Tobramycin Pharmacokinetics in Children with Febrile Neutropenia Undergoing Stem Cell Transplantation: Once‐Daily versus Thrice‐Daily Administration

Dupuis, L. Lee; Sung, Lillian; Taylor, Tracey; Abdolell, Mohamed; Allen, Upton; Doyle, John; Taddio, Anna

doi:10.1592/phco.24.6.564.34743

Cited by 12 publications

(21 citation statements)

References 37 publications

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“…There is no reliable evidence in transplant recipients for why the efficacy of teicoplanin is low. However, some reports exist about the pharmacokinetics of antibiotics in transplant recipients: (1) teicoplanin pharmacokinetics are modified in neutropenic patients compared to in healthy volunteers, indicated by the increased CL cr values [7], and (2) the fluid balance of patients undergoing stem cell transplantation is highly scrutinized, and these patients are likely to be very well hydrated in comparison to patients receiving chemotherapy [15]. This difference may account for the higher volume of distribution and lower C min .…”

Section: Discussionmentioning

confidence: 99%

Optimal Trough Concentration of Teicoplanin in Febrile Neutropenic Patients with Hematological Malignancy

et al. 2017

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Background: Teicoplanin is a glycopeptide antibiotic currently used for the treatment of methicillin-resistant Staphylococcus aureus. The need for therapeutic drug monitoring of teicoplanin has been increasingly highlighted as important. It is generally accepted that whereas a plasma trough concentration (C_min) of ≥10 mg/L is appropriate for the majority of infections, it should exceed 20 mg/L for severe infections. The target C_min of teicoplanin in patients with febrile neutropenia (FN) has not been reported. The aim of this study was to estimate the target C_min for the treatment of FN in patients with hematological malignancy. Methods: In this retrospective, single-center, observational cohort study, the records of 52 hospitalized patients with hematological malignancy who were treated with teicoplanin for FN due to bacteriologically documented or presumptive gram-positive infections were analyzed. Results: A significant difference in the first C_min of teicoplanin was observed between the response and nonresponse groups in patients with bacteremia. The areas under the receiver operating characteristic curves were 0.80 for clinical efficacy. The cut-off value of teicoplanin C_min on days 4-6 was 15.2 mg/L (sensitivity 80.0%, specificity 75.0%). Conclusions: The authors propose a target teicoplanin C_min of ≥15.2 mg/L for FN in patients with hematological malignancy.

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Section: Discussionmentioning

confidence: 99%

Optimal Trough Concentration of Teicoplanin in Febrile Neutropenic Patients with Hematological Malignancy

et al. 2017

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“…Children may experience febrile neutropenia as a result of cancer chemotherapy or transplantation immunosuppressive therapy. Depending on patient age, gentamicin or tobramycin administered at 6 to 10.5 mg/kg/day achieves C max /MIC ∼10, which is necessary to treat infections caused by P aeruginosa in these children . Age‐related differences in renal CL necessitate a higher milligram per kilogram dose of gentamicin for younger children with febrile neutropenia.…”

Section: Clinical Pharmacology Optimizing Bedside Care Of Pediatric Imentioning

confidence: 99%

“…Depending on patient age, gentamicin or tobramycin administered at 6 to 10.5 mg/kg/day achieves C max /MIC ß10, which is S117 necessary to treat infections caused by P aeruginosa in these children. [66][67][68] Age-related differences in renal CL necessitate a higher milligram per kilogram dose of gentamicin for younger children with febrile neutropenia. In addition, once-daily administration is preferred to thrice-daily administration to maximize efficacy and minimize nephrotoxicity and has the concomitant benefit of less nursing time for drug administration.…”

Section: Aminoglycosidesmentioning

confidence: 99%

Optimizing Antibiotic Drug Therapy in Pediatrics: Current State and Future Needs

Lê

Bradley

2018

The Journal of Clinical Pharma

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The selection of the right antibiotic and right dose necessitates clinicians understand the contribution of pharmacokinetic variability stemming from age‐related physiologic maturation and the pharmacodynamics to optimize drug exposure for clinical response. The complexity of selecting the right dose arises from the multiplicity of pediatric age groups, from premature neonates to adolescents. Body size and age (which relate to organ function) must be incorporated to optimize antibiotic dosing in this vulnerable population. In the effort to optimize and individualize drug dosing regimens, clinical pharmacometrics that incorporate population‐based pharmacokinetic modeling, Bayesian estimation, and Monte Carlo simulations are utilized as a quantitative approach to understanding and predicting the pharmacology and clinical and microbiologic efficacy of antibiotics. In addition, opportunistic study designs and alternative blood sampling strategies can serve as practical approaches to ensure successful conduct of pediatric studies. This review article examines relevant literature on optimization of antibiotic pharmacotherapy in pediatric populations published within the last decade. Specific pediatric antibiotic data, including beta‐lactam antibiotics, aminoglycosides, and vancomycin, are critically evaluated.

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“…Studies have also been conducted in special populations including pediatrics (Marik et al 1991 ;Nicolau et al 1997 ;Sung et al 2003 ;Mercado et al 2004 ;BhattMeht and Donn 2003 ;Dupuis et al 2004 ;Piekarczyk et al 2003 ;English et al 2004 ;Botha et al 2003 ;Kosalaraksa et al 2004 ;Knight et al 2003 ;Hansen et al 2003 ) cystic fi brosis (Moss 2001 ;Ramsey et al 1999 ) and pregnant populations (Bourget et al 1991 ) for determination of serum concentrations, as well as comparisons for effi cacy and safety between conventional administration and extended interval regimens. The majority of research has pointed to the international acceptance of extended interval dosing in infants and neonates including pre-term and full-term babies, although factors such as postnatal and gestational age and physiological status should be considered to determine patient-specifi c extended interval regimens.…”

Section: Clinical Usage and Application Of Pharmacodynamicsmentioning

confidence: 99%

Aminoglycosides

Bulik

Nightingale

Nicolau³

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Aminoglycoside antibiotics, bactericidal agents which irreversibly bind to the 30s ribosomal subunit and cause the inhibition of protein synthesis, have remained a vital aspect of the antimicrobial armamentarium since their introduction over 5 decades ago. Aminoglycosides are broad-spectrum agents with activity against a wide range of aerobic Gram-negative and Gram-positive pathogens, in addition to certain mycobacteria. Due to poor oral absorption, aminoglycosides are mainly administered as parenteral or inhalational agents. They demonstrate low protein binding and distribute freely into the interstitial or extracellular fl uid. These agents are eliminated from the body via glomerular fi ltration with 99% of a dose excreted unchanged in the urine. As such, the aminoglycosides require dose adjustment in the presence of renal dysfunction to avoid drug related toxicities. Understanding of the pharmacokinetic-pharmacodynamic properties of the aminoglycosides has allowed practitioners to utilize these agents with minimization of drug related toxicities. Pharmacodynamically optimized dosing of the aminoglycosides includes the administration of large doses once daily to both minimize the drug toxicities associated with elevated trough levels, and to optimize the postantibiotic eff ects observed with these agents. For patients who are not candidates for high-dose once daily dosing, these patients are administered aminoglycosides via the "traditional method" which involves multiple administrations of smaller doses every 8 hours. Overall, despite some drug related toxicities which can be overcome through the optimization of PK-PD, the aminoglycosides remain a vital component of a practitioner's arsenal against infection.

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Tobramycin Pharmacokinetics in Children with Febrile Neutropenia Undergoing Stem Cell Transplantation: Once‐Daily versus Thrice‐Daily Administration

Abstract: Children undergoing SCT who receive tobramycin every 24 hours should receive an initial dose based on age. Further validation of the proposed dosing guidelines is required.

Cited by 12 publications

References 37 publications

Optimal Trough Concentration of Teicoplanin in Febrile Neutropenic Patients with Hematological Malignancy

Optimal Trough Concentration of Teicoplanin in Febrile Neutropenic Patients with Hematological Malignancy

Optimizing Antibiotic Drug Therapy in Pediatrics: Current State and Future Needs

Aminoglycosides

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