Vancomycin therapeutic drug monitoring: is there a consensus view? The results of a UK National External Quality Assessment Scheme (UK NEQAS) for Antibiotic Assays questionnaire.

This study investigated vancomycin therapeutic drug monitoring (TDM) and issues related to patient management. Questionnaires were distributed to 310 participants in the UK National External Quality Assessment Scheme (NEQAS) for Antibiotic Assays. The response rate was 57.4%. The majority (76%) had an 'in-house' assay service based, almost exclusively, in the microbiology department, and a fluorescence polarization immunoassay (FPIA) was used by 97%. Almost half (48.7%) had an assay service available for 24 h/day, 7 days/week and 92.7% expected same-day results. The majority (80%) had issued guidelines for vancomycin use. A 12 hourly initial dosing regimen was used by 89%. Trough assay samples were taken <10 min before the dose by 91.5%. For post-dose assay samples, 44% took a sample at 1 h, 28% at 2 h and the remainder at 'other' times. For trough target ranges, 93% quoted <10 mg/L or 5-10 mg/L. There was no consensus with regard to post-dose assay sample times and 23 ranges were quoted. The majority (74.4%) regarded a trough level of >or=10 mg/L as 'toxic' but 13 concentrations were quoted as toxic post-dose measurements. In conclusion, there was a wide variability and poor consensus with regard to post-dose vancomycin assay sampling times, target ranges and what constituted a toxic level.

External quality assessment of laboratory performance in analysis of toxicological cases.

A mean of 44 members of the United Kingdom national external quality assessment scheme (UKNEQAS) for toxicology reported analytical findings on 10 toxicological cases circulated between December 1995 and February 2000. Material distributed usually consisted of a 5ml blood and a 20ml urine sample simulated by quantitative addition of drugs and their metabolites to material donated by volunteers and patients. The samples were accompanied by a brief outline of the circumstances surrounding the case. Laboratories were requested to report their analytical findings, list methods of analysis, and provide interpretation of their findings. The mean overall success rate for identification of drugs or their pharmacological group was 76%, failure being largely by laboratories providing an immunoassay-based screening service for a fixed range of drug groups. The latter laboratories indicated that cases would be referred to regional toxicology centres for further investigation or confirmation. The coefficient of variation of measurements was <7% for routine analytes, such as ethanol and paracetamol, but 26-44% for tricyclics and opiates. There were 3% false positive reports. The quantity and content of interpretative comment provided by the laboratories was very variable. A number provide nothing in addition to the analytical result.

An audit of therapeutic drug monitoring service provision by laboratories participating in an external quality assessment scheme.

Therapeutic drug monitoring services were investigated in a questionnaire sent to all subscribers to the United Kingdom National External Quality Assessment Scheme for Therapeutic Drug Assays. Questions were posed on assay availability and use, target ranges, and reporting procedures for digoxin, lithium, phenytoin, phenobarbitone, carbamazepine, theophylline, and valproic acid. One hundred fifty-seven laboratories replied and, except for lithium, 45% reported in mass units, 34% in molar units, and 22% a mixture of mass and molar units. Target ranges for lithium, digoxin, carbamazepine, and phenobarbitone were highly variable but ranges for phenytoin, theophylline, and valproic acid were more consistent. Immunoassay was the most popular methodology although high-performance liquid chromatography was commonly used for anticonvulsants. Paper copies of results were provided by 93% of laboratories, 40% reported by telephone, 12% by fax, and 28% by computer. Additional data, mainly dose, time of last dose, and duration of therapy were requested by 55% to 67% of laboratories. Grades of staff authorizing results ranged from nurses to senior consultants, and collaboration with pharmacists occurred in 26% of laboratories. Most laboratories provided a daily analytical service and 73% offered a 24-hour emergency service. This audit unexpectedly identified use of a wide range of target concentrations, particularly for digoxin and lithium.

Functional assessment of therapeutic anti-D immunoglobulin using Fc-mediated assays.

Therapeutic anti-D immunoglobulin preparations issued by the Scottish National Blood Transfusion Service, between 1980 and 1986, were evaluated using in-vitro Fc-mediated functional tests that reflect potential in-vivo mechanisms of specific red cell destruction and clearance. All batches tested were found to: (a) contain anti-D of mainly IgG1 subclass and lesser amounts of IgG3; (b) mediate lymphocyte and monocyte rosetting; and (c) produce lytic activity in both K cell and monocyte ADCC. The functional activity of the therapeutic immunoglobulin preparations over this period of production had not altered despite increased plasma contributions latterly to the pool from deliberately immunized male donors. This is the first in-vitro study of the Fc-mediated function of therapeutic polyclonal anti-D preparations. As these preparations were clinically effective in the prophylactic anti-D programme, such bioassays of FcRI/II and FcRIII activity are justified for the future evaluation of immune plasma before blending for fractionation and production of therapeutic anti-D immunoglobulin.