scholarly journals Reduced Chance of Hearing Loss Associated with Therapeutic Drug Monitoring of Aminoglycosides in the Treatment of Multidrug-Resistant Tuberculosis

2017 ◽  
Vol 61 (3) ◽  
Author(s):  
R. van Altena ◽  
J. A. Dijkstra ◽  
M. E. van der Meer ◽  
J. F. Borjas Howard ◽  
J. G. W. Kosterink ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Body Weight ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Controlled Trial ◽  
Successful Outcome ◽  
Prolonged Treatment ◽  
Therapeutic Drug ◽  
Tb Treatment ◽  
Resistant Tuberculosis

ABSTRACT Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our tuberculosis center, we used therapeutic drug monitoring (TDM) targeting preset pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of tuberculosis (TB) patients treated with amikacin or kanamycin in the period from 2000 to 2012. Patients with culture-confirmed multiresistant or extensively drug-resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study. Clinical data, including maximum concentration (C max), C min, and audiometry data, were extracted from the patients' medical charts. A total of 80 patients met the inclusion criteria. The mean weighted C max/MIC ratios obtained from 57 patients were 31.2 for amikacin and 12.3 for kanamycin. The extent of hearing loss was limited and correlated with the cumulative drug dose per kg of body weight during daily administration. At follow-up, 35 (67.3%) of all patients had successful outcome; there were no relapses. At a median dose of 6.5 mg/kg, a correlation was found between the dose per kg of body weight during daily dosing and the extent of hearing loss in dB at 8,000 Hz. These findings suggest that the efficacy at this lower dosage is maintained with limited toxicity. A randomized controlled trial should provide final proof of the safety and efficacy of TDM-guided use of aminoglycosides in MDR-TB treatment.

scholarly journals Early Therapeutic Drug Monitoring for Isoniazid and Rifampin among Diabetics with Newly Diagnosed Tuberculosis in Virginia, USA

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Scott K. Heysell ◽  
Jane L. Moore ◽  
Debbie Staley ◽  
Denise Dodge ◽  
Eric R. Houpt
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Prolonged Treatment ◽  
Therapeutic Drug ◽  
Diabetic Patients ◽  
Newly Diagnosed ◽  
Tb Treatment ◽  
A Value ◽  
Drug Concentrations

Slow responders to tuberculosis (TB) treatment in Virginia have prolonged treatment duration and consume more programmatic resources. Diabetes is an independent risk factor for slow response and low serum anti-TB drug concentrations. Thus, a statewide initiative of early therapeutic drug monitoring (TDM) for isoniazid and rifampin at 2 weeks after TB treatment was piloted for all diabetics with newly diagnosed TB. During the period of early TDM, 12/01/2011–12/31/2012, 21 diabetics hadC2 hrconcentrations performed and 16 (76%) had a value below the expected range for isoniazid, rifampin, or both. Fifteen had follow-up concentrations after dose adjustment and 12 (80%) increased to within the expected range (including all for rifampin). Of 16 diabetic patients with pulmonary TB that had early TDM, 14 (88%) converted their sputum culture to negative in <2 months. Early TDM for diabetics was operationally feasible, may speed response to TB therapy, and can be considered for TB programs with high diabetes prevalence.

scholarly journals Viral load Guided Immunosuppression after Lung Transplantation (VIGILung) – study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Jens Gottlieb ◽  
Alexander Reuss ◽  
Konstantin Mayer ◽  
Karin Weide ◽  
Carmen Schade-Brittinger ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Lung Transplantation ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Controlled Trial ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Randomized Controlled ◽  
Lung Transplant Recipients ◽  
Trough Levels

Abstract Background:Immunosuppression including high dose calcineurin-inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with risk of graft-injury.Adaptation of CNI-based immunosuppression by monitoring of Torque-Teno-Virus (TTV) – a latent nonpathogenic DNA virus, measured in whole blood in addition to conventional therapeutic drug monitoring may reduce toxicity of immunosuppression with similar efficacy.Methods/Design:An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 - 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (Arm 1: Immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (Arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements on renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss and infections.Discussion:The results of this randomized controlled trial may reduce toxicity of immunosuppression after lung transplantation while maintaining efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.Trial registration: ClinicalTrials.gov, NCT04198506. Registered 12 December 2019, https://www.clinicaltrials.gov/show/NCT04198506

scholarly journals Population Pharmacokinetics of Gentamicin and Dosing Optimization for Infants

2014 ◽  
Vol 59 (1) ◽  
pp. 482-489 ◽  
Author(s):  
Susanna E. Medellín-Garibay ◽  
Aída Rueda-Naharro ◽  
Silvia Peña-Cabia ◽  
Benito García ◽  
Silvia Romano-Moreno ◽  
...  
Keyword(s):  
Body Weight ◽  
Therapeutic Drug Monitoring ◽  
Population Pharmacokinetics ◽  
Drug Monitoring ◽  
Pediatric Population ◽  
External Validation ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Time Data ◽  
Age Related

ABSTRACTThe aim of this study was to characterize and validate the population pharmacokinetics of gentamicin in infants and to determine the influences of clinically relevant covariates to explain the inter- and intraindividual variabilities associated with this drug. Infants receiving intravenous gentamicin and with routine therapeutic drug monitoring were consecutively enrolled in the study. Plasma concentration and time data were retrospectively collected from 208 infants (1 to 24 months old) of the Hospital Universitario Severo Ochoa (Spain), of whom 44% were males (mean age [± standard deviation], 5.8 ± 4.8 months; mean body weight, 6.4 ± 2.2 kg). Data analysis was performed with NONMEM 7.2. One- and two-compartment open models were analyzed to estimate the gentamicin population parameters and the influences of several covariates. External validation was carried out in another population of 55 infants. The behavior of gentamicin in infants exhibits two-compartment pharmacokinetics, with total body weight being the covariate that mainly influences central volume (Vc) and clearance (CL); this parameter was also related to creatinine clearance. Both parameters are age related and different from those reported for neonatal populations. On the basis of clinical presentation and diagnosis, a once-daily dosage regimen of 7 mg/kg of body weight every 24 h is proposed for intravenous gentamicin, followed by therapeutic drug monitoring in order to avoid toxicity and ensure efficacy with minimal blood sampling. Gentamicin pharmacokinetics and disposition were accurately characterized in this pediatric population (infants), with the parameters obtained being different from those reported for neonates and children. These differences should be considered in the dosing and therapeutic monitoring of this antibiotic.

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