Tomofumi Ohmori

Simultaneous determination of eight β-lactam antibiotics in human serum by liquid chromatography-tandem mass spectrometry.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of eight β-lactam antibiotics, including ampicillin, cefazolin, cefepime, cefmetazole, cefotaxime, doripenem, meropenem, and piperacillin, in human serum. Sample specimens were subjected to solid phase extraction (SPE) using Waters Oasis® HLB cartridges (30 mg). Chromatographic separation was performed with a high-resolution octadecyl silica column compatible with hydrophilic compounds, using a gradient of 10mM aqueous ammonium formate containing 0.1% formic acid-methanol. Antibiotics were detected by a triple quadrupole mass spectrometer (MS/MS) with electrospray ionization and quantified by the multiple reaction monitoring mode. A total run time of 13 min was applied. Linearity in the calibration was obtained over a range of 0.1-50 μg/mL of the β-lactam antibiotics, except for doripenem. The lower limit of quantification was 0.005-0.5 μg/mL, using 50 μL serum. The recovery rate exceeded 80.2% for these analytes, except for doripenem (49.1%) and meropenem (62.3%). The present method is applicable to routine therapeutic monitoring of β-lactam antibiotics in clinical practice.

Outcome measurement of extensive implementation of antimicrobial stewardship in patients receiving intravenous antibiotics in a Japanese university hospital

Background:  Antimicrobial stewardship has not always prevailed in a wide variety of medical institutions in Japan.

Simultaneous determination of benzodiazepines and their metabolites in human serum by liquid chromatography–tandem mass spectrometry using a high‐resolution octadecyl silica column compatible with aqueous compounds

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using a high-resolution octadecyl silica column compatible with aqueous compounds was developed for the simultaneous determination of benzodiazepines and their metabolites in human serum. This method enabled us to determine multiple benzodiazepines, including flurazepam, bromazepam, chlordiazepoxide, nitrazepam, clonazepam, flunitrazepam, estazolam, clobazam, lorazepam, alprazolam, triazolam, brotizolam, fludiazepam, diazepam, quazepam, prazepam and their metabolites such as 7-aminonitrazepam, 7-aminoclonazepam, 7-acetamidonitrazepam, N-desmethylclobazam and N-desmethyldiazepam. The analytes spiked into human serum were subjected to solid-phase extraction followed by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. The running time was within 25 min for the measurement of 22 benzodiazepines and their metabolites. The recovery rates exceeded 58.1% for those compounds except for quazepam, which showed a recovery of 45.8%. The limit of detection ranged from 0.3 to 11.4 ng/mL. Linearity was satisfactory for all compounds. These data suggest that the present method can be applicable to routine assay for benzodiazepines in the clinical setting.

Significance of individual adjustment of initial loading dosage of teicoplanin based on population pharmacokinetics.

An initial loading dose of teicoplanin is required to reach the optimal trough concentration (> or = 10 microg/mL) rapidly. To attain the optimal teicoplanin concentration efficiently, an individual loading dose regimen based on population pharmacokinetics, in which the target trough concentration was set to 15 microg/mL, was defined. Among 70 patients, 33 patients received the individual loading dose regimen, 33 patients received the conventional loading dose regimen (200mg or 400mg every 12h on Day 1 followed by 200mg once daily) and 4 patients received no loading dose. The proportion of patients showing an optimal plasma concentration was 88% in the individual loading dose regimen but only 33% in the conventional loading dose regimen. No patient without a loading dose showed the optimal concentration. Both total loading dose and plasma concentration were significantly (P<0.001) higher in the individual loading dose group than in the conventional loading dose group. Notably, the trough concentration was almost constant in patients with individual loading doses ranging from 800 mg to 1800 mg. These findings suggest that individual adjustment of the initial loading dose of teicoplanin is potentially useful to attain the optimal concentration rapidly.

Reduction of linezolid-associated thrombocytopenia by the dose adjustment based on the risk factors such as basal platelet count and body weight☆ , ☆☆

The aim of the present study was to evaluate the efficacy of dose modification based on the risk factor for linezolid-induced thrombocytopenia. A multivariate logistic regression analysis performed in the observational study showed that low body weight of <55 kg (odds ratio [OR]: 33.2, 95% confidence interval [CI]: 2.16-510.1, P = 0.012) and the baseline platelet count of <200 × 10(3)/mm(3) (OR: 24.9, 95% CI: 1.53-404.7, P = 0.024) were found to be risk factors for linezolid-induced thrombocytopenia. In the subsequent intervention study, in which daily dose of linezolid was set to 20 mg/kg in patients with either one of the risk factors or 1200 mg in those without any risk factor, the onset of thrombocytopenia was significantly prolonged in the intervention study group (P = 0.043), without reducing clinical efficacy. These findings suggest that dose adjustment of linezolid is effective in preventing thrombocytopenia without reducing its clinical efficacy in patients having risk factors.

Usefulness of serum cystatin C to determine the dose of vancomycin in critically ill patients

Objectives  Serum creatinine (Scr) is not a reliable marker of renal function in critically ill patients because of an enhancement of protein catabolism, which makes it difficult to adjust the dosage of renally eliminated drugs such as antibiotics. This study aimed to investigate whether serum cystatin C (Scys‐C) could be used as a reliable marker of renal function.

Rapid Attainment of Optimal Trough Concentrations in Organ Failure Mitigated by Teicoplanin

The effective treatment of infections with teicoplanin requires an initial loading dose to reach optimal trough concentrations rapidly enough. The optimal dosage of teicoplanin was previously established, and an optimal trough concentration of 15-20 μg/mL was assumed based on weight and estimated creatinine clearance. Teicoplanin treatment was performed with software-based monitoring of teicoplanin concentrations. We compared serum chemistry parameters and sequential organ failure assessment (SOFA) scores in patients with initial teicoplanin trough concentrations 0.05). Teicoplanin initial trough concentrations have been thought to contribute to improvement of organ failure. To maintain therapeutic concentrations of teicoplanin in patients with high disease severity, it was useful to ensure that initial trough values were ≥ 15 μg/mL. The initial dosage schedule of teicoplanin in emergency intensive care should consider disease severity.