Protective effect of trovafloxacin, ciprofloxacin and ampicillin against Streptococcus pneumoniaein a murine sepsis model

Lacy, Melinda K.; Nicolau, David P.; Banevicius, Mary Anné; Nightingale, Charles H.; Quintiliani, Richard

doi:10.1093/jac/44.4.477

Cited by 31 publications

(41 citation statements)

References 17 publications

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“…Our in vivo findings reflect those obtained in recent in vitro models which have evaluated the influence of drug exposure on both the kill and regrowth profiles of pneumococci (6)(7)(8). 6 13 100 9 33 100 12 47 100 18 64 100 30 100 100 40 93 100 a 100% mortality was observed in all untreated control animals in both strains.…”

Section: Discussionsupporting

confidence: 85%

Pharmacodynamic Assessment of Gatifloxacin against Streptococcus pneumoniae

Mattoes¹,

Banevicius²,

Li³

et al. 2001

Antimicrob Agents Chemother

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The pharmacodynamic parameters of peak serum drug concentration/MIC (peak/MIC) ratio and the area under the curve (AUC)/MIC ratio have been used to characterize in vivo drug exposure and its relationship to bacterial killing for the fluoroquinolones. Our study objectives were to describe the pharmacodynamic relationship between gatifloxacin exposure and outcome as assessed by bacterial density and survival in an immunocompromised murine thigh model of pneumococcal infection and to assess the relationship between drug exposure and these outcomes in an immunocompetent host. ICR mice were rendered neutropenic, and thigh infection was induced by intramuscular administration of 0.1 ml of 10 5 to 10 7 CFU of Streptococcus pneumoniae/ml. Mice received 1 to 5 mg of uranyl nitrate/kg of body weight at day ؊3 and were randomized to receive 10 to 80 mg of gatifloxacin/kg every 6 to 24 h orally, starting at 2 h postinoculation. Bacterial density studies were completed 24 h after initiation of therapy, and survival was assessed after 4 days of treatment. MICs for clinical isolates (n ‫؍‬ 8) ranged from 0.25 to 1.0 g/ml. Correlations were assessed between the change in bacterial density, as well as survival, and the AUC/MIC ratio, peak/MIC ratio, and the duration of time that serum drug concentration remained above the MIC. The best predictor of bacterial response was the AUC/MIC ratio for both outcome measures. There was greater efficacy, as measured by a decrease in log change in CFU as well as by survival data, in the immunocompetent mice compared to the immunocompromised mice. These data demonstrate (i) the appropriateness of the AUC/MIC ratio as a dynamic predictor of response to pneumococcal infection for the fluoroquinolones, (ii) that gatifloxacin AUC/MIC ratios of 30 to 40 appear to optimize bactericidal activity and survival in this model, and (iii) that immunocompetency of the host plays a role in efficacy.Considerable controversy exists regarding the most appropriate way to administer antibiotics to maximize bacterial killing and minimize toxicity. In the case of the fluoroquinolones, debate exists as to not only the best pharmacodynamic parameter (i.e., peak serum drug concentration/MIC [peak/MIC] ratio or area under the curve [AUC]/MIC ratio) to characterize bactericidal activity but also the magnitude of the required interaction to optimize therapeutic outcome (10, 13).The current study was undertaken to investigate the pharmacodynamic relationship between gatifloxacin exposure and outcome as assessed by bacterial density and survival in a murine thigh model of pneumococcal infection. Additionally, the influence of the host on these outcomes was assessed in an immunocompetent model. MATERIALS AND METHODSAntimicrobial test agents. Gatifloxacin analytical grade standard was obtained for in vitro testing from Bristol-Myers Squibb, Princeton, N.J. For all in vivo studies, laboratory standard grade gatifloxacin (lot no. 9D07329; expiration date, Sept. 2000) was obtained from the manufacturer, reconstituted based on ...

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Section: Discussionsupporting

confidence: 85%

Pharmacodynamic Assessment of Gatifloxacin against Streptococcus pneumoniae

Mattoes¹,

Banevicius²,

Li³

et al. 2001

Antimicrob Agents Chemother

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“…FQs show a concentration-dependent bactericidal action, and the AUC/minimal inhibitory concentration (MIC) ratio showed the highest correlation with the therapeutic effect among PK-PD parameters [Craig, 1998[Craig, , 2001Lacy et al 1999;Andes and Craig, 2002], indicating the necessity of a sufficient drug concentration for the prevention of drug resistance. Repeated respiratory tract infections are often experienced particularly in the elderly and in patients with an underlying disease, resulting in the repeated prescription of antibacterial agents and increasing the risk of drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of consecutive oral moxifloxacin (400 mg/day) in patients with respiratory tract infection

Ito

Ohno

Toyoshi

et al. 2015

Ther Adv Respir Dis

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A population pharmacokinetic analysis was performed to investigate the pharmacokinetics of moxifloxacin (400 mg) following a once-daily oral administration in 28 patients with respiratory tract infection disease. The maximum plasma concentration and the area under the plasma concentration-time curve were 3.97 µg/ml and 51.74 µg·h/ml, respectively; these values were nearly equivalent to those of healthy adult men. Two adverse drug reactions (nausea, vomiting) occurred, but both reactions were mild and nonserious and the patients recovered without treatment. The pharmacokinetic profile of moxifloxacin in Japanese patients with respiratory tract infection and an underlying disease should thus be considered safe and comparable with that in healthy adult men, and adjustment of dose may do not need for age, sex, body weight, or renal function.

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“…They have widely been used for analyzing pathogenicity mechanisms of pneumonia (50,58,114,120,125,131), sepsis (109,131,251), and meningitis (59,95,160,268). In addition, outbred mice have also been employed to evaluate active and passive protection against pneumonia and sepsis (4, 115, 163) and the efficacy of antibiotic therapy against invasive pneumococcal disease (13,141,169,220,223). The host genetic factors controlling the response to infection by S. pneumoniae are still unknown.…”

Section: Considerations Of Animal and Pneumococcal Strainsmentioning

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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Protective effect of trovafloxacin, ciprofloxacin and ampicillin against Streptococcus pneumoniaein a murine sepsis model

Cited by 31 publications

References 17 publications

Pharmacodynamic Assessment of Gatifloxacin against Streptococcus pneumoniae

Pharmacodynamic Assessment of Gatifloxacin against Streptococcus pneumoniae

Pharmacokinetics of consecutive oral moxifloxacin (400 mg/day) in patients with respiratory tract infection

Animal Models ofStreptococcus pneumoniaeDisease

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