Therapeutic drug monitoring of ganciclovir for postnatal cytomegalovirus infection in an extremely low birth weight infant: a case report

Abstract

BackgroundGanciclovir is a therapeutic choice for extremely premature infants with severe postnatal cytomegalovirus disease, but little is known about its optimal dose size and dosing interval for them.Case presentationWe treated an extremely premature female infant with postnatal cytomegalovirus infection with intravenous administration of ganciclovir since 49 days of life (postmenstrual age of 31 weeks). After ganciclovir treatment was initiated at a dose of 5 mg/kg every 12 h, cytomegalovirus loads in the peripheral blood were markedly decreased. However, since plasma ganciclovir trough level was too high, the interval was extended to every 24 h. Subsequently, the trough level and the estimated 12-h area under the concentration–time curve (AUC0–12) were decreased from 3.5 mg/L to 0.3 mg/L and 53.9 mg · h/L to 19.2 mg · h/L, respectively, resulting in an exacerbation of viremia and clinical condition. Adjustment of dosing interval from 24 h to 12 h led to a peak level of 4.2 mg/L, trough level of 1.1 mg/L, and AUC0–12 of 31.8 mg · h/L, resulting in a marked suppression of viral load.ConclusionsMonitoring the therapeutic drug levels and cytomegalovirus loads is useful in obtaining a proper treatment effect and preventing overdosage during ganciclovir therapy in premature infants with postnatal cytomegalovirus infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-016-0683-x) contains supplementary material, which is available to authorized users.

Relationship of Ganciclovir Therapeutic Drug Monitoring with Clinical Efficacy and Patient Safety

“…Unique clinical scenarios may warrant ganciclovir TDM to ensure adequate serum concentrations while attempting to minimize drug toxicity, including ganciclovirresistant viral strains, infections requiring antiviral penetration to sanctuary sites, or treatment for viral infections other than CMV (25,(33)(34)(35). Patient populations with different pharmacokinetic profiles, including pediatric, geriatric, and obese patients and those with dynamic changes in renal function, may also require ganciclovir TDM due to alterations in drug metabolism and elimination (20,(36)(37)(38). As such, further research may be necessary to better guide specific patient populations in whom ganciclovir TDM may be recommended.…”

Postnatal Cytomegalovirus Infection: Is it Important? A 10-Year Retrospective Case-control Study of Characteristics and Outcomes in Very Preterm and Very Low Birth Weight Infants

“…3,4,6 Adverse short-and long-term outcomes of pCMV infection in vulnerable infants may include death, [7][8][9][10] bronchopulmonary dysplasia (BPD), [11][12][13][14][15] retinopathy of prematurity (ROP), 16 increased length of stay (LOS) [12][13][14][17][18][19] and neurodevelopmental impairment (NDI), [20][21][22][23] but studies reporting these outcomes have been inconsistent. Guidance on the treatment of pCMV infection is limited to a number of case reports and small retrospective studies, 7,10,24,25 with treatment generally reserved for significantly symptomatic infants, as outlined in a recent review by Kadambari et al 26 Consensus guidelines to prevent, identify and treat pCMV infections are lacking. We conducted a retrospective, matched casecontrol study to investigate the incidence, characteristics, management and outcomes of pCMV infection in VP and VLBW infants, to contribute to the development of evidence-based guidelines for screening, prevention and treatment of pCMV infection.…”

“…Clinical manifestations vary from new-onset laboratory abnormalities, including thrombocytopenia, to symptoms of organ-specific inflammation or a systemic CMV-sepsis-like syndrome (CMV-SLS). 3,4,6 Adverse short-and long-term outcomes of pCMV infection in vulnerable infants may include death, [7][8][9][10] bronchopulmonary dysplasia (BPD), [11][12][13][14][15] retinopathy of prematurity (ROP), 16 increased length of stay (LOS) [12][13][14][17][18][19] and neurodevelopmental impairment (NDI), [20][21][22][23] but studies reporting these outcomes have been inconsistent. Guidance on the treatment of pCMV infection is limited to a number of case reports and small retrospective studies, 7,10,24,25 with treatment generally reserved for significantly symptomatic infants, as outlined in a recent review by Kadambari et al 26 Consensus guidelines to prevent, identify and treat pCMV infections are lacking.…”

Challenges and Clinical Implications of the Diagnosis of Cytomegalovirus Lung Infection in Children

“…Premature infants, especially very-low birth weight (VLBW) babies (< 1500 g) are particulalry vulnerable to postnatal CMV infections developing pneumonitis and sepsis-like symptoms in up to 15% of cases [55,57]. Common symptoms of postnatal CMV infections include apnea, bradycardia, pneumonia, hepatitis, gastrointestinal tract symptoms, and hematological signs (thrombocytopenia, neutropenia, and lymphocytosis) [57,58]. Diffuse severe interstitial pneumonitis may develop in premature or immunocompromised infants (e.g., children with primary immunodeficiencies), and it is potentially life-threatening [21].…”

“…In these settings, lung CMV infections can contribute to lung damage by direct effects, as a result of tissue inflammation, predisposition to additional infections, and secondarily through the exposure to mechanical ventilation and supplemental oxygen, highlighting the importance of prevention efforts, prompt diagnosis and proper management strategies of prenatal and perinatal lung CMV infections in these vulnerable groups. [58,[63][64][65]…”