Cefepime therapeutic drug monitoring: Evaluation of agreement between peripheral and central venous blood sampling

ABSTRACTInvasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P= 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling.

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Peripheral versus central venous blood sampling does not influence the assessment of platelet activation in cirrhosis

Platelets ◽

10.1080/09537104.2021.2007868 ◽

2022 ◽

pp. 1-8

Author(s):

Ksenia Brusilovskaya ◽

Benedikt Simbrunner ◽

Silvia Lee ◽

Beate Eichelberger ◽

David Bauer ◽

...

Keyword(s):

Platelet Activation ◽

Venous Blood ◽

Blood Sampling ◽

Central Venous ◽

Central Venous Blood ◽

Venous Blood Sampling

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Therapeutic Drug Monitoring of Methotrexate on the Pediatric Oncology Ward: Can Blood Sampling From Central Venous Accesses Substitute for Capillary Finger Punctures?

Therapeutic Drug Monitoring ◽

10.1097/ftd.0b013e318063e5e5 ◽

2007 ◽

Vol 29 (4) ◽

pp. 447-451 ◽

Cited By ~ 10

Author(s):

Carina Ritzmo ◽

Freidoun Albertioni ◽

Karin Cosic ◽

Stefan S??derh??ll ◽

Staffan Eksborg

Keyword(s):

Therapeutic Drug Monitoring ◽

Pediatric Oncology ◽

Drug Monitoring ◽

Blood Sampling ◽

Therapeutic Drug ◽

Central Venous ◽

Oncology Ward

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Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for therapeutic drug monitoring in patients with inflammatory bowel disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab128 ◽

2021 ◽

Author(s):

Desmond Chee ◽

Rachel Nice ◽

Ben Hamilton ◽

Edward Jones ◽

Sarah Hawkins ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Blood Sampling ◽

Therapeutic Drug ◽

Linear Regression Models ◽

Cross Sectional ◽

Immune Mediated ◽

Low Volume ◽

Antibody Levels ◽

At Home

Abstract Background & Aims Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) compared to conventional venepuncture. Methods We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. Results Therapeutic drug monitoring requests for adalimumab (96.5 [70.5 - 106] per week to 52 [33.5 - 57.0], p < 0.001) but not infliximab (184.5 [161.2 - 214.2] to 161 [135 – 197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding six months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab, and ustekinumab drug, and anti-adalimumab and -infliximab antibody levels. The median (IQR) volume of serum obtained using intracapillary sampling was 195µL (130-210). More than 87% (90/103) patients agreed that intracapillary testing was easy and 69% (71/103) preferred it to conventional venepuncture. In routine care, 75.3% (58/77) patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. Conclusions Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.

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Saliva Versus Blood Sampling for Therapeutic Drug Monitoring in Children

Therapeutic Drug Monitoring ◽

10.1097/00007691-199410000-00001 ◽

1994 ◽

Vol 16 (5) ◽

pp. 437-443 ◽

Cited By ~ 43

Author(s):

Rafael Gorodischer ◽

Pascale Burtin ◽

Paul Hwang ◽

Mitchell Levine ◽

Gideon Koren

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Blood Sampling ◽

Therapeutic Drug

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Impact of Pharmacist Scheduling of Blood-Sampling Times for Therapeutic Drug Monitoring

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/45.2.380 ◽

1988 ◽

Vol 45 (2) ◽

pp. 380-382 ◽

Cited By ~ 1

Author(s):

Peter J. Ambrose ◽

Michael Nitake ◽

Carl W. Kildoo

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Blood Sampling ◽

Therapeutic Drug ◽

Sampling Times

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Real-life isoniazid and rifampicin plasma concentrations in children: a tool for therapeutic drug monitoring of tuberculosis

BMC Infectious Diseases ◽

10.1186/s12879-021-06764-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chiara Tersigni ◽

Giulia Boiardi ◽

Lorenzo Tofani ◽

Elisabetta Venturini ◽

Carlotta Montagnani ◽

...

Keyword(s):

Plasma Concentration ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Venous Blood ◽

Plasma Concentrations ◽

Age Groups ◽

Real Life ◽

Therapeutic Drug ◽

Blood Samples ◽

Drug Concentrations

Abstract Background Low plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to promote tailored treatments for both child and adult patients. The main aim of the study was to evaluate serum concentrations of isoniazid (INH) and rifampicin (RIF) and to investigate reasons for sub-therapeutic plasma concentrations in order to fix dosages. Methods Children with TB were prospectively enrolled from January to August 2019. Two venous blood samples were collected (the first at least 15 days after the beginning of antitubercular treatment, and the second between 1 and 8 weeks later). Plasma concentrations were determined by a validated high-performance liquid chromatography method. Results In all, 45 children were included. Seventy blood samples for INH plasma concentration were collected between 120 and 240 min after drug intake. Adjusting for dose (mg/kg/day) and time of INH administration, when considering three different age groups (≤ 2 years, 2–12 years, > 12 years), a statistically significant lower INH plasma concentration was observed in younger children compared to the older age groups in the multivariate analysis (p < 0.001 and p < 0.001). A total of 68 blood samples were evaluated for RIF concentrations. Both for INH and RIF a statistically significant lower plasma concentration was also observed in adolescents (p < 0.001). Fifteen children (15/45, 33%) presented drug concentrations under the referral therapeutic range. Conclusions Based on our findings, monitoring patients’ drug plasma concentrations in children under 2 years of age and in adolescents can make treatment more patient-tailored.

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Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol

Cancers ◽

10.3390/cancers13246281 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6281

Author(s):

Anna Mc Laughlin ◽

Eduard Schmulenson ◽

Olga Teplytska ◽

Sebastian Zimmermann ◽

Patrick Opitz ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Anticancer Drugs ◽

Drug Monitoring ◽

Drug Exposure ◽

Plasma Concentrations ◽

Blood Sampling ◽

Therapeutic Drug ◽

Study Phase ◽

Blood Samples ◽

Drug Concentrations

Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.

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788. Therapeutic Drug Monitoring for Pyrazinamide During Tuberculosis Treatment: What Is the Diagnostic Accuracy?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.795 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S282-S283

Author(s):

Ginger Anderson ◽

Christopher Vinnard

Keyword(s):

High Risk ◽

Therapeutic Drug Monitoring ◽

Diagnostic Accuracy ◽

Roc Curve ◽

Drug Monitoring ◽

Sparse Sampling ◽

Blood Sampling ◽

Successful Outcome ◽

Therapeutic Drug ◽

Blood Levels

Abstract Background Pyrazinamide (PZA) is a key drug for both drug-sensitive and drug-resistant tuberculosis (TB). Patients co-infected with TB and human immunodeficiency virus (HIV) are more likely to have low blood levels of PZA, associated with inferior outcomes. Therapeutic drug monitoring (TDM) with sparse blood sampling is recommended for high-risk groups, including HIV/TB patients, but the accuracy is uncertain. We performed a pharmacokinetic (PK) simulation study to estimate the diagnostic accuracy of TDM for PZA among HIV/TB patients. Methods We recently performed a population PK study among HIV/TB patients in Botswana, identifying a 1-compartment model with first-order elimination. In the current work, we performed an intensive PK simulation (n = 10,000 patients) to determine the accuracy of sparse blood sampling in identifying HIV/TB patients with low PZA blood levels, as defined by the AUC in a dosing interval (AUC0-24) predictive of successful outcome (363 mg*hr/L). PZA dosing followed WHO guidelines with weight-based dosing bands. In secondary analysis, we examined the peak concentration (Cmax) target predictive of 2-month sputum conversion (58 mg/L). To determine the accuracy of sparse sampling (2- and 6-hours), we performed receiver-operating-characteristic (ROC) analysis, with bootstrapping (n = 1,000) for 95% confidence intervals (CI), and defined accuracy as the area under the ROC curve. Results In this simulation PK study of PZA among HIV/TB patients, the PZA AUC0-24 fell below the target in 29% of patients, while in 71% of patients the PZA Cmax was below the target. For the AUC0-24 target, the area under the ROC curve was 0.69 (95% CI 0.68–0.70) for a single 2-hour sample, increasing to 0.75 (95% CI 0.74–0.76) for 2- and 6-hour samples. For the Cmax target, diagnostic accuracy was similar for a 2-hour sample (0.87, 95% CI 0.86–0.87) and 2- and 6-hour samples (0.88, 95% CI 0.88–0.89). Conclusion We observed modest diagnostic accuracy of TDM for identifying in silico HIV/TB patients with low PZA AUC0-24, and higher accuracy for low Cmax. By identifying diagnostic performance characteristics of sparse sampling strategies, including optimal cut-offs, the ROC framework can support wider implementation of TDM in high-risk TB populations. Disclosures All authors: No reported disclosures.

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