Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia

Preheim, Laurel C.; Olsen, Keith M.; Yue, Mei; Snitily, Mary U.; Gentry-Nielsen, Martha J.

doi:10.1016/j.diagmicrobio.2004.09.008

Cited by 6 publications

(6 citation statements)

References 45 publications

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“…The impact of EtOH on the efficacies of antibiotics that have significant hepatic elimination is unknown. Trovafloxacin was as effective as ceftriaxone or azithromycin in a rat cirrhosis model of pneumococcal infection, but treatment with this antibiotic resulted in a significantly slower normalization of peripheral white blood cell counts (45). In the current study, we chose two different dosage regimens designed to achieve pharmacodynamic ratios for the lower dose just above the reported therapeutic threshold of clinical response.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

Olsen

Gentry-Nielsen

Yue³

et al. 2006

Antimicrob Agents Chemother

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This investigation compared the effect of ethanol on fluoroquinolone antibiotic efficacy and pharmacodynamics in an ethanol-fed rat model of pneumococcal pneumonia. Male Sprague-Dawley rats received a liquid diet containing 36% of total calories as ethanol. Paired controls (pair-fed controls) were fed a liquid diet without ethanol or received rat chow. Diets began 7 days before and continued for 10 days after transtracheal infections with 10 times the 50% lethal dose of type 3 Streptococcus pneumoniae. Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight. White blood cell counts were determined, blood samples were collected for culture, and mortality was recorded. Additional rats were killed on day 5 for pharmacodynamic studies and quantitative cultures of bronchoalveolar lavage fluid. Bacteremia occurred by day 3 in 20 of 22 untreated rats. All 22 untreated rats died by day 9. Moxifloxacin treatment was effective in all diet groups at both the 50-and 100-mg/kg doses. In contrast, 50-mg/kg doses of levofloxacin and trovafloxacin improved survival in ethanol-fed rats but were ineffective in chow-fed rats. High-dose trovafloxacin at 100 mg/kg was associated with increased mortality in pair-fed rats. The free-fraction area under the concentration-time curve/MIC ratio exceeded 50 with all antibiotics in the ethanol group but dropped below 30 with levofloxacin and trovafloxacin in the pairand chow-fed rats, with higher mortality. Achievement of adequate antibiotic-free fraction area under the concentration-time curve/MIC ratios helps overcome ethanol-induced immune defects induced in experimental pneumococcal pneumonia.

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Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated in an experimental model of hepatic cirrhosis that trovafloxacin has excellent efficacy, with superior area under the serum concentration-time curve (AUC)/MIC and maxi-mum concentration of drug in serum (C max )/MIC pharmacodynamic ratios compared to those of either a macrolide or a beta-lactam antibiotic (45).…”

mentioning

confidence: 99%

Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

Olsen

Gentry-Nielsen

Yue³

et al. 2006

Antimicrob Agents Chemother

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“…In both cases, rats showed increased susceptibility to pneumococcal pneumonia. These models have been used by the same research group in studies on phagocytosis and antibiotic efficacy (84,184,199). A sophisticated surgical method based on the delivery of bacteria into the apical lobe bronchi of adult rats was described in the early 1990s (79).…”

Section: Rat and Rabbit Modelsmentioning

confidence: 99%

Animal Models ofStreptococcus pneumoniaeDisease

2008

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SUMMARY Streptococcus pneumoniae is a colonizer of human nasopharynx, but it is also an important pathogen responsible for high morbidity, high mortality, numerous disabilities, and high health costs throughout the world. Major diseases caused by S. pneumoniae are otitis media, pneumonia, sepsis, and meningitis. Despite the availability of antibiotics and vaccines, pneumococcal infections still have high mortality rates, especially in risk groups. For this reason, there is an exceptionally extensive research effort worldwide to better understand the diseases caused by the pneumococcus, with the aim of developing improved therapeutics and vaccines. Animal experimentation is an essential tool to study the pathogenesis of infectious diseases and test novel drugs and vaccines. This article reviews both historical and innovative laboratory pneumococcal animal models that have vastly added to knowledge of (i) mechanisms of infection, pathogenesis, and immunity; (ii) efficacies of antimicrobials; and (iii) screening of vaccine candidates. A comprehensive description of the techniques applied to induce disease is provided, the advantages and limitations of mouse, rat, and rabbit models used to mimic pneumonia, sepsis, and meningitis are discussed, and a section on otitis media models is also included. The choice of appropriate animal models for in vivo studies is a key element for improved understanding of pneumococcal disease.

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“…12,31,32,33 Data from control, sham and LPT treatment rats were analyzed by analysis of variance (ANOVA) followed by a Tukey multiple comparisons post test using Graphpad Prism version 5.0 for Windows, (GraphPad Software, San Diego, CA). Differences among mean values with P £ 0.05 were considered statistically significant.Data are presented as arithmetic means ± standard error (SE).…”

Section: Lymphatic Pump Techniques For the Treatment Of Pneumoniamentioning

confidence: 99%

Osteopathic lymphatic pump techniques to enhance immunity and treat pneumonia

Hodge

2012

International Journal of Osteopathic Medicine

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Pneumonia is a common cause of morbidity and mortality worldwide. While antibiotics are generally effective for the treatment of infection, the emergence of resistant strains of bacteria threatens their success. The osteopathic medical profession has designed a set of manipulative techniques called lymphatic pump techniques (LPT), to enhance the flow of lymph through the lymphatic system. Clinically, LPT is used to treat infection and oedemaand might be an effective adjuvant therapy in patients with pneumonia.The immune system uses the lymphatic and blood systems to survey to rid the body of pathogens; however, only recently have the effects of LPT on the lymphatic and immune systems been investigated. This short review highlightsclinical and basic science research studies that support the use of LPT to enhance the lymphatic and immune systems and treat pneumonia, and discusses the potential mechanisms by which LPT benefits patients with pneumonia.

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Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia

Cited by 6 publications

References 45 publications

Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

Animal Models ofStreptococcus pneumoniaeDisease

Osteopathic lymphatic pump techniques to enhance immunity and treat pneumonia

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