Antimicrobial Agent Dosing in Infants

AbstractPurposeThe goal of this article was to review infant physiology and its effects on the pharmacokinetic properties of antimicrobial agents.MethodsA review of the drug development process was performed. A literature search was conducted on the pharmacokinetics of various antimicrobial agents in infants.FindingsThe pharmacokinetic properties of antimicrobial agents in infants are most often affected by the renal maturation of premature infants. Hepatic metabolism and volume of distribution play a common role as well.ImplicationsThe dosing and dosing intervals of various medications were reviewed and compared with details of adult dosing. It is vital to continue to gather pharmacokinetic data in infants to ensure adequate safety and dosing of medications

Sedation, Analgesia, and Paralysis during Mechanical Ventilation of Premature Infants

To characterize administration of sedatives, analgesics, and paralytics in a large cohort of mechanically ventilated, premature infants

Fluconazole Pharmacokinetics and Safety in Premature Infants

Invasive candidiasis (IC) in the premature infant population is a common infection that results in substantial morbidity and mortality. For these patients, fluconazole is among the first line therapies to treat and prevent IC, and yet few prospective studies investigating its pharmacokinetics (PK) and safety have been performed in this vulnerable population. We review five phase I studies examining the PK of fluconazole in premature infants, which demonstrate markedly differing kinetics compared to adults. Based on these data, a treatment dose of 12 mg/kg/day, with the potential need of a loading dose of 25 mg/kg to achieve rapid steady state concentrations, achieves surrogate pharmacodynamic targets. Additionally, fluconazole appears to be safe to use in this population, with only minimal reversible hepatobiliary effects

A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants

Bronchopulmonary dysplasia (BPD) is the most common cause of pulmonary morbidity in premature infants and is associated with life-long morbidities. Developing drugs for the prevention of BPD would improve public health. We sought to determine characteristics of favorable randomized controlled trials (RCTs) of drugs for BPD prevention

Pharmacokinetics of Moxifloxacin in an Infant With Mycoplasma hominis Meningitis

Treatment of Mycoplasma hominis meningitis in infants is limited by a lack of consensus regarding therapy and limited pharmacokinetic data for agents to which M. hominis is susceptible. We report the successful treatment of a premature infant with M. hominis meningitis with doxycycline and moxifloxacin and provide a pharmacokinetic profile of moxifloxacin

Surfactant status and respiratory outcome in premature infants receiving late surfactant treatment.

BACKGROUND:Many premature infants with respiratory failure are deficient in surfactant, but the relationship to occurrence of bronchopulmonary dysplasia (BPD) is uncertain. METHODS:Tracheal aspirates were collected from 209 treated and control infants enrolled at 7-14 days in the Trial of Late Surfactant. The content of phospholipid, surfactant protein B, and total protein were determined in large aggregate (active) surfactant. RESULTS:At 24 h, surfactant treatment transiently increased surfactant protein B content (70%, p < 0.01), but did not affect recovered airway surfactant or total protein/phospholipid. The level of recovered surfactant during dosing was directly associated with content of surfactant protein B (r = 0.50, p < 0.00001) and inversely related to total protein (r = 0.39, p < 0.0001). For all infants, occurrence of BPD was associated with lower levels of recovered large aggregate surfactant, higher protein content, and lower SP-B levels. Tracheal aspirates with lower amounts of recovered surfactant had an increased proportion of small vesicle (inactive) surfactant. CONCLUSIONS:We conclude that many intubated premature infants are deficient in active surfactant, in part due to increased intra-alveolar metabolism, low SP-B content, and protein inhibition, and that the severity of this deficit is predictive of BPD. Late surfactant treatment at the frequency used did not provide a sustained increase in airway surfactant

External Evaluation of a Gentamicin Infant Population Pharmacokinetic Model Using Data from a National Electronic Health Record Database

Gentamicin is a common antibiotic used in neonates and infants. A recently published population pharmacokinetic (PK) model was developed using data from multiple studies, and the objective of our analyses is to evaluate the feasibility of using a national electronic health record (EHR) database to further externally evaluate this model. Our results suggest that with proper data capture procedures, EHR data can serve as a potential data source for external evaluation of PK models

Urinary tract infection concordance with positive blood and cerebrospinal fluid cultures in the neonatal intensive care unit

Urinary tract infections (UTI) are common in the neonatal intensive care unit (NICU). Blood, urine, and cerebrospinal fluid (CSF) cultures are frequently obtained to evaluate for infection. We sought to determine the concordance between positive urine cultures and blood or CSF cultures

Coagulase-Negative Staphylococcal Infections in the Neonatal Intensive Care Unit

Background. Coagulase-negative staphylococci (CoNS) are the most commonly isolated pathogens in the neonatal intensive care unit (NICU). CoNS infections are associated with increased morbidity, including neurodevelopmental impairment. Objective. To describe the epidemiology of CoNS infections in the NICU. To determine mortality among infants with definite, probable, or possible CoNS infections. Methods. We performed a retrospective cohort study of all blood, urine, and cerebrospinal fluid cultures from samples obtained from infants aged <121 postnatal days. Setting. A total of 248 NICUs managed by the Pediatrix Medical Group from 1997 to 2009. Results. We identified 16,629 infants with 17,624 episodes of CoNS infection: 1,734 (10%) definite, 3,093 (17%) probable, and 12,797 (73%) possible infections. Infants with a lower gestational age and birth weight had a higher incidence of CoNS infection. When controlling for gestational age, birth weight, and 5-minute Apgar score, we found that infants with definite, probable, or possible CoNS infection had lower mortality (odds ratio [OR], 0.74 [95% confidence interval {CI}: 0.61, 0.89], 0.68 [95% CI, 0.59, 0.79], and 0.69 [95% CI, 0.63, 0.76], respectively) compared with infants who had negative culture results ( P <.001). No significant difference in overall mortality was found in infants who had definite CoNS infection compared with those who had probable or possible CoNS infection (OR, 0.93 [95% CI, 0.75, 1.16] and 0.85 [95% CI, 0.70, 1.03], respectively). Conclusions. CoNS infection was strongly related to lower gestational age and birth weight. Infants with clinical sepsis and culture-positive CoNS infection had lower mortality rates than infants with clinical sepsis and negative blood culture results. No difference in mortality between infants with a diagnosis of definite, probable, or possible CoNS infection was observed

Repeat lumbar punctures in infants with meningitis in the neonatal intensive care unit

The purpose of this study is to examine the results of repeat lumbar puncture in infants with initial positive cerebrospinal fluid (CSF) cultures in order to determine the clinical characteristics and outcomes of infants with repeat positive cultures