Antifungal Treatment and Outcome in Very Low Birth Weight Infants

Fortmann, Ingmar; Hartz, Annika; Paul, Pia; Pulzer, F.; Müller, Andreas; Böttger, Ralf; Proquitté, Hans; Dawczynski, K; Simon, Arne; Rupp, Jan; Herting, Egbert; Göpel, Wolfgang; Härtel, Christoph

doi:10.1097/inf.0000000000002001

Cited by 8 publications

(4 citation statements)

References 33 publications

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“…The concept that sustained inflammation contributes to short- and long-term complications after preterm birth has been largely accepted. Numerous observational studies demonstrate a risk association between unfavorable immune adaptation and long-term vulnerability for infections [ 248 ], CPIP and asthma [ 56 , 249 ], neurodevelopmental impairment, and stress incontinence [ 250 , 251 ]. The underlying mechanisms, in particular the host factors determining resilience or long-term vulnerability, remain to be elucidated.…”

Section: Conclusion and Future Outlookmentioning

confidence: 99%

Preterm birth and sustained inflammation: consequences for the neonate

et al. 2020

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Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis (“first inflammatory hit”). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia (“second inflammatory hit”). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important “third-trimester” adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome.

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Section: Conclusion and Future Outlookmentioning

confidence: 99%

Preterm birth and sustained inflammation: consequences for the neonate

et al. 2020

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“…cognitive development. Total, verbal, and performance intelligence were assessed using the Wechsler Preschool and Primary Scale of Intelligence -Third Edition [WPPSI I-III, German]37 .…”

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confidence: 99%

Surgical necrotizing enterocolitis but not spontaneous intestinal perforation is associated with adverse neurological outcome at school age

Humberg

Spiegler

Fortmann

et al. 2020

Sci Rep

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the German neonatal network (Gnn) † Gastrointestinal complications during the neonatal period, i.e. necrotizing enterocolitis (nec) and spontaneous intestinal perforation (Sip), are associated with adverse short-term outcome in very-lowbirthweight infants (VLBWi, <1500 g birth weight). However, little is known about the neurological outcome of survivors at school age. We analysed data of 2241 infants followed-up at the age of 6 years. To determine the effect of NEC and SIP on cognitive outcome in consideration of other important confounding factors, we used multivariable logistic regression models. in addition, infants with surgical diagnosis of nec (n = 43) or SIP (n = 41) were compared to NEC (n = 43) or SIP (n = 41) negative controls using Mahalanobis distance matching. infants with a history for nec had a three times increased risk (RR 3.0 [1.8-4.2], p < 0.001) to develop IQ scores <85 while history of surgical SIP did not increase the relative risk for lower IQs at school age (RR 1.0 [0.4-2.1], p = 1.000). In a matched-cohort analysis, we confirmed that infants with surgical NEC had lower mean IQ results than unaffected controls (±SD) (85±17 vs. 94±14, p = 0.023) while no differences were found for history of SIP. Our results reflect that the different aetiology and inflammatory extent of NEC and SIP may lead to disparate neurodevelopment trajectories. Hence, our data suggest a potential role of early gut-brain axis distortion in infants with nec which needs to be further explored. Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are typical gastrointestinal complications in very-low-birthweight infants (VLBWI) and have a remarkable impact on mortality and long-term morbidity in this vulnerable group 1-4. In VLBWI, NEC mainly occurs during day 14-28 of life 5 and seems to have multifactorial facets including genetic predisposition, intestinal immaturity, inflammation, oxidative stress, ischemia, nutritional aspects and gut dysbiosis 2,6,7. SIP usually occurs in the first 14 days of life 8 and is mainly associated with extreme prematurity, use of non-steroidal and steroidal anti-inflammatory drugs and prolonged evacuation of meconium 9,10. Recently, we noted an increased SIP risk in infants <25 weeks of gestation who were primarily managed with less invasive respiratory care 3. Epidemiological data of infants with NEC or SIP show delayed neurodevelopment in early childhood 2,9,11 , but little is known about outcome at school age. Roze et al. found an increased rate of reduced intelligence quotient (IQ) and motor testing scores among children at school age who suffered from NEC or SIP 11 compared to controls without these complications. However, the authors did not adjust for confounding variables such as gestational age or maternal education level and did not differentiate between NEC and SIP.

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“…Beyond BSA-based dosing, considering blood biochemical parameters and physiological conditions, such as serum ALB level, hepatic function, and blood flow, is crucial. Caspofungin is occasionally used in very low-birth-weight infants, but PK data for this group are scarce [ 40 ]. This scarcity emphasizes the necessity for large-scale, prospective trials to establish caspofungin’s efficacy, safety, optimal dosage, and role in neonatal candidiasis, particularly in infants under three months with a very low birth weight.…”

Section: Discussionmentioning

confidence: 99%

Development and Quality Control of a Population Pharmacokinetic Model Library for Caspofungin

Xu,

Shi,

Wang

et al. 2024

Pharmaceutics

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Background: Caspofungin is an echinocandin antifungal agent commonly used as the first-line therapy for invasive candidiasis, salvage therapy for invasive aspergillosis, and empirical therapy for presumed fungal infections. Pharmacokinetic (PK) variabilities and suboptimal exposure have been reported for caspofungin, increasing the risk of insufficient efficacy. Objective: This work aimed to develop a caspofungin population pharmacokinetic (popPK) library and demonstrate its utility by assessing the probability of target attainment across diverse settings. Methods: We established a caspofungin popPK model library following a rigorous literature review, re-implementing selected models in R with rxode2. Quality control procedures included a comparison of different studies and assessing covariate impacts. Model libraries were primarily used to perform Monte Carlo simulations to estimate target attainment and guide personalized dosing in Candida infections. Results: A total of 13 models, one- or two-compartment models, were included. The most significant covariates were body size (weight and body surface area), liver function, and albumin level. The results show that children and adults showed considerable differences in pharmacokinetics. For C. albicans and C. parapsilosis, none of the populations achieved a PTA of ≥90% at their respective susceptible MIC values. In contrast, for C. glabrata, 70% of the adult studies reached a PTA of ≥90%, while all pediatric studies achieved the same PTA level. Conclusion: At the recommended dosage, adult patients showed notably lower exposure to caspofungin compared to pediatric patients. Considering body size, liver function, and serum albumin is crucial when determining caspofungin dosage regimens. Furthermore, further research is required to comprehensively understand the pharmacokinetics of caspofungin in pediatric patients.

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Antifungal Treatment and Outcome in Very Low Birth Weight Infants

Cited by 8 publications

References 33 publications

Preterm birth and sustained inflammation: consequences for the neonate

Preterm birth and sustained inflammation: consequences for the neonate

Surgical necrotizing enterocolitis but not spontaneous intestinal perforation is associated with adverse neurological outcome at school age

Development and Quality Control of a Population Pharmacokinetic Model Library for Caspofungin

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