Kelley R. Lee

Evaluation of vancomycin use in a pediatric teaching hospital based on CDC criteria.

This study was performed to determine whether vancomycin use at our pediatric hospital was consistent with modified Centers for Disease Control and Prevention guidelines. Vancomycin use was inappropriate in 54% of patients. Inappropriate use briefly decreased by 14% after educational efforts. Further education regarding vancomycin use was deemed necessary and is continuing.

Prophylactic antibiotic use in pediatric cardiovascular surgery: a survey of current practice.

There is little information on prophylactic antibiotic practice in pediatric cardiovascular surgery. A consensus prophylactic antibiotic practice, if identified, might serve as a standard to which alternative prophylactic antibiotic practice could be compared. We surveyed North American academic centers with pediatric cardiovascular surgery programs regarding their standard antimicrobial prophylaxis regimens, duration of prophylaxis and modification of prophylaxis for lesion, patient age or medical device considerations. Forty-three (81%) of 53 centers responded; not all responses were complete. Monotherapy was used by 39 (91%) of 43; 38 (97%) of 39 used a 1st or 2nd generation cephalosporin (cefazolin 24, cefamandole 8, cefuroxime 4, cephapirin 1, unspecified 1) and 1 of 39 used vancomycin. Only 4 (9%) of 43 used 2 antibiotics. Prophylactic antibiotics were started pre- or intraoperatively by 41 of 43 centers and discontinued within 2 days by 25 of 37. Prophylactic antibiotics were often continued while thoracostomy tubes (29 of 43), mediastinal tubes (31 of 43) or transthoracic vascular catheters (22 of 43) were in place, but usually not for endotracheal tubes (6 of 43), arterial (9 of 43) or percutaneous central venous (13 of 43) catheters or temporary pacing wires (6 of 43). Our survey indicates that the consensus prophylactic antibiotic regimen for pediatric cardiovascular surgery is monotherapy with a first or second generation cephalosporin, used for < or = 2 days or until transthoracic medical devices are removed.

Drug Use Evaluation of Antibiotics in a Pediatric Teaching Hospital

OBJECTIVE To determine the incidence and type of antibiotic use variances at our institution. DESIGN Inpatient bacterial culture and susceptibility results were reviewed for 1 week per month. Medication administration records were evaluated to determine whether antibiotic selection was appropriate, given the susceptibility of the organism. Process indicators included use of the least costly antibiotic, as well as appropriate dose, interval, and route of administration. The complete medical record was reviewed for all patients if management did not appear to meet criteria. SETTING A 225-bed, tertiary-care childrens teaching hospital. RESULTS Thirty-five (8.2%) of 428 patients reviewed over 12 months had a total of 49 variances: failure to treat (3), treatment of contaminant/colonizer (2), use of more costly agent (10), failure to revise therapy (8), inappropriate route (2), inappropriate empiric antibiotic (4), incorrect dose (3), unnecessary multiple antibiotics (6), inappropriate drug (8), and prolonged prophylaxis (3). CONCLUSIONS Thirty-five patients with 10 types of variances were identified during the study. Follow-up monitoring will assess the impact of educational efforts on the incidence of variances. Specific problem antibiotics have been identified for further audits.

Altered Phenytoin Pharmacokinetics in Children with Severe, Acute Traumatic Brain Injury

The purpose of this study was to determine if phenytoin protein binding and metabolism were altered in prepubescent pediatric patients within the first 10 days following severe, acute traumatic brain injury. Patients (n = 10) received phenytoin loading doses (15–20 mg/kg) followed by a maintenance regimen (7 mg/kg/day) initiated within 12 hours of the loading dose. Phenytoin serum concentrations were measured serially on days 1, 2, 3, 5, 7, 9, and 10 at 1, 6, and 12 hours. Time‐invariant and time‐variant Michaelis‐Menten pharmacokinetic models were fit to the unbound phenytoin concentration‐time data (ADAPT II™). Albumin concentrations significantly decreased over time (p < 0.001) and were predictive of the phenytoin binding ratio (r2 = 0.373, p < 0.0001). The time‐variant model provided a superior fit of the data in 7 patients with no difference between models in 3 patients. Rapid inhibition of metabolism (Vmaxbaseline = 2.82 ± 2.35 mg/kg/day) was observed initially following injury. This was followed by induction of metabolism as reflected by a Vmaxinduced of 20.79 ± 13.71 mg/kg/day, which was approximately twofold higher than reported values for nonstressed children. Children with severe, acute neurotrauma were found to have markedly altered protein binding and phenytoin metabolism.

Comparison of microparticle enzyme and fluorescence polarization immunoassays in pediatric patients not receiving digoxin.

Previously, investigators have measured endogenous digoxin-like immunoreactive substances (DLIS) in pediatric patients. Digoxin-like immunoreactive substances may cross-react with digoxin assays to produce false-positive digoxin concentrations; hence, the validity of digoxin concentrations in pediatric patients is questionable. The authors compared the presence and magnitude of apparent DLIS using the microparticle enzyme immunoassay (MEIA) AxSYM Digoxin II and the fluorescence polarization immunoassay (FPIA) TDx Digoxin II, in the serum of 80 pediatric patients who were hospitalized with normal serum creatinine but had not been administered digoxin. Patients ranged in age from 1 day to 16 years (mean age, 4.96 +/- 5.17 years). Serum creatinine and total bilirubin were 0.5 +/- 0.18 mg/dl and 1.3 +/- 0.17 mg/dl, respectively. Forty-eight percent of MEIA samples and 79% of FPIA samples had measurable DLIS values. Digoxin-like immunoreactive substance concentrations for the MEIA (0.07 +/- 0.09 ng/ml) and FPIA assays (0.1 +/- 0.1 ng/ml) were statistically different (p = 0.01); however, no sample had a DLIS value >0.38 ng/ml. A poor correlation was noted between patient age, serum creatinine, total bilirubin, and DLIS concentration. The MEIA and FPIA assays effectively minimized DLIS cross-reactivity making both technologies clinically acceptable for serum digoxin measurement in pediatric patients with normal serum creatinine and total bilirubin.

Hemodynamic response to intentionally altered flow continuity of dobutamine and dopamine by an infusion pump in infants.

Study Objective. To evaluate the effect of an intentional alteration in infusion pump flow continuity on the hemodynamic stability of infants receiving either dobutamine or dopamine.

Implementation of Vancomycin Monitoring Criteria in a Pediatric Hospital

OBJECTIVES The primary objective of this retrospective study was to determine if implementation of vancomycin monitoring criteria could reduce the number of serum vancomycin concentrations obtained without adversely affecting patient outcomes. BACKGROUND Controversy regarding the correlation between serum vancomycin concentrations and its efficacy and/or toxicity persists. Little evidence has shown a correlation between vancomycin peak concentration (20–40 mg/L) and toxicity. Likewise, there is little information that supports an association between trough (5–15 mg/L) serum concentrations and clinical cure or in vitro killing rates. For these reasons, many question the clinical utility and cost-effectiveness of monitoring serum vancomycin concentrations. METHODS We reviewed medical records of 193 patients (1 d-19 yrs) who received vancomycin during a 2-month period before (Group 1; n = 100) and after (Group 2; n = 93) implementation of vancomycin monitoring criteria. RESULTS There was no difference (P > 0...

SEVERE, ACUTE NEUROTRAUMA ALTERS PHENYTOIN (DPH) PHARMACOKINETICS (PK) IN CHILDREN. |[dagger]| 463

In adults following acute, severe neurotrauma the metabolism of DPH is increased and albumin concentrations decrease. We evaluated 10 prepubescent children (3-11 yrs) who had severe, acute closed head injury (GCS 3-6) to determine the PK of IV DPH. Patients received a loading dose (17.7 ± 3.3 mg/kg) followed by a maintenance dose of 6.8 ± 1.6 mg/kg/day. DPH serum concentration-time data were collected up to 10 days following injury. DPH and albumin concentrations were determined by FPIA and RID, respectively. The Michaelis-Menten (MM) PK model and a time-variant MM model were fit to the total and unbound DPH concentration-time data (ADAPT II™). Unbound concentration-time data were the most reliable since albumin decreased over time (p<0.001). Also, the unbound fraction of DPH was inversely correlated with albumin concentration (r=0.578, p<0.001). The DPH PK parameters (mean ± sd) are summarized as follows:Table V, volume; Km, MM constant; Kind, rate constant of induction; Vmax, maximal velocity †Time variant MM model[Vmax=Vmaxinitial + Vmaxinduced (l-e-kind•T) for time-variant MM model] The time-variant MM model provided a superior fit of the data in 8 patients with no difference between models in 2 patients. In view of the Vmax for DPH reported for normal, non-stressed children (ie. 9.5-11 mg/kg/day), our PK data demonstrate that severe, acute neurotrauma markedly alters the metabolism of this drug. Specifically, a previously unrecognized rapid inhibition of metabolism (ie. mean Vmax = 0.11 mg/kg/day) occurs during the first hours post injury. This is followed by an induction of clearance as reflected by a Vmax (20.8 mg/kg/day) which is approximately 2 fold higher than “normal” values by 10 days post injury. These changes in DPH metabolism are associated with neurotrauma, and explain to a great degree, the variable dose requirements for DPH in these patients.

Increasing Linezolid-resistant Enterococcus in a Children's Hospital

We report a reduction in susceptibility to linezolid among Enterococcus isolates (98% in 2007 vs. 46% in 2014) in parallel with a 5-fold increase in linezolid use. A direct association could not be established as the majority of patients with linezolid nonsusceptible isolates did not have prior linezolid exposure. Nosocomial transmission of the nonsusceptible isolates could certainly have contributed.