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Purpose There is variability in the pharmacokinetics (PK) of antibiotics (AB) in critically ill patients. Therapeutic drug monitoring (TDM) could overcome this variability and increase PK target attainment. The objective of this study was to analyse the effect of a dose-adaption strategy based on daily TDM on target attainment. Methods This was a prospective, partially blinded, and randomised controlled trial in patients with normal kidney function treated with meropenem (MEM) or piperacillin/tazobactam (PTZ). The intervention group underwent daily TDM, with dose adjustment when necessary. The predefined PK/pharmacodynamic (PK/PD) target was 100 % f T >4MIC [percentage of time during a dosing interval that the free ( f ) drug concentration exceeded 4 times the MIC]. The control group received conventional treatment. The primary endpoint was the proportion of patients that reached 100 % f T >4MIC and 100 % f T >MIC at 72 h. Results Forty-one patients (median age 56 years) were included in the study. Pneumonia was the primary infectious diagnosis. At baseline, 100 % f T >4MIC was achieved in 21 % of the PTZ patients and in none of the MEM patients; 100 % f T >MIC was achieved in 71 % of the PTZ patients and 46 % of the MEM patients. Of the patients in the intervention group, 76 % needed dose adaptation, and five required an additional increase. At 72 h, target attainment rates for 100 % f T >4MIC and 100 % f T >MIC were higher in the intervention group: 58 vs. 16 %, p  = 0.007 and 95 vs. 68 %, p  = 0.045, respectively. Conclusions Among critically ill patients with normal kidney function, a strategy of dose adaptation based on daily TDM led to an increase in PK/PD target attainment compared to conventional dosing.

Measurement of antibiotic concentrations is increasingly used to optimize antibiotic therapy. Plasma samples are typically used for this, but other matrices such as exhaled air could be an alternative. We studied 11 spontaneously breathing intensive care unit patients receiving either piperacillin/tazobactam or meropenem. Patients exhaled in the ExaBreath® device, from which the antibiotic was extracted. The presence of antibiotics was also determined in the condensate found in the device and in the plasma. Piperacillin or meropenem could be detected in the filter in 9 patients and in the condensate in 10. Seven patients completed the procedure as prescribed. In these patients the median quantity of piperacillin in the filter was 3083 pg/filter (range 988–203,895 pg/filter), and 45 pg (range 6–126 pg) in the condensate; meropenem quantity was 21,168 pg/filter, but the quantity in the condensate was below the lower limit of quantification. There was no correlation between the concentrations in the plasma and quantities detected in the filter or condensate. Piperacillin and meropenem can be detected and quantified in exhaled air of non-ventilated intensive care unit patients; these quantities did not correlate with plasma concentrations of these drugs. •Piperacillin and meropenem can be found in exhaled air of non-ventilated ICU patients.•Piperacillin and meropenem can also be detected in the condensate of exhaled air.•Concentrations in plasma did not correlate with quantities detected in the filter or condensate.

Although dried blood spot (DBS) sampling is increasingly receiving interest as a potential alternative to traditional blood sampling, the impact of hematocrit (Hct) on DBS results is limiting its final breakthrough in routine bioanalysis. To predict the Hct of a given DBS, potassium (K + ) proved to be a reliable marker. The aim of this study was to evaluate whether application of an algorithm, based upon predicted Hct or K + concentrations as such, allowed correction for the Hct bias. Using validated LC-MS/MS methods, caffeine, chosen as a model compound, was determined in whole blood and corresponding DBS samples with a broad Hct range (0.18–0.47). A reference subset ( n  = 50) was used to generate an algorithm based on K + concentrations in DBS. Application of the developed algorithm on an independent test set ( n  = 50) alleviated the assay bias, especially at lower Hct values. Before correction, differences between DBS and whole blood concentrations ranged from −29.1 to 21.1 %. The mean difference, as obtained by Bland-Altman comparison, was −6.6 % (95 % confidence interval (CI), −9.7 to −3.4 %). After application of the algorithm, differences between corrected and whole blood concentrations lay between −19.9 and 13.9 % with a mean difference of −2.1 % (95 % CI, −4.5 to 0.3 %). The same algorithm was applied to a separate compound, paraxanthine, which was determined in 103 samples (Hct range, 0.17–0.47), yielding similar results. In conclusion, a K + -based algorithm allows correction for the Hct bias in the quantitative analysis of caffeine and its metabolite paraxanthine. Graphical Abstract Percentage differences between uncorrected DBS and whole blood paraxanthine concentrations (upper panel) and between corrected and whole blood paraxanthine concentrations (lower panel) ( n = 103)

Hemoglobin released into the circulation during hemolysis or therapy with chemically modified hemoglobins, exert oxidative and NO-scavenging toxic effects. Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) is one of the second-generation hemoglobin-based oxygen carriers (HBOCs). We wanted to investigate the metabolism of PHP with a special focus on its consequences for interpreting hemolysis-related diagnostic parameters in PHP-treated patients. Clinical samples were analyzed from 3 patients, who received PHP (as part of the PHOENIX phase III trial) for treatment of catecholamine- resistant distributive shock. In contrast to expectations, clearance of PHP by hemopexin, instead of haptoglobin was documented by increased hemolysis indices, absence of decreased haptoglobin values, presence of free PHP-hemoglobin and exhausted hemopexin concentrations. The present case report is important for both clinicians and laboratorians since it nicely illustrates that a hemolytic aspect of plasma is not necessarely synonymous with hemolysis. A hemolytic aspect of plasma or serum (high hemolysis index) in combination with normal or increased haptoglobin values should draw the attention; additional determination of lactate dehydrogenase and hemopexin may then be useful to distinguish the condition from in vitro hemolysis and to monitor the in vivo elimination of the heme compounds.

Conclusion: We conclude that NRBC are a common finding in critically ill patients. [...]WBC measurements on the IC unit should always include the measurement of NRBC, to prevent falsely elevated WBC reporting. [...]our results corroborate the findings of Stachon et al.

Objective: Anion gap (AG) metabolic acidosis is an indicator of possible toxic ingestion, with methanol, uremia, diabetic ketoacidosis, propylene glycol, isoniazid, lactic acidosis, ethylene glycol, salicylates (MUDRILES) as most common causes. N-acetylcysteine is an effective treatment through restoration of intracellular glutathione levels, inhibiting y-glutamylcysteine synthetase. 5OP is a rare, yet underreported cause of metabolic acidosis with increased AG. After exclusion of usual causes of high AG acidosis, urine organic acids should be analysed, exploring increase 5OP levels. Because acetaminophen use is so common, it may not be mentioned in anamnesis or the association may not be recognized.

Total protein, albumin, alpha-1-acid glycoprotein and IgA analyses were performed on the Roche Cobas 8000 c502 analyser and Siemens BNII Nephelometer. Free concentrations obtained via equilibrium dialysis correlated well with those obtained via ultrafiltration (at 4°C: r=0.9457; at 37°C: r=0.9478; both p<0.0001) and no significant difference was found between free vancomycin results of microdialysis and ultrafiltration at 37°C (p=0.13, paired t-test).

Results: Within-run CVs were <2% for benzodiazepine, <5% for barbiturates and <8% for tricyclic antidepressants. 20-day imprecision data resulted in CVs <12% for all three assays at concentrations of 15 mg/L and 25 mg/L for benzodiazepines and barbiturates and 147 mg/L and 294 mg/L for TCA. The optimal cut-off, sensitivity, specificity and area under the ROC-curve each time with 95% confidence interval were respectively 48 mg/L, 98.6% [92.6 - 99.9], 93.5% [78.6 - 99.2] and 0.981 [0.933-0.998] for benzodiazepines (n = 104) with 2 false positive and 1 false negative and 115 mg/L, 97.8% [88.5 - 99.9], 85.7% [71.5 - 94.6] and 0.964 [0.901-0.992] for tricyclic antidepressants (n=84) observing 1 false negative and 6 false positives (3 contained citalopram(-metabolites), 1 fluoxetine and 1 venlafaxine).

The goal was to evaluate the performance of the Quantitative Microsphere System (QMS) Telcoplanln Immunoassay, a homogeneous turbidimetric assay, applied on the Thermo Scientific Indiko Plus system (Thermo Fisher Scientific, Vantaa, Finland) using the manufacturer's assay protocol. Anonymized frozen leftover serum samples (n=58) were used for the method comparison with a fluorescence polarization immunoassay assay (LABfx Teicoplanin, RolfGreiner Bi°Chemica, Flacht, Germany) on the TDxFLx (Abbott Laboratories, Abbott Park, IL).