Posts filed under ‘Infecciones y Obesidad’

Dosing vancomycin in the super obese: less is more

Journal of Antimicrobial Chemotherapy 1 November 2018 V.73 N.11 P.3081–3086


Ryan L Crass; Ryan Dunn; Joseph Hong; Lynne C Krop; Manjunath P Pai


Vancomycin remains the mainstay of empirical therapy directed against MRSA. National guidelines recommend empirical dosing based on total body weight with trough-level therapeutic drug monitoring (TDM), which may not be optimal in obese and super obese patients. Furthermore, nomograms for empirical vancomycin dosing by estimated kidney function pre-date standardization of creatinine assays.


To determine an empirical vancomycin dosing strategy for obese and super obese adults that is consistent with the AUC monitoring paradigm.


We conducted a population pharmacokinetic study using data obtained from routine peak and trough TDM of vancomycin in obese and super obese adults. An empirical dosing nomogram was developed using Monte Carlo simulation to identify vancomycin doses that optimize the probability of efficacy and minimize the probability of acute kidney injury based on AUC.


A total of 346 patients were included encompassing a wide range of body weight (69.6–293.6 kg) and BMI (30.1–85.7 kg/m2) values. In the final model, vancomycin clearance (CLV) was described using a linear combination of age, serum creatinine, sex and allometrically scaled body weight. Monte Carlo simulation demonstrated that maintenance doses >4500 mg/day were not required to achieve pharmacodynamic AUC targets in obese and super obese patients at clinically relevant values of CLV.


Empirical vancomycin dosing informed by common clinical variables, including standardized creatinine, with subsequent individualization using AUC-targeted TDM can optimize therapy in obese and super obese adults.



January 5, 2019 at 11:45 pm

Cefazolin Prophylaxis for Total Joint Arthroplasty: Obese Patients Are Frequently Underdosed and at Increased Risk of Periprosthetic Joint Infection

Journal of Arthroplasty November 2018 V.33 N.11 P. 3551–3554

Alexander J. Rondon, Michael M. Kheir, Timothy L. Tan, Noam Shohat, Max R. Greenky, Javad Parvizi


One of the most effective prophylactic strategies against periprosthetic joint infection (PJI) is administration of perioperative antibiotics. Many orthopedic surgeons are unaware of the weight-based dosing protocol for cefazolin. This study aimed at elucidating what proportion of patients receiving cefazolin prophylaxis are underdosed and whether this increases the risk of PJI.


A retrospective study of 17,393 primary total joint arthroplasties receiving cefazolin as perioperative prophylaxis from 2005 to 2017 was performed. Patients were stratified into 2 groups (underdosed and adequately dosed) based on patient weight and antibiotic dosage. Patients who developed PJI within 1 year following index procedure were identified. A bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify risk factors for PJI.


The majority of patients weighing greater than 120 kg (95.9%, 944/984) were underdosed. Underdosed patients had a higher rate of PJI at 1 year compared with adequately dosed patients (1.51% vs 0.86%, P = .002). Patients weighing greater than 120 kg had higher 1-year PJI rate than patients weighing less than 120 kg (3.25% vs 0.83%, P < .001). Patients who were underdosed (odds ratio, 1.665; P = .006) with greater comorbidities (odds ratio, 1.259; P < .001) were more likely to develop PJI at 1 year.


Cefazolin underdosing is common, especially for patients weighing more than 120 kg. Our study reports that underdosed patients were more likely to develop PJI. Orthopedic surgeons should pay attention to the weight-based dosing of antibiotics in the perioperative period to avoid increasing risk of PJI.



November 30, 2018 at 8:28 am

Severely Obese Patients Have a Higher Risk of Infection After Direct Anterior Approach Total Hip Arthroplasty

Journal of Arthroplasty September 2016 V.31 N.9 P.162–165

Richard L. Purcell, Nancy L. Parks, Jeanine M. Gargiulo, William G. Hamilton


The orthopedic literature documents that obesity can place patients at increased risk for complications. This is the first study to document the increased risk of infection in obese patients after direct anterior approach (DAA) primary total hip arthroplasty (THA).


We retrospectively evaluated 1621 consecutive primary THAs performed with a DAA. Patients were stratified by body mass index <35 kg/m2 (group 1) or ≥35 kg/m2 (group 2). Rates of postoperative infection requiring revision, superficial wound dehiscence, return to the operating room, and total wound complications were compared. There were 1417 cases in group 1 and 204 in group 2.


Five cases in each group had a deep infection, resulting in a significantly higher rate in group 2 (0.35% vs 2.5%, P = .0044, relative risk = 7.1). Superficial wound dehiscence was diagnosed in 13 (0.92%) THA in group 1 and 4 (1.96%) in group 2 (P = .256). The all-cause reoperation rate was 0.92% and 3.43% in each group, respectively (P = .008). The total rate of all studied complications was 1.27% compared to 4.41% (P = .0040, relative risk = 3.5).


This is the first study to report on significantly increased rates of postoperative infection requiring revision in patients with body mass index ≥35 kg/m2 after anterior approach hip arthroplasty. We believe it is the combination of immune dysfunction and proximity of the anterior incision to the inguinal crease and genitalia with overlying abdominal pannus that contributes to this risk. Further studies comparing other surgical approaches in obese patients are needed to determine if this complication is truly attributable to the DAA alone.


December 1, 2016 at 8:26 am

Consensus on surgical aspects of managing osteomyelitis in the diabetic foot.

Diabet Foot Ankle. 2016 Jul 12;7:30079.

Allahabadi S1, Haroun KB1, Musher DM2, Lipsky BA3,4,5, Barshes NR6.

Author information

1Baylor College of Medicine, Houston, Texas.

2Division of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, Texas.

3Department of Medicine, University of Washington, Seattle.

4Department of Medicine (Infectious Diseases), University of Geneva, Geneva, Switzerland.

5Department of Medicine, Green Templeton College, University of Oxford, Oxford, United Kingdom.

6Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine / Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas;



The aim of this study was to develop consensus statements that may help share or even establish ‘best practices’ in the surgical aspects of managing diabetic foot osteomyelitis (DFO) that can be applied in appropriate clinical situations pending the publication of more high-quality data.


We asked 14 panelists with expertise in DFO management to participate. Delphi methodology was used to develop consensus statements. First, a questionnaire elicited practices and beliefs concerning various aspects of the surgical management of DFO. Thereafter, we constructed 63 statements for analysis and, using a nine-point Likert scale, asked the panelists to indicate the extent to which they agreed or disagreed with the statements. We defined consensus as a mean score of greater than 7.0.


The panelists reached consensus on 38 items after three rounds. Among these, seven provide guidance on initial diagnosis of DFO and selection of patients for surgical management. Another 15 statements provide guidance on specific aspects of operative management, including the timing of operations and the type of specimens to be obtained. Ten statements provide guidance on postoperative management, including wound closure and offloading, and six statements summarize the panelists’ agreement on general principles for surgical management of DFO.


Consensus statement on the perioperative management of DFO were formed with an expert panel comprised of a variety of surgical specialties. We believe these statements may serve as ‘best practice’ guidelines until properly performed studies provide more robust evidence to support or refute specific surgical management steps in DFO.


October 20, 2016 at 8:20 am

Body mass and weight thresholds for increased prosthetic joint infection rates after primary total joint arthroplasty.

Acta Orthop. 2016;87(2):132-8.

Lübbeke A1, Zingg M1, Vu D2, Miozzari HH1, Christofilopoulos P1, Uçkay I1,2, Harbarth S3, Hoffmeyer P1.

Author information

1a Division of Orthopedics and Trauma Surgery , Geneva University Hospitals and Faculty of Medicine, University of Geneva , Geneva , Switzerland .

2b Division of Infectious Diseases , Geneva University Hospitals and Faculty of Medicine, University of Geneva , Geneva , Switzerland .

3c Infection Control Program , Geneva University Hospitals and Faculty of Medicine, University of Geneva , Geneva , Switzerland.



Obesity increases the risk of deep infection after total joint arthroplasty (TJA). Our objective was to determine whether there may be body mass index (BMI) and weight thresholds indicating a higher prosthetic joint infection rate.


We included all 9,061 primary hip and knee arthroplasties (mean age 70 years, 61% women) performed between March 1996 and December 2013 where the patient had received intravenous cefuroxime (1.5 g) perioperatively. The main exposures of interest were BMI (5 categories: < 24.9, 25-29.9, 30-34.9, 35-39.9, and ≥ 40) and weight (5 categories: < 60, 60-79, 80-99, 100-119, and ≥ 120 kg). Numbers of TJAs according to BMI categories (lowest to highest) were as follows: 2,956, 3,350, 1,908, 633, and 214, respectively. The main outcome was prosthetic joint infection. The mean follow-up time was 6.5 years (0.5-18 years).


111 prosthetic joint infections were observed: 68 postoperative, 16 hematogenous, and 27 of undetermined cause. Incidence rates were similar in the first 3 BMI categories (< 35), but they were twice as high with BMI 35-39.9 (adjusted HR = 2.1, 95% CI: 1.1-4.3) and 4 times higher with BMI ≥ 40 (adjusted HR = 4.2, 95% CI: 1.8-9.7). Weight ≥ 100 kg was identified as threshold for a significant increase in infection from the early postoperative period onward (adjusted HR = 2.1, 95% CI: 1.3-3.6).


BMI ≥ 35 or weight ≥ 100 kg may serve as a cutoff for higher perioperative dosage of antibiotics.


August 27, 2016 at 6:08 pm

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.

Author information

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.

Author information

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.

Author information

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.

Author information

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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