Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial (original) (raw)
Related papers
Antibiotics
The outcome for critically ill patients is burdened by a double mortality rate and a longer hospital stay in the case of sepsis or septic shock. The adequate use of antibiotics may impact on the outcome since they may affect the pharmacokinetics (Pk) and pharmacodynamics (Pd) of antibiotics in such patients. Acute renal failure (ARF) occurs in about 50% of septic patients, and the consequent need for continuous renal replacement therapy (CRRT) makes the renal elimination rate of most antibiotics highly variable. Antibiotics doses should be reduced in patients experiencing ARF, in accordance with the glomerular filtration rate (GFR), whereas posology should be increased in the case of CRRT. Since different settings of CRRT may be used, identifying a standard dosage of antibiotics is very difficult, because there is a risk of both oversimplification and failing the therapeutic efficacy. Indeed, it has been seen that, in over 25% of cases, the antibiotic therapy does not reach the nece...
Antibiotic Dosing in Patients With Acute Kidney Injury: "Enough But Not Too Much
Journal of intensive care medicine, 2014
Increasing evidence suggests that antibiotic dosing in critically ill patients with acute kidney injury (AKI) often does not achieve pharmacodynamic goals, and the continued high mortality rate due to infectious causes appears to confirm these findings. Although there are compelling reasons why clinicians should use more aggressive antibiotic dosing, particularly in patients receiving aggressive renal replacement therapies, concerns for toxicity associated with higher doses are real. The presence of multisystem organ failure and polypharmacy predispose these patients to drug toxicity. This article examines the pharmacokinetic and pharmacodynamic consequences of critical illness, AKI, and renal replacement therapy and describes potential solutions to help clinicians give "enough but not too much" in these very complicated patients.
Pharmacokinetics and pharmacodynamics of antibiotics in critically ill acute kidney injury patients
Pharmacology Research & Perspectives, 2016
Sepsis is the most common cause of death in critically ill patients and is associated with multiorgan failure, including acute kidney injury (AKI). This situation can require acute renal support and increase mortality. Therefore, it is essential to administer antimicrobials in doses that achieve adequate serum levels, avoiding both overdosing and drug toxicity as well as underdosing and the risk of antibiotic resistance and higher mortality. Currently, there are no validated guidelines on antibiotic dose adjustments in septic patients with AKI. The current recommendations were extrapolated from studies conducted in noncritical patients with end-stage chronic kidney disease receiving chronic renal replacement therapy. This study aimed to review and discuss the complexity of this issue, considering several factors related to drug metabolism, the characteristics of critically ill patients, the properties of antimicrobial drugs and dialysis methods.
2021
Background: Inappropriate antibiotics dosing in critically ill patients with augmented renal clearance (ARC) may be associated with pathogens resistance and worse outcomes. Unfortunately, studies regarding the relationship between ARC and clinical outcomes in patients treated with antibiotics medication are rare. The study evaluates the efficacy and clinical outcomes of selected broad-spectrum hydrophilic antibiotics in ARC critically ill patients with confirmed infections. Methods: A retrospective cohort study in adult critically ill patients who were admitted to intensive care units (ICUs) at King Abdulaziz Medical City (KAMC)-Riyadh and received standard dosing of selected broad-spectrum hydrophilic antibiotics (Meropenem, Imipenem, or Piperacillin/Tazobactam) with confirmed infection. All the patients who met our inclusion criteria during the study period (01/01/2018 – 31/12/2019) were included. Eligible patients have been divided into two groups (ARC Vs. non-ARC) according to t...
Clinical Infectious Diseases, 2020
Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) ...
Antibiotic Dosing in Sustained Low-Efficiency Dialysis in Critically Ill Patients
Canadian journal of kidney health and disease, 2018
Sustained low-efficiency dialysis (SLED) is increasingly used as a renal replacement modality in critically ill patients with acute kidney injury (AKI) and hemodynamic instability. There is, therefore, a greater need for the understanding of the antibiotic dosage and pharmacokinetics in these patients, to provide them with optimal therapy. PubMed/Medline, Embase, and Google Scholar. PubMed/Medline, Embase, and Google Scholar databases were searched using a combination of key words: dialysis, end stage renal disease, renal failure, sustained low efficiency dialysis, extended daily dialysis, prolonged intermittent renal replacement therapy (PIRRT), and antibiotic dosing. Studies that investigated antibiotic dosing and pharmacokinetics during SLED/extended daily dialysis/PIRRT were selected for this review. Eleven studies met inclusion criteria and selected for data extraction. The data with regard to dialysis specifications, type of antibiotic including dosages, drug clearances, and d...
Critical Care Medicine, 2012
ciprofloxacin). The median (interquartile range) trough concentrations (mg/L) for meropenem was 12.1 (7.8-18.4), 105.0 (74.4-204.0)/3.8 (3.4-21.8) for piperacillin/tazobactam, 12.0 (9.8-16.0) for vancomycin, and 3.7 (3.0-5.6) for ciprofloxacin. Overall, 15% of dosing intervals did not meet predetermined minimum therapeutic target concentrations, 40% did not achieve the higher target concentration, and, during 10% of dosing intervals, antibiotic concentrations were excessive. No difference, however, was found between patients on the basis of the intensity of continuous renal replacement therapy; this effect may have been obscured by differences in dosing regimens, time off the filter, or altered pharmacokinetics. Conclusions: There is significant variability in antibiotic trough concentrations in critically ill patients receiving continuous renal replacement therapy, which did not only appear to be influenced by effluent flow rate. Here, empirical dosing of antibiotics failed to achieve the target trough antibiotic concentration during 25% of the dosing intervals.
Antimicrobial Agents and Chemotherapy, 2019
A careful management of antimicrobials is essential in the critically ill with acute kidney injury, especially if renal replacement therapy is required. Acute kidney injury may lead per se to clinically significant modifications of drugs’ pharmacokinetic parameters, and the need for renal replacement therapy represents a further variable that should be considered to avoid inappropriate antimicrobial therapy.
Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy
Clinical Infectious Diseases, 2005
Continuous renal replacement therapy (CRRT) is now commonly used as a means of support for critically ill patients with renal failure. No recent comprehensive guidelines exist that provide antibiotic dosing recommendations for adult patients receiving CRRT. Doses used in intermittent hemodialysis cannot be directly applied to these patients, and antibiotic pharmacokinetics are different than those in patients with normal renal function. We reviewed the literature for studies involving the following antibiotics frequently used to treat critically ill adult patients receiving CRRT: vancomycin, linezolid, daptomycin, meropenem, imipenem-cilastatin, nafcillin, ampicillin-sulbactam, piperacillin-tazobactam, ticarcillin-clavulanic acid, cefazolin, cefotaxime, ceftriaxone, ceftazidime, cefepime, aztreonam, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, colistin, amikacin, gentamicin, tobramycin, fluconazole, itraconazole, voriconazole, amphotericin B (deoxycholate and lipid formulations), and acyclovir. We used these data, as well as clinical experience, to make recommendations for antibiotic dosing in critically ill patients receiving CRRT.
The use of antimicrobials in septic patients with acute kidney injury
Jornal brasileiro de nefrologia : 'orgao oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Sepsis is the most common cause of death in critically ill patients and it may be associated with multiorgan failure, including acute kidney injury (AKI). This situation can require acute renal support and increase mortality. Therefore, it is essential to administrate antimicrobials in dosis to achieve adequate serum levels, preventing overdosis and drug toxicity or underdosing and risk for resistance to antibiotics and higher mortality. To date, there aren't validated guidelines on antibiotic dosis adjustment in septic patients with AKI and the recommendations are extrapolated from studies conducted in non-critical patients with chronic kidney disease in end stage receiving chronic renal replacement therapy. This study aimed to review and discuss the complexity of that issue, considering the several factors related to the drugs removal: critically ill patient characteristics, antimicrobial properties and dialysis method.