Effects of Parenterally Administered Ciprofloxacin in a Murine Model of Pulmonary &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt; Infection Mimicking Ventilator-Associated Pneumonia

Kaneko, Yukihiro; Yanagihara, Katsunori; Kuroki, Misuzu; Ohi, Hideo; Kakeya, Hiroshi; Miyazaki, Yoshitsugu; Higashiyama, Yasuhito; Hirakata, Yoichi; Tomono, Kazunori; Kadota, Jun‐ichi; Kohno, Shigeru

doi:10.1159/000048553

Cited by 9 publications

(4 citation statements)

References 19 publications

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“…The intubation procedure was performed under pentobarbital anesthesia (40 mg/kg delivered by intraperitoneal injection). Intubation was induced as described previously (15). Briefly, the blunt end of the inner needle of an intravenous catheter (Angiocath; Becton, Dickinson Vascular Access, Sandy, UT) was inserted through the oral cavity with the outer sheath and the attached tube at the tip.…”

Section: Methodsmentioning

confidence: 99%

Azithromycin Attenuates Lung Inflammation in a Mouse Model of Ventilator-Associated Pneumonia by Multidrug-Resistant Acinetobacter baumannii

Yamada

Yanagihara

Kaku

et al. 2013

Antimicrob Agents Chemother

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c; Global COE Program, Nagasaki University, Nagasaki, Japan d Acinetobacter baumannii is one of the main pathogens that cause ventilator-associated pneumonia (VAP) and is associated with a high rate of mortality. Little is known about the efficacy of macrolides against A. baumannii. In order to confirm the efficacy of azithromycin (AZM) against VAP caused by multidrug-resistant A. baumannii (MDRAB), we used a mouse model that mimics VAP by placement of a plastic tube in the bronchus. AZM (10 and 100 mg/kg of body weight) was administered subcutaneously every 24 h beginning at 3 h after inoculation. Phosphate-buffered saline was administered as the control. Survival was evaluated over 7 days. At 48 h postinfection, mice were sacrificed and the numbers of viable bacteria in lungs and bronchoalveolar lavage fluid were compared. Histopathological analysis of lung specimens was also performed. The treatment groups displayed significantly longer survival than the control group (P < 0.05). AZM did not have an antimicrobial effect. Histopathological examination of lung specimens indicated that the progression of lung inflammation was prevented in the AZM-treated groups. Furthermore, total cell and neutrophil counts, as well as cytokine levels, in bronchoalveolar lavage fluid were significantly decreased (P < 0.05) in the AZM-treated groups. AZM may have a role for the treatment of VAP with MDRAB because of its anti-inflammatory effects.

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Section: Methodsmentioning

confidence: 99%

Azithromycin Attenuates Lung Inflammation in a Mouse Model of Ventilator-Associated Pneumonia by Multidrug-Resistant Acinetobacter baumannii

Yamada

Yanagihara

Kaku

et al. 2013

Antimicrob Agents Chemother

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“…We also tested the ability of Ga to prevent biofilm formation in a chronic airway infection model (37,38). In this model a small plastic tube is inserted in either main bronchus of mice.…”

Section: Figurementioning

confidence: 99%

The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity

et al. 2007

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A novel antiinfective approach is to exploit stresses already imposed on invading organisms by the in vivo environment. Fe metabolism is a key vulnerability of infecting bacteria because organisms require Fe for growth, and it is critical in the pathogenesis of infections. Furthermore, humans have evolved potent Fewithholding mechanisms that can block acute infection, prevent biofilm formation leading to chronic infection, and starve bacteria that succeed in infecting the host. Here we investigate a "Trojan horse" strategy that uses the transition metal gallium to disrupt bacterial Fe metabolism and exploit the Fe stress of in vivo environments. Due to its chemical similarity to Fe, Ga can substitute for Fe in many biologic systems and inhibit Fe-dependent processes. We found that Ga inhibits Pseudomonas aeruginosa growth and biofilm formation and kills planktonic and biofilm bacteria in vitro. Ga works in part by decreasing bacterial Fe uptake and by interfering with Fe signaling by the transcriptional regulator pvdS. We also show that Ga is effective in 2 murine lung infection models. These data, along with the fact that Ga is FDA approved (for i.v. administration) and there is the dearth of new antibiotics in development, make Ga a potentially promising new therapeutic for P. aeruginosa infections.

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“…Because this represents a common, potentially devastating, clinical problem in critically ill patients, P. aeruginosa pneumonia is an increasingly used animal model of sepsis (3,(6)(7)(8)(9)(10)(11)(12)(13). Morbidity and mortality vary in this model, depending on the dose and strain of bacteria used, although multiple publications indicate that the histologic features seen in pneumonia in patients are reproduced in the murine model (3,7,11,13). However, no published report examines the mortality effect of the clinically relevant scenario of giving commonly used antibiotics to treat the bacterial infection in mice.…”

Section: Introductionmentioning

confidence: 99%

Antibiotics Improve Survival and Alter the Inflammatory Profile in a Murine Model of Sepsis From Pseudomonas aeruginosa Pneumonia

Coopersmith¹,

Amiot²,

Stromberg³

et al. 2003

Shock

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Differing antibiotic regimens can influence both survival and the inflammatory state in sepsis. We investigated whether the addition and/or type of antimicrobial agent could effect mortality in a murine model of Pseudomonas aeruginosa pneumonia-induced sepsis and if antibiotics altered systemic levels of cytokines. FVB/N mice were subjected to intratracheal injection of pathogenic bacteria and were given gentamicin, imipenem, or 0.9% NaCl 2 h after surgery, which continued every 12 h for a total of six doses. Survival at 7 days (n = 24 in each group) was 100% for mice given gentamicin, 88% for mice given imipenem, and 8% for sham mice treated with 0.9% NaCl (P < 0.0001). Systemic interleukin (IL) 6 levels were assayed 6 h postoperatively on all mice to see if they were predictive of outcome. Plasma IL-6 levels above 3,600 pg/mL were associated with a 100% mortality, levels under 1,200 pg/mL were associated with a 100% survival, and levels between 1,200 and 3,600 pg/mL had no utility in predicting mortality. In a separate experiment, mice were sacrificed at 3, 6, 12 or 24 h after instillation of P. aeruginosa and were assayed for levels of TNF-alpha, IL-6, IL-10, and IL-12. Significant alterations in the proinflammatory cytokines TNF-alpha and IL-6 were present at all time points except 3 h between mice treated with antibiotics and sham controls. In contrast, statistically significant differences in the anti-inflammatory cytokine IL-10 were present between the groups only at 6 h, and levels of IL-12 were similar at all time points. These results indicate that both gentamicin and imipenem increase survival at least 10-fold in a model of pneumonia-induced monomicrobial sepsis, and this is predominantly associated with a down-regulation of proinflammatory cytokines.

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Effects of Parenterally Administered Ciprofloxacin in a Murine Model of Pulmonary <i>Pseudomonas aeruginosa</i> Infection Mimicking Ventilator-Associated Pneumonia

Cited by 9 publications

References 19 publications

Azithromycin Attenuates Lung Inflammation in a Mouse Model of Ventilator-Associated Pneumonia by Multidrug-Resistant Acinetobacter baumannii

Azithromycin Attenuates Lung Inflammation in a Mouse Model of Ventilator-Associated Pneumonia by Multidrug-Resistant Acinetobacter baumannii

The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity

Antibiotics Improve Survival and Alter the Inflammatory Profile in a Murine Model of Sepsis From Pseudomonas aeruginosa Pneumonia

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