Pharmacokinetics and Pharmacodynamics of Antimicrobial Agents in Burn Patients

Pruskowski, Kaitlin A

doi:10.1089/sur.2020.375

Cited by 16 publications

(5 citation statements)

References 34 publications

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“…Patients were eligible when meeting the following inclusion criteria: (1) adult patients (age ≥ 18 years); (2) admitted to a general ward of AMC or NWZ; and (3) receiving therapeutic dosages of ceftazidime as part of standard care prescribed by their attending physician and according to the current local guideline, which is adapted from the national antimicrobial guide [ 12 , 13 , 14 ]. Patients were excluded if: (1) written informed consent was not obtained; (2) a patient was mentally incapacitated; or (3) patients with known altered pharmacokinetics compared to patients on general wards, i.e., patients in the ICU, patients undergoing renal replacement therapy, patients with cystic fibrosis and patients with severe burns [ 31 , 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Target Attainment of Ceftazidime in Adult Patients on General Wards with Different Degrees of Renal Function: A Prospective Observational Bicenter Cohort Study

et al. 2023

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No prospective evidence exists on the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of ceftazidime in adult patients on general wards. We aimed to investigate whether the PK/PD target of ceftazidime (50% T > MIC) is attained in adult patients on general wards with adequate and impaired renal function receiving regular and guideline-recommended reduced doses of ceftazidime. In this observational, prospective, bicenter cohort study, adult patients admitted to a general ward receiving ceftazidime as part of standard care were included. Three blood samples per patient within 72 h after start of treatment were collected. Data were analyzed with nonlinear mixed effects modeling. The primary endpoint was target attainment of 50% T > MIC during the first 24 h of treatment (50% T0–24 > MIC). Forty patients were included from whom 121 blood samples were obtained. All 25/25 patients with adequate renal function, 9/10 patients with moderately impaired renal function (eGFR 30–50 mL/min/1.73 m2) and 5/5 patients with severe impaired renal function (eGFR < 30 mL/min/1.73 m2) attained 50% T0–24 > MIC when applying the clinical breakpoint MIC for Pseudomonas aeruginosa of 8 mg/L. The one patient not attaining the PK/PD target did not differ in any of the collected patients’ characteristics, except that this patient was the oldest in the study population. However, age was not statistically significantly associated with clearance or volume of distribution in the population pharmacokinetic model and, therefore, not likely the cause for this patient not attaining the PK/PD target. Our results suggest ≥90% probability of the PK/PD target attainment of ceftazidime in patients on general wards with adequate and impaired renal function receiving regular and guideline-recommended reduced doses of ceftazidime for treatment of infections with Pseudomonas aeruginosa and all bacteria with lower MIC-values.

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Target Attainment of Ceftazidime in Adult Patients on General Wards with Different Degrees of Renal Function: A Prospective Observational Bicenter Cohort Study

et al. 2023

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“…The value of plasma concentration being the result of PK processes is the main determinant of PD. PD characterizes parameters of antibacterial activity and describes the effect of AB on the target pathogens, relying on the minimum inhibitory concentration (MIC) [ 38 , 39 , 40 ].…”

Section: General Considerations On Ab Pharmacokinetics In the Elderlymentioning

confidence: 99%

Pharmacokinetics of Antibacterial Agents in the Elderly: The Body of Evidence

et al. 2023

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Infections are important factors contributing to the morbidity and mortality among elderly patients. High rates of consumption of antimicrobial agents by the elderly may result in increased risk of toxic reactions, deteriorating functions of various organs and systems and leading to the prolongation of hospital stay, admission to the intensive care unit, disability, and lethal outcome. Both safety and efficacy of antibiotics are determined by the values of their plasma concentrations, widely affected by physiologic and pathologic age-related changes specific for the elderly population. Drug absorption, distribution, metabolism, and excretion are altered in different extents depending on functional and morphological changes in the cardiovascular system, gastrointestinal tract, liver, and kidneys. Water and fat content, skeletal muscle mass, nutritional status, use of concomitant drugs are other determinants of pharmacokinetics changes observed in the elderly. The choice of a proper dosing regimen is essential to provide effective and safe antibiotic therapy in terms of attainment of certain pharmacodynamic targets. The objective of this review is to perform a structure of evidence on the age-related changes contributing to the alteration of pharmacokinetic parameters in the elderly.

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“…Antibiotic selection and dosing strategies are of particular interest in burn patients because of the unique environment created by their systemic inflammatory state. Car-diovascular, renal, respiratory, and hematological dysfunction are common and lead to frequent changes in peripheral perfusion, endovascular permeability, and fluid balance [80]. Conventional treatment regimens used in non-critically ill patients are unlikely to be effective or sufficient.…”

Section: Pharmacokinetics and Pharmacodynamics Of Antibioticsmentioning

confidence: 99%

Infection and Burn Injury

Kelly

Oliver

Carney

et al. 2022

EBJ

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Burn injury is debilitating and among one of the most frequently occurring traumas. Critical care improvements have allowed for increasingly positive outcomes. However, infection, whether it be localized to the site of the wound or systemic in nature, remains a serious cause of morbidity and mortality. Immune suppression predisposes the burn population to the development of invasive infections; and this along with the possibility of inhalation injury puts them at a significant risk for mortality. Emerging multi-drug-resistant pathogens, including Staphylococcus aureus, Enterococcus, Pseudomonas, Acinetobacter, Enterobacter, and yeast spp., continue to complicate clinical care measures, requiring innovative therapies and antimicrobial treatment. Close monitoring of antimicrobial regimens, strict decontamination procedures, early burn eschar removal, adequate wound closure, proper nutritional maintenance, and management of shock and resuscitation all play a significant role in mitigating infection. Novel antimicrobial therapies such as ultraviolet light, cold plasma and topical antiseptics must continue to evolve in order to lower the burden of infection in burn.

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Pharmacokinetics and Pharmacodynamics of Antimicrobial Agents in Burn Patients

Cited by 16 publications

References 34 publications

Pharmacokinetic/Pharmacodynamic Target Attainment of Ceftazidime in Adult Patients on General Wards with Different Degrees of Renal Function: A Prospective Observational Bicenter Cohort Study

Pharmacokinetic/Pharmacodynamic Target Attainment of Ceftazidime in Adult Patients on General Wards with Different Degrees of Renal Function: A Prospective Observational Bicenter Cohort Study

Pharmacokinetics of Antibacterial Agents in the Elderly: The Body of Evidence

Infection and Burn Injury

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