Retrospective Evaluation of Infants Aged 1 to 60 Days with Residual Cerebrospinal Fluid (CSF) Tested Using the FilmArray Meningitis/Encephalitis (ME) Panel.

In pediatric practice it is common for infants under 2 months of age to undergo evaluation for sepsis when they are ill, often including lumbar puncture to assess for central nervous system (CNS) infection. The FilmArray Meningitis/Encephalitis (ME) panel is a newly approved test for rapid identification of CNS pathogens. Our objective was to study the epidemiology of CNS infection in young infants and the potential impact of rapid multiplex PCR on their care. A performance evaluation of the FilmArray ME panel was conducted from February 2014 to September 2014 at 11 sites. FilmArray ME panel results were compared to reference standards but not shared with providers. In our study, medical records for infants (aged 1 to 60 days) enrolled at three sites were reviewed for clinical, laboratory, and outcome data. A total of 145 infants were reviewed. The median age was 25 days. Most of the infants were hospitalized (134/145 [92%]) and received antibiotics (123/145 [85%]), and almost half (71/145 [49%]) received acyclovir. One infant had a bacterial pathogen, likely false positive, identified by the FilmArray ME panel. Thirty-six infants (25%) had a viral pathogen detected, including 21 enteroviruses. All infants with enteroviral meningitis detected by the FilmArray ME panel and conventional PCR were hospitalized, but 20% were discharged in less than 24 h when conventional PCR results became available. The FilmArray ME panel may play a role in the evaluation of young infants for CNS infection. Results may be used to guide management, possibly resulting in a decreased length of stay and less antimicrobial exposure for infants with low-risk viral infection detected.

Comparative Effectiveness of Oral Versus Outpatient Parenteral Antibiotic Therapy for Empyema.

BACKGROUND: Treatment of pediatric parapneumonic empyema (PPE) requires several weeks of antibiotic therapy that is typically completed in the outpatient setting. The route of outpatient therapy can be oral or intravenous (outpatient parenteral antibiotic therapy [OPAT]). No studies have compared outcomes between oral therapy and OPAT for PPE. METHODS: We identified children <18 years hospitalized from 2005 to 2014 at Primary Children's Hospital with PPE and discharged with oral therapy or OPAT. The primary outcome was the percentage of children who experienced all-cause complications after discharge. Complications included those that were related to pneumonia (including treatment failure, defined as readmission with reaccumulation of pleural fluid or abscess requiring drainage) or antibiotic therapy (eg, allergy, line clot) resulting in either a hospital readmission or emergency department/urgent care visit. All-cause complications were compared between oral therapy and OPAT by using propensity score-weighted logistic regression. RESULTS: A total of 391 children were hospitalized with PPE; 337 (86%) were discharged with OPAT; 35 (9%) children experienced an all-cause complication, including 5 with oral (9.3%) and 30 (8.9%) with OPAT. Pneumonia and treatment-related complications were comparable (P = .25 and .78, respectively). Two patients treated with OPAT (1%) experienced treatment failure. After adjustment using propensity score weighting, the frequency of complications was similar between groups (adjusted odds ratio 0.97, 95% confidence interval 0.23-4.65). CONCLUSIONS: The frequency of complications was similar with oral therapy and OPAT for children with PPE. Oral antibiotics may be considered safe and effective for children with PPE who will be discharged to complete therapy in the outpatient setting.

Predictive Performance of a Vancomycin Population Pharmacokinetic Model in Neonates.

INTRODUCTION: The pharmacokinetics of vancomycin are highly variable among neonates, which makes dosing challenging in this population. However, adequate drug exposure is critical, especially when treating methicillin-resistant Staphylococcus aureus (MRSA) infections. Utilization of population pharmacokinetic models and Bayesian methods offers the potential for developing individualized therapeutic approaches. To meet this need, a neonatal vancomycin population pharmacokinetic model was recently published. The current study sought to externally evaluate the predictive performance and generalizability of this model. METHODS: A retrospective chart review of neonates who received vancomycin and had ≥1 peak and ≥1 trough concentrations at five Intermountain Healthcare neonatal intensive care units from 2006 to 2013 was performed and served as the external validation cohort. The published population pharmacokinetic model was implemented in NONMEM 7.2 with the structural and variance parameter values set equal to the estimates reported previously. The model was then used to predict the first peak and trough concentration for each neonate in the validation cohort and the model prediction error and absolute prediction error were calculated. Normalized prediction distribution errors (NPDE) were also evaluated. RESULTS: A total of 243 neonates were studied with a median postmenstrual age of 33 (range: 23-54) weeks and a median weight of 1.6 (range: 0.4-6.8) kg. The model predicted the observed vancomycin concentrations with reasonable precision. For all vancomycin concentrations, the median prediction error was -0.8 (95% CI: -1.4 to -0.4) mg/L and the median absolute prediction error was 3.0 (95% CI: 2.7-3.5) mg/L. No trends in NPDE across weight, postmenstrual age, serum creatinine, or time after dose were observed. CONCLUSION: An evaluation of a recently published neonatal vancomycin population pharmacokinetic model in a large external dataset supported the predictive performance and generalizability of the model. This model may be useful in evaluating neonatal vancomycin dosing regimens and estimating the extent of drug exposure.

Pediatric vancomycin dosing: Trends over time and the impact of therapeutic drug monitoring.

Monitoring of vancomycin trough concentrations is recommended for pediatric patients in the product label and by several professional societies. However, among a network of freestanding children's hospitals vancomycin therapeutic drug monitoring (TDM) practices were reported to be highly variable. In this study, we sought to evaluate whether trends in vancomycin use and TDM changed across a large healthcare delivery system in Utah and Idaho from 2006 to 2012. Children ≤18 years who received ≥2 vancomycin doses were included. Overall, vancomycin TDM was performed during 5,035 (80%) of 6,259 hospital encounters, in which 85,442 doses were administered and 7,935 concentrations were obtained. Across this time period, the median trough concentration increased from 10.9 to 13.7 µg/mL (P < .001), which temporally coincided with recommendations published by the Infectious Disease Society of America that recommend targeting higher trough concentrations. Two or more abnormally low trough concentrations were accompanied by an increase in the dose 75% of the time. Similarly, ≥2 abnormally high trough concentrations were followed by a decrease in the dose 35% of the time. In aggregate, these data suggest that vancomycin TDM is commonly performed among children and the majority of abnormal trough concentrations were associated with an appropriate modification to the dosing regimen.

Epidemiological Evaluation of Blood Culture Patterns among Neonates Receiving Vancomycin.

The objective of this study was to assess the frequency of blood culture (BC) collection among neonates who received vancomycin. Demographic, clinical, microbiologic, and pharmacy data were collected for 1275 neonates (postnatal age 0-27 days) who received vancomycin at an Intermountain Healthcare facility between 1/2006 and 9/2011. Neonates treated with vancomycin had a BC collected 94 % (n = 1198) of the time, of which 37 % (n = 448) grew one or more bacterial organisms (BC positive). Of these, 1 % (n = 5) grew methicillin-resistant Staphylococcus aureus (MRSA), 71 % (n = 320) grew coagulase-negative Staphylococci (CoNS), 9 % (n = 40) grew methicillin-sensitive Staphylococcus aureus (MSSA), and 22 % (n = 97) grew other bacterial species (total exceeds 100 % due to co-detection). In patients with negative BC or no BC, vancomycin therapy was extended beyond 72 h 52 % of the time. The median duration of vancomycin therapy for patients with a negative BC was 4 (IQR: 2-10) days. BCs were frequently obtained among neonates who received vancomycin. Vancomycin therapy beyond the conventional 'empiric' treatment window of 48-72 h was common without isolation of resistant gram-positive bacteria.

Clinical Value of an Ambulatory-Based Antibiogram for Uropathogens in Children.

Unnecessarily broad-spectrum antibiotic prescribing for ambulatory pediatric urinary tract infection may result from clinicians not having antibiograms specific to this population. Comparing an existing hospital-based with a proposed ambulatory uropathogen antibiogram for children in Utah, Escherichia coli accounted for a larger percentage and was more susceptible to narrower-spectrum antibiotics, demonstrating the potential need for ambulatory pediatric antibiograms.