In vitro activity of doripenem and other carbapenems against contemporary Gram-negative pathogens isolated from hospitalised patients in the Asia-Pacific region: results of the COMPACT Asia-Pacific Study

Christiansen, Keryn; Ip, Margaret; Ker, H.B.; Mendoza, Michael Antonio F.; Hsu, Li Yang; Kiratisin, Pattarachai; Chongthaleong, Anan; Redjeki, Ike Sri; Quintana, Alvaro; Flamm, Robert K.; Garcia, Jemelyn; Cassettari, M.; Cooper, D.B.; Okolo, P.; Morrissey, Ian

doi:10.1016/j.ijantimicag.2010.08.002

Cited by 14 publications

(15 citation statements)

References 17 publications

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“…For A. baumannii, which is commonly MDR, empirical combination antibiotic therapy is currently preferred instead of doripenem monotherapy in our ICU. Furthermore, the MIC 90 for doripenem against A. baumannii in the Asia-Pacific region was reported as Ն32 mg/liter (15,16). For such an MIC, even with a dose of 2,000 mg every 8 h as a 4-h infusion, optimal exposure was only achieved for patients with reduced CL CR in our cohort (e.g., Ͻ70 ml/min).…”

Section: Discussionmentioning

confidence: 74%

“…In two large antibiotic susceptibility prevalence studies conducted in the Asia-Pacific region (15,16), the MIC 90 for doripenem against P. aeruginosa was 8 mg/liter. 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.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, local microbiology and antibiotic resistance patterns may greatly vary across different geographical regions, affecting antibiotic dosing requirements (15). In this context, it is imperative to consider regional antibiotic susceptibility data whereby, in the Asia-Pacific region, the MIC required to inhibit the growth of 90% of organisms (MIC 90 ) for doripenem against P. aeruginosa was reported as 8 mg/liter (15,16). However, a typical dose of 500 mg every 8 h as a 1-h infusion is reported to be effective only against pathogens with an MIC of Յ2 mg/liter; its application, therefore, is likely to fail in such a scenario (4,6).…”

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confidence: 99%

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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: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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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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“…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%

“…Additionally, local microbiology and antibiotic resistance patterns may greatly vary across different geographical regions affecting antibiotic dosing requirements [332]. In this context, it is imperative to consider regional antibiotic susceptibility data whereby in the Asia-Pacific region, the MIC90 for doripenem against P. aeruginosa was reported as 8 mg/L [332,333]. As previously mentioned, the commonly administered dose of 500 mg 8-hourly as a 1-hour infusion is reported to only be effective against pathogens with an MIC of ≤2 mg/L and its application is therefore likely to fail in such a scenario [313,316].…”

Section: Introductionmentioning

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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Recent updates of carbapenem antibiotics

El‐Gamal

Brahim

Hisham

et al. 2017

European Journal of Medicinal Chemistry

191

101

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In vitro activity of doripenem and other carbapenems against contemporary Gram-negative pathogens isolated from hospitalised patients in the Asia-Pacific region: results of the COMPACT Asia-Pacific Study

Cited by 14 publications

References 17 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

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

Recent updates of carbapenem antibiotics

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