Pharmacokinetics and pharmacodynamics of antibiotics in critically ill acute kidney injury patients

Zamoner, Welder; Freitas, Felipe; Garms, Durval S. S.; Oliveira, Marcel de Campos; Balbi, André Luís; Ponce, Daniela

doi:10.1002/prp2.280

Cited by 33 publications

(44 citation statements)

References 30 publications

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“…Despite having the availability to realize therapeutic monitoring of the drug, which is not unanimous in all centers, difficulties have been observed with reaching and sustaining adequate serum concentrations, due to factors related to collection, patients, and pharmacokinetic variation of the drug in septic patients. 8 In our study, this Notes: *Mean ± SD. T0-T2, serum concentration between the start and second day of usage of vancomycin (0-48 hours); T2-T4: serum concentration between the second and fourth days of usage of vancomycin (48-96 hours); T4-T6: serum concentration between the fourth and sixth days of usage of vancomycin (96-144 hours); T6-T8: serum concentration between the sixth and eighth days of usage of vancomycin (144-192 hours difficulty was also present, with elevated rates of subtherapeutic and toxic concentrations.…”

Section: Discussionmentioning

confidence: 57%

“…6 The main polemic points on vancomycin relate to its efficacy and safety. [5][6][7][8][9] Regarding efficacy, the concern is the alteration in pharmacokinetics, usually related to the distribution, metabolism, and elimination of the drug, 6,8 which can lead to subtherapeutic concentrations, leading to the emergence of bacterial resistance due to the inefficacy of the treatment and consequently leading to higher mortality. Regarding safety, emphasis has been given to the main side effect of the medicationnephrotoxicitywhich can aggravate the clinical picture and contribute to unfavorable outcomes.…”

Section: Introductionmentioning

confidence: 99%

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<p>Serum Concentration of Vancomycin Is a Diagnostic Predictor of Nephrotoxic Acute Kidney Injury in Septic Patients in Clinical and Surgical Wards</p>

Zamoner¹,

Pierri²,

Eid³

et al. 2020

IDR

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Introduction and Aim: There have been few studies to evaluate the monitoring of plasmatic concentrations of vancomycin in septic patients and their association with acute kidney injury (AKI) and death. This study aimed to evaluate the prevalence of adequate, subtherapeutic, and toxic serum concentrations of vancomycin in hospitalized septic patients and to associate the adequacy of therapeutic monitoring with clinical outcomes. Methodology: This was a cohort-unicentric study that evaluated septic patients aged >18 years using vancomycin admitted to clinical and surgical wards of a Brazilian university center from August 2016 to July 2017 in a daily and uninterrupted way. We excluded patients with AKI prior to the introduction of vancomycin or with AKI development <48 hours after use, patients with AKI of other etiologies, stage V chronic kidney disease, and pregnant women. Results: We evaluated 225 patients, and 135 were included. Evaluation of serum concentration of vancomycin was realized in 94.1%, and of those, 59.3% presented toxic concentrations. The prevalence of AKI was 27.4% and happened on average on the ninth day of vancomycin usage. Between the fourth and sixth days, vancomycin serum concentration of >21.5 mg/L was a predictor of AKI, with area under the curve of 0.803 (95% CI 0.62-0.98, p=0.005), preceding the diagnosis of AKI by at least 3 days. Of these patients, 20.7% died, and serum concentrations of vancomycin between the fourth and sixth days were identified as risk factors associated with negative outcomes. Conclusion: Serum concentration of vancomycin is an excellent predictor of AKI in patients admitted to wards, preceding the diagnosis of AKI by at least 72 hours. Toxic concentrations of vancomycin are associated with AKI, and AKI was a risk factor for death. Also, serum concentration of vancomycin >21.5 mg/L was the only variable associated with death in the Cox model.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

<p>Serum Concentration of Vancomycin Is a Diagnostic Predictor of Nephrotoxic Acute Kidney Injury in Septic Patients in Clinical and Surgical Wards</p>

Zamoner¹,

Pierri²,

Eid³

et al. 2020

IDR

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“…Vancomycin is a glycopeptide antimicrobial with antibacterial action, acting by inhibition of cell wall synthesis. It was introduced in clinical practice in the mid‐1950s for the treatment of bacterial infections caused by Gram‐positive bacteria and it is considered by the Infectious Disease Society of America (IDSA) as the first treatment option for methicillin‐resistant Staphylococcus aureus (MRSA) infections . However, it also presents action against Streptococcus pneumoniae , Streptococcus pyogenes , Streptococcus agalactiae , Streptococcus bovis , Streptococcus viridans , Enterococcus , species of Clostridium , diphtheroids , Listeria monocitogenes , Actinomyces , and species of Lactobacillus .…”

Section: Vancomycinmentioning

confidence: 99%

“…Despite its wide use in clinical practice, there are unresolved concerns about its effectiveness and safety. Regarding efficacy, mainly in critically ill patients, its pharmacokinetics is altered, due to drug distribution, metabolism and elimination, which could lead to subtherapeutic serum concentration and develop bacterial resistance, with possible increased mortality . In terms of safety, its main side effect—nephrotoxicity—has been widely discussed, with risk of AKI and complications in the short and long term …”

Section: Vancomycinmentioning

confidence: 99%

Vancomycin dosing, monitoring and toxicity: Critical review of the clinical practice

Zamoner

Prado

Balbi

et al. 2019

Clin Exp Pharma Physio

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Summary Vancomycin is an antibiotic used in the treatment of infections caused by multidrug‐resistant Gram‐positive bacteria, especially methicillin‐resistant Staphylococcus aureus. In the last decades, vancomycin has been widely used in hospital environments due to the increasing incidence of sepsis and septic shock. Sepsis may lead to multiple organ failure; it is considered a risk factor for the development of acute kidney injury (AKI), with an overall mortality rate of around 45%, which can reach the surprising rate of 70% with the combination of AKI and sepsis. Considering the high mortality rate of sepsis and its related costs of hospitalization and treatment, specific measures should be adopted, such as early‐goal treatment protocols: proper and early administration of antimicrobials, fluids, vasoactive drugs and transfusion support. Besides the careful selection of the antimicrobial, another concern related to critically ill patients is the proper dose of the antimicrobial, since pharmacokinetic changes are observed due to drug absorption, distribution, metabolism and elimination. Gram‐positive pathogens are very common in hospitalized patients with septic shock, so vancomycin has been the antimicrobial of choice for more than 60 years. However, discussions about its dosage, administration and monitoring are extremely important, considering the risk of nephrotoxicity and the emergence of resistant S. aureus. This narrative review aims to discuss controversial aspects related to the efficacy and safety of vancomycin, correlating them with data available in the literature and identifying knowledge gaps in guide future lines of research.

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“…A progressão da DRC pode levar a um quadro de uremia ou inadequado volume de diurese, casos em que os pacientes são encaminhados para a Terapia Renal Substitutiva (TRS) ou para transplante renal. Encontram-se disponíveis diferentes modalidades de TRS, como hemodiálise intermitente, TRS contínuas (que incluem técnicas de hemodiálise estendida como a Slow Low Efficient Dialysis (SLED), diálise peritoneal e, ainda, troca terapêutica do plasma [102,104,105].…”

Section: Doença Renal Crônicaunclassified

Alterações farmacocinéticas de antimicrobianos em situações especiais: uma revisão narrativa

Sousa¹,

Frade²,

Vieira³

et al. 2019

Rev. Ciênc. Méd.

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Até o ano de 1940, as doenças infecciosas eram uma das principais causas de morte no Brasil. Atualmente, apesar de um grande declínio, a mortalidade ainda é elevada em relação a países desenvolvidos e a outros países da América Latina. Dessa maneira, o objetivo do presente trabalho foi relatar as alterações fi siológicas em condições específi cas, as consequências na farmacocinética dos antimicrobianos e ainda o impacto do ajuste de dose em tais situações. Realizou-se uma revisão narrativa de artigos publicados sobre a utilização de antimicrobianos nas seguintes situações: doença crítica e sepse, alcoolismo, tabagismo, extremos de idade, obesidade, nutrientes, polimorfismo genético, gravidez e lactação, insuficiência cardíaca, insuficiência hepática e renal. Observou-se que as alterações fisiológicas em tais situações afetam a farmacocinética dos antimicrobianos, modificando os processos de absorção, distribuição, metabolismo e excreção, os quais dependem muitas vezes da natureza do fármaco, podendo requerer ajuste de dose. Pôde-se concluir que as alterações observadas reduzem a precisão de uma dose terapêutica eficaz, evidenciando, dessa maneira, a importância do ajuste de dose.

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Pharmacokinetics and pharmacodynamics of antibiotics in critically ill acute kidney injury patients

Cited by 33 publications

References 30 publications

<p>Serum Concentration of Vancomycin Is a Diagnostic Predictor of Nephrotoxic Acute Kidney Injury in Septic Patients in Clinical and Surgical Wards</p>

<p>Serum Concentration of Vancomycin Is a Diagnostic Predictor of Nephrotoxic Acute Kidney Injury in Septic Patients in Clinical and Surgical Wards</p>

Vancomycin dosing, monitoring and toxicity: Critical review of the clinical practice

Alterações farmacocinéticas de antimicrobianos em situações especiais: uma revisão narrativa

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