Ertapenem Once Daily Versus Piperacillin‐Tazobactam 4 Times per Day for Treatment of Complicated Skin and Skin‐Structure Infections in Adults: Results of a Prospective, Randomized, Double‐Blind Multicenter Study

Graham, Donald R.; Lucasti, Christopher; Malafaia, Osvaldo; Nichols, Ronald Lee; Holtom, Paul; Perez, Nora Quintero; McAdams, Andrea; Woods, Gail L.; Ceesay, T. Paulette; Gesser, Richard M.

doi:10.1086/340348

Cited by 123 publications

(102 citation statements)

References 11 publications

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“…Study 2 was an open-label, randomized, four-period crossover study with single i.v. doses of 0.5, 1, 2, and 3 g. Study 3 was an open-label study to investigate the disposition of [ 14 C]ertapenem following a 1-g (ϳ100-Ci) i.v. dose.…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetics of Ertapenem in Healthy Young Volunteers

Majumdar

Musson

Birk

et al. 2002

Antimicrob Agents Chemother

137

107

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Ertapenem (INVANZ) is a new once-a-day parenteral ␤-lactam antimicrobial shown to be effective as a single agent for treatment of various community-acquired and mixed infections. The single-and multiple-dose pharmacokinetics of ertapenem at doses up to 3 g were examined in healthy young men and women volunteers. Plasma and urine samples collected were analyzed using reversed-phase high-performance liquid chromatography with UV detection. Ertapenem is highly bound to plasma protein. The protein binding changes from ϳ95% bound at concentrations of <50 g/ml to ϳ92% bound at concentrations of 150 g/ml (concentration at the end of a 30-min infusion following the 1-g dose). The nonlinear protein binding of ertapenem resulted in a slightly less than dose proportional increase in the area under the curve from 0 h to infinity (AUC 0-ؕ ) of total ertapenem. The single-dose AUC 0-ؕ of unbound ertapenem was nearly dose proportional over the dose range of 0.5 to 2 g. The mean concentration of ertapenem in plasma ranged from ϳ145 to 175 g/ml at the end of a 30-min infusion, from ϳ30 to 34 g/ml at 6 h, and from ϳ9 to 11 g/ml at 12 h. The mean plasma t 1/2 ranged from 3.8 to 4.4 h. About 45% of the plasma clearance (CL P ) was via renal clearance. The remainder of the CL P was primarily via the formation of the ␤-lactam ring-opened metabolite that was excreted in urine. There were no clinically significant differences between the pharmacokinetics of ertapenem in men and women. Ertapenem does not accumulate after multiple once-daily dosing.Ertapenem (INVANZ; MK-0826; Merck & Co., Inc.) is a once-a-day parenteral ␤-lactam antimicrobial agent with excellent in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria generally associated with community-acquired and mixed infections (1; C. J. Gill, J. J. Jackson, J. G. Sundelof, H. Rosen, and H. Kropp, Abstr. 36th Intersci. Conf. Antimicrob. Agents Chemother., abstr. F125, p. 121, 1996). Moreover, ertapenem has been shown to be effective for treating several community-acquired and mixed infections, including intra-abdominal infections, skin and skinstructure infections, community-acquired pneumonia, acute pelvic infections, and urinary tract infections (3, 5; J. S. L-855, 2001). This structurally unique carbapenem (Fig. 1) exhibits a long plasma half-life (t 1/2 ) (about 4 h) due largely to its high plasma protein binding and stability against human renal dehydropeptidase.The objectives of this study were to (i) assess the dose proportionality of intravenous (i.v.) doses of ertapenem across the dose range of 0.5 to 3 g, (ii) evaluate the plasma protein MATERIALS AND METHODSStudy design. This report includes data from five clinical studies. The design of these studies are as follows. Study 1 was a two-part, double-blind, placebocontrolled study; part I was a two-panel, four-period single rising dose study with doses of 0.04, 0.25, 1, and 2 g in one panel and 0.1, 0.5, 1.5, and 3 g in the second panel. Pharmacokinetic analysis was performed for doses of...

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Section: Methodsmentioning

confidence: 99%

“…F125, p. 121, 1996). Moreover, ertapenem has been shown to be effective for treating several community-acquired and mixed infections, including intra-abdominal infections, skin and skinstructure infections, community-acquired pneumonia, acute pelvic infections, and urinary tract infections (3,5 ). This structurally unique carbapenem ( Fig.…”

mentioning

confidence: 99%

Pharmacokinetics of Ertapenem in Healthy Young Volunteers

Majumdar

Musson

Birk

et al. 2002

Antimicrob Agents Chemother

137

107

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“…The few published multi-centre studies characterising SSTI pathogens have been limited to specific types of organisms [30], with almost all reports on SSTIs in diabetic patients limited to foot infections [31][32][33]. Few studies have addressed the interaction of specific pathogens with various clinical and economic outcomes [34].…”

Section: Introductionmentioning

confidence: 99%

Skin and soft tissue infections in hospitalised patients with diabetes: culture isolates and risk factors associated with mortality, length of stay and cost

Tabak²,

et al. 2010

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Aims/hypothesis Skin and soft tissue infections (SSTIs) cause substantial morbidity in persons with diabetes. There are few data on pathogens or risk factors associated with important outcomes in diabetic patients hospitalised with SSTIs. Methods Using a clinical research database from CareFusion, we identified 3,030 hospitalised diabetic patients with positive culture isolates and a diagnosis of SSTI in 97 US hospitals between 2003 and 2007. We classified the culture isolates and analysed their association with the anatomic location of infection, mortality, length of stay and hospital costs. Results The only culture isolate with a significantly increased prevalence was methicillin-resistant Staphylococcus aureus (MRSA); prevalence for infection of the foot was increased from 11.6 to 21.9% (p<0.0001) and for non-foot locations from 14.0% to 24.6% (p=0.006). Patients with non-foot (vs foot) infections were more severely ill at presentation and had higher mortality rates (2.2% vs 1.0%, p<0.05). Significant independent risk factors associated with higher mortality rates included having a polymicrobial culture with Pseudomonas aeruginosa (OR 3

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“…Most recent studies of complicated skin and skin structure (including diabetic foot) infections in developed (especially northern) countries have reported that P. aeruginosa is isolated in <10% of wounds [117,118]. Furthermore, even when isolated, patients often improve despite therapy with antibiotics ineffective against P. aeruginosa [79,90,[119][120][121]. Conversely, in countries where P. aeruginosa is a frequent isolate [122][123][124], or in patients who have been soaking their feet, who have failed therapy with nonpseudomonal therapy, or who have a severe infection, empiric antipseudomonal therapy may be advisable.…”

Section: Evidence Summarymentioning

confidence: 99%