UHPLC-MS/MS method for simultaneous quantification of doripenem, meropenem, ciprofloxacin, levofloxacin, pazufloxacin, linezolid, and tedizolid in filtrate during continuous renal replacement therapy.

BACKGROUND: Since severe infections frequently cause acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is often initiated for regulation of inflammatory mediators and renal support. Thus, it is necessary to decide the antibiotic dosage considering the CRRT clearance in addition to residual renal function. Some of the hemofilters used in CRRT are known to adsorb antibiotics, and clearance of antibiotics may differ depending on the adsorptive characteristics of hemofilters. Although assay systems for blood and CRRT filtrate concentrations are required, no method for measuring antibiotics concentrations in filtrate has been reported. We developed a UHPLC-MS/MS method for simultaneous quantification of antibiotics commonly used in ICU, comprising carbapenems [doripenem (DRPM) and meropenem (MEPM)], quinolones [ciprofloxacin (CPFX), levofloxacin (LVFX) and pazufloxacin (PZFX)] and anti-MRSA agents [linezolid (LZD), and tedizolid (TZD)] in CRRT filtrate samples. METHODS: Filtrate samples were pretreated by protein precipitation. The analytes were separated with an ACQUITY UHPLC CSH C18 column under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate. RESULTS: The method showed good linearity over wide ranges. Within-batch and batch-to-batch accuracy and precision for each drug fulfilled the criteria of the US Food and Drug Administration guidance. The recovery rate was more than 87.20%. Matrix effect ranged from 99.57% to 115.60%. Recovery rate and matrix effect did not differ remarkably between quality control samples at different concentrations. CONCLUSION: This is the first report of a simultaneous quantification method of multiple antibiotics in filtrate of CRRT circuit.

Impact of high-density mapping on outcome of the second ablation for atrial fibrillation.

PURPOSE: Identification of a conduction gap between the left atrium and pulmonary vein (LA-PV gap) and the circuit of atrial tachycardia after pulmonary vein isolation (PVI) is an important process during the second ablation for atrial fibrillation (AF). The high-density mapping system RHYTHMIA® is useful for identification of an LA-PV gap and the circuit of atrial tachycardia. Therefore, this study was performed to investigate the effect of RHYTHMIA® in terms of the outcome of the second ablation for AF. METHODS: One hundred patients underwent a second ablation for AF in our institute from April 2015 to December 2018. We retrospectively evaluated 49 patients using RHYTHMIA® (group 1) and 51 patients using the conventional method with additional anatomical guide by CARTO® system. RESULTS: In group 1, we performed redo PVI for 41 patients with 49 LA-PV countable gaps and ablation for other atrial arrhythmias in 7 patients. In group 2, we performed redo PVI in 40 patients with 33 LA-PV countable gaps and ablation for other atrial arrhythmias in 9 patients. Three and two unstable arrhythmias in each group were not ablated. The final recurrence of atrial arrhythmia was significantly lower in group 1 than 2 (8/49 (16%) vs. 17/51 (33%), respectively; P = 0.017). Atrial arrhythmias other than AF after the second ablation occurred in only one patient in group 1 but seven patients in group 2. CONCLUSION: Using high-density mapping for the second ablation of AF was found to be superior to the conventional ablation method in terms of the suppression of atrial events in this study. This technique warrants further investigation.

The influence of the electrodes spacing of a mapping catheter on the atrial voltage substrate map.

BACKGROUND: Detailed substrate mapping is important for catheter ablation. However, the influence of the electrode spacing of the mapping catheter on the substrate map has not been well clarified. The aim of this study was to investigate the influence of the electrode spacing of the mapping catheter on the voltage of the substrate map. METHODS: Protocol 1: We recorded the local atrial potentials of the left atrium (LA) using the ablation catheter during sinus rhythm in six atrial fibrillation (AF) patients. The voltage of each atrial potential was compared between a close-bipolar (1-2 electrode) recording and wide-bipolar (1-4 electrode) recording. Protocol 2: Two voltage-maps of the LA were constructed separately using a 20-pole circular catheter and 10-pole circular catheter during sinus rhythm in 42 AF patients. The low voltage zone (LVZ) (<0.5mV) areas obtained by 2 voltage maps using the 10-pole and 20-pole circular catheters were compared. RESULTS: Protocol 1: The close-bipolar voltage of the local potentials was significantly smaller than that of the wide-bipolar voltages (0.76±0.39mV vs. 0.63±0.41mV, p<0.0001). Protocol 2: The size of the LVZ areas identified by the 10-pole and 20-pole catheters was 1.12±1.92cm2 (1.47±2.78%) and 8.30±7.80cm2 (8.83±8.32%), respectively (p<0.0001). CONCLUSIONS: The voltage of the local atrial potential using the close-bipolar catheter was significantly smaller than that using the wide-bipolar catheter. Care should be given to the electrode spacing of mapping catheters when analyzing the voltage of the atrial myocardial potentials.

Pharmacokinetics of ceftriaxone in patients undergoing continuous renal replacement therapy.

BACKGROUND: The duration of time for which the serum levels exceed the minimum inhibitory concentration (MIC) is an important pharmacokinetics (PK)/pharmacodynamics (PD) parameter correlating with efficacy for the antibiotic, ceftriaxone (CTRX). However, no reports exist regarding the PK or PD in patients undergoing continuous renal replacement therapy (CRRT). The purpose of this study was to examine the PK and safety of CTRX in patients undergoing CRRT in order to establish safer and more effective regimens. METHODS: CTRX (1 g once a day) was intravenously administered four or more times to nine patients undergoing CRRT. Blood was collected after administration to measure CTRX concentrations in serum and the filtration fraction of CRRT by high-performance liquid chromatography. In addition to calculating PK parameters from serum CTRX, we (a) estimated by simulation CTRX concentrations when the dose interval was extended to once every 2 or 3 days, (b) calculated CTRX clearance via CRRT from CTRX concentrations in the filtration fraction, and (c) assessed the safety of CTRX use. RESULTS: Total body clearance and the half-life of CTRX were 7.46 mL/min (mean) and 26.5 h, respectively, in patients undergoing CRRT. CTRX was found in the filtration fraction, and the estimated clearance by CRRT was about 70% of total body clearance. Simulations revealed that even when the dose interval is increased to 2 or 3 days, CTRX would retain its efficacy. CONCLUSIONS: Our findings suggest that, depending on the condition of patients undergoing CRRT, CTRX could be used safely against pathogens with a CTRX MIC ≤2 µg/mL, even when extending the dose interval.

The impact of oxidative stress levels on the clinical effectiveness of sivelestat in treating acute lung injury: an electron spin resonance study.

BACKGROUND: Sivelestat, a neutrophil elastase inhibitor, has been used to treat acute lung injury (ALI) with varying levels of clinical success. Variable baseline levels of oxidative stress in patients with ALI have been proposed as one explanation for inconsistent results. METHODS: Using a bedside electron spin resonance spectrometer, we evaluated electron spin resonance signal intensities of serum ascorbyl free radicals supplemented with dimethyl sulfoxide (AFR/DMSO) in patients with ALI. RESULTS: We found a positive correlation between AFR/DMSO and ascorbate levels, suggesting that serum AFR/DMSO measurements may serve as a surrogate for real-time assessments of oxidative stress. Levels of AFR/DMSO in patients with ALI were significantly lower than those found in healthy controls. Stratified analyses revealed that baseline AFR/DMSO levels were significantly lower in patients with ALI who failed to respond to sivelestat compared with those who did respond. CONCLUSIONS: Our results suggest that the clinical efficacy of sivelestat is dependent on baseline oxidative stress levels.