scholarly journals Immunoassay Analysis of Kanamycin in Serum Using the Tobramycin Kit

2016 ◽  
Vol 60 (8) ◽  
pp. 4646-4651 ◽  
Author(s):  
J. A. Dijkstra ◽  
A. J. Voerman ◽  
B. Greijdanus ◽  
D. J. Touw ◽  
J. W. C. Alffenaar

ABSTRACTKanamycin is one of the aminoglycosides used in the treatment of multidrug-resistant tuberculosis. Blood concentrations of kanamycin are predictive for the treatment efficacy and the occurrence of side effects, and dose adjustments can be needed to optimize therapy. However, an immunoassay method for the quantification of kanamycin is not commercially available. We modified the existing tobramycin immunoassay to analyze kanamycin. This modified method was tested in a concentration range of 0.3 to 80.0 mg/liter for inaccuracy and imprecision. In addition, the analytical results of the immunoassay method were compared to those obtained by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method using Passing and Bablok regression. Within-day imprecision varied from 2.3 to 13.3%, and between-day imprecision ranged from 0.0 to 11.3%. The inaccuracy ranged from −5.2 to 7.6%. No significant cross-reactivity with other antimicrobials and antiviral agents was observed. The results of the modified immunoassay method were comparable with the LC-MS/MS analytical outcome. This new immunoassay method enables laboratories to perform therapeutic drug monitoring of kanamycin without the need for complex and expensive LC-MS/MS equipment.

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Samiksha Ghimire ◽  
Bhagwan Maharjan ◽  
Erwin M. Jongedijk ◽  
Jos G. W. Kosterink ◽  
Gokarna R. Ghimire ◽  
...  

ABSTRACT Saliva may be a useful alternative matrix for monitoring levofloxacin concentrations in multidrug-resistant tuberculosis (MDR-TB) patients. The objectives of this study were (i) to evaluate the correlation between plasma and salivary levofloxacin (Lfx) concentrations in MDR-TB patients and (ii) to gauge the possibility of using saliva as an alternative sampling matrix for therapeutic drug monitoring of Lfx in areas where TB is endemic. This was a prospective pharmacokinetic study that enrolled MDR-TB patients receiving levofloxacin (750- to 1,000-mg once-daily dosing) under standardized treatment regimen in Nepal. Paired blood and saliva samples were collected at steady state. Lfx concentrations were quantified using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental kinetics. Lfx drug exposures were evaluated in 23 MDR-TB patients. During the first month, the median (interquartile range [IQR]) areas under the concentration-time curve from 0 to 24 h (AUC0–24) were 67.09 (53.93 to 98.37) mg ⋅ h/liter in saliva and 99.91 (76.80 to 129.70) mg ⋅ h/liter in plasma, and the saliva plasma (S/P) ratio was 0.69 (0.53 to 0.99). Similarly, during the second month, the median (IQR) AUC0–24 were 75.63 (61.45 to 125.5) mg ⋅ h/liter in saliva and 102.7 (84.46 to 131.9) mg ⋅ h/liter in plasma, with an S/P ratio of 0.73 (0.66 to 1.18). Furthermore, large inter- and intraindividual variabilities in Lfx concentrations were observed. This study could not demonstrate a strong correlation between plasma and saliva Lfx levels. Despite a good Lfx penetration in saliva, the variability in individual saliva-to-plasma ratios limits the use of saliva as a valid substitute for plasma. Nevertheless, saliva could be useful in semiquantitatively predicting Lfx plasma levels. (This study has been registered at ClinicalTrials.gov under identifier NCT03000517.)


2020 ◽  
Vol 24 (1) ◽  
pp. 110-112 ◽  
Author(s):  
E. Dang ◽  
F. Sayagh ◽  
M. P. Lê ◽  
M. Neuville ◽  
F. Sinnah ◽  
...  

We present the case of a 21-year-old man admitted to the intensive care unit with multi-organ failure due to multidrug-resistant tuberculosis (TB). TB treatment initially comprised moxifloxacin, ethambutol, linezolid and amikacin administered intravenously. Due to suspected moxifloxacin-induced liver injury, we stopped all fluoroquinolones and switched to bedaquiline (BDQ), which is only available in tablets for oral administration. Since our patient had to be fed through a nasogastric tube (NGT), BDQ was administered after being crushed and dissolved in water; drug pharmacokinetics were studied using repeated blood sampling. Therapeutic drug monitoring showed that BDQ was detectable in blood plasma with a trough concentration above the supposed efficacy threshold, suggesting that this molecule could be administered through NGT.


2016 ◽  
Vol 5 ◽  
pp. S44-S45 ◽  
Author(s):  
Mathieu S. Bolhuis ◽  
Onno W. Akkerman ◽  
Marieke G.G. Sturkenboom ◽  
Wiel C.M. de Lange ◽  
Tjip S. van der Werf ◽  
...  

2012 ◽  
Vol 56 (11) ◽  
pp. 5758-5763 ◽  
Author(s):  
D. H. Vu ◽  
M. S. Bolhuis ◽  
R. A. Koster ◽  
B. Greijdanus ◽  
W. C. M. de Lange ◽  
...  

ABSTRACTLinezolid is a promising antimicrobial agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its use is limited by toxicity. Therapeutic drug monitoring (TDM) may help to minimize toxicity while adequate drug exposure is maintained. Conventional plasma sampling and monitoring might be hindered in many parts of the world by logistical problems that may be solved by dried blood spot (DBS) sampling. The aim of this study was to develop and validate a novel method for TDM of linezolid in MDR-TB patients using DBS sampling. Plasma, venous DBS, and capillary DBS specimens were obtained simultaneously from eight patients receiving linezolid. A DBS sampling method was developed and clinically validated by comparing DBS with plasma results using Passing-Bablok regression and Bland-Altman analysis. This study showed that DBS analysis was reproducible and robust. Accuracy and between- and within-day precision values from three validations presented as bias and coefficient of variation (CV) were less than 17.2% for the lower limit of quantification and less than 7.8% for other levels. The method showed a high recovery of approximately 95% and a low matrix effect of less than 8.7%. DBS specimens were stable at 37°C for 2 months and at 50°C for 1 week. The ratio of the concentration of linezolid in DBS samples to that in plasma was 1.2 (95% confidence interval [CI], 1.12 to 1.27). Linezolid exposure calculated from concentrations DBS samples and plasma showed good agreement. In conclusion, DBS analysis of linezolid is a promising tool to optimize linezolid treatment in MDR-TB patients. An easy sampling procedure and high sample stability may facilitate TDM, even in underdeveloped countries with limited resources and where conventional plasma sampling is not feasible.


2013 ◽  
Vol 42 (6) ◽  
pp. 1449-1453 ◽  
Author(s):  
Shashikant Srivastava ◽  
Charles A. Peloquin ◽  
Giovanni Sotgiu ◽  
Giovanni Battista Migliori

2013 ◽  
Vol 57 (8) ◽  
pp. 3676-3680 ◽  
Author(s):  
M. S. Bolhuis ◽  
R. van Altena ◽  
K. van Hateren ◽  
W. C. M. de Lange ◽  
B. Greijdanus ◽  
...  

ABSTRACTLinezolid plays an increasingly important role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, patients should be carefully monitored due to time- and dose-dependent toxicity. Clarithromycin plays a more modest role. Therapeutic drug monitoring may contribute to assessment of treatment regimens, helping to reduce toxicity while maintaining adequate drug exposure. Oral fluid sampling could provide a welcome alternative in cases where conventional plasma sampling is not possible or desirable. The aim of this study was to clinically validate the analysis of linezolid and clarithromycin and its metabolite hydroxyclarithromycin in oral fluid of patients with multidrug-resistant tuberculosis. Serum and oral fluid samples were simultaneously obtained and analyzed by using validated methods, after extensive cross-validation between the two matrices. Passing-Bablok regressions and Bland-Altman analysis showed that oral fluid analysis of linezolid and clarithromycin appeared to be suitable for therapeutic drug monitoring in MDR-TB patients. No correction factor is needed for the interpretation of linezolid oral fluid concentrations with a ratio of the linezolid concentration in serum to that in oral fluid of 0.97 (95% confidence interval [CI], 0.92 to 1.02). However, the clarithromycin concentration serum/clarithromycin concentration in oral fluid ratio is 3.07 (95% CI, 2.45 to 3.69). Analysis of hydroxyclarithromycin in oral fluid was not possible in this study due to a nonlinear relationship between the concentration in serum and that in oral fluid. In conclusion, the analysis of linezolid (no correction factor) and clarithromycin (correction factor of 3) in oral fluid is applicable for therapeutic drug monitoring in cases of multidrug-resistant tuberculosis as an alternative to conventional serum sampling. Easy sampling using a noninvasive technique may facilitate therapeutic drug monitoring for specific patient categories.


2010 ◽  
Vol 32 (1) ◽  
pp. 97-101 ◽  
Author(s):  
Jan-Willem C Alffenaar ◽  
Jos G W Kosterink ◽  
Richard van Altena ◽  
Tjip S van der Werf ◽  
Donald R A Uges ◽  
...  

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