Role for Dual Individualization with Cefmenoxime

Schentag, Jerome J.; Smith, Ian; Swanson, Douglas J.; DeAngelis, Carlo; Fracasso, Joseph E.; Vari, A.; Vance, John W.

doi:10.1016/s0002-9343(84)80074-1

Cited by 127 publications

(66 citation statements)

References 5 publications

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“…For β-lactams, superior clinical and microbiologic cures appear to be associated with a longer duration of plasma concentration above the pathogen MIC, particularly in critically ill patients [137][138][139][140].…”

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confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods:The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.

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confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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“…Experience with other classes of anti-infectives has demonstrated that animal model experiments that delineate which pharmacodynamic variable (peak concentration/50% inhibitory concentration [IC 50 ], area under the concentration-time curve [AUC]/IC 50 , or time Ͼ IC 50 ) is most closely linked to outcome have been highly predictive of the results seen for humans (3)(4)(5)8).…”

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confidence: 99%

Pharmacodynamic Evaluation of RWJ-270201, a Novel Neuraminidase Inhibitor, in a Lethal Murine Model of Influenza Predicts Efficacy for Once-Daily Dosing

Drusano

Preston

Smee

et al. 2001

Antimicrob Agents Chemother

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We examined RWJ-270201 in a lethal model of influenza in BALB/c mice. The aim was to delineate the pharmacodynamically linked variable for the drug. Challenge was performed with influenza virus A/Shongdong/09/93 (H3N2). Treatment was administered by gavage. Five doses (1 to 10 mg/kg of body weight) and three schedules (every 24, 12, and 8 h) were evaluated with 10 mice per group. There were 39 placebo-treated mice. Drug exposure was evaluated for infected mice. Exposures were calculated after population modeling of all the plasma concentration-time data simulataneously using the NPEM3 program. Evaluation of dose and schedule with Kaplan-Meier analysis and Cox proportional hazards modeling demonstrated that schedule offered no explanatory power relative to dose alone. Evaluation of peak concentration, trough concentration, and area under the concentration-time curve (AUC) by the same methods revealed that AUC was the dynamically linked variable. Again, schedule offered no further explanatory power when included in the model with AUC. This indicates that AUC is the linked variable and that the anti-influenza effect of RWJ-270201 is independent of schedule. We conclude that once-daily dosing of RWJ-270201 should be evaluated in clinical trials of influenza therapy.Influenza virus infections caused by both A and B strains continue to be a cause of morbidity and mortality, particularly for patients who are elderly or otherwise immunocompromised (2, 9).The viral neuraminidase is a logical target for antiviral chemotherapy, as it is readily accessible and is a necessary site for ongoing spread of viral infection. In addition, this enzyme is appealing as a target for chemotherapy because it would be expected to affect clinical outcome, even after infection initiation, because of its ability to interrupt viral spread. Further, it differs from older agents like amantadine and rimantadine in having a lower probability of viral emergence of resistance (7).RWJ-270201 is a new, potent member of the neuraminidase inhibitor class of influenza antivirals. Other members of this class currently available to the physician have been well reviewed (1). Previous studies with mice have demonstrated a pharmacokinetic profile that produced sufficient exposure to conclude that this agent would be useful for the therapy of influenza infection (data on file, R. W. Johnson Pharmaceutical Research Institute, Raritan, N.J.).Experience with other classes of anti-infectives has demonstrated that animal model experiments that delineate which pharmacodynamic variable (peak concentration/50% inhibitory concentration [IC 50 The ability to delineate which aspect of the concentrationtime curve affects outcome is extremely valuable, as it allows the choice of the proper dosing schedule and facilitates the setting of a therapeutic goal. For these reasons, we decided to investigate RWJ-270201 in a lethal murine model of influenza infection and attempt to delineate the pharmacodynamic variable most closely linked to outcome. MATERIALS AND METHODS Virus....

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“…An AUC24/MIC of 125 was considered to be the minimally effective value, with values of 250 to 500 exhibiting an increased in vivo bactericidal rate and a shorter time to bacterial eradication. Since the time above the MIC is the most important exposure parameter in predicting the response of gramnegative bacteria to ,-lactam antibiotics (11), the duration of inhibitory activity must be considered along with target AUC2,IMICs. When these dosing interval considerations are respected, then, theoretically, AUC24/MIC should also be predictive of the bacterial response to these agents, because of covariance between time greater than the MIC and the AUC/ MIC ratio.…”

mentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic activities of ciprofloxacin against strains of Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa for which MICs are similar

Hyatt

Nix

Schentag

1994

Antimicrob Agents Chemother

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The serum bactericidal activity of ciprofloxacin against strains of Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa for which MICs are similar (0.4 ,g/ml) was assessed with serum ultrafiltrates from five healthy volunteers receiving ciprofloxacin at 400 mg intravenously every 8 h. In addition, human serum was supplemented with ciprofloxacin to achieve a mean steady-state concentration (Cs,) (716) 887-4566. (AUIC) and the area under the bactericidal titer curve (AUBC) have been described as measures of patient-specific antibiotic pharmacokinetics integrated with bacteria-and antimicrobial agent-specific pharmacodynamics (1). In order to measure the AUBC, SBT tests are performed with patient serum at several time points following antibiotic dosing. The measured AUBC is calculated as the area under the reciprocal SBT versus time curve (1). The AUIC is a measure of inhibitory activity and is calculated as the AUC of the reciprocal SITs versus time. Ellner and Neu (5)

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Role for Dual Individualization with Cefmenoxime

Cited by 127 publications

References 5 publications

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Pharmacodynamic Evaluation of RWJ-270201, a Novel Neuraminidase Inhibitor, in a Lethal Murine Model of Influenza Predicts Efficacy for Once-Daily Dosing

Pharmacokinetic and pharmacodynamic activities of ciprofloxacin against strains of Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa for which MICs are similar

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