deoxycholic-acid and Candidiasis--Invasive

Echinocandins are recommended for the treatment of suspected or confirmed invasive candidiasis (IC) in adults. Less is known about the use of echinocandins for the management of IC in children. The aim of this study was to investigate the overall efficacy and safety of echinocandin class in neonatal and pediatric patients with IC.. PubMed, Cochrane Central, Scopus and Clinical trial registries were searched up to July 27, 2017. Eligible studies were randomized controlled trials that evaluated the efficacy and safety of any echinocandin versus agents of other antifungal classes for the treatment of IC in pediatric patients. The primary outcome was treatment success with resolution of symptoms and signs, and absence of IC. In the meta-analysis a random effects model was used, and the odds ratio (OR) and 95% confidence intervals (CIs) were calculated.. Four randomized clinical trials (324 patients), 2 confirmed IC (micafungin vs. liposomal amphotericin B (L-AmB) and caspofungin vs. L-AmB) and 2 empirical therapy trials (caspofungin vs. deoxycholate amphotericin B and caspofungin vs. L-AmB) were included. There was no significant difference between echinocandins and comparator in terms of treatment success (OR = 1.61, 95% CI: 0.74-3.50) and incidence of treatment-related adverse events (OR = 0.70, 95% CI: 0.39-1.26). However, fewer children treated with echinocandins discontinued treatment because of adverse events than amphotericin B formulations (OR = 0.26, 95% CI: 0.08-0.82, P = 0.02).. In the treatment of IC in children, echinocandins show non-inferior efficacy compared with amphotericin B formulations with fewer discontinuations than in comparator arm.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis, Invasive; Caspofungin; Child; Child, Preschool; Deoxycholic Acid; Drug Combinations; Echinocandins; Female; Humans; Infant; Infant, Newborn; Lipopeptides; Male; Micafungin; Randomized Controlled Trials as Topic; Treatment Outcome

Neonatal fungal and viral infections are associated with mortality and neurologic impairment among survivors. Advances in pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial medications have led to improved dosing guidance for neonates. This article discusses the basic PK/PD properties and dosing of the most common antifungal and antiviral medications used in neonates.

Topics: Acyclovir; Amphotericin B; Antifungal Agents; Antiviral Agents; Candidiasis, Invasive; Cytomegalovirus Infections; Deoxycholic Acid; Drug Combinations; Fluconazole; Ganciclovir; Herpes Simplex; Humans; Infant; Infant, Newborn; Mycoses; Practice Guidelines as Topic; Pregnancy Complications, Infectious; Valganciclovir; Virus Diseases

Invasive candidiasis is responsible for ∼ 10% of nosocomial sepsis in very-low-birth-weight infants and is associated with substantial morbidity and mortality. Over the last two decades, the antifungal armamentarium against Candida spp. has increased; however, efficacy and safety studies in this population are lacking.. We reviewed the medical literature and extracted information on clinical and observational studies evaluating the use of antifungal agents in neonates with invasive candidiasis.. Efficacy and safety data for antifungals in neonates are lacking, and the majority of studies conducted to date have concentrated on pharmacokinetic/pharmacodynamic evaluations. Unlike other anti-infective agents, efficacy data in the setting of neonatal candidiasis cannot be extrapolated from adult studies due to differences in the pathophysiology of the disease in this population relative to older children and adults. Data for amphotericin B deoxycholate, fluconazole, and micafungin suggest that these are the current agents of choice for this disease in neonates until data for newer antifungal agents become available. For prophylaxis, data from fluconazole randomized controlled trials will be submitted to the regulatory agencies for labeling. Ultimately, the field of therapeutics for neonatal candidiasis will require multidisciplinary collaboration given the numerous challenges associated with conducting clinical trials in neonates.

Topics: Amphotericin B; Antifungal Agents; Candidiasis, Invasive; Deoxycholic Acid; Drug Combinations; Echinocandins; Humans; Infant, Newborn; Lipopeptides; Micafungin; Triazoles

Invasive fungal infections due to Candida are the third most common late-onset infection in infants born with birth weight <1500 g. Invasive candidiasis in infants born with birth weight <1000 g is associated with a 30% mortality and with neurodevelopmental impairment in more than half the survivors. A high degree of suspicion and a thorough multisystem evaluation is necessary for diagnosis of invasive fungal infections and to detect complications or sequalae. Amphotericin B deoxycholate is the mainstay in the treatment of invasive fungal infections in newborns. Early initiation of enteral feeds with human milk, decreasing dependence on catheters and avoidance of antacids, steroids and broad-spectrum antibiotics are the recommended preventive measures. Fluconazole prophylaxis should be targeted towards neonates born with <1000 g in neonatal units where baseline rates of invasive candidiasis are more than 5%.

Topics: Amphotericin B; Antifungal Agents; Candidiasis, Invasive; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Echinocandins; Humans; Infant, Low Birth Weight; Infant, Newborn; Nucleosides; Risk Factors; Triazoles

Investigate the efficacy of caspofungin in participants <3 months of age with invasive Candida infection (ICI).. This multicentre, randomized, double-blind, comparator-controlled, Phase 2 study (protocol MK0991-064; NCT01945281) enrolled participants <3 months of age with culture-confirmed ICI within 96 h of study entry. Participants were randomly assigned 2:1 to once-daily intravenous 2 mg/kg caspofungin or intravenous 1 mg/kg amphotericin B deoxycholate (dAMB). The primary endpoint was fungal-free survival (FFS) 2 weeks after treatment in the full-analysis-set (FAS) population, defined as participants with culture-confirmed ICI who received ≥1 dose of therapy. Planned enrolment was 90 participants.. Fifty-one participants were enrolled; 49 received treatment (caspofungin, n=33; dAMB, n=16); 2 additional participants did not have confirmed infections at study entry. The study was terminated after ∼ 3.5 years because of low enrolment. Forty-seven participants were included in the FAS population (caspofungin, n=31; dAMB, n=16). FFS rate at 2 weeks after treatment was 71.0% (22/31) in the caspofungin arm and 68.8% (11/16) in the dAMB arm [difference, stratified by weight, - 0.9% (95% CI, - 24.3%-27.7%)]. Adverse events developed in 84.8% (28/33) of participants in the caspofungin arm and 100% (16/16) in the dAMB arm.. Among neonates and infants with confirmed ICI, FFS at 2 weeks was similar in the caspofungin and dAMB treatment arms. A smaller proportion of participants who received caspofungin experienced adverse events.

Topics: Amphotericin B; Antifungal Agents; Candidiasis, Invasive; Caspofungin; Deoxycholic Acid; Double-Blind Method; Drug Combinations; Female; Humans; Infant; Infant, Newborn; Male; Treatment Outcome

Amphotericin B deoxycholate (AmB-D) is standard of care treatment for neonatal invasive candidiasis (IC). Micafungin (MCA) has broad-spectrum fungicidal activity against Candida spp. We compared the efficacy and safety of intravenous MCA with intravenous AmB-D and assessed the pharmacokinetics of MCA in infants >2-120 days of age with proven IC in a phase 3, randomized, double-blind, multicenter, parallel-group, noninferiority study (NCT00815516).. Infants were randomized 2:1 to MCA (10 mg/kg/d) or AmB-D (1 mg/kg/d) for ≥21 days. Primary efficacy endpoint was fungal-free survival (FFS) 1 week after last study drug dose. MCA population pharmacokinetics included simulated area under the curve (AUC) at steady state and maximum plasma concentration after 2-hour infusion. AUC pharmacodynamic target exposure was 170 µg·h/mL.. Thirty infants received MCA (n = 20) or AmB-D (n = 10). The trial was terminated early because of slow recruitment. FFS was observed in 12 of 20 [60%; 95% confidence interval (CI): 36%-81%] MCA-group infants and in 7 of 10 (70%; 95% CI: 35%-93%) AmB-D-group infants. The most common treatment-emergent adverse events were anemia [MCA: n = 9 (45%); AmB-D: n = 3 (30%)] and thrombocytopenia [n = 2 (10%) and n = 3 (30%), respectively]. Model-derived mean AUC at steady state for MCA was 399.3 ± 163.9 µg·h/mL (95% prediction interval: 190.3-742.3 µg/mL); steady state and maximum plasma concentration after 2-hour infusion was 31.1 ± 10.5 µg/mL (95% prediction interval: 17.0-49.7 µg/mL). MCA exposures were above the AUC pharmacodynamic target exposure.. Within the study limitations, infants with IC treated with MCA achieved similar FFS compared with AmB-D. Both agents were safe and well tolerated.

Topics: Administration, Intravenous; Amphotericin B; Antifungal Agents; Area Under Curve; Candida; Candidiasis, Invasive; Deoxycholic Acid; Double-Blind Method; Drug Combinations; Female; Hematologic Tests; Humans; Infant; Infant, Newborn; Male; Micafungin; Treatment Outcome

Invasive candidiasis is a leading cause of mortality and morbidity in neonatal intensive care units. Treatment recommendations are limited by a lack of comparative outcomes data.. We identified all infants ≤ 120 days of age with positive blood, urine, or cerebrospinal fluid cultures for Candida species who received amphotericin B deoxycholate, fluconazole, amphotericin B lipid products, or combination therapy admitted to one of 192 neonatal intensive care units in the United States between 1997 and 2003. Primary outcome measures included overall mortality and therapeutic failure (combined outcome of duration of infection >7 days, need for additional antifungal therapy, or death before discharge). We compared outcomes by antifungal therapy using logistic regression, controlling for gestational age, day of life at start of antifungal therapy, delay in therapy, and site of infection.. Overall, 138 of 730 (19%) infants died. On multivariable logistic regression, we observed higher overall mortality for infants receiving amphotericin B lipid products compared with infants receiving amphotericin B deoxycholate (odds ratio 1.96 [95% confidence intervals: 1.16, 3.33]; P = 0.01) or fluconazole (odds ratio 2.39 [1.18, 4.83]; P = 0.02).. Infants treated with amphotericin B lipid products had higher mortality than infants treated with either amphotericin B deoxycholate or fluconazole. This finding may be related to inadequate penetration of amphotericin B lipid products into the kidneys, inappropriate dosing in premature infants, or unknown differences in acuity of illness in infants treated with amphotericin B lipid products.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis, Invasive; Deoxycholic Acid; Drug Combinations; Female; Fluconazole; Humans; Infant; Infant Mortality; Infant, Newborn; Intensive Care Units, Neonatal; Logistic Models; Male; Treatment Outcome; United States