Penetration of cefotetan into suction skin blister fluid and tissue homogenates in patients undergoing abdominal surgery

Mazzei, Teresita; Tonelli, Francesco; Novelli, Andréa; Ficari, Ferdinando; Mazzoni, Carlotta; Anastasi, Alessandro; Periti, P

doi:10.1128/aac.38.9.2221

Cited by 12 publications

(8 citation statements)

References 13 publications

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“…First, clean incisional sites and other uninfected tissues are represented by high ratios of surface area to volume and by rapid equilibration of antibiotic levels between serum and wound fluid (2,15,19). The use of gentamicin, with low protein binding and rapid distribution into extracellular fluid, further justifies the use of concentrations in serum to approximate intraoperative levels in tissue.…”

Section: Discussionmentioning

confidence: 99%

Antibiotic Pharmacodynamics in Surgical Prophylaxis: an Association between Intraoperative Antibiotic Concentrations and Efficacy

Zelenitsky

Ariano

Harding

et al. 2002

Antimicrob Agents Chemother

125

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The objective of this study was to characterize the relationship between gentamicin concentrations during surgery and the development of wound infection following colorectal operations. Despite decades of research in surgical prophylaxis, the relationship between intraoperative antibiotic concentrations and postoperative infection and the concentrations required for effective prophylaxis have not been established. A pharmacodynamic analysis was conducted using data from a previous prospective, randomized, double-blind clinical study which compared two dosage regimens of gentamicin plus metronidazole for prophylaxis in connection with elective colorectal surgery. Univariate and multivariate analyses of risk factors for postoperative wound infection were conducted, and the relationship between intraoperative gentamicin concentrations and surgical outcome was characterized. The gentamicin concentration at the time of surgical closure was one of the strongest independent risk factors for infection (P ‫؍‬ 0.02), along with the presence of diabetes mellitus (P ‫؍‬ 0.02), stoma (P ‫؍‬ 0.04), and advanced age (P ‫؍‬ 0.05). Gentamicin concentrations at closure of less than 0.5 mg/liter were associated with an infection rate of 80% (representing 8 of 10 patients with concentrations below that level) (P ‫؍‬ 0.003). Receiver operating characteristic curve analysis identified a critical closure concentration of 1.6 mg/liter for effective surgical prophylaxis (P ‫؍‬ 0.002; sensitivity, 70.8%; specificity, 65.9%). This study provides new and important information on antibiotic pharmacodynamics in surgical prophylaxis. It demonstrates the critical effect of the antibiotic concentration at closure on wound infection and suggests a significant association between the concentration and other well-established risk factors, like the timing of preoperative antibiotic administration and surgery duration.Surgical site infections, a significant postoperative complication, can lead to considerable patient morbidity and mortality (5, 14). Wound infections account for 38% of surgical infections and 17% of all nosocomial infections (14, 22). The benefits of preoperative antibiotics, which reduce bacterial contamination during clean-contaminated and contaminated operations, are well known (8,14). However, the relationship between intraoperative antibiotic concentrations and postoperative infection and the concentrations required for effective prophylaxis have not been established. Over the past decade, pharmacodynamic research has advanced the treatment of infectious diseases by characterizing relationships between antibiotic concentrations and clinical response (7,12,20). Although the application of similar principles to surgical prophylaxis has been suggested, there is a notable lack of supportive study (1,16,18). It is probable that low antibiotic concentrations during surgery due to inappropriate timing of the preoperative antibiotic (3), prolonged surgery (9, 11, 21), and patient obesity (13,17) contribute to the high infection rates as...

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Section: Discussionmentioning

confidence: 99%

Antibiotic Pharmacodynamics in Surgical Prophylaxis: an Association between Intraoperative Antibiotic Concentrations and Efficacy

Zelenitsky

Ariano

Harding

et al. 2002

Antimicrob Agents Chemother

125

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“…This pharmacokinetic property of ertapenem, as for other carbapenems and the ␤-lactams in general, is mainly due to their low molecular weight and hydrophilic characteristics. Moreover, the chronic inflammatory state of Crohn's patients (approximately one-half of our cases) as demonstrated in previous studies appears to increase the rate of drug flow from the central compartment and to cause a diminution in tissue clearance of antibiotics [9,10].…”

Section: Discussionmentioning

confidence: 84%

Ertapenem peritoneal fluid concentrations in adult surgical patients

Arrigucci

Garcea

Fallani

et al. 2009

International Journal of Antimicrobial Agents

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“…Applying a partial negative pressure to the skin disrupts the epidermal‐dermal junction and forms a blister which fills progressively with interstitial fluid and serum 63,64 . (Figure 3) This liquid offers a pharmacokinetic compartment, in which a previously applied drug can be sampled with a hypodermic needle and quantified; if multiple blisters are raised (as is possible with certain commercially available devices), then a concentration‐time profile of the drug in the skin can be obtained 55 .…”

Section: Classification Of Methodsmentioning

confidence: 99%

Methods for evaluating penetration of drug into the skin: A review

Supe

Takudage

2020

Skin Research and Technology

119

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Background Skin being the largest organ of the human body plays a very important role in the permeation and penetration of the drug. In addition, the transdermal drug delivery system (TDDS) plays a major role in managing dermal infections and attaining sustained plasma drug concentration. Thus, evaluation of percutaneous penetration of the drug through the skin is important in developing TDDS for human use. Material and methods Various techniques are used for getting the desired drug penetration, permeation, and absorption through the skin in managing these dermal disorders. The development of novel pharmaceutical dosage forms for dermal use is much explored in the current era. However, it is very important to evaluate these methods to determine the bioequivalence and risk of these topically applied drugs, which ultimately penetrate and are absorbed through the skin. Results Currently, numerous skin permeation models are being developed and persuasively used in studying dermatopharmacokinetic (DPK) profile and various models have been developed, to evaluate the TDD which include ex vivo human skin, ex vivo animal skin, and artificial or reconstructed skin models. Conclusion This review discusses the general physiology of the skin, the physiochemical characteristics affecting particle penetration, understand the models used for human skin permeation studies and understanding their advantages, and disadvantages.

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Penetration of cefotetan into suction skin blister fluid and tissue homogenates in patients undergoing abdominal surgery

Cited by 12 publications

References 13 publications

Antibiotic Pharmacodynamics in Surgical Prophylaxis: an Association between Intraoperative Antibiotic Concentrations and Efficacy

Antibiotic Pharmacodynamics in Surgical Prophylaxis: an Association between Intraoperative Antibiotic Concentrations and Efficacy

Ertapenem peritoneal fluid concentrations in adult surgical patients

Methods for evaluating penetration of drug into the skin: A review

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