Trial reportCritical care (London, England)2010
Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock.
Trial report in Critical care (London, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 4 syntheses or guidelines pooled it, 198 citations in OpenAlex.
- Systematic review of high-dose amikacin regimens for the treatment of Gram-negative infections based on EUCAST dosing recommendations.European journal of hospital pharmacy : science and practice · 2023Pooled it
- [S3 Guideline Sepsis-prevention, diagnosis, therapy, and aftercare : Long version].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2020Guideline
- What Antibiotic Exposures Are Required to Suppress the Emergence of Resistance for Gram-Negative Bacteria? A Systematic Review.Clinical pharmacokinetics · 2019Pooled it
- Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.Intensive care medicine · 2017Guideline
- Quantification and Explanation of the Variability of First-Dose Amikacin Concentrations in Critically Ill Patients Admitted to the Emergency Department: A Population Pharmacokinetic Analysis.European journal of drug metabolism and pharmacokinetics · 2021Trial
- Optimizing the initial amikacin dosage in adults.Antimicrobial agents and chemotherapy · 2015Trial
- Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia.European journal of clinical pharmacology · 2015Trial
- Ceftazidime dosage regimen in intensive care unit patients: from a population pharmacokinetic approach to clinical practice via Monte Carlo simulations.British journal of clinical pharmacology · 2012Trial
- Article
- The relation between inflammatory biomarkers and drug pharmacokinetics in the critically ill patients: a scoping review.Critical care (London, England) · 2024Article
- A narrative review on antimicrobial dosing in adult critically ill patients on extracorporeal membrane oxygenation.Critical care (London, England) · 2024Review
- Understanding antimicrobial pharmacokinetics in critically ill patients to optimize antimicrobial therapy: A narrative review.Journal of intensive medicine · 2024Review
- Inoculum-Based Dosing: A Novel Concept for Combining Time with Concentration-Dependent Antibiotics to Optimize Clinical and Microbiological Outcomes in Severe Gram Negative Sepsis.Antibiotics (Basel, Switzerland) · 2023Review
- Failure to predict amikacin elimination in critically ill patients with cancer based on the estimated glomerular filtration rate: applying PBPK approach in a therapeutic drug monitoring study.European journal of clinical pharmacology · 2023Article
- Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Obese Patients.Antibiotics (Basel, Switzerland) · 2023Article
- Aminoglycosides for the Treatment of Severe Infection Due to Resistant Gram-Negative Pathogens.Antibiotics (Basel, Switzerland) · 2023Review
- Optimization of antimicrobial dosing in patients with acute kidney injury: a single-centre observational study.JAC-antimicrobial resistance · 2022Article
- Towards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomes.Antibiotics (Basel, Switzerland) · 2022Article
- Antimicrobial Stewardship Programs: A Review of Strategies to Avoid Polymyxins and Carbapenems Misuse in Low Middle-Income Countries.Antibiotics (Basel, Switzerland) · 2022Review
- Evaluation of amikacin dosing schedule in critically ill elderly patients with different stages of renal dysfunction.European journal of hospital pharmacy : science and practice · 2022Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionIt has been proposed that doses of amikacin of >15 mg/kg should be used in conditions associated with an increased volume of distribution (Vd), such as severe sepsis and septic shock. The primary aim of this study was to determine whether 25 mg/kg (total body weight) of amikacin is an adequate loading dose for these patients.
methodsThis was an open, prospective, multicenter study in four Belgian intensive care units (ICUs). All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom amikacin treatment was indicated, were included in the study.
resultsIn 74 patients, serum samples were collected before (t = 0 h) and 1 hour (peak), 1 hour 30 minutes, 4 hours 30 minutes, 8 hours, and 24 hours after the first dose of amikacin. Blood amikacin levels were measured by using a validated fluorescence polarization immunoassay method, and an open two-compartment model with first-order elimination was fitted to concentrations-versus-time data for amikacin (WinNonlin). In 52 (70%) patients, peak serum concentrations were >64 microg/ml, which corresponds to 8 times the clinical minimal inhibitory concentration (MIC) breakpoints defined by EUCAST for Enterobacteriaceae and Pseudomonas aeruginosa (S<8, R>16 microg/ml). Vd was 0.41 (0.29 to 0.51) L/kg; elimination half-life, 4.6 (3.2 to 7.8) hours; and total clearance, 1.98 (1.28 to 3.54) ml/min/kg. No correlation was found between the amikacin peak and any clinical or hemodynamic variable.
conclusionsAs patients with severe sepsis and septic shock have an increased Vd, a first dose of >or= 25 mg/kg (total body weight) of amikacin is required to reach therapeutic peak concentrations. However, even with this higher amikacin dose, the peak concentration remained below therapeutic target levels in about one third of these patients. Optimizing aminoglycoside therapy should be achieved by tight serum-concentration monitoring because of the wide interindividual variability of pharmacokinetic abnormalities.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.