Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery

Grupper, Mordechai; Kuti, Joseph L.; Swank, Morgan; Maggio, Lindsay; Hughes, Brenna L.; Nicolau, David P.

doi:10.1002/jcph.851

Cited by 24 publications

(24 citation statements)

References 30 publications

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“…A different option for improving preventive measures in obese patients receiving total hip arthroplasty is to increase the dosage of cefazolin, especially since previous studies showed that the currently applied cefazolin dosage as antibiotic prophylaxis may not be sufficient to achieve adequate tissue concentrations in obese patients [11–13]. Another reason to increase the dosage of cefazolin is the higher rate of infections caused by Proteus species in obese patients in our cohort, since Proteus species have a higher minimum inhibitory concentration for cefazolin than other Enterobacteriaceae [24].…”

Section: Discussionmentioning

confidence: 99%

“…Secondly, higher glucose levels in obese patients with diabetes mellitus increase the risk of infection [10]. Thirdly, the applied cefazolin dosage as antibiotic prophylaxis may not be sufficient to achieve adequate tissue concentrations in obese patients, especially in patients weighing more than 120kg or with a BMI >40kg/m 2 [11–13]. Finally, obese patients have increased bacterial colonization of the skin compared with non-obese patients, particularly in the groin [14, 15].…”

Section: Introductionmentioning

confidence: 99%

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Obese patients have higher rates of polymicrobial and Gram-negative early periprosthetic joint infections of the hip than non-obese patients

et al. 2019

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Background Obese patients are more likely to develop periprosthetic joint infection (PJI) after primary total joint arthroplasty. This study compared the clinical and microbiological characteristics of non-obese, obese and severely obese patients with early PJI, in order to ultimately optimize antibiotic prophylaxis and other prevention measures for this specific patient category. Methods We retrospectively evaluated patients with early PJI of the hip and knee treated with debridement, antibiotics and implant retention (DAIR) between 2006 and 2016 in three Dutch hospitals. Only patients with primary arthroplasties indicated for osteoarthritis were included. Early PJI was defined as an infection that developed within 90 days after index surgery. Obesity was defined as a BMI ≥30kg/m 2 and severe obesity as a BMI ≥35kg/m 2 . Results A total of 237 patients were analyzed, including 64 obese patients (27.0%) and 62 severely obese patients (26.2%). Compared with non-obese patients, obese patients had higher rates of polymicrobial infections (60.3% vs 33.3%, p<0.001) with more often involvement of Enterococcus species (27.0% vs 11.7%, p = 0.003). Moreover, severely obese patients had more Gram-negative infections, especially with Proteus species (12.9% vs 2.3%, p = 0.001). These results were only found in periprosthetic hip infections, comprising Gram-negative PJIs in 34.2% of severely obese patients compared with 24.7% in obese patients and 12.7% in non-obese patients (p = 0.018). Conclusions Our results demonstrate that obese patients with early periprosthetic hip infections have higher rates of polymicrobial infections with enterococci and Gram-negative rods, which stresses the importance of improving preventive strategies in this specific patient category, by adjusting antibiotic prophylaxis regimens, improving disinfection strategies and optimizing postoperative wound care.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Obese patients have higher rates of polymicrobial and Gram-negative early periprosthetic joint infections of the hip than non-obese patients

et al. 2019

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“…In evaluating the effectiveness of vac dressings, the primary goal was to assess the presence of a superficial incisional surgical site infection (SSI). Eleven studies assessed the use of cefazolin in perioperative prophylaxis [48][49][50][51][52][53][54][55][56][57][58], six of which were prospective [48,52,[54][55][56][57][58], and two were randomized and double-blind [51,53].…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

A Systematic Review and Meta-Analysis of Wound Complications after a Caesarean Section in Obese Women

Słabuszewska-Jóźwiak

Szymański

Jóźwiak

et al. 2021

JCM

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(1) Background: Caesarean sections in obese patients are associated with an increased risk of surgical wound complications, including hematomas, seromas, abscesses, dehiscence, and surgical site infections. The aim of the present study is to perform a meta-analysis and systematic review of the current literature focusing on the strategies available to decrease wound complications in this population. (2) Methods: We reviewed the data available from the PubMed and the Science Direct databases concerning wound complications after caesarean sections in obese women. The following key words were used: “caesarean section”, “cesarean section”, “wound complication”, “wound morbidity”, and “wound infection”. A total of 540 papers were retrieved, 40 of which were selected for the final systematic review and whereas 21 articles provided data for meta-analysis. (3) Results: The conducted meta-analyses revealed that the use of prophylactic drainage does not increase the risk of wound complications in obese women after a caesarean sections (pooled OR = 1.32; 95% CI 0.64–2.70, p = 0.45) and that vertical skin incisions increase wound complications (pooled OR = 2.48; 95% CI 1.85–3.32, p < 0.01) in obese women, including extremely obese women. (4) Conclusions: Subcutaneous drainage does not reduce the risk of a wound complications, wound infections, and fever in obese women after caesarean sections. Negative prophylactic pressure wound therapy (NPWT) may reduce the risk of surgical site infections. The evidence of using a prophylactic dose of an antibiotic before the caesarean section is still lacking.

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“…This exercise also suggests that the degree of adherence needed to have a high probability of protection differs based on the site of tissue exposure to the virus through sexual intercourse. Several other examples in both infectious diseases (cefazolin dosing in obese pregnant women undergoing Cesarean delivery (31), distribution of liposomal amphotericin B(32)), antibody design(33), and oncology ((34)) demonstrate the clinical utility of establishing tissue target concentrations or exposures and then using those to optimize drug dosing. This improvement in pharmacotherapy should be one more step in our ultimate goal of achieving full HIV prevention and cure.…”

Section: Discussionmentioning

confidence: 99%

Comparison of tenofovir plasma and tissue exposure using a population pharmacokinetic model and bootstrap: a simulation study from observed data

Collins

Dumond

2017

J Pharmacokinet Pharmacodyn

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Sparse tissue sampling with intensive plasma sampling creates a unique data analysis problem in determining drug exposure in clinically relevant tissues. Tissue exposure may govern drug efficacy, as many drugs exert their actions in tissues. We compared tissue area-under-the-curve (AUC) generated from bootstrapped noncompartmental analysis (NCA) methods and compartmental nonlinear mixed effect (NLME) modeling. A model of observed data after single-dose tenofovir disoproxil fumarate was used to simulate plasma and tissue concentrations for two destructive tissue sampling schemes. Two groups of 100 data sets with densely-sampled plasma and one tissue sample per individual were created. The bootstrapped NCA (SAS 9.3) used a trapezoidal method to calculate geometric mean tissue AUC per dataset. For NLME, individual post-hoc estimates of tissue AUC were determined, and the geometric mean from each dataset calculated. Median normalized prediction error (NPE) and absolute normalized prediction error (ANPE) were calculated for each method from the true values of the modeled concentrations. Both methods produced similar tissue AUC estimates close to true values. Although the NLME-generated AUC estimates had larger NPEs, it had smaller ANPEs. Overall, NLME NPEs showed AUC under-prediction but improved precision and fewer outliers. The bootstrapped NCA method produced more accurate estimates but with some NPEs >100%. In general, NLME is preferred, as it accommodates less intensive tissue sampling with reasonable results, and provides simulation capabilities for optimizing tissue distribution. However, if the main goal is an accurate AUC for the studied scenario, and relatively intense tissue sampling is feasible, the NCA bootstrap method is a reasonable, and potentially less time-intensive solution.

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Population Pharmacokinetics of Cefazolin in Serum and Adipose Tissue From Overweight and Obese Women Undergoing Cesarean Delivery

Cited by 24 publications

References 30 publications

Obese patients have higher rates of polymicrobial and Gram-negative early periprosthetic joint infections of the hip than non-obese patients

Obese patients have higher rates of polymicrobial and Gram-negative early periprosthetic joint infections of the hip than non-obese patients

A Systematic Review and Meta-Analysis of Wound Complications after a Caesarean Section in Obese Women

Comparison of tenofovir plasma and tissue exposure using a population pharmacokinetic model and bootstrap: a simulation study from observed data

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