Population Pharmacokinetics of Intraventricular Vancomycin in Neonatal Ventriculitis, A Preterm Pilot Study

Parasuraman, Jaya Madhura; Kloprogge, Frank; Standing, Joseph F.; Albur, Mahableshwar; Heep, Axel

doi:10.1016/j.ejps.2020.105643

Cited by 5 publications

(8 citation statements)

References 27 publications

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“…No guideline on IVT antibiotic administration in neonates has appeared since that of the 2012 Cochrane database, 8 but several publications reported successful IVT therapy for infections caused by MDR bacteria. 6 14 16 17 20 22 24 28 30 31 35 37 39 40 The drug of choice depends on the nature and antibiotic susceptibility of the pathogen. Aminoglycosides (amikacin, gentamycin, tobramycin, netilmicin, and streptomycin), polymyxins (colistin, polymyxin B, and daptomycin), glycopeptides (vancomycin and teicoplanin), quinupristin-dalfopristin, tigecycline, and antifungals including amphotericin-B and caspofungin can be delivered IVT.…”

Section: Discussionmentioning

confidence: 99%

“…Another search on Google Scholar was performed to identify articles published in non-PubMed indexed journals. Seven publications were found, so we finally reviewed 37 texts (20 case reports, 6 case series, 6 7 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 and 11 original articles 2 3 9 38 39 40 41 42 43 44 45 [5 retrospective and 3 epidemiological surveillance studies, 1 prospective observational study, 1 pilot population pharmacokinetic modeling study, and 1 research article]).…”

Section: Methodsmentioning

confidence: 99%

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Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

Ongun,

Kihtir,

Zarif

et al. 2024

J Pediatr Infect Dis

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Objective Ventriculitis is an example of the increasing global trend in difficult-to-treat infections in neonates caused by pathogens resistant to conventional therapies. This article describes the first use of intravenous and intraventricular tigecycline to treat ventriculitis caused by vancomycin-resistant enterococci in a preterm neonate and systematically review the literature on challenges posed by the definitions, diagnosis, and treatment of neonatal ventriculitis Methods The authors searched PubMed and Internet search engines for “ventriculitis” in the period from 2003 to 2023 restricting the research to “Newborn,” “Human,” “English language,” and “full-text availability.” Results Thirty-seven publications (20 case reports, 6 case series, and 11 research articles) were extracted upon research. Preterm birth, posthemorrhagic ventricular dilatation requiring placement of ventricular access devices, and sepsis preceded neonatal ventriculitis. Infections caused by rare microorganisms, in particular gram-negative bacteria resistant to conventional therapies, predominated in the publications describing the need for a combination of intravenous (IV) and intraventricular (IVT) therapies. Survivors of neonatal ventriculitis developed neurodevelopmental impairments such as hydrocephalus, seizures, motor function, hearing, and vision impairment. Conclusion Clinical suspicion of ventriculitis indicated by subtle signs is key for prompt diagnosis. Effective IV and IVT antibiotics are essential to prevent serious sequelae and mortality. The drug delivery method should be changed if there is no clinical response. This study emphasizes the urgent need for pediatric trials of antibiotics against organisms resistant to other drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

Ongun,

Kihtir,

Zarif

et al. 2024

J Pediatr Infect Dis

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“…In addition, CSF vancomycin levels were not significantly associated with the ventricular index and the CSF protein level. However, a larger data pool is needed to ascertain dosing strategies [ 43 ].…”

Section: Vancomycinmentioning

confidence: 99%

Efficacy of Vancomycin and Meropenem in Central Nervous System Infections in Children and Adults: Current Update

2022

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The current antimicrobial therapy of bacterial infections of the central nervous system (CNS) in adults and pediatric patients is faced with many pitfalls as the drugs have to reach necessary levels in serum and cross the blood-brain barrier. Furthermore, several studies report that different factors such as the structure of the antimicrobial agent, the severity of disease, or the degree of inflammation play a significant role. Despite the available attempts to establish pharmacokinetic (PK) modeling to improve the required dosing regimen for adults and pediatric patients, conclusive recommendations for the best therapeutic strategies are still lacking. For instance, bacterial meningitis, the most common CNS infections, and ventriculitis, a severe complication of meningitis, are still associated with 10% and 30% mortality, respectively. Several studies report on the use of vancomycin and meropenem to manage meningitis and ventriculitis; therefore, this review aims to shed light on the current knowledge about their use in adults and pediatric patients. Consequently, studies published from 2015 until mid-July 2021 are included, and data about the study population, levels of drugs in serum and cerebrospinal fluid (CSF), and measured PK data in serum and CSF are provided. The overall aim is to provide the readers a recent reference that summarizes the pitfalls and success of the current therapy and emphasizes the importance of performing more studies to improve the clinical outcome of the current therapeutical approach.

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“…In a preterm pilot study, the authors used data from eight preterm infants with neonatal ventriculitis (median GA 25.3 weeks; range 23.9–27.7) treated with intraventricular vancomycin at a standard starting dose of 15 mg/kg, in order to develop a popPK model on the use of intraventricular vancomycin in the preterm population [ 199 ]. Three covariates (serum creatinine, ventricular index (VI), and CSF protein) were tested on the model, whilst the AUC and average CSF concentration predictions were generated from the final model.…”

Section: Pk Of Antibiotics In Pretermsmentioning

confidence: 99%

“…The results show that covariates of VI and the CSF protein did not demonstrate any influence on CSF vancomycin and that time to sterilization with higher CSF AUC (0–24) and average concentration tends to be shorter. The authors conclude that further study with a larger data pool will be necessary to investigate the influence of VI on CSF vancomycin and to optimize the best dosing strategy [ 199 ].…”

Section: Pk Of Antibiotics In Pretermsmentioning

confidence: 99%

Use of Antibiotics in Preterm Newborns

et al. 2022

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Due to complex maturational and physiological changes that characterize neonates and affect their response to pharmacological treatments, neonatal pharmacology is different from children and adults and deserves particular attention. Although preterms are usually considered part of the neonatal population, they have physiological and pharmacological hallmarks different from full-terms and, therefore, need specific considerations. Antibiotics are widely used among preterms. In fact, during their stay in neonatal intensive care units (NICUs), invasive procedures, including central catheters for parental nutrition and ventilators for respiratory support, are often sources of microbes and require antimicrobial treatments. Unfortunately, the majority of drugs administered to neonates are off-label due to the lack of clinical studies conducted on this special population. In fact, physiological and ethical concerns represent a huge limit in performing pharmacokinetic (PK) studies on these subjects, since they limit the number and volume of blood sampling. Therapeutic drug monitoring (TDM) is a useful tool that allows dose adjustments aiming to fit plasma concentrations within the therapeutic range and to reach specific drug target attainment. In this review of the last ten years’ literature, we performed Pubmed research aiming to summarize the PK aspects for the most used antibiotics in preterms.

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Population Pharmacokinetics of Intraventricular Vancomycin in Neonatal Ventriculitis, A Preterm Pilot Study

Abstract: Highlights Pharmacokinetics modelling of intraventricular vancomycin in a preterm pilot study. Intraventricular vancomycin follows a one compartment model in neonatal ventriculitis treatment. Ventricular Index, a dosing parameter, does not influence cerebrospinal fluid vancomycin levels.

Cited by 5 publications

References 27 publications

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

Efficacy of Vancomycin and Meropenem in Central Nervous System Infections in Children and Adults: Current Update

Use of Antibiotics in Preterm Newborns

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