Update on Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Critically Ill Patients-A Narrative Review.

Beta-lactam antibiotics remain one of the most preferred groups of antibiotics in critical care due to their excellent safety profiles and their activity against a wide spectrum of pathogens. The cornerstone of appropriate therapy with beta-lactams is to achieve an adequate plasmatic concentration of a given antibiotic, which is derived primarily from the minimum inhibitory concentration (MIC) of the specific pathogen. In a critically ill patient, the plasmatic levels of drugs could be affected by many significant changes in the patient's physiology, such as hypoalbuminemia, endothelial dysfunction with the leakage of intravascular fluid into interstitial space and acute kidney injury. Predicting antibiotic concentration from models based on non-critically ill populations may be misleading. Therapeutic drug monitoring (TDM) has been shown to be effective in achieving adequate concentrations of many drugs, including beta-lactam antibiotics. Reliable methods, such as high-performance liquid chromatography, provide the accurate testing of a wide range of beta-lactam antibiotics. Long turnaround times remain the main drawback limiting their widespread use, although progress has been made recently in the implementation of different novel methods of antibiotic testing. However, whether the TDM approach can effectively improve clinically relevant patient outcomes must be proved in future clinical trials.

Emergency medicine pharmacotherapy compromises accuracy of plasma creatinine determination by enzyme-based methods: real-world clinical evidence and implications for clinical practice.

Background: Assessment of kidney function in emergency settings is essential across all medical subspecialties. Daily assessment of patient creatinine results from emergency medical services showed that some deviated from expected values, implying drug-related interference. Methods: Real-time clinical evaluation of an enzyme method (Roche CREP2) in comparison with the Jaffé gen. 2 method (Roche CREJ2) was performed. During the period of December 2022 and January 2023, we analyzed 8,498 patient samples, where 5,524 were heavily medicated STAT patient specimens, 500 were pediatric specimens, and 2,474 were from a distant general population in a different region using the same methods. Results: In 109 out of 5,524 hospital specimens (1.97%, p < 0.001), the CREP2 value was apparently (25% or more) lower than CREJ2. Suspect interfering medication was found in a sample of 43 out of 46 reviewed patients where medication data were available. This phenomenon was not observed in the general population. Conclusion: In a polymedicated urgent care hospital population, a creatinine enzyme method produces unreliable results, apparently due to multiple drug-related interferences.

Evaluation of FUS-2000 urine analyzer: analytical properties and particle recognition.

This study evaluates the performance of microscopic part of a hybrid analyzer FUS-2000 (Dirui Industrial Co., Changchun, China), its analytical properties and particle recognition. The evaluation of trueness, repeatability, detection limit, carry-over, linearity range and analytical stability was performed according to Dirui protocol guidelines designed by Dirui Company to guarantee the quality of the instrument. Trueness for low, medium and high-value concentrations was calculated with bias of 15.5, 4.7 and -6.6%, respectively. Detection limit of 5 Ery/µl was confirmed. Coefficient of variation of 11.0, 5.2 and 3.8% was measured for within-run repeatability of low, medium and high concentration. Between-run repeatability for daily quality control had coefficient of variation of 3.0%. Carry-over did not exceed 0.05%. Linearity was confirmed for range of 0-16,000 particles/µl (R2 = 0.9997). The analytical stability had coefficient of variation of 4.3%. Out of 1258 analyzed urine samples, 362 positive were subjected to light microscopy urine sediment analysis and compared to the analyzer results. Cohen's kappa coefficients were calculated to express the concordance. Squared kappa coefficient was 0.927 (red blood cells), 0.888 (white blood cells), 0.908 (squamous epithelia), 0.634 (transitional epithelia), 0.628 (hyaline casts), 0.843 (granular casts) and 0.623 (bacteria). Single kappa coefficients were 0.885 (yeasts) and 0.756 (crystals), respectively. Aforementioned results show good analytical performance of the analyzer and tight agreement with light microscopy of urine sediment.

Ethamsylate (Dicynone) interference in determination of serum creatinine, uric acid, triglycerides, and cholesterol in assays involving the Trinder reaction; in vivo and in vitro.

BACKGROUND: The aim of our research was the quantification of interfering properties of the haemostatic drug Dicynone (ethamsylate) in serum creatinine, uric acid, cholesterol, and triglyceride assays using the Trinder reaction. METHODS: Blood from patients was collected before and 15 minutes after administration of 500 mg Dicynone dose i.v. and the above mentioned analytes were quantified using Roche assays (Cobas 8000). In our in vitro experiment, we measured concentrations of the analytes in pooled serum aliquots with final concentrations of Dicynone additions 0, 30, 60, 150, and 300 mg/L. Aliquots with 60 mg/L Dicynone were also measured at 2, 6, and 8 hours after initial measurement when stored in 22 degrees C and 4 degrees C for comparison. RESULTS: Concentrations of the measured analytes in samples from patients administered with a 500 mg dose of Dicynone were lower in all cases (n = 10) when compared to values in samples taken immediately before treatment. The in vitro samples showed that considerable negative interference occurred even with the low concentrations of Dicynone additions (30 and 60 mg/L), showing the strongest negative interference in creatinine values, followed by uric acid, triglycerides, and cholesterol. Using in vitro samples, we showed strong time and temperature dependence on Dicynone interference. CONCLUSIONS: We found and proved significant negative interference of the drug Dicynone (ethamsylate) in the clinical analysis of blood using in vivo and in vitro experiments. Furthermore, we observed a change of this effect in serum matrix over time and at different storage temperatures.

Strong negative interference of ethamsylate (Dicynone®) in serum creatinine quantification via enzymatic assay using Trinder reaction.

BACKGROUND: With discrepancies encountered as early as the verification of enzymatic method for quantification of serum creatinine, our research pointed to a later confirmed interference caused by a compound called ethamsylate present in the commonly used antihemorrhagic drug Dicynone. METHODS: We measured concentrations of creatinine of 10 patients with blood taken before and 15 minutes after the intravenous administration of a 500 mg dose of Dicynone. The creatinine concentration was determined using Jaffe method and enzymatic method that utilize Trinder reaction (Roche) in analyzer Cobas c 501 (Roche AG, Basel, Switzerland). We also monitored concentration of blood creatinine in three patients before and 15 minutes after application of Dicynone (500 mg i.v.) and in the following 6th, 12th, 18th, and 24th hours. RESULTS: We discovered a significant negative bias in creatinine results using enzymatic assay with Trinder reaction in blood taken 15 min after i.v. application of 500 mg Dicynone to patients compared to their pre-application values (average decrease of 47%). Unlike this, the results of compensated Jaffe method yielded steady results in all samples (average deviation 0.6% from original values). However, 12 h after the drug administration comparable results were seen as before the administration. CONCLUSION: Considering the strong negative interference of ethamsylate in enzymatic assay using Trinder reaction for creatinine quantification, blood from patients with prescribed Dicynone should be taken at least 12 h after the last application of the drug for obtaining the correct creatinine values.