Relationship between Cefquinome PK/PD Parameters and Emergence of Resistance of Staphylococcus aureus in Rabbit Tissue-Cage Infection Model

Xiong, Mingpeng; Wu, Xun; Ye, Xiaomei; Zhang, Longfei; Zeng, Shu-Yi; Huang, Zibin; Wu, Yuzhi; Sun, Jian; Ding, Huanzhong

doi:10.3389/fmicb.2016.00874

Cited by 30 publications

(35 citation statements)

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“…Our results differ from many in vitro studies and a few in vivo studies in which the evolution of resistance was reduced at higher doses [71][72][73]. The discordance between these studies and ours likely arises from the existence of the so-called inverted U, where resistance evolution is minimized at very low or very high doses and maximized somewhere in-between [3,4].…”

Section: Dose and The Emergence Of Resistancecontrasting

confidence: 99%

The effect of drug dose and timing of treatment on the emergence of drug resistancein vivoin a malaria model

Acosta

Sim

Bram

et al. 2020

Preprint

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Background and objectives:There is significant interest in identifying clinically effective drug treatment regimens that minimize the de novo evolution of antimicrobial resistance in pathogen populations. However, in vivo studies that vary treatment regimens and directly measure drug resistance evolution are rare. Here, we experimentally investigate the role of drug dose and treatment timing on resistance evolution in an animal model. Methodology: In a series of experiments, we measured the emergence of atovaquone-resistant mutants of Plasmodium chabaudi in laboratory mice, as a function of dose and timing of treatment with the antimalarial drug atovaquone. Results: Increasing the concentration of atovaquone increased the likelihood of high-level resistance emergence. Treating very early or late in infection reduced the risk of resistance, likely as a result of population size at time of treatment, but we were not able to exclude influence of the immune response in the latter. When we varied starting inoculum, resistance was more likely at intermediate inoculum sizes, but this did not correlate directly with population sizes at time of treatment. Conclusions and implications: (i) Higher doses do not always minimize resistance emergence and can result in competitive release of parasites with high-level resistance. (ii) Altering treatment timing affects the risk of resistance emergence, but not as a simple function of population size at the time of treatment. (iii) Finding the 'right' dose and 'right' time to maximize clinical gains and limit resistance emergence can vary depending on biological context and was non-trivial even in our simplified experiments.

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Section: Dose and The Emergence Of Resistancecontrasting

confidence: 99%

The effect of drug dose and timing of treatment on the emergence of drug resistancein vivoin a malaria model

Acosta

Sim

Bram

et al. 2020

Preprint

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“…In the veterinary field, the tissue-cage model is widely used for PK/PD studies and has been reported useful in several species, such as calves (Bengtsson and Greko, 2002), piglets (Zhang et al, 2014), goats (Sidhu et al, 2010), and rabbits (Xiong et al, 2016). However, there are few reported studies of macrolide drugs on PK/PD models.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Modeling of Tulathromycin against Pasteurella multocida in a Porcine Tissue Cage Model

et al. 2017

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Tulathromycin, a macrolide antibiotic, is used for the treatment of respiratory disease in cattle and swine. The aim of our study was to investigate the in vitro and ex vivo activities of tulathromycin in serum, (non-inflamed) transudate, and (inflamed) exudate against Pasteurella multocida in piglets. The pharmacokinetics properties of tulathromycin were studied for serum, transudate, and exudate using a tissue cage model. In vitro antibiotic susceptibility of P. multocida and dynamic time-kill curve experiments over eight tulathromycin concentrations were determined. The ratio of 24-h area under the concentration–time curve to minimum inhibitory concentration [AUC(0-24 h)/MIC] was recognized as an important pharmacokinetic/pharmacodynamic (PK/PD) parameter of tulathromycin for antibacterial efficiency (R2 = 0.9969). In serum ex vivo, for bacteriostatic, bactericidal activity, and virtual bacterial eradication AUC(0-24 h)/MIC values for tulathromycin were 44.55, 73.19, and 92.44 h by using sigmoid Emax model WinNonlin software, respectively, and lower values were obtained for exudate and transudate. In conjunction with the data on MIC90, the dose of tulathromycin for a bacteriostatic effect and virtual elimination of P. multocida as computed using the value of the PK/PD breakpoint obtained in serum were 6.39 and 13.25 mg/kg. However, it would be preferable to calculate a dose combined with population pharmacokinetics data to optimize the dosage regimen for bacteriological and clinical cure.

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“…Thus, resistance is thought to be promoted when antimicrobial concentrations fall within the MSW (11). This has been shown using in vitro studies and studies in animals (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

mentioning

confidence: 99%

In Vitro Resistance Selection in Shigella flexneri by Azithromycin, Ceftriaxone, Ciprofloxacin, Levofloxacin, and Moxifloxacin

Allen

Harris

2017

Antimicrob Agents Chemother

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Shigella flexneri continues to be a major cause of diarrhea-associated illness, and increasing resistance to first-line antimicrobials complicates the treatment of infections caused by this pathogen. We investigated the pharmacodynamics of current antimicrobial treatments for shigellosis to determine the likelihood of resistance promotion with continued global antimicrobial use. The mutant prevention concentration (MPC) and mutant selection window (MSW) were determined for azithromycin, ceftriaxone, ciprofloxacin, levofloxacin, and moxifloxacin against a wildtype strain of S. flexneri (ATCC 12022) and an isogenic gyrA mutant (m-12022). Timekill assays were performed to determine antimicrobial killing. Concentrations of approved doses of ciprofloxacin, levofloxacin, and moxifloxacin are predicted to surpass the MPC for a majority of the dosage interval against ATCC 12022. However, against m-12022, concentrations of all fluoroquinolones are predicted to fall below the MPC and remain in the MSW for a majority of the dosage interval. Concentrations of ceftriaxone fall within the MSW for the majority of the dosage interval for both strains. All agents other than azithromycin displayed bactericidal activity in time-kill assays. Results of pharmacodynamic analyses suggest that all tested fluoroquinolones would achieve a favorable area under the concentration-time curve (AUC)/MPC ratio for ATCC 12022 and would restrict selective enrichment of mutants but that mutant selection in m-12022 would be likely if ciprofloxacin were used. Based on pharmacodynamic analyses, azithromycin and ceftriaxone are predicted to promote mutant selection in both strains. Confirmation of these findings and examination of novel treatment regimens using in vivo studies are warranted.KEYWORDS Shigella flexneri, mutant prevention concentration, mutant selection window T he pathogenic bacterium Shigella flexneri is a major cause of dysentery and related morbidity and mortality worldwide, particularly in children less than 5 years of age in developing countries and travelers returning from tropical areas. In the 1990s, the number of annual cases of shigellosis worldwide was approximately 164.7 million, with 1.1 million resulting in death (1). Data from 2014 demonstrated an average of 5.81 cases per 100,000 individuals in the United States (2). The treatment of shigellosis has been complicated by the emergence of strains of S. flexneri that are resistant to many antimicrobials, including former first-line treatment options such as ampicillin, chloramphenicol, tetracyclines, and trimethoprim-sulfamethoxazole (SXT) (1). Current treatment guidelines for infectious diarrhea from the Infectious Diseases Society of America, published in 2001, recommend SXT, a fluoroquinolone (ofloxacin, norfloxacin, or ciprofloxacin), ceftriaxone, or azithromycin (3). In guidelines published by the WHO in 2005, ciprofloxacin was considered the first-line treatment for shigellosis, with ceftriaxone and azithromycin considered to be alternative therapies (4). Howe...

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Relationship between Cefquinome PK/PD Parameters and Emergence of Resistance of Staphylococcus aureus in Rabbit Tissue-Cage Infection Model

Cited by 30 publications

References 28 publications

The effect of drug dose and timing of treatment on the emergence of drug resistancein vivoin a malaria model

The effect of drug dose and timing of treatment on the emergence of drug resistancein vivoin a malaria model

Pharmacokinetic/Pharmacodynamic Modeling of Tulathromycin against Pasteurella multocida in a Porcine Tissue Cage Model

In Vitro Resistance Selection in Shigella flexneri by Azithromycin, Ceftriaxone, Ciprofloxacin, Levofloxacin, and Moxifloxacin

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