of a specific NE inhibitor, sivelestat sodium hydrate (sivelestat), was examined using a murine model of severe pneumonia with Streptococcus pneumoniae. Male mice (CBA/JNCrj, aged 5 weeks) were inoculated intranasally with penicillin-susceptible S. pneumonia (1.0 x 10(5) CFU/mouse). Sivelestat (3 mg/kg) or physiological saline was administered every 12 hours beginning at 12 hours after inoculation. Survival was primarily evaluated. Bronchoalveolar lavage fluid (BALF) and blood were collected at 30 hours after inoculation. Thus, cell counts in BALF and numbers of viable bacteria in blood were determined. Histopathological analysis was also performed. Sivelestat significantly prolonged survival when compared with the control group (P < .05), although all animals died within 4 days. Cell count and histopathological analysis indicated that sivelestat prevented the progression of lung inflammation, such as alveolar neutrophil infiltration and hemorrhage. Furthermore, the number of viable bacteria in blood was significantly lower in the sivelestat group than in the control group (5.69 +/- 0.27 and 6.75 +/- 0.32 log CFU/mL, respectively; mean +/- SEM, P < .01). Sivelestat prolonged survival in this model. A possible explanation for the improved survival is that sivelestat prevents tissue damage by inhibiting NE activity in the lung. Therefore, NE inhibitors may be useful for treating with patients with severe pneumonia.

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Section: Laboratory Animalsmentioning

confidence: 99%

Section: Bacteria Preparationmentioning

confidence: 99%

Effects of Specific Neutrophil Elastase Inhibitor, Sivelestat Sodium Hydrate, in Murine Model of Severe Pneumococcal Pneumonia

Yanagihara

Fukuda

Seki

et al. 2007

Experimental Lung Research

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“…First, in the present study immunocompetent healthy mice were used with a fluoroquinolone-susceptible H. influenzae strain. We consider that if mice had damaged lung or the bacteria were a drug-resistant strain, STFX may show better effectiveness than CPFX because it has been reported that STFX can achieve a higher tissue concentration than CPFX [9]. Second, it is also considered that the levels of STFX and CPFX in lung tissue of mice may differ from those of humans so that the differences could not be shown in this study.…”

Section: Discussionmentioning

confidence: 92%

“…Each single dose was 10 mg/kg [9]. Each group was killed by cervical dislocation 12 h after the last drug administration.…”

Section: Antibiotic Examinationsmentioning

confidence: 99%

In vivo efficacy of sitafloxacin in a new murine model of non-typeable Haemophilus influenzae pneumonia by sterile intratracheal tube

Nakamura¹,

Yanagihara²,

Araki³

et al. 2009

International Journal of Antimicrobial Agents

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A novel murine model of non-typeable Haemophilus influenzae (NTHi) pneumonia was established. A plastic tube was inserted into the trachea 7 days before bacterial inoculation. Numbers of NTHi recovered from the lungs and trachea were determined for 7 days. Histologically, bronchioles and adjacent alveoli in the intubation group were filled with numerous inflammatory cells. The efficacy of sitafloxacin was compared with ciprofloxacin using the new murine pneumonia model. The data suggest that sitafloxacin displays equivalent efficacy to ciprofloxacin against H. influenzae pneumonia. This new murine NTHi pneumonia model appears useful not only for in vivo evaluation of antibiotics but also for analysis of the pathogenesis of H. influenzae pneumonia.

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“…The excellent in vitro activities (Tables 1, 5 and 6) and pharmacokinetic profiles (Table 7) of compound 4 showed a promising result compound 4 exhibited potent in vivo efficacies on gram-positive bacteria such as PRSP in animal models of pneumonia. Indeed, in the recent study of Kohno and co-workers, 43 compound 4 had high degrees of efficacy against penicillin-susceptible S. pneumoniae (PSSP) and PRSP in a mouse lung infection model.…”

Section: Resultsmentioning

confidence: 98%

Design, synthesis and biological evaluations of novel 7-[3-(1-aminocycloalkyl)pyrrolidin-1-yl]-6-desfluoro-8-methoxyquinolones with potent antibacterial activity against multi-drug resistant Gram-positive bacteria

Miyauchi

Kawakami

Ito

et al. 2009

Bioorganic & Medicinal Chemistry

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In Vivo Efficacies and Pharmacokinetics of DX-619, a Novel Des-Fluoro(6) Quinolone, against Streptococcus pneumoniae in a Mouse Lung Infection Model

Cited by 11 publications

References 23 publications

Effects of Specific Neutrophil Elastase Inhibitor, Sivelestat Sodium Hydrate, in Murine Model of Severe Pneumococcal Pneumonia

Effects of Specific Neutrophil Elastase Inhibitor, Sivelestat Sodium Hydrate, in Murine Model of Severe Pneumococcal Pneumonia

In vivo efficacy of sitafloxacin in a new murine model of non-typeable Haemophilus influenzae pneumonia by sterile intratracheal tube

Design, synthesis and biological evaluations of novel 7-[3-(1-aminocycloalkyl)pyrrolidin-1-yl]-6-desfluoro-8-methoxyquinolones with potent antibacterial activity against multi-drug resistant Gram-positive bacteria

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