Efficacy and safety of moxifloxacin for community-acquired bacterial pneumonia based on pharmacokinetic analysis

Yoshida, Koichiro; Okimoto, Niro; Kishimoto, Michihiro; Fukano, Hiroshi; Yoneyama, Hirohide; Moriya, Osamu; Kawanishi, Masayoshi; Kimura, Makoto; Matsushima, Toshiharu; Niki, Yoshihito

doi:10.1007/s10156-011-0282-6

Cited by 10 publications

(10 citation statements)

References 19 publications

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“…Previous reports involving the analysis of PK parameters associated with MFLX treatment mostly included patients who had continuous hemodiafiltration or peritoneal dialysis; as mentioned above, the data from HD patients were limited ( 17 , 18 ). Our data showed no significant differences in comparison to the results of 9 non-HD patients with bacterial pneumonia who received MFLX in a Japanese clinical trial ( 19 ). The parameters in that trial were as follows: AUC 0→24 , 38.9-65.42 μg h/mL; C max , 3.69-5.47 μg/mL; and C trough , 0.57-1.21 μg/mL.…”

Section: Discussioncontrasting

confidence: 66%

A Prospective Study of the Efficacy, Safety and Pharmacokinetics of Enteral Moxifloxacin in the Treatment of Hemodialysis Patients with Pneumonia

et al. 2017

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Objectives To investigate the efficacy of oral moxifloxacin (MFLX) as a treatment for pneumonia in hemodialysis (HD) patients and the pharmacokinetic (PK) profile of MFLX after oral administration. Methods Thirteen adult patients who required HD due to chronic renal failure were enrolled in the present study, which was performed to investigate the treatment of community-acquired pneumonia in HD patients. A standard dose of MFLX (400 mg, once daily) was administered. The therapy was continued, discontinued, or switched to another antibiotic depending on the response of the pneumonia to MFLX. A population PK model was developed using the post-hoc method. Results In total, 13 HD patients with pneumonia (male, n=7; female, n=6) were enrolled in the present study. The evaluation on the 3rd day showed that treatment was successful in 11 patients (84.6%) and that 10 patients were cured (76.9%). In the one case in which MFLX treatment failed, the patient was cured by switching to ceftriaxone (CTRX) (2 g, intravenously) plus levofloxacin (LVFX) (250 mg, orally). The causative bacterium in this male patient was P. aeruginosa. It did not display resistance to fluoroquinolones. One patient had liver dysfunction due to MFLX. The estimated PK parameters of MFLX were as follows: AUC0→24, 61.04±17.74 μg h/mL; Cmax, 5.25±1.12 μg/mL; and Ctrough, 1.15±0.45 μg/mL. The PK parameters of MFLX among the patients in whom adverse events occurred or in whom a cure was not achieved did not differ from those of the other patients to a statistically significant extent. Conclusion MFLX showed good efficacy and safety in HD patients with community-acquired pneumonia and the results of the PK analysis were favorable. Further prospective studies with larger numbers of patients will be needed to draw definitive conclusions.

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Section: Discussioncontrasting

confidence: 66%

A Prospective Study of the Efficacy, Safety and Pharmacokinetics of Enteral Moxifloxacin in the Treatment of Hemodialysis Patients with Pneumonia

et al. 2017

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“…Moxifloacin was expected to be useful as an anti-infective agent for respiratory tract, skin, soft tissues and intra-abdominal infections, including biliary tract and uterine infection [4][5][6]11,12,31], which was accordance with our results. Meanwhile, drug abuse could cause organ damage both in human and animal [34,35].…”

Section: Discussionsupporting

confidence: 81%

“…Knowledge on pharmacokinetics in plasma alone, therefore, is often not sufficient to estimate if certain bacterial pathogens can be killed at the infected site. Previous researches have studied the pharmacokinetics and penetration of moxifloxacin under different pathological state [4][5][6][7][8][9][10]. Only Stass [11] and Rink [12] have studied the pharmacokinetics of moxifloxacin in abdominal infection and reported that it has a good penetration into peritoneal exudates and abscess fluid in peritonitis and intra-abdominal abscess patients, respectively.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

Zhu

Yang

Zhang

et al. 2015

Korean J Physiol Pharmacol

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The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intraabdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra-abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, Cmax was 11.151 μ g/mL at 5 min after the intravenous injection and t1/2 was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. W hen rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

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“…Our ability to successfully treat disease is often determined by our capacity to manage drug resistance [1][2][3][4][5][6]. To minimize the risk of resistance evolution, treatment is often aimed at rapidly reducing -and hopefully clearing -the pathogen population [7][8][9][10][11][12][13][14][15][16][17]. This principle dominates our approach to both infectious disease and cancer, where treatment is often aimed at achieving rapid and dramatic reductions in tumor burden [18][19][20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Antibiotics can be used to contain drug-resistant bacteria by maintaining sufficiently large sensitive populations

Hansen

Karslake

Woods

et al. 2019

Preprint

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Treatment strategies for infectious disease often aim to rapidly clear the pathogen population in hopes of minimizing the potential for antibiotic resistance. However, a number of recent studies highlight the potential of alternative strategies that attempt to inhibit the growth of resistant pathogens by maintaining a competing population of drug-sensitive cells. Unfortunately, to date there is little direct experimental evidence that drug sensitive cells can be leveraged to enhance antibiotic containment strategies. In this work, we combine in vitro experiments in computer-controlled bioreactors with simple mathematical models to show that drug-sensitive cells can enhance our ability to control bacterial populations with antibiotics. To do so, we measured the "escape time" required for drug-resistant E. coli populations to eclipse a threshold density maintained by adaptive antibiotic dosing. While populations containing only resistant cells rapidly escape containment, we found that matched populations with sensitive cells added could be contained for significantly longer. The increase in escape time occurs only when the threshold density-the acceptable bacterial burden-is sufficiently high, an effect that mathematical models attribute to increased competition. The results provide direct experimental evidence linking the presence of sensitive cells to improved control of microbial populations.

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Efficacy and safety of moxifloxacin for community-acquired bacterial pneumonia based on pharmacokinetic analysis

Cited by 10 publications

References 19 publications

A Prospective Study of the Efficacy, Safety and Pharmacokinetics of Enteral Moxifloxacin in the Treatment of Hemodialysis Patients with Pneumonia

A Prospective Study of the Efficacy, Safety and Pharmacokinetics of Enteral Moxifloxacin in the Treatment of Hemodialysis Patients with Pneumonia

Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

Antibiotics can be used to contain drug-resistant bacteria by maintaining sufficiently large sensitive populations

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