Caspofungin for the treatment of azole resistant candidemia in a premature infant

Smith, P. Brian; Steinbach, William J.; Cotten, C. Michael; Schell, Wiley A.; Perfect, John R.; Walsh, Thomas J.; Benjamin, Daniel K.

doi:10.1038/sj.jp.7211637

Cited by 34 publications

(15 citation statements)

References 7 publications

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“…Pharmacokinetic data have recently been published for fluconazole, micafungin, and caspofungin [14][15][16][17][18][19][20][21][22][23] . With studies examining pharmacokinetic data targeting comparable levels in adults, neonatal data are needed regarding safety.…”

Section: Treatment Of Invasive Fungal Infectionsmentioning

confidence: 99%

Challenging issues in neonatal candidiasis

Kaufman

2010

Current Medical Research and Opinion

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In an era of quality improvement and 'getting to zero (infections and/or related mortality),' neonatal candidiasis is ripe for evidence-based initiatives. Knowledge of each institution's invasive Candida infection (ICI) incidence and infection-related mortality is critical to evaluate disease burden and effective interventions. Evidenced-based interventions include: antifungal prophylaxis, starting with appropriate dosing, and prompt removal of central venous catheters (CVC). There is A-I evidence supporting antifungal prophylaxis with fluconazole, and it should be considered in every neonatal intensive care unit (NICU). The literature supports targeting infants51000 g and/or 27 weeks, because this group has high infection-related mortality and neurodevelopmental impairment in 57% of survivors. Antifungal prophylaxis has been shown to nearly eliminate infection-related mortality. Interventions start with prenatal initiatives, with women being treated for vaginal candidiasis, especially with preterm labor or complications. Targeting modifiable risk factors, including restriction policies for use of third-and fourth-generation cephalosporins, carbapenems, H2-antagonists, proton pump inhibitors, and postnatal steroids; guidelines for CVC care and removal; and feeding practices, with promotion of early feedings and breast milk, may also reduce risk. A few studies have emerged on empiric antifungal therapy with sepsis evaluations for preterm infants 51500 g and other high-risk patients that have shown favorable effects of eliminating mortality, but these have not been compared to appropriate antifungal therapy and central line removal. Further study of empiric therapy, prospective treatment studies with higher targeted dosing of amphotericin B preparations, fluconazole, and new antifungals with prompt CVC removal may contribute to a 100% survival rate for those infants41000 g and 28 weeks not receiving antifungal prophylaxis. Evaluation of ICI incidence and mortality by gestational age and birth week should be followed in each NICU, to evaluate infection control and prevention.

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Section: Treatment Of Invasive Fungal Infectionsmentioning

confidence: 99%

Challenging issues in neonatal candidiasis

Kaufman

2010

Current Medical Research and Opinion

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“…Data for younger children (3 to 24 months of age) who received caspofungin at 50 mg/m 2 daily (11) show pharmacokinetic results similar to those seen for the 2-to 11-yearold cohort (20). Several reports suggest that caspofungin may be useful for the treatment of candidemia in neonates (10,12,15,21); however, the appropriate dosage for this population has not been clearly defined. We conducted a prospective study to evaluate the safety, tolerability, and plasma levels of caspofungin in neonates/infants of Ͻ3 months of age given 25 mg/m 2 daily.…”

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confidence: 99%

Pharmacokinetics and Safety of Caspofungin in Neonates and Infants Less than 3 Months of Age

Sáez-Llorens

Macías

Maiya

et al. 2009

Antimicrob Agents Chemother

118

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Candida infections represent a major threat in neonatal intensive care units. This is the first prospective study to obtain caspofungin plasma levels and safety data for neonates and very young infants. Patients of <3 months of age receiving intravenous amphotericin B for documented or highly suspected candidiasis were enrolled in a single-dose (n ‫؍‬ 6) or subsequent multiple-dose (n ‫؍‬ 12) panel; all received caspofungin at 25 mg/m 2 once daily as a 1-hour infusion. Caspofungin plasma levels were measured by high-performance liquid chromatography and compared to historical data from adults. Patient chronological ages ranged from 1 to 11 weeks, and weights ranged from 0.68 to 3.8 kg. Gestational ages ranged from 24 to 41 weeks. Geometric mean (GM) peak (C 1 h ) and trough (C 24 h ) caspofungin levels were 8.2 and 1.8 g/ml, respectively, on day 1, and 11.1 and 2.4 g/ml, respectively, on day 4. GM ratios for C 1 h and C 24 h for neonates/infants relative to adults receiving caspofungin at 50 mg/day were 1.07 and 1.36, respectively, on day 1, and 1.18 and 1.21, respectively, on day 4. Clinical and laboratory adverse events occurred in 17 (94%) and 8 (44%) patients, respectively. Five patients (28%) had serious adverse events, none of which were considered drug related. Caspofungin at 25 mg/m 2 once daily was well tolerated in this group of neonates/infants of <3 months of age and appears to provide relatively similar plasma exposure to that obtained in adults receiving 50 mg/day. However, the small number of patients studied precludes any definitive recommendations about caspofungin dosing for this group comprising a broad range of ages and weights.Candida infections are a major concern in neonatal intensive care units, especially for infants with very low birth weights (Ͻ1,500 g). Late-onset sepsis develops in approximately 20% of critically ill neonates and low-birth-weight infants, and Candida species account for at least 10% of these infections (16). Antifungal regimens currently used in neonates are associated with increasing fungal resistance, notable toxicity, drug-drug interactions, or a limited spectrum of activity (4). Hence, there is a medical need to pursue the use of newer antifungal agents for the neonatal population.Caspofungin is an echinocandin antifungal that is effective as primary therapy for esophageal candidiasis (1, 6, 19), candidemia (8), and other invasive Candida infections (5) in adults. In a pharmacokinetic study of 39 children and adolescents (2 to 17 years of age), a caspofungin dose of 50 mg/m 2 daily (based on body surface area [BSA] dosing) resulted in plasma concentrations commensurate with the 50-mg daily dose used in adults (20). Data for younger children (3 to 24 months of age) who received caspofungin at 50 mg/m 2 daily (11) show pharmacokinetic results similar to those seen for the 2-to 11-yearold cohort (20). Several reports suggest that caspofungin may be useful for the treatment of candidemia in neonates (10,12,15,21); however, the appropriate dosage for this population h...

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“…Thus, we replaced amphotericin B with caspofungin, which has been reported as effective for controlling neonatal candidemia refractory to amphotericin B therapy 9,16 and as a possible salvage therapy. 10,17,18 However, the use of caspofungin to treat preterm babies is limited. We reviewed reports on caspofungin usage in preterm babies with Candida infections as far back as 2003.…”

Section: Discussionmentioning

confidence: 99%

Disseminated candidemia refractory to caspofungin therapy in an infant with extremely low birth weight

Hsueh

et al. 2012

Journal of the Formosan Medical Association

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Systemic fungal infections have high morbidity and mortality rates in neonates, especially neonates with an extremely low birth weight (ELBW). Here, we describe a 21-day-old ELBW female infant with an amphotericin B-unresponsive congenital Candida albicans infection that was treated with caspofungin. Blood sterilization was performed during the first episode, but a second episode of candidemia occurred after the discontinuation of caspofungin. Blood sterilization was again performed during the second round of caspofungin treatment, but fungal endocarditis and renal fungal balls still developed during the second episode. Caspofungin can be considered for invasive candidiasis in premature infants, especially in life-threatening situations. As for the focal lesions, more aggressive treatments other than just parenteral antibiotics should be considered. The literature regarding caspofungin therapy for neonatal candidiasis is also reviewed.

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Caspofungin for the treatment of azole resistant candidemia in a premature infant

Cited by 34 publications

References 7 publications

Challenging issues in neonatal candidiasis

Challenging issues in neonatal candidiasis

Pharmacokinetics and Safety of Caspofungin in Neonates and Infants Less than 3 Months of Age

Disseminated candidemia refractory to caspofungin therapy in an infant with extremely low birth weight

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