Unexpectedly high inter‐ and intrapatient variability of Ganciclovir levels in children

Vethamuthu, Jennifer; Feber, Janusz; Chretien, Ann; Lampe, Dagmar; Filler, Guido

doi:10.1111/j.1399-3046.2006.00669.x

Cited by 46 publications

(31 citation statements)

References 26 publications

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interindividual heterogeneity has previously been described 15 and suggests the need for drug monitoring, particularly in the case of viral failure or toxicity. 16 The need for routine drug monitoring is less clear due to the lack of established PK-PD parameters for preemptive strategy in pediatric practice.

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confidence: 88%

Rising Rates of Macrolide-Resistant Mycoplasma pneumoniae in the Central United States

Yamada

Buller

Bledsoe

et al. 2012

Pediatric Infectious Disease Journal

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Macrolide-resistant Mycoplasma pneumoniae is widespread in Asia, and severe cases of pneumonia have been described in children. Little information is available about the resistance pattern in the United States. We collected respiratory samples from 49 patients with Mycoplasma infection in the central United States between 2007 and 2010. We found a macrolide resistance rate of 8.2%. Resistance should be considered when patients with M. pneumoniae infection do not have a satisfactory response to macrolides. Alternative antibiotics include tetracyclines or fluoroquinolones.

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confidence: 88%

Rising Rates of Macrolide-Resistant Mycoplasma pneumoniae in the Central United States

Yamada

Buller

Bledsoe

et al. 2012

Pediatric Infectious Disease Journal

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“…Studies have shown significant pharmacokinetic variability depending on the child’s age, weight, and creatinine clearance, suggesting that pediatric dosing should take into account those parameters and may need pharmacokinetic monitoring (10, 11). Vaudry et al (12) recently reported good tolerance of oral valganciclovir in a pediatric solid-organ transplant cohort (n=63) at doses based on body surface area and creatinine clearance: 11% of patients were reported as having serious adverse events, most commonly hematologic laboratory abnormalities, and no patients were found to have CMV disease.…”

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confidence: 99%

24 Weeks of Valganciclovir Prophylaxis in Children After Renal Transplantation: A 4-Year Experience

et al. 2011

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Background Cytomegalovirus (CMV) is the most common opportunistic infection after solid-organ transplant. Valganciclovir prophylaxis significantly reduces disease, but limited data are available on its use in children. Recently, an increase in delayed-onset CMV disease has been noted with some arguing that longer prophylaxis may decrease late-onset disease. Methods Single-center, retrospective analysis of pediatric renal transplant patients receiving 24 weeks valganciclovir prophylaxis (15 mg/kg/day, maximum 900 mg/day) from January 2004 to December 2008, aiming to measure the incidence of CMV disease and toxicity of valganciclovir. Results We enrolled 111 patients, 60% males, 46% African Americans, and median age at transplant 14.5 years (range 1.4–20.4 years). Sixty-nine percent of donors and 44% of recipients were seropositive pretransplant. Median duration of valganciclovir use was 5.9 months (range 0.5–24 months). CMV viremia and disease occurred in 27% and 4.5%, respectively. All patients with disease presented after prophylaxis ended and all were D+/R−. Thymoglobulin use (P=0.04) and positive donor CMV status (P=0.02) were associated with a higher risk of CMV viremia. Twenty-four percent had hematologic toxicity directly associated with valganciclovir. Conclusions Valganciclovir use in children was effective as prophylaxis against CMV disease; no children at our institution developed disease while on therapy. Our regimen of 24 weeks of prophylaxis was associated with a lower rate of late-onset disease than previous reports with 12-week regimens. Further controlled studies should be considered to compare longer versus shorter periods of prophylaxis and dose reductions and their impact on prevention of late-onset disease, resistance, cost, and toxicity.

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“…Although a significant difference was only seen between median peak levels in those aged <6 months old compared with adults, the lowest median levels were actually noted in the 5-18 year age group. Low trough levels have been previously reported in a small study of paediatric transplant patients, with levels <0.5 mg/L being significantly more common in younger patients [12]. The observation that fewer babies <28 days had trough levels <0.5 mg/L compared with the overall age group <6 months would be in keeping with the almost exclusive renal excretion of GCV and the known immature renal function Peak levels were also in keeping with those reported in other clinical studies and were well above the MIC and IC 50 observed in vitro [6,7].…”

Section: Discussionmentioning

confidence: 58%

“…Given that such algorithms do not currently exist for i.v. GCV, and the wide interpatient and intrapatient variability reported in younger children when weight alone is used for dosing, TDM may be of particular benefit to guide GCV dosing in the paediatric age group [12]. We propose that TDM should be considered in M a n u s c r i p t M a n u s c r i p t A c c e p t e d M a n u s c r i p t b Includes those babies <28 days of age.…”

Section: Discussionmentioning

confidence: 99%

Ganciclovir treatment in children: evidence of subtherapeutic levels

Luck

Lovering

Griffiths

2011

International Journal of Antimicrobial Agents

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Ganciclovir (GCV) is used to treat babies and older children with cytomegalovirusrelated disease. Treatment courses are generally derived from adult studies and there are few data relating to the pharmacokinetics of GCV in children. In adults, low trough GCV levels have been associated with treatment failure and virological resistance. Data regarding suitable drug levels for use in therapeutic drug monitoring (TDM) in the paediatric age group do not currently exist. In this study, anonymised data for all GCV levels sent to the UK Antibiotic Reference Laboratory from 1 November 1999 to 31 March 2007 were reviewed and analysed by age group. In total, 339 specimens were received from 129 patients; 192 specimens were from patients aged <18 years. There were significantly more trough GCV levels <0.5 mg/L in those aged <6 months and 6-12 months compared with adults (64.8% and 53.9%, respectively, vs. 15.9%; P < 0.001). Those aged 5-18 years also had significantly more trough samples with levels <0.5 mg/L (80.0% vs. 15.9%; P < 0.001). There was a significant difference between median peak GCV levels in those aged <6 months and adults (4.8 mg/L vs. 5.7 mg/L, respectively; P = 0.047). In conclusion, GCV levels associated with treatment failure and considered subtherapeutic in adult patients were observed more often in specimens from paediatric patients. These lower levels may have implications for dosing in the paediatric age group, particularly during periods of rapid change in renal function such as the neonatal period.Clinicians should be aware of the relatively low drug exposure noted in this study and consider TDM and increasing drug dose where virological response is poor.

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Unexpectedly high inter‐ and intrapatient variability of Ganciclovir levels in children

Cited by 46 publications

References 26 publications

Rising Rates of Macrolide-Resistant Mycoplasma pneumoniae in the Central United States

Rising Rates of Macrolide-Resistant Mycoplasma pneumoniae in the Central United States

24 Weeks of Valganciclovir Prophylaxis in Children After Renal Transplantation: A 4-Year Experience

Ganciclovir treatment in children: evidence of subtherapeutic levels

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