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Biomedical subjects

C M Tobin

Publications and source records attributed to C M Tobin.

10 recordsLinked to original sources

Linezolid penetration into osteo-articular tissues.

Penetration of linezolid into osteo-articular tissue and fluid was studied in 10 patients undergoing primary total knee replacement. Linezolid 600 mg 12 hourly was given orally over the 48 h before operation and intravenously 1 h before induction of anaesthesia. Mean concentrations of linezolid at 90 min after the final dose, in serum, synovial fluid, synovium, muscle and cancellous bone, assayed by HPLC, were at least twice the MIC(90) for staphylococci and streptococci. The concentrations obtained indicate good penetration of this antibiotic and support its use in the management of multidrug-resistant Gram-positive bone, joint and deep-seated soft-tissue infections.

Acetamides↗

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.

Drug Monitoring↗

Antimicrobial activity of fluoroquinolone photodegradation products determined by parallel-line bioassay and high performance liquid chromatography.

The fluoroquinolones produce multiple photodegradation products. Little is known about these products, particularly whether any possess antimicrobial activity. To investigate this, we used the parallel-line bioassay to investigate discrepancies in zone of inhibition size in conjunction with high performance liquid chromatography (HPLC) analysis. A continuous flow photochemical reaction unit ('Beam-Boost') was used to partially photodegrade the fluoroquinolones ofloxacin, levofloxacin, ciprofloxacin and moxifloxacin (0.02 mM) by between 15 and 89%, as confirmed by HPLC. The concentration of residual parent fluoroquinolone in each irradiated sample was measured by HPLC and a non-irradiated control solution was prepared at the same concentration. These were compared by parallel-line bioassays using Escherichia coli, Enterobacter cloacae and Klebsiella oxytoca. With ofloxacin and levofloxacin, the zone size for the control solution was significantly less than that of the irradiated solutions, with >15% photodegradation in at least two of the indicator organisms, indicating that the photodegradation products possess antimicrobial activity. No difference was seen with ciprofloxacin at any level of photodegradation with any of the indicator organisms, nor with moxifloxacin at 30 and 54% photodegradation. A significant difference was observed with E. cloacae only, at 83% photodegradation.

Anti-Infective Agents↗

A simple, isocratic high-performance liquid chromatography assay for linezolid in human serum.

A rapid high-performance liquid chromatography (HPLC) assay for the detection of linezolid in human serum was developed. The method used a Hypersil 5ODS stationary phase. The mobile phase was 1% ortho-phosphoric acid, 30% methanol, 2 g/L heptane sulphonic acid, pH 5. UV absorbance detection was used (lambda(max) 254 nm). Samples were prepared by mixing with acetonitrile and an injection volume of 20 microL was used. The inter- and intra-day assay reproducibility were assessed. Assay linearity, specificity and accuracy were investigated. The detection limit and recovery of linezolid from serum were determined. In addition, the stability of linezolid, stored under a variety of conditions, was assessed. The retention time of linezolid was c. 6.5 min. The intra- and inter-day reproducibility was good and the assay was linear across the therapeutic range. Serum recovery was c. 100% at all concentrations tested. The detection limit was 0.1 mg/L and the assay was accurate. The assay was specific as there was no significant interference with the linezolid peak. Linezolid was demonstrated to be stable. This rapid assay is ideal for busy clinical laboratories with basic HPLC equipment.

Acetamides↗