Archive for August 20, 2016

Population Pharmacokinetics and Target Attainment of Meropenem in Plasma and Tissue of Morbidly Obese Patients after Laparoscopic Intraperitoneal Surgery.

Antimicrob Agents Chemother. 2015 Oct;59(10):6241-7.

Wittau M1, Scheele J2, Kurlbaum M3, Brockschmidt C2, Wolf AM2, Hemper E2, Henne-Bruns D2, Bulitta JB4.

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1Department of Visceral Surgery, University of Ulm, Ulm, Germany

2Department of Visceral Surgery, University of Ulm, Ulm, Germany.

3Department of Clinical Chemistry, University of Ulm, Ulm, Germany.

4Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Parkville, Victoria, Australia.


Meropenem serves as a clinically important, broad-spectrum antibiotic. While meropenem is commonly used in obese patients, its pharmacokinetics in this patient group is not well known. Our aim was to characterize the population pharmacokinetics and target attainment in plasma, subcutaneous tissue, and peritoneal fluid for meropenem in morbidly obese patients. Four doses of 1g meropenem were given as 15-min infusions every 8 h to five morbidly obese patients (body mass index [BMI], 47.6 to 62.3 kg/m(2)). After the fourth dose, serial meropenem concentrations were determined in plasma and, via microdialysis, in subcutaneous tissue and peritoneal fluid. All concentrations were analyzed simultaneously via population modeling, and target attainment probabilities predicted via Monte Carlo simulations using the target of unbound meropenem concentrations above the MIC for at least 40% of the dosing interval. For patients with 53 kg fat-free mass, total clearance was 18.7 liters/h and volume of distribution at steady state was 27.6 liters. The concentrations in subcutaneous tissue and peritoneal fluid largely paralleled those in plasma (equilibration half-life, <30 min). The area under the curve (AUC) in subcutaneous tissue divided by the plasma AUC had a mean of 0.721. For peritoneal fluid, this AUC ratio had a mean of 0.943. Target attainment probabilities were >90% after 1 g meropenem every 8 h as a 15-min infusion for MICs of up to 2 mg/liter in plasma and peritoneal fluid and 0.5 mg/liter in subcutaneous tissue. Meropenem pharmacokinetics in plasma and peritoneal fluid of obese patients was predictable, but subcutaneous tissue penetration varied greatly. (This study has been registered at under registration no. NCT01407965.).



August 20, 2016 at 4:32 pm

ATB PROPHYLAXIS IN BARIATRIC SURGERY – Continuous infusion of cefazolin vs ampicillin/sulbactam and ertapenem

Arq Gastroenterol. 2015 Apr-Jun;52(2):83-7.

Ferraz ÁA1, Siqueira LT1, Campos JM1, Araújo GC1, Martins Filho ED1, Ferraz EM1.

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1Department of Surgery, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brasil.



The incidence of surgical site infection in bariatric patients is significant and the current recommendations for antibiotic prophylaxis are sometimes inadequate. Objective: The aim of this study was to analyze the effect of three prophylactic antibiotic regimens on the incidence of surgical site infection.


A prospective, cross-sectional study was conducted between January 2009 and January 2013 in which 896 Roux-en-Y gastric bypasses were performed to treat obesity. The study compared three groups of patients according to the perioperative antibiotic prophylaxis administered intravenously and beginning at anesthesia induction: Group I consisting of 194 patients treated with two 3-g doses of ampicillin/sulbactam; Group II with 303 patients treated with a single 1-g dose of ertapenem; and Group III with 399 patients treated with a 2-g dose of cefazolin at anesthesia induction followed by a continuous infusion of cefazolin 1g throughout the surgical procedure. The rate of surgical site infection was analyzed, as well as its association with age, sex, preoperative weight, body mass index and comorbidities.


The rates of surgical site infection were 4.16% in the group treated prophylactically with ampicillin/sulbactam, 1.98% in the ertapenem group and 1.55% in the continuous cefazolin group.


The prophylactic use of continuous cefazolin in surgeries for morbid obesity shows very promising results. These findings suggest that some prophylactic regimens need to be reconsidered and even substituted by more effective therapies for the prevention of surgical site infections in bariatric patients.


August 20, 2016 at 4:31 pm

Daptomycin dosing greater than 6 mg/kg/day depending on pharmacokinetic and pharmacodynamic parameters infections by Staph aureus.

Farm Hosp. 2013 Nov-Dec;37(6):534-8.

Article in Spanish

Gutiérrez Urbón JM1, Linares Mondéjar P, Martin Herranz I.

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1Servicio de Farmacia. Complejo Hospitalario Universitario. A Coruña.

Abstractin English, Spanish

Daptomycin is a cyclic lipopeptide antibiotic whose approved dose is 4 to 6 mg/kg/day. Today it is a matter of controversy the use of higher doses of daptomycin in a range of 8-12 mg/kg/ day, for the treatment of Staphylococcus aureus infections, justified by its concentration-dependent action and its tolerability and safety profile, but the available studies are inconclusive. Stratification is performed by groups of patients, on the recommendation of using doses above 6 mg/kg/day based on the PK/PD parameters predictive of efficacy and safety. We conclude that doses of 8-12 mg/kg/day may be beneficial in patients with severe sepsis, patients with hypoalbuminemia and infections involving potentially high bacterial load or where there is a bacterial kidnapping. However it is not suitable exceed the dose of 6 mg/kg/day in patients with obesity and/or creatinine clearance less than 50 ml/min


August 20, 2016 at 4:29 pm

Pharmacokinetics of intravenous linezolid in moderately to morbidly obese adults.

Antimicrob Agents Chemother. 2013 Mar;57(3):1144-9.

Bhalodi AA1, Papasavas PK, Tishler DS, Nicolau DP, Kuti JL.

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1Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.


The pharmacokinetics of linezolid was assessed in 20 adult volunteers with body mass indices (BMI) of 30 to 54.9 kg/m(2) receiving 5 intravenous doses of 600 mg every 12 h. Pharmacokinetic analyses were conducted using compartmental and noncompartmental methods. The mean (±standard deviation) age, height, and weight were 42.2 ± 12.2 years, 64.8 ± 3.5 in, and 109.5 ± 18.2 kg (range, 78.2 to 143.1 kg), respectively. Linezolid pharmacokinetics in this population were best described by a 2-compartment model with nonlinear clearance (original value, 7.6 ± 1.9 liters/h), which could be inhibited to 85.5% ± 12.2% of its original value depending on the concentration in an empirical inhibition compartment, the volume of the central compartment (24.4 ± 9.6 liters), and the intercompartment transfer constants (K(12) and K(21)) of 8.04 ± 6.22 and 7.99 ± 5.46 h(-1), respectively. The areas under the curve for the 12-h dosing interval (AUCτ) were similar between moderately obese and morbidly obese groups: 130.3 ± 60.1 versus 109.2 ± 25.5 μg · h/ml (P = 0.32), and there was no significant relationship between the AUC or clearance and any body size descriptors. A significant positive relationship was observed for the total volume of distribution with total body weight (r(2) = 0.524), adjusted body weight (r(2) = 0.587), lean body weight (r(2) = 0.495), and ideal body weight (r(2) = 0.398), but not with BMI (r(2) = 0.171). Linezolid exposure in these obese participants was similar overall to that of nonobese patients, implying that dosage adjustments based on BMI alone are not required, and standard doses for patients with body weights up to approximately 150 kg should provide AUCτ values similar to those seen in nonobese participants.


August 20, 2016 at 4:28 pm


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