We present a case of intensified therapeutic drug monitoring (TDM) of citalopram in mother and newborn infant after clinically observed selective serotonin reuptake inhibitor (SSRI)-associated symptoms 2 weeks until 2 months after delivery. The SSRI-associated symptoms observed in the infant (up to 3 weeks after delivery) were irregular breathing, sleep disorders, hypotonia, and hypertonia. We conclude that the SSRI-associated symptoms in the infant represent citalopram withdrawal effects rather than side effects caused by breastfeeding. This case illustrates the importance of a flexible TDM program and a multidisciplinary approach in a hospital setting to deal with cases of drug-associated adverse effects, such as SSRI withdrawal effects.

Introduction: Tobramycin is one of the components used for selective decontamination of the digestive tract (SDD), applied to prevent colonization and subsequent infections in critically ill patients. Tobramycin is administered in the oropharynx and gastrointestinal tract and is normally not absorbed. However, critical illness may convey gut barrier failure. The aim of the study was to assess the prevalence and amount of tobramycin leakage from the gut into the blood, to quantify tobramycin excretion in urine, and to determine the association of tobramycin leakage with markers of circulation, kidney function and other organ failure. Methods: This was a prospective observational cohort study. The setting was the 20-bed closed format-mixed ICU of a teaching hospital. The study population was critically ill patients with an expected stay of more than two days, receiving SDD with tobramycin, polymyxin-E and amphotericin-B four times daily in the oropharynx and stomach. Tobramycin concentration was measured in serum (sensitive high performance liquid chromatography - mass spectrometry/mass spectrometry (HLPC-MS/MS) assay) and 24-hour urine (conventional immunoassay), in 34 patients, 24 hours after ICU admission, and in 71 patients, once daily for 7 days. Tobramycin leakage was defined as tobramycin detected in serum at least once (> 0.05 mg/L). Ototoxicity was not monitored. Results: Of the 100 patients with available blood samples, 83 had tobramycin leakage. Median highest serum concentration for each patient was 0.12 mg/L; 99% of the patients had at least one positive urinary sample (> 0.5 mg/L), 49% had a urinary concentration ≥ 1 mg/L. The highest tobramycin serum concentration was significantly associated with vasopressor support, renal and hepatic dysfunction, and C-reactive protein. At binary logistic regression analysis, high dopamine dose and low urinary output on Day 1 were the significant predictors of tobramycin leakage. Nephrotoxicity could not be shown. Conclusions: The majority of acute critically ill patients treated with enteral tobramycin as a component of SDD had traces of tobramycin in the blood, especially those with severe shock, inflammation and subsequent acute kidney injury, suggesting loss of gut barrier and decreased renal removal. Unexpectedly, urinary tobramycin was above the therapeutic trough level in half of the patients. Nephrotoxicity could not be demonstrated.

Toxicology screening tests for drugs-of-abuse and therapeutic drugs in urine (TST-U) are often used to assess whether a patient's clinical condition can be explained by the use of drugs-of-abuse (DOA) and/or therapeutic drugs. TST-U have clinical value when they support clinical decision making by influencing diagnosis and patient care. We aim to quantify the influence of TST-U results on diagnosis and patient care in an emergency department. Our secondary objective is to identify specific patients for which a TST-U is most warranted or mostly unhelpful. This prospective observational study was performed at the emergency department of a middle-sized urban teaching hospital. A point of care TST-U has been used in this department for three years. When a TST-U is considered indicated by a physician, the influence of the TST-U result on diagnosis and patient care is quantified before and after the test results are available, by means of a questionnaire. Urgency and complaints upon admission have also been registered. Of 100 TST-U results 37% were reported having a substantial influence on diagnosis and 25% on patient care. TST-U had a substantial influence on diagnosis in 48% of patients with decreased consciousness, 47% of patients with psychiatric symptoms and in 47% of patients with "other" complaints. In this last category patients with neurological symptoms benefited most. In patients who were already suspected to be intoxicated, only 18% of the TST-U results had substantial influence on diagnosis. The use of point of care TST-U in an Emergency Department helps physicians to understand the clinical condition of a patient. They influence the way a patient is treated to a lesser extent. These tests are most helpful in patients with decreased consciousness, psychiatric or neurological symptoms and mostly unhelpful in patients who, upon admission, are already known to be intoxicated.

Background: The number of reports of serious adverse effects and intoxication after the use of the new drug 4-fluoroamphetamine (4-FA) increases. At the Emergency Department of the OLVG-Oost Hospital in Amsterdam, an on-site drug test, the Triage TOX Drug Screen, is available to assist in a rapid diagnosis. In less urgent cases, an EMIT II Plus immunoassay is used to determine semiquantitatively the presence of drugs of abuse (DOA). The antibodies in these immunoassays are designed to detect classic DOA and its urinary metabolites. Amphetamine-like drugs that may cause serious toxicity or impairment may not cross-react with the available immunoassay kits, and therefore may stay undetected. The question arises as to whether 4-FA and paramethoxymethamphetamine (PMMA) are detectable in the toxicological screening procedures commonly used for testing in urine.Methods: Synthetic urine was spiked with the drug under investigation to create spiking standards of 50, 100, 250, 500, 2500, and 5000 ng/mL. Urine drug screens were performed on the automated analyzer Biosite Triage MeterPro using the Triage TOX Drug Screen test and on a Siemens Drug Testing System Viva-E using the EMIT II Plus Ecstasy Assay and the EMIT II Plus Amphetamines Assay.Results: In this concentration range, the EMIT II Plus did not screen positive for PMMA, but there was some cross-reactivity for PMMA on the EMIT II Plus Ecstasy assay. The Triage TOX Drug Screen did test positive for PMMA at a concentration of 2500 ng/mL. The EMIT II Plus Amphetamines did test positive for 4-FA at a concentration of 5000 ng/mL, whereas the Ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] assay only showed low cross-reactivity for 4-FA. The Triage TOX Drug Screen did not test positive for 4-FA.Conclusions: The available immunoassays lack sensitivity to detect 4-FA and PMMA in lower urine concentrations. Awareness of the fact that novel DOA may lead to false-negative urinary drug tests is of great importance.