Evaluation of 4 quantification methods for monitoring 16 antibiotics and 1 beta-lactamase inhibitor in human serum by high-performance liquid chromatography with tandem mass spectrometry detection.

Antibiotic (ATB) prescription in an intensive care unit (ICU) requires continuous monitoring of serum dosages due to the patient's pathophysiological condition. Dosing adjustment is necessary to achieve effective targeted concentrations. Since ICUs routinely use a large number of ATBs, global monitoring needs to be developed. In the present study, we developed a global analytical method for extracting, separating and quantifying the most widely used ATBs in ICUs: amoxicillin, piperacillin, cefazolin, cefepime, cefotaxime, ceftazidime, ceftolozane, ceftriaxone, ertapenem, meropenem, ciprofloxacin, moxifloxacin, levofloxacin, daptomycin, dalbavancin, linezolid and a beta-lactamase inhibitor: tazobactam. To guarantee the robustness of the quantification, we differentiated the 16 ATBs and the beta lactamase inhibitor into 4 pools (ATB1 to ATB4), taking into account prescription frequency in the ICU, the physicochemical properties and the calibration ranges of the ATBs selected. The whole ATB was then separated with two LC columns in reversed phase: Kinetex Polar-C18 100 Å and Polar-RP-80 synergy, in less than 6.5 min. Detection was carried out by electrospray in positive ion mode, by tandem mass spectrometry (LC-MS/MS. The four quantification methods were validated according to the European guidelines on bioanalytical method validation (EMEA guide), after determining the extraction yields, matrix effects, recovery, precision, accuracy, within-run precision and between-run precision. For all analyses, bias is < 15% and is comparable to the literature and LOQs vary from 0.05 mg.L-1 for ciprofloxacin to 1.00 mg.L-1 for ceftriaxone and dalbavancin. The stability time of cefepime and piperacillin is 3 hrs and for the other ATBs 6 hrs in serum at room temperature. For long-term stability, freezing at - 80 °C guarantees 3 months of stability for ceftriaxone and dalbavancin and more than 6 months for the other ATBs.

Securing a diagnosis in patients presenting with suspected paracetamol (acetaminophen) poisoning: A retrospective cohort study.

BACKGROUND: Paracetamol (acetaminophen) is the most commonly ingested drug in self-poisoning. The correlation between an ingested self-reported dose of paracetamol and plasma paracetamol concentration is moderate. The usefulness of this correlation to rule out paracetamol ingestion has to be investigated. The objective of this study is to evaluate the performance of medical history in diagnosis of paracetamol ingestion in patients admitted to the Emergency Department (ED) for deliberate self-poisoning. MATERIALS AND METHODS: This retrospective cohort study was carried out in two EDs at an urban university hospital in Toulouse, France, from January 1 to June 30, 2018. All patients older than 15 years of age attending the ED for suspected deliberate self-poisonings who underwent blood testing were included. Medical history was considered positive for paracetamol intoxication if patients directly reported the use of paracetamol for deliberate self-poisoning during their ED admission or if paramedics reported the presence of paracetamol packages at the patient's home. We defined paracetamol ingestion as any concentration of paracetamol > 5 mg/L measured on presentation. RESULTS: We included 709 patients. 151 (21%) patients had a positive plasma paracetamol concentration. 165 (23%) patients revealed a positive medical history in terms of paracetamol ingestion. 29 (4%) patients had a false-negative medical history, and 45 (6%) patients had a false-positive history. The sensitivity of the medical history (95% confidence interval) was 79% (72 - 87), and its specificity was 92% (89 - 94). CONCLUSION: Diagnosis of self-poisoning involving paracetamol cannot be made using patient's medical history alone. Screening for paracetamol intoxication is proposed.