Therapeutic drug monitoring guided fluconazole therapy in a patient with cholangitis sepsis

Candida and other fungal species play an increasing role in nosocomial infections, including cholangitis and cholangiosepsis. Early diagnosis and prompt treatment are essential in successful patient outcomes. Fluconazole is an antifungal of choice in fluconazole-sensitive Candida infections. Little information is known about the fluconazole biliary excretion. Decreased tissue penetration may be one of the possible causes of treatment failure. Due to favorable pharmacokinetics, therapeutic drug monitoring of this antifungal has not been recommended routinely. In the presented case we report the successful therapeutic drug monitoring-guided fluconazole treatment in a patient with cholangitis and cholangiosepsis caused by fluconazole-sensitive Candida spp.

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1737. Impact of Therapeutic Drug Monitoring (TDM) of Azole Prophylaxis in Lung Transplant Recipients on the Development of Positive Fungal Events

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1600 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S636-S636

Author(s):

Anooj Shah ◽

Carly D’Agostino ◽

Kathleen Cunningham ◽

Clare Kane ◽

Michael G Ison ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Lung Transplant ◽

Study Groups ◽

Fungal Species ◽

Therapeutic Drug ◽

Transplant Recipients ◽

Lung Transplant Recipients ◽

Index Value ◽

The Impact

Abstract Background The utility and clinical impact of therapeutic drug monitoring (TDM) of prophylactic azole antifungals in lung transplant recipients is not well described. The objective of this study was to investigate the impact of TDM of azole prophylaxis in lung transplant recipients on the development of positive fungal events. Methods A retrospective analysis was performed on 47 lung transplant recipients between 2013 and 2018 at Northwestern Memorial Hospital. A positive fungal event was defined as fungal species on BAL culture and/or positive BAL Aspergillus galactomannan (GM) with an index value ≥1.0. Study groups were defined based on attainment of therapeutic trough levels after initiation of oral therapy (therapeutic if posaconazole level ≥0.7 μg/mL or voriconazole ≥1–5.5 μg/mL, subtherapeutic if ≥2 consecutive levels of posaconazole <0.7 μg/mL or voriconazole <1 μg/mL after initial dose increase). Results There were no differences in baseline characteristics (Figure 1). There were a total of 11 fungal events with 3 (12.0%) occurring in the therapeutic cohort and 8 (36.4%) in those subtherapeutic (P = 0.08). In the 5 patients with a positive GM, the mean index was 2.02 ± 0.95. 7/30 (23.3%) of patients on posaconazole had a fungal event, with 2/7 (28.6%) requiring treatment at the time of event. For patients on voriconazole, 4/17 (23.5%) had a fungal event, with 1/4 (25.0%) requiring treatment. Mean time to fungal event was 164.5 ± 8.9 days vs. 135.9 ± 13.7 days in the therapeutic and subtherapeutic group, respectively (P = 0.05). All patients on posaconazole suspension who experienced a fungal event were subtherapeutic (3/3, 100%) compared with the majority of patients on posaconazole delayed release (DR) tablets who achieved therapeutic levels (17/22, 77.3%). Mean posaconazole trough level observed in the patients receiving DR tablet was 2.15 ± 0.95 μg/mL. Conclusion There was an association between two consecutive subtherapeutic azole prophylaxis levels and positive fungal events indicating a role for TDM in lung transplant recipients. Time to fungal event post-transplant was shorter in subtherapeutic patients. As anticipated, the use of posaconazole suspension resulted in subtherapeutic levels. This study presents an opportunity for further research of the impact of TDM on clinical outcomes to optimize patient care. Disclosures All authors: No reported disclosures.

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What Are the Current Approaches to Optimising Antimicrobial Dosing in the Intensive Care Unit?

Pharmaceutics ◽

10.3390/pharmaceutics12070638 ◽

2020 ◽

Vol 12 (7) ◽

pp. 638

Author(s):

Ming G. Chai ◽

Menino O. Cotta ◽

Mohd H. Abdul-Aziz ◽

Jason A. Roberts

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Therapeutic Drug Monitoring ◽

Patient Outcomes ◽

Drug Monitoring ◽

Point Of Care ◽

Statistical Modelling ◽

Therapeutic Drug ◽

Dosing Regimens ◽

Point Of Care System

Antimicrobial dosing in the intensive care unit (ICU) can be problematic due to various challenges including unique physiological changes observed in critically ill patients and the presence of pathogens with reduced susceptibility. These challenges result in reduced likelihood of standard antimicrobial dosing regimens achieving target exposures associated with optimal patient outcomes. Therefore, the aim of this review is to explore the various methods for optimisation of antimicrobial dosing in ICU patients. Dosing nomograms developed from pharmacokinetic/statistical models and therapeutic drug monitoring are commonly used. However, recent advances in mathematical and statistical modelling have resulted in the development of novel dosing software that utilise Bayesian forecasting and/or artificial intelligence. These programs utilise therapeutic drug monitoring results to further personalise antimicrobial therapy based on each patient’s clinical characteristics. Studies quantifying the clinical and cost benefits associated with dosing software are required before widespread use as a point-of-care system can be justified.

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Abstract P200: Computerized Clinical Decision Support Systems for Therapeutic Drug Monitoring and Dosing: A Decision Maker--Researcher Partnership Systematic Review

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.4.suppl_2.ap200 ◽

2011 ◽

Vol 4 (suppl_2) ◽

Author(s):

Robby Nieuwlaat ◽

Stuart J Connolly ◽

Jean A MacKay ◽

Lorraine Weise-Kelly ◽

Tamara Navarro ◽

...

Keyword(s):

Systematic Review ◽

Therapeutic Drug Monitoring ◽

Decision Maker ◽

Patient Outcomes ◽

Vitamin K ◽

Drug Monitoring ◽

Vitamin K Antagonist ◽

Therapeutic Drug ◽

Process Of Care ◽

Cluster Randomization

Background Optimization of the return on investments in information technology innovations requires that current best evidence be considered for an effect on care processes and health outcomes. Computerized clinical decisions support systems (CCDSSs) might improve therapeutic drug monitoring and dosing (TDMD) by providing patient-tailored clinical recommendations. We summarized current evidence from randomized controlled trials (RCTs) for the effect of CCDSSs on TDMD. Methods A decision-maker - researcher partnership systematic review was performed to optimize the practical implementation of results. Studies from a previous review on the effect of CCDSSs (Garg AX, 2005) were included if they addressed TDMD and were RCTs. Additional RCTs were sought until January 2010 in MEDLINE, EMBASE, Evidence-Based Medicine Reviews and Inspec databases. RCTs assessing the effect of a CCDSS on process of care or patient outcomes were selected by pairs of independent reviewers. Results In total, 33 RCTs were identified that assessed the effect of a CCDSS on management of vitamin K antagonists (14), insulin (6), theophylline/aminophylline (4), aminoglycosides (3), digoxin (2), lidocaine (1), or as part of a multifaceted approach (3). All studies combined enrolled 24,627 patients; 13,219 were in the largest study, and only 6 other studies enrolled over 500 patients. Most studies were performed in one center (63%) and cluster randomization, of either clinics or physicians, was rarely used (18%). CCDSSs were usually stand-alone systems (76%) primarily used by physicians (85%). Overall, 18 of 30 studies (60%) showed an improvement in the process of care and 4 of 19 (21%) an improvement in patient outcomes. All evaluable studies assessing insulin dosing for glycemic control showed an improvement. In meta-analysis, CCDSSs for vitamin K antagonist dosing improved the time that patients spent in the therapeutic range by 6.1% (95% confidence interval: 0.46-11.83; p=0.03). Conclusions CCDSSs have potential for improving process of care for TDMD, specifically insulin and vitamin K antagonist dosing, but effects on patient outcomes were uncertain. More potent CCDSSs are needed and should be evaluated using cluster randomization, primarily assessing patient outcomes.

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Towards precision medicine: Therapeutic drug monitoring–guided dosing of vancomycin and β-lactam antibiotics to maximize effectiveness and minimize toxicity

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxaa128 ◽

2020 ◽

Vol 77 (14) ◽

pp. 1104-1112 ◽

Cited By ~ 4

Author(s):

Jaclyn A Cusumano ◽

Kenneth P Klinker ◽

Angela Huttner ◽

Megan K Luther ◽

Jason A Roberts ◽

...

Keyword(s):

Older Adults ◽

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Patient Outcomes ◽

Drug Monitoring ◽

Therapeutic Index ◽

Patient Specific ◽

Therapeutic Drug ◽

Specific Care ◽

Event Rates

Abstract Purpose The goal of this review is to explore the role of antimicrobial therapeutic drug monitoring (TDM), especially in critically ill, obese, and older adults, with a specific focus on β-lactams and vancomycin. Summary The continued rise of antimicrobial resistance prompts the need to optimize antimicrobial dosing. The aim of TDM is to individualize antimicrobial dosing to achieve antibiotic exposures associated with improved patient outcomes. Initially, TDM was developed to minimize adverse effects during use of narrow therapeutic index agents. Today, patient and organism complexity are expanding the need for precision dosing through TDM services. Alterations of pharmacokinetics and pharmacodynamics (PK/PD) in the critically ill, obese, and older adult populations, in conjunction with declining organism susceptibility, complicate attainment of therapeutic targets. Over the last decade, antimicrobial TDM has expanded with the emergence of literature supporting β-lactam TDM and a shift from monitoring vancomycin trough concentrations to monitoring of the ratio of area under the concentration (AUC) curve to minimum inhibitory concentration (MIC). PK/PD experts should be at the forefront of implementing precision dosing practices. Conclusion Precision dosing through TDM is expanding and is especially important in populations with altered PK/PD, including critically ill, obese, and older adults. Due to wide PK/PD variability in these populations, TDM is vital to maximize antimicrobial effectiveness and decrease adverse event rates. However, there is still a need for studies connecting TDM to patient outcomes. Providing patient-specific care through β-lactam TDM and transitioning to vancomycin AUC/MIC monitoring may be challenging, but with experts at the forefront of this initiative, PK-based optimization of antimicrobial therapy can be achieved.

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Therapeutic Drug Monitoring of Gentamicin in Patients with Bronchopneumonia: Cost Considerations and Patient Outcomes

Eurasian Journal of Medicine ◽

10.5152/eajm.2012.01 ◽

2012 ◽

Vol 44 (1) ◽

pp. 1-5

Author(s):

Hisham Elhag Ahmed Abdelrahim ◽

Ab Fatah Ab Rahman ◽

Mohamad Izham Mohamed Ibrahim

Keyword(s):

Therapeutic Drug Monitoring ◽

Patient Outcomes ◽

Drug Monitoring ◽

Therapeutic Drug

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Diagnose und Monitoring bei chronisch-entzündlicher Darmerkrankung

Therapeutische Umschau ◽

10.1024/0040-5930/a001002 ◽

2018 ◽

Vol 75 (5) ◽

pp. 316-328

Author(s):

Christian Ansprenger ◽

Emanuel Burri

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Morbus Crohn ◽

Therapeutic Drug ◽

Körperliche Untersuchung

Zusammenfassung. Die Diagnose und auch die Überwachung von chronisch entzündlichen Darmerkrankungen ruht auf mehreren Säulen: Anamnese, körperliche Untersuchung, Laborwerte (im Blut und Stuhl), Endoskopie, Histologie und Bildgebung. Die Diagnose kann nicht anhand eines einzelnen Befundes gestellt werden. In den letzten Jahren hat sich das Therapieziel weg von klinischen Endpunkten hin zu endoskopischen und sogar histologischen Endpunkten entwickelt. Für einige dieser neuen Therapieziele existiert allerdings noch keine allgemein gültige Definition. Regelmässige Endoskopien werden von Patienten schlecht toleriert, weshalb Surrogat-Marker wie Calprotectin untersucht wurden und eine gute Korrelation mit der mukosalen Entzündungsaktivität nachgewiesen werden konnte. Entsprechend zeigte sich bei Morbus Crohn eine Algorithmus-basierte Therapiesteuerung – unter anderem basierend auf Calprotectin – einer konventionellen Therapiesteuerung überlegen. Die Überwachung der medikamentösen Therapie («Therapeutic Drug Monitoring» [TDM]) ist ein zweites Standbein des Monitoring von chronisch entzündlichen Darmerkrankungen. Mit zunehmendem Einsatz vor allem der Biologika-Therapien wurden sowohl reaktives TDM (in Patienten mit klinischem Rezidiv) als auch proaktives TDM (in Patienten in Remission / stabiler Erkrankung) untersucht und haben (teilweise) Eingang in aktuelle Richtlinien gefunden. Zukünftige Studien werden die vorgeschlagenen Therapieziele besser definieren und den Nutzen der medikamentösen Therapieüberwachung auf den Krankheitsverlauf weiter untersuchen müssen.

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