Therapeutic Drug Monitoring of Levofloxacin in an Obese Adolescent with Intra-abdominal Infection Jeffrey J. Cies, PharmD, MPH, BCPS-AQ ID1-3; Wayne S. Moore II, PharmD1; Jason Parker, DO2-3; Paul Shea, MD2-3; Arun Chopra, MD1,4-5 1The Center for Pediatric Pharmacotherapy, LLC, Pottstown, PA, USA; 2St. Christopher’s Hospital for Children, Philadelphia, PA, USA; 3Drexel University College of Medicine, Philadelphia, PA, USA; 4NYU Langone Medical Center; 5 NYU Langone School of Medicine INTRODUCTION RESULTS RESULTS Levofloxacin, a broad-spectrum fluoroquinolone, is not commonly utilized in the pediatric intensive care unit (PICU) Pharmacokinetic (PK) parameters can be significantly altered for individuals in the PICU as a result of SIRS and sepsis in addition to extra-corporeal therapies such as continuous renal replacement and extra-corporeal life support Further, the impact of obesity on PK parameters in pediatrics in general is not well described Therefore, an understanding of the PK changes in critically ill obese children in the PICU is imperative to determining an optimal anti-microbial regimen for use Table 2. Pediatric Levofloxacin PK Parameters A 168 kg, 153 cm, 15 year old female with PMH of Prader-Willi syndrome and asthma Initially presented with respiratory distress secondary to asthma exacerbation due to non-adherence with her treatment regimen She failed non-invasive ventilation and was subsequently intubated for respiratory failure and progressed to requiring high frequency oscillatory ventilation On HD #11 an infectious workup was begun due to a fever, worsening clinical status and initiation of vasopressors and an empiric anti-microbial regimen of cefepime and clindamycin The urine culture subsequently grew E. coli and the respiratory culture grew Pseudomonas aeruginosa She continued to be febrile which was thought to be due to an intra-abdominal abscess On HD#14, the anti-microbial regimen was changed to levofloxacin due to continued fevers and no significant improvement in clinical status Levofloxacin was initiated at a dose of 1000 mg IV q24h Package Insert 750 mg IV Patient 1000 mg q24h 1000 mg q12h Co (mcg/mL) 12 8.79 10.5 Half-life (hrs) 8 6.4 5.18 AUC (mg*hr/L) 120-160 80 200 Based on the serum concentrations, the levofloxacin regimen was adjusted to 1000 mg IV q12h on day XX of therapy. XX days after the adjustment in levofloxacin regimen, she became afebrile, had WBC resolution and improvement in her overall clinical status while receiving a total duration of 21 days of levofloxacin therapy AIM The purpose of this case report is to describe the therapeutic drug monitoring of levoflocaxin in an obese, adolescent female in the PICU METHODS DISCUSSION AND CONCLUSIONS The highest dose reported to be given is 1000 mg IV q24h for patients with Mycobacterium tuberculosis The observed levofloxacin PK in our patient was different than what is represented in the package insert Obesity had a dramatic effect on the levofloxacin PK requiring a dose that is twice the highest dose reported to be given resulting in appropriate serum concentrations Anti-infective therapeutic drug monitoring must be part of the routine for patients with critical illness Samples: Levofloxacin was started at a dose of 1000 mg IV q24h that was infused over 60 minutes. Upon completion of the 60 minute infusion, levofloxacin levels were obtained at 0.5, 3.5, and 11.5 hours post infusion. Drug Levels: Concentrations for levofloxacin in plasma were determined by high performance liquid chromatography at the National Jewish PK lab (Denver, CO). The standard curve for the levofloxacin assay had an inter-day assay variability that was less than 15% across all reference samples. In the event samples were outside the upper limit of determination on the standard curve, a 1:2 or 1:5 dilution was made until the sample was within the standard curve. If samples were below the lower limit of determination on the standard curve, a value of “undetectable” was reported by the reference laboratory. Pharmacokinetics: A non-compartmental PK analysis was conducted to determine the elimination rate constant (ke), half-life (t1/2), volume of distribution (Vd), and calculate the area under the curve (AUC). Ct = Co (mcg/mL) *e-kt, Dose (mg)= Co (mcg/mL) *Vd (L) AUC = dose (mg) /CL, where CL = ke (hr-1) * Vd (L/kg). Ct= concentration at specified time, Co= initial concentration; CL = clearance; ke = elimination rate constant; Vd = volume of distribution; hr = hour AUC = area under the curve Table 1. Serum concentrations Time post infusion (hrs) Serum concentration 1000 mg q24h (mcg/mL) 1000 mg q12h 0.5 8.61 9.91 3.5 5.76 6.56 11.5 2.7 3.27 REFERENCES CORRESPONDENCE Levofloxacin package insert Lexi-Comp online Jeffrey J. Cies, PharmD, MPH, BCPS-AQ ID Pharmacy Clinical Coordinator Critical Care Clinical Pharmacist Infectious Diseases Clinical Pharmacist St. Christopher's Hospital for Children 3601 A Street, Philadelphia, PA 19134-1095 jeffrey.cies@tenethealth.com