Clinical Outcome and Antimicrobial Therapeutic Drug Monitoring for the Treatment of Infections in Acute Burn Patients

Machado, Anna Silva; Oliveira, Maura Salaroli de; Sanches, Cristina; Silva, Carlindo Vieira da; Gómez, David S.; Gemperli, Rolf; Santos, Sílvia Regina Cavani Jorge; Levin, Anna S.

doi:10.1016/j.clinthera.2017.06.008

Cited by 19 publications

(26 citation statements)

References 23 publications

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“…Few studies have assessed the impact of beta-lactam therapeutic drug monitoring (TDM) in ICU patients, and none of these studies reported an impact on clinical outcome [109–111]. However, drug exposure and PK-PD target attainment have been shown to be higher when using TDM.…”

Section: Guidelinesmentioning

confidence: 99%

Optimization of the treatment with beta-lactam antibiotics in critically ill patients—guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique—SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d’Anesthésie et Réanimation—SFAR)

et al. 2019

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Background Beta-lactam antibiotics (βLA) are the most commonly used antibiotics in the intensive care unit (ICU). ICU patients present many pathophysiological features that cause pharmacokinetic (PK) and pharmacodynamic (PD) specificities, leading to the risk of underdosage. The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) have joined forces to provide guidelines on the optimization of beta-lactam treatment in ICU patients. Methods A consensus committee of 18 experts from the two societies had the mission of producing these guidelines. The entire process was conducted independently of any industry funding. A list of questions formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes) was drawn-up by the experts. Then, two bibliographic experts analysed the literature published since January 2000 using predefined keywords according to PRISMA recommendations. The quality of the data identified from the literature was assessed using the GRADE® methodology. Due to the lack of powerful studies having used mortality as main judgement criteria, it was decided, before drafting the recommendations, to formulate only “optional” recommendations. Results After two rounds of rating and one amendment, a strong agreement was reached by the SFPT-SFAR guideline panel for 21 optional recommendations and a recapitulative algorithm for care covering four areas: (i) pharmacokinetic variability, (ii) PK-PD relationship, (iii) administration modalities, and (iv) therapeutic drug monitoring (TDM). The most important recommendations regarding βLA administration in ICU patients concerned (i) the consideration of the many sources of PK variability in this population; (ii) the definition of free plasma concentration between four and eight times the Minimal Inhibitory Concentration (MIC) of the causative bacteria for 100% of the dosing interval as PK-PD target to maximize bacteriological and clinical responses; (iii) the use of continuous or prolonged administration of βLA in the most severe patients, in case of high MIC bacteria and in case of lower respiratory tract infection to improve clinical cure; and (iv) the use of TDM to improve PK-PD target achievement. Conclusions The experts strongly suggest the use of personalized dosing, continuous or prolonged infusion and therapeutic drug monitoring when administering βLA in critically ill patients. Electronic supplementary material The online version of this article (10.1186/s13054-019-2378-9) contains supplementary material, which is available to authorized users.

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Section: Guidelinesmentioning

confidence: 99%

Optimization of the treatment with beta-lactam antibiotics in critically ill patients—guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique—SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d’Anesthésie et Réanimation—SFAR)

et al. 2019

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“…Although there was a low level of statistical evidence to include albumin as a covariate on V d , there was physiologic relevance and support from prior literature. Although direct comparisons are lacking, imipenem V d is generally 2‐ to 5‐fold higher in severe burn patients compared with other patient populations 31,32,34,50,52,55–57 . Specifically, Gomez et al demonstrated that imipenem V d nearly doubled in patients with >40% total burn surface area (TBSA), 0.97 L/kg, compared with those with <19% TBSA (0.56 L/kg) 34 .…”

Section: Discussionmentioning

confidence: 99%

“…To date, numerous studies have evaluated imipenem PK in a variety of populations to include healthy, 50 , 52 renally impaired, 55 and burn 31 , 32 , 33 , 34 , 56 , 57 patients. Taken together, these analyses have provided crucial understanding of physiological alterations and their impact on key imipenem PK parameters, namely, clearance and volume.…”

Section: Discussionmentioning

confidence: 99%

“…Although direct comparisons are lacking, imipenem V d is generally 2‐ to 5‐fold higher in severe burn patients compared with other patient populations. 31 , 32 , 34 , 50 , 52 , 55 , 56 , 57 Specifically, Gomez et al demonstrated that imipenem V d nearly doubled in patients with >40% total burn surface area (TBSA), 0.97 L/kg, compared with those with <19% TBSA (0.56 L/kg). 34 Therefore, we also sought to explore the effects of large changes in V d related to severe burn injury on imipenem dosing.…”

Section: Discussionmentioning

confidence: 99%

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Population Pharmacokinetic Modeling and Simulations of Imipenem in Burn Patients With and Without Continuous Venovenous Hemofiltration in the Military Health System

Por

Akers

Chung

et al. 2021

The Journal of Clinical Pharma

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Continuous venovenous hemofiltration (CVVH) is a life-sustaining procedure in patients with severe burns and acute kidney injury. Physiologic changes from burn injury and use of CVVH may alter imipenem pharmacokinetics (PK). We aimed to compare imipenem clearance (CL) in burn patients with and without CVVH, determine the effect of burn on imipenem volume of distribution (CVVH, n = 12; no CVVH, n = 11), in combination with previously published models. Model qualification was performed with standard diagnostics and comparing predicted PK parameters/time-concentration profiles with those in the existing literature. Monte Carlo simulations were conducted to evaluate the probability of target attainment. A 2-compartment model best described the data. Utilizing albumin as a covariate on volume parameters and leveraging the clearance model from prior literature, our model predicted imipenem central volume and CL within a 10% margin of error across healthy, renally impaired, and burn populations. We provide direct comparison of imipenem CL in burn patients with and without CVVH. Notably, there was no significant difference. Large imipenem V d in patients with severe burns is likely explained by increased capillary permeability, for which serum albumin may be a reasonable surrogate. Dosing 500 mg every 6 hours is adequate for burn patients on renally dosed CVVH; however, suspicion of augmented renal clearance or patients placed on CVVH without renal impairment may necessitate dosing of 1000 mg every 6 hours.

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“…Bloodstream infection (BSI) is one of the most dangerous complications in patients with severe burns [1]. Empirical treatment with broad-spectrum antibiotics is a standard treatment option available for early anti-infection therapy [2]. However, the uncontrolled and indiscriminate use of antibiotics has resulted in increased numbers cases of antibiotic drug resistance and multidrug resistance (MDR) [3], with almost half of the world’s antibiotics currently prescribed in China [4].…”

Section: Introductionmentioning

confidence: 99%

Lytic Bacteriophage Screening Strategies for Multidrug-Resistant Bloodstream Infections in a Burn Intensive Care Unit

et al. 2019

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BackgroundIncreasing antibiotic resistance and multidrug resistance (MDR) in patients with bloodstream infection (BSI) has resulted in treatment using bacteriophage. This study aimed to identify Gram-negative bacilli and Gram-positive cocci and antibiotic resistance in patients with BSI in a burn intensive care unit (BICU). The environment, including sewage systems, were investigated for the presence of lytic bacteriophage.Material/MethodsBetween January 2011 to December 2017, 486 patients with BSI were admitted to the BICU. Blood culture identified the main infectious organisms. Bacterial screening tests for antibiotic resistance included the D test and the modified Hodge test (MHT). Lytic bacteriophage was isolated from the environment.ResultsIn 486 patients with BSI, the main causative organisms were Gram-negative bacilli (64.6%), Gram-positive cocci (27.7%), and fungi (7.7%). The main pathogenic organisms that showed multidrug resistance (MDR) were Acinetobacter baumannii (26.0%), Staphylococcus aureus (16.8%), and Pseudomonas aeruginosa (14.2%). Bacteriophage was mainly isolated from Gram-negative bacilli. Screening of hospital and residential sewage systems identified increased levels of bacteriophage in hospital sewage.ConclusionsThe causative organisms of BSI and the presence of MDR in a hospital BICU were not typical, which supports the need for routine bacterial monitoring. Hospital sewage provides a potential source of bacteriophage for the treatment of MDR pathogenic bacteria.

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Clinical Outcome and Antimicrobial Therapeutic Drug Monitoring for the Treatment of Infections in Acute Burn Patients

Cited by 19 publications

References 23 publications

Population Pharmacokinetic Modeling and Simulations of Imipenem in Burn Patients With and Without Continuous Venovenous Hemofiltration in the Military Health System

Lytic Bacteriophage Screening Strategies for Multidrug-Resistant Bloodstream Infections in a Burn Intensive Care Unit

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