Development and Implementation of One-Step, Broad-Spectrum, High-Sensitivity Drug Screening by Tandem Mass Spectrometry in a Pediatric Population.

BACKGROUND: Drug screening by immunoassay is common in pediatric populations. However, false-positive and -negative results due to antibody cross-reactivity and dilute urine are frequent and underappreciated. Accurate ascertainment of drug exposure in children has significant clinical and medico-legal consequences. DESIGN AND METHODS: We developed and characterized an LC-MS/MS drug screening assay to supplant immunoassay and detect 38 compounds at the lowest concentrations distinguishable from analytic noise. Once implemented, we conducted a retrospective analysis of 3985 pediatric urine drug screens performed a year before (n = 1663) and after (n = 2322) implementation to examine the frequency and breadth of drug detection in our pediatric population. RESULTS: Using immunoassay, 23% (293/1269) of samples from the general pediatric and 37% (147/394) of nursery populations had presumptively positive results. Of the presumptive positive compounds, 85% (288/338) from the general pediatric population and 40% (65/162) from the nursery cohort were confirmed by mass spectrometry. After LC-MS/MS implementation, 31% (628/2052) of general pediatric, and 18% (48/270) of the nursery samples were positive for 1 or more compounds. In the nursery population, immunoassays over-detected the presence of THC but under-detected exposure to cocaine. CONCLUSION: A broadly targeted, analytically sensitive LC-MS/MS drug screening assay detects a larger number and variety of compounds in a single step compared to a screen-then-confirm approach initiated by immunoassay in our pediatric population. Rapid delivery of accurate results enables timely, appropriate disposition of patients in a variety of settings including the emergency department and labor/delivery.

Vancomycin Concentrations in Paraspinal Muscles During Posterior Spinal Fusions for Neuromuscular Scoliosis.

STUDY DESIGN: Prospective consecutively enrolled cohort. OBJECTIVES: To evaluate paraspinal muscle concentration of intravenously administered vancomycin, at predetermined time points, during posterior spinal fusion (PSF) with instrumentation in neuromuscular scoliosis (NMS). SUMMARY: Surgical site infection (SSI) after PSF for NMS can be a devastating complication, which may lead to prolonged antibiotic use, multiple additional surgical procedures, pseudarthroses, and sepsis. Because of significant morbidity of SSIs in NMS, the prophylactic use of vancomycin has been adopted at our institution as standard wound prophylaxis, despite any high-level evidence of its efficacy. METHODS: A prospective study of 20 patients who underwent definitive PSF for NMS and received vancomycin infusion preoperatively per institutional protocol. Serum levels were obtained immediately after infusion, at surgical incision, and then at 1, 2, and 4 hours post incision. Muscle tissue samples were simultaneously obtained at incision and at 1, 2, and 4 hours post incision. Samples were analyzed by a validated liquid chromatography-tandem mass spectrometry method. RESULTS: 10 males and 10 females with a mean age of 14+11 years (9-20 years) received a mean infusion of 15.0 mg/kg vancomycin. Mean serum levels were 26.7 µg/mL after infusion, 18.1 at incision, 13.2 at 1 hour, 11.8 at 2 hours, and 7.6 at 4 hours post infusion. Mean muscle levels were 0.5 µg/mL at incision, 0.6 at 1 hour, 0.5 at 2 hours, and 0.7 at 4 hours post infusion. Mean serum levels reached minimum inhibitory concentration (MIC) for Staphylococcus aureus at incision and at all timepoints during surgery. Mean muscle vancomycin levels never reached MIC. No patients had any cardiac or kidney disease, and all patients had normal kidney function according to their preoperative laboratory values. CONCLUSIONS: Using accepted guidelines for the administration of intravenous vancomycin preoperatively, serum levels reached MIC at incision and at all timepoints tested during PSF for neuromuscular scoliosis. At no timepoint tested did muscle levels reach MIC. LEVEL OF EVIDENCE: Level II.