Comparative in vitro activity of carbapenems against major Gram-negative pathogens: results of Asia-Pacific surveillance from the COMPACT II study

Kiratisin, Pattarachai; Chongthaleong, Anan; Tan, Thean Yen; Lagamayo, Evelina; Roberts, Sally; Garcia, Jemelyn; Davies, Todd A.

doi:10.1016/j.ijantimicag.2012.01.002

Cited by 75 publications

(78 citation statements)

References 21 publications

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“…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%

“…To further complicate matters, pathogens that are usually isolated in the ICU differ from those in the general wards, as they are commonly less susceptible to the current antibiotic armamentarium (13,14). 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).…”

mentioning

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: 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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“…Because of its chemical instability, this carbapenem was never developed as a therapeutic agent, but was stabilized by adding the N-formimidoyl group to the 2-position, resulting in imipenem (Table 4). Imipenem has been widely used for infections caused by Gram-positive, Gram-negative, nonfermentative, and anaerobic bacteria based on its sustained high activity against these organisms, particularly among non-carbapenemase-producing enteric bacteria (Bradley et al 1999;Kiratisin et al 2012). Carbapenems, in general, bind strongly to PBP2 in Gram-negative bacteria, but may also bind to PBP1a, 1b, and 3, thus providing supplemental killing mechanisms that may serve to lessen the emergence of resistance (Sumita and Fukasawa 1995;Yang et al 1995).…”

Section: Carbapenemsmentioning

confidence: 99%

β-Lactams and β-Lactamase Inhibitors: An Overview

Bush

Bradford

2016

Cold Spring Harb Perspect Med

785

587

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b-Lactams are the most widely used class of antibiotics. Since the discovery of benzylpenicillin in the 1920s, thousands of new penicillin derivatives and related b-lactam classes of cephalosporins, cephamycins, monobactams, and carbapenems have been discovered. Each new class of b-lactam has been developed either to increase the spectrum of activity to include additional bacterial species or to address specific resistance mechanisms that have arisen in the targeted bacterial population. Resistance to b-lactams is primarily because of bacterially produced b-lactamase enzymes that hydrolyze the b-lactam ring, thereby inactivating the drug. The newest effort to circumvent resistance is the development of novel broad-spectrum b-lactamase inhibitors that work against many problematic b-lactamases, including cephalosporinases and serine-based carbapenemases, which severely limit therapeutic options. This work provides a comprehensive overview of b-lactam antibiotics that are currently in use, as well as a look ahead to several new compounds that are in the development pipeline.

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“…The prevalence of CRE in South East Asia was about 2.8% as documented in one 39 study (13 carbapenamase genes showed that the sensitivity and specificity reached 100% and it is a 70 robust, reliable and rapid method for detection of the most prevalent carbapenamases (24).…”

mentioning

confidence: 99%

Diagnostic Use of PCR in Carbapenamase-producing Enterobacteriaceae (CPE): An Improved Method to Overcome the presence of inhibitors for DNA Extraction from Blood Cultures

Salmuna

Hassan

2018

Preprint

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Comparative in vitro activity of carbapenems against major Gram-negative pathogens: results of Asia-Pacific surveillance from the COMPACT II study

Cited by 75 publications

References 21 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

β-Lactams and β-Lactamase Inhibitors: An Overview

Diagnostic Use of PCR in Carbapenamase-producing Enterobacteriaceae (CPE): An Improved Method to Overcome the presence of inhibitors for DNA Extraction from Blood Cultures

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