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Therapeutic Drug Monitoring of Prolonged Infusion Aztreonam for Multi-Drug Resistant Pseudomonas aeruginosa: A Case Report.

Aztreonam, a broad-spectrum monobactam, is typically reserved for multidrug resistant (MDR) infections. Pharmacokinetic (PK) data to guide dosing in children, however, are limited to healthy volunteers or nonintensive care unit (ICU) patients. Impaired antibiotic delivery into tissue remains a major concern and may explain the high morbidity and mortality associated with MDR infections. Therefore, evaluating the PK changes in pediatric ICU patients is necessary to elucidate the most appropriate antimicrobial regimen. We describe the PK of prolonged infusion aztreonam in a patient with MDR Pseudomonas aeruginosa empyema. The 16-year-old tetraplegic male with a cervical spinal cord injury, chronic respiratory failure, and tracheostomy was admitted with a 2-day history of fever and hypoxemia. Chest x-ray revealed a left lower lobe infiltrate. On hospital day 2, computed tomography scan noted a massive collapse of the left lung with bronchiectasis and hepatization with a pneumatocele. He underwent bronchoscopy on days 2, 6, and 10 and the cultures subsequently grew P aeruginosa only sensitive to aztreonam (minimum inhibitory concentration [MIC] of 2-6 mg/L). A regimen of aztreonam 2 grams intravenously (IV) every 6 hours (each dose infused over 4 hours) and polymyxin B 1,000,000 units IV every 12 hours (each dose infused over 30 minutes) was initiated on day 3. On day 8, the aztreonam serum plateau concentration was 71 mg/L. Repeat respiratory and bronchoscopy cultures from days 19 to 37 remained negative. Aztreonam clearance was 2.3 mL/kg/min, which was significantly increased when compared with the 1.3 mL/kg/min suggested in the prescribing information based on adult data. A prolonged infusion of 2 grams of aztreonam every 6 hours (each dose infused over 4 hours) successfully attained 100% of the target serum and lung concentrations above the MIC for at least 40% of the dosing interval, and was associated with successful treatment of MDR P aeruginosa empyema.

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