Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003)

Fritsche, Thomas R.; Stilwell, Matthew G.; Jones, Ronald N.

doi:10.1111/j.1469-0691.2005.01271.x

Cited by 117 publications

(133 citation statements)

References 26 publications

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“…No difference was observed for all tigecycline combina- carbapenem, and the next generation of cephalosporins with activity against MRSA, ceftobiprole and ceftaroline. At this point, none of these agents appear to have significant advantages over current antimicrobials for A. baumannii, but in vitro data for doripenem suggest a slight advantage over meropenem (175,275,378,379). Clinical data for doripenem against A. baumannii are still awaited.…”

Section: New Antimicrobialsmentioning

confidence: 99%

Acinetobacter baumannii : Emergence of a Successful Pathogen

2008

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SUMMARY Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.

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Section: New Antimicrobialsmentioning

confidence: 99%

Acinetobacter baumannii : Emergence of a Successful Pathogen

2008

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“…Doripenem is a parenteral carbapenem with in vitro microbiological activity against a broad spectrum of clinically important Gram-positive and Gram-negative pathogens (9,14,23). It is approved for complicated intra-abdominal and complicated urinary tract infections (UTI) in the United States and in Europe, where it is also approved for nosocomial pneumonia (15).…”

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confidence: 99%

Population Pharmacokinetics of Doripenem Based on Data from Phase 1 Studies with Healthy Volunteers and Phase 2 and 3 Studies with Critically Ill Patients

Nandy

Samtani

Lin

2010

Antimicrob Agents Chemother

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A population pharmacokinetic model of doripenem was constructed using data pooled from phase 1, 2, and 3 studies utilizing nonlinear mixed effects modeling. A 2-compartment model with zero-order input and first-order elimination best described the log-transformed concentration-versus-time profile of doripenem. The model was parameterized in terms of total clearance (CL), central volume of distribution (V c ), peripheral volume of distribution (V p ), and distribution clearance between the central and peripheral compartments (Q). The final model was described by the following equations (for jth subject): CL j (liters/h) ‫؍‬ 13. interindividual variability (percent coefficient of variation [% CV]) for CL (liters/h), V c (liters), V p (liters), and Q (liters/h) were 13.6 (19%), 11.6 (19%), 6.0 (25%), and 4.7 (42%), respectively. Residual variability, estimated using three separate additive residual error models, was 0.17 standard deviation (SD), 0.55 SD, and 0.92 SD for phase 1, 2, and 3 data, respectively. Creatinine clearance was the most significant predictor of doripenem clearance. Mean Bayesian clearance was approximately 33%, 55%, and 76% lower for individuals with mild, moderate, or severe renal impairment, respectively, than for those with normal renal function. The population pharmacokinetic model based on healthy volunteer data and patient data informs us of doripenem disposition in a more general population as well as of the important measurable intrinsic and extrinsic factors that significantly influence interindividual pharmacokinetic differences.

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“…; and 8 µg/mL for Enterococcus faecalis and Pseudomonas aeruginosa, according to the latest global surveillance. 20) In the case of infections by Acinetobacter, E. faecalis, P aeruginosa and other bacteria with MIC ≥8 µg/mL, even the recommended higher dosage regimen may be insufficient to ensure success in empirical therapy. Previous PK/PD modeling of DRPM in healthy volunteers and patients with renal dysfunction found that 1-h infusion of 0.5 g of DRPM every 8 h achieved good coverage for bacteria with MICs up to 1 µg/mL, while 4-h infusion of 1 g every 8 h achieved good coverage for pathogens with MICs of 8 µg/mL.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Analysis for Doripenem Regimens in Intensive Care Unit Patient

Tanaka

Sato

Goto

et al. 2017

Biological & Pharmaceutical Bulletin

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Doripenem (DRPM) is a broad-spectrum antibacterial agent often used as empirical therapy for critically ill patients, although there is a lack of studies validating the recommended dosage regimen for patients admitted to intensive care unit (ICU), based on pharmacokinetic (PK)/pharmacodynamic (PD) index. In this study, we estimated the free time above minimum inhibitory concentration (fT>MIC (%)) of DRPM using population PK analysis of 12 patients in ICU, and evaluated the validity of the dosage regimen stratified by creatinine clearance. Using a 2-compartment population PK model reported previously, the mean total clearance or distribution volume of DRPM estimated by Bayesian estimation was significantly lower or higher than that of based on population PK model. The estimated fT>MIC (%) of the recommended standard (normal renal function: 0.5 g every 8 h, moderate: 0.25 g every 8 h, severe renal impairment: 0.25 g every 12 h) and higher doses (normal: 1.0 g every 8 h, moderate: 0.5 g every 8 h, severe: 0.25 g every 8 h) against MICs of 0.5, 1 and 2 µg/mL exceeded 40% in all patients. When stratified by creatinine clearance, the PK/PD breakpoints estimated by Monte Carlo simulation in three grades of renal function tended to be higher than the previously reported PK/PD breakpoints for patients with urinary tract infection, an infection of lesser severity than ICU patients. These results suggest that the dosage regimen stratified by renal function derived from Japanese package insert may be sufficient to achieve effective treatment in ICU patients.Key words doripenem; pharmacokinetic/pharmacodynamic analysis; intensive care unit; breakpoint Doripenem (DRPM) is a newer carbapenem antimicrobial agent with potent and broad spectrum activities against Grampositive, Gram-negative and anaerobic bacteria, and is more potent against Pseudomonas aeruginosa than other carbapenems.1-3) Doses of 0.5-3.0 g daily in two or three divided doses administered by 0.5 or 1 h infusion are used commonly to treat infectious diseases such as pneumonia, complicated urinary tract infection and intra-abdominal infections. In order to provide optimal antimicrobial therapy, selecting an effective and well-tolerated dosage regimen based on pharmacokinetic (PK)/ pharmacodynamic (PD) index is important. For DRPM and other β-lactams with time-dependent antimicrobial activity, an effective dosage regimen requires that the blood concentrations exceed the minimum inhibitory concentration (MIC) of the infecting bacteria for at least 40% of the dosing interval.4) Therefore, the appropriate dosage regimen based on time above MIC (%T>MIC) is of great importance when using DRPM.Critically ill patients in the intensive care unit (ICU) are often affected by infections, and are given antimicrobial agents with a broad spectrum. 5) In particular, since severe sepsis and septic shock are major causes of morbidity and mortality in the ICU, early use of carbapenems including DRPM as an empirical therapy is recommended by international guidelines for the manageme...

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Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003)

Cited by 117 publications

References 26 publications

Acinetobacter baumannii : Emergence of a Successful Pathogen

Acinetobacter baumannii : Emergence of a Successful Pathogen

Population Pharmacokinetics of Doripenem Based on Data from Phase 1 Studies with Healthy Volunteers and Phase 2 and 3 Studies with Critically Ill Patients

Pharmacokinetic/Pharmacodynamic Analysis for Doripenem Regimens in Intensive Care Unit Patient

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