ABSTRACT
Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (fT>MIC) of MEPM and its therapeutic efficacy in P. aeruginosa bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % fT>MIC of MEPM as 75%. The retrospective study spanned 14 years and included hospitalized patients treated with MEPM for P. aeruginosa bacteremia. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) for each patient, and the threshold for a PTA of 75% fT>MIC associated with in-hospital survival was determined using receiver operating characteristic (ROC) curves. The ROC curve-derived PTA associated with improved in-hospital survival was 65.0%, a significant finding in multivariate logistic regression analysis adjusted for patient background factors (odds ratio: 20.49, 95% confidence interval: 3.02-245.23, p = 0.005). This result suggests a dosing regimen that achieves a PTA of at least 65% when the target fT>MIC of MEPM for treating P. aeruginosa bacteremia is defined as 75%.
ABSTRACT
This study was undertaken to evaluate the differences in chronotherapeutic effects of angiotensin-II receptor blockers, valsartan and olmesartan in hypertensive patients with non-dipper blood pressure (BP) pattern during valsartan at morning. Ninety four patients were enrolled, and 40 patients were judged to be non-dippers. In these patients, same dose of valsartan was changed to evening (Val-E, n = 12), or olmesartan (equivalent dose of valsartan) was given at morning (Olm-M, n = 13) or evening (Olm-E, n = 15) for 4 months. BP decreased during sleep and increased during waking hours in Val-E group. In Olm-M and Olm-E groups, BP decreased during sleep and waking hours. Percent reduction in BP at night-time compared to BP at waking hours significantly increased after changing the dose regimen in each group. Serum creatinine decreased and estimated glomerular filtration rate (eGFR) elevated in Olm-M and Olm-E, but not Val-E groups. Positive correlation between systolic BP (SBP) during sleep and serum creatinine, and negative correlation between SBP during sleep and eGFR were detected. These data suggest that dipper BP pattern could be obtained by chronotherapeutic approach using valsartan and olmesartan in non-dipper patients with valsartan at morning. Morning and evening olmesartan, but not evening valsartan improved renal function in these patients.
Subject(s)
Antihypertensive Agents/therapeutic use , Drug Chronotherapy , Hypertension/drug therapy , Imidazoles/therapeutic use , Tetrazoles/therapeutic use , Valsartan/therapeutic use , Aged , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Creatinine/blood , Female , Glomerular Filtration Rate/drug effects , Humans , Hypertension/blood , Imidazoles/administration & dosage , Imidazoles/pharmacology , Male , Middle Aged , Tetrazoles/administration & dosage , Tetrazoles/pharmacology , Valsartan/administration & dosage , Valsartan/pharmacologyABSTRACT
9, 10-Phenanthrenequinone (PQ) is regarded as a harmful environmental pollutant and its presence has been reported in atmospheric environment. The measurement of PQ in environment should be necessary to evaluate the influence of PQ on human health. We found that PQ reacted with 2-aminothiophenol under acidic condition to form fluorescent derivative which emits green fluorescence at 510nm. Based on this reaction, a simple and rapid determination method for PQ was developed by HPLC with post-column derivatization and fluorescence detection. By the proposed HPLC system, PQ was detected at 24min and the detection limit was 67fmol/injection (S/N=3). The proposed method was able to determine the atmospheric PQ concentrations by the direct injection of extract from airborne particulates.