Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region

Kiratisin, Pattarachai; Keel, Rebecca A.; Nicolau, David P.

doi:10.1016/j.ijantimicag.2012.09.007

Cited by 15 publications

(7 citation statements)

References 26 publications

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“…Our data suggest that, for such an MIC, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL CR of 30 to 100 ml/min and that a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL CR Ͼ100 ml/ min. Such recommendations are consistent with several large pharmacodynamic simulation studies conducted in the Asia-Pacific region (50,51) as well as in other parts of the world (3,52). This study provides additional PK/PD data to support an alternative doripenem dosing approach in critically ill patients, particularly when pathogens with high MICs are involved.…”

Section: Discussionsupporting

confidence: 85%

Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit

Abdul‐Aziz

Rahman

Mat-Nor

et al. 2016

Antimicrob Agents Chemother

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g Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL CR ), such that a 30-ml/min increase in the estimated CL CR would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL CR of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL CR of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.

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Section: Discussionsupporting

confidence: 85%

Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit

Abdul‐Aziz

Rahman

Mat-Nor

et al. 2016

Antimicrob Agents Chemother

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“…This observation is consistent with those of previous reports in the literature. 24,25 Staphylococci are a common cause of invasive infections. The adaptability of staphylococci is one of the reasons why antibiotics should not be prescribed systematically.…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial profiles of bacterial clinical isolates from the Gabonese National Laboratory of Public Health: data from routine activity

Rerambiah¹,

Ndong

Massoua³

et al. 2014

International Journal of Infectious Diseases

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“…Our data suggest that for such an MIC, a dose of 1000 mg 8-hourly as a 4-hour infusion is optimal for patients with CLCR of 30-100 mL/min and a dose of 2000 mg every 8-hourly as a 4-hour infusion is best for patients manifesting a CLCR >100 mL/min. Such recommendations are consistent with several large PD simulation studies conducted in the Asia-Pacific region [331,355] as well as other parts of the world [314,356]. This study provides additional PK/PD data to support an alternative doripenem dosing approach in critically ill patients, particularly when pathogens with high MIC are involved.…”

Section: Discussionsupporting

confidence: 86%

“…For example, a doripenem dose of 500 mg every 8 hours as a 1-hour infusion is only effective against pathogens with a MIC of ≤2 mg/L. This standard doripenem dose is likely to fail in critically ill patients, who may have altered PK and who are commonly infected with pathogens with higher MICs [331][332][333][334][335]. In this context, it is important to highlight the recent termination of an industry-sponsored clinical trial investigating the use of doripenem in ventilator-associated pneumonia (VAP) [336].…”

Section: Doripenemmentioning

confidence: 99%

Optimizing beta-lactam antibiotic dosing in critically ill patients: Prolonged infusion versus intermittent bolus administration

Abdul‐Aziz¹,

Mohd²

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Severe sepsis is a major burden in the intensive care unit (ICU) with persistently high mortality rates. Optimization of antibiotic dosing has been suggested as an intervention to improve clinical outcomes for critically ill patients with severe sepsis. However, current antibiotic dosing guidelines may not be appropriate for these patients, as they rarely consider the altered physiology and illness severity associated with this population. Optimizing antibiotic dosing using pharmacokinetic (PK) and pharmacodynamic (PD) principles can address these critical illness-related changes and promote therapeutic success. Due to their wide spectrum of antibiotic activity and excellent safety profile, beta-lactam antibiotics are commonly used for severe infections in the ICU. Two alternative dosing approaches to traditional intermittent bolus (IB) dosing, namely continuous infusion (CI) and extended infusion (EI), have been suggested to maximize the therapeutic potential of these antibiotics in critically ill patients. Collectively, the two dosing approaches can also be referred as prolonged infusion (PI).This Thesis aims to better characterize the pharmacokinetics/pharmacodynamics (PK/PD) of betalactam antibiotics to determine whether there is any therapeutic advantage associated with PI dosing (CI and/or EI) as compared to IB dosing. This Thesis comprises of eight chapters. Chapter 1 is an introductory chapter which provides an overview of the published literature on the area of research. The discussion in Chapter 1 presents a theoretical framework behind the Thesis objectives. Chapter 1 concludes with the specific aims of this Thesis.Chapter 2 reports the findings of a prospective PK study which aimed to describe the population PK of doripenem in critically ill patients with sepsis and perform dosing simulations to develop clinically relevant dosing guidelines for these patients. Twelve critically ill participants receiving 500 mg of doripenem 8-hourly as a 1-hr infusion were enrolled. The volume of distribution (Vd) and clearance (CL) of doripenem in this patient cohort were substantially different than those usually described in non-critically patients. As current dosing guidelines were mostly derived from the non-critically ill, findings from this study suggest that the licensed "one-dose-fits-all" dosing for doripenem is unlikely to achieve optimal exposures in critically ill patients. Empirical use of PI dosing should be considered to account for PK and illness severity differences, particularly when less-susceptible pathogens are involved.ii Chapter 3 incorporates a published systematic review which compares the PK/PD data and clinical outcomes between CI and IB dosing to describe any potential merits supporting either of the two dosing approaches for critically ill patients. The findings suggest that beta-lactam CI may not be advantageous for all critically ill patients and may be beneficial in patients with severe infections.Chapter 4 describes the findings of a post hoc analysis on the Defining...

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Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region

Cited by 15 publications

References 26 publications

Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit

Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit

Antimicrobial profiles of bacterial clinical isolates from the Gabonese National Laboratory of Public Health: data from routine activity

Optimizing beta-lactam antibiotic dosing in critically ill patients: Prolonged infusion versus intermittent bolus administration

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