Relationship between vancomycin dosage and serum trough vancomycin concentrations in pediatric patients with cystic fibrosis

Durham, Spencer H.; Garza, Kimberly B.; Eiland, Lea S.

doi:10.2146/ajhp150605

Cited by 10 publications

(8 citation statements)

References 15 publications

(13 reference statements)

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“…Previous studies have attempted to fit dose against trough without any transformations, resulting in a poor fit. In the current study, fitting the raw data of dose (mg/kg) against trough (μg/mL) resulted in an r 2 of 0.0005 and also indicated a very poor linear fit, in agreement with previous results . To improve the linear fit, regression models were developed to obtain prediction models with better statistical properties…”

Section: Resultssupporting

confidence: 77%

“…Vancomycin is a key antibiotic used in the treatment of multiple conditions including cystic fibrosis (CF). Obtaining the proper trough concentration is a major goal to achieve optimal patient outcome, which is complicated by increasing antimicrobial resistance. In the case of children, there are also no guidelines on therapeutic monitoring of vancomycin from the Infectious Disease Society of America.…”

mentioning

confidence: 99%

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Prediction of Vancomycin Dose for Recommended Trough Concentrations in Pediatric Patients With Cystic Fibrosis

Amin

Guttmann

Harris

et al. 2018

The Journal of Clinical Pharma

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Vancomycin is a key antibiotic used in the treatment of multiple conditions including infections associated with cystic fibrosis and methicillin-resistant Staphylococcus aureus. The present study sought to develop a model based on empirical evidence of optimal vancomycin dose as judged by clinical observations that could accelerate the achievement of desired trough level in children with cystic fibrosis. Transformations of dose and trough were used to arrive at regression models with excellent fit for dose based on weight or age for a target trough. Results of this study indicate that the 2 proposed regression models are robust to changes in age or weight, suggesting that the daily dose on a per-kilogram basis is determined primarily by the desired trough level. The results show that to obtain a vancomycin trough level of 20 μg/mL, a dose of 80 mg/kg/day is needed. This analysis should improve the efficiency of vancomycin usage by reducing the number of titration steps, resulting in improved patient outcome and experience.

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Section: Resultssupporting

confidence: 77%

mentioning

confidence: 99%

Prediction of Vancomycin Dose for Recommended Trough Concentrations in Pediatric Patients With Cystic Fibrosis

Amin

Guttmann

Harris

et al. 2018

The Journal of Clinical Pharma

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“…111,112 Achieving therapeutic vancomycin levels in pediatric CF patients, especially those younger than 12 years, requires high doses with high patient-topatient variability. 113,114 A study evaluating change in lung function during exacerbations did not find a correlation between change in FEV 1 and vancomycin serum levels or dosages. 115 Addition of rifampin for synergy and its excellent penetration into mucus membranes is frequently used in non-CF decolonization protocols.…”

Section: Adaptation and Persistence Of Mrsamentioning

confidence: 99%

“…Even outside of CF, the clinical implications of MIC creep remain poorly defined given heterogeneity in epidemiologic reports and study populations . Achieving therapeutic vancomycin levels in pediatric CF patients, especially those younger than 12 years, requires high doses with high patient‐to‐patient variability . A study evaluating change in lung function during exacerbations did not find a correlation between change in FEV 1 and vancomycin serum levels or dosages …”

Section: Antibiotic Choices For Mrsa Infectionsmentioning

confidence: 99%

Biology and management of methicillin resistantStaphylococcus aureusin cystic fibrosis

Akil

Muhlebach

2018

Pediatric Pulmonology

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Staphylococcus aureus is one of the earliest bacteria isolated from the respiratory tract in people with cystic fibrosis (CF). Its methicillin resistant form, MRSA, has gained attention due to the rapid increase in the last decades and worse outcomes with chronic infection. In the United States, prevalence of MRSA in CF is around 27%, but is much lower (3-18%) in most other countries. Methicillin is typically genetically encoded by the mecA gene, which encodes for an alternative penicillin binding protein (PRBa). This PRBa has low affinity to β-lactams, thereby enabling growth of S. aureus in the presence of penicillinase resistant penicillins and most other β-lactams. Non-mecA positive strains of MRSA, so-called borderline resistant (BORSA) have also been described. In addition to production of toxins, the virulence of S. aureus is conferred by its adaptability allowing persistence in face of antibiotic therapies and host defense. These adaptive growth mechanisms include small colony variants, biofilms, and growth under anaerobic conditions. Several reports have described successful eradication of MRSA, yet only two randomized trials of eradication during early infection have been conducted. A list of MRSA specific antibiotics with dosing relevant to CF patients is presented here. Many of these require special dosing in people with CF. Novel antibiotics are in trials for skin and soft tissue infections and it is unclear if and when those might be available for lung infections. Thus the best strategies for MRSA would be primary prevention.

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“…Attaining target serum concentrations with IIV in children requires larger mg/kg doses and more frequent dosing intervals as compared to adults and, in some cases, is not achievable even with doses as high as 100 mg/kg/day. 14,15 In adults, use of CIV following an initial loading dose shortens the time to therapeutic concentration achievement, demonstrates longer duration above target concentrations, and reduces toxicity, particularly among critically ill patients and those with serious infections. [16][17][18][19][20][21][22][23][24] Continuous administration avoids the transiently elevated serum peak concentrations that occur with IIV dosing, which results in smaller total daily doses that are needed to achieve target serum concentrations.…”

Section: Introductionmentioning

confidence: 99%

Continuous Infusion Vancomycin in Pediatric Patients: A Critical Review of the Evidence

Girand¹

2020

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVE To evaluate the use of continuous infusion vancomycin in pediatric patients. DATA SOURCES AND STUDY SELECTION PubMed, Cochrane Library, International Pharmaceutical Abstracts, and Google Scholar were searched to identify relevant published articles (1977 to November 2019) using the following search terms: vancomycin, neonates, pediatrics, infusion, continuous, administration, children, nephrotoxicity, pharmacokinetics, and pharmacodynamics. All English-language primary references that evaluated continuous infusion vancomycin in pediatric patients were included in this review. DATA SYNTHESIS Vancomycin is typically administered with intermittent infusions, but continuous infusion is an alternative delivery method used to improve achievement of target serum concentrations. Fifteen articles were reviewed that evaluated continuous infusion vancomycin in pediatric patients. Study data were heterogeneous with limited evidence to support improved clinical or microbiologic outcomes as compared with intermittent dosing. Potential benefits and limitations of continuous infusions are discussed. CONCLUSIONS Currently available evidence is lacking to support routine implementation of continuous infusion vancomycin in pediatric patients. However, it is a therapeutic option in certain clinical conditions and could be beneficial for individuals with serious Gram-positive infections where rapid achievement of target serum concentrations is critical. Continuous infusions may also benefit individuals who do not achieve target concentrations or who experience significant red man syndrome with traditional dosing, particularly when high daily doses are required. Optimal dosing and ideal target serum concentrations have not been established and may vary for different populations. Future prospective randomized clinical trials should be performed to identify optimal dosing and monitoring regimens and determine comparative safety and efficacy with traditional intermittent dosing in various pediatric populations.

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Relationship between vancomycin dosage and serum trough vancomycin concentrations in pediatric patients with cystic fibrosis

Cited by 10 publications

References 15 publications

Prediction of Vancomycin Dose for Recommended Trough Concentrations in Pediatric Patients With Cystic Fibrosis

Prediction of Vancomycin Dose for Recommended Trough Concentrations in Pediatric Patients With Cystic Fibrosis

Biology and management of methicillin resistantStaphylococcus aureusin cystic fibrosis

Continuous Infusion Vancomycin in Pediatric Patients: A Critical Review of the Evidence

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