Source: Annual Congress 2002 - Clinical aspects of antibiotic and nonantibiotic therapy of pneumonia in the ICU
Disease area: Respiratory critical care, Respiratory infections

Abstract

Direct delivery of antibiotics could achieve effective bronchial drug concentrations without systemic toxicity. Aim: To assess which method of administration, endotracheal instillation vs nebulization, obtains effective concentrations in lower respiratory tract of imipenem (I) or tobramycin (T). Methods: Prospective, randomized, non-blind clinical study. We included 18 ICU patients on mechanical ventilation. Two doses of 1g of I separated 8 hours and two doses of 200 mg of T separated 12 hours were either nebulized or instilled directly in the tracheal tube according to a random list. Five bronchoaspirates (2 fiberoptic bronchoscopy, 3 blind) and 5 blood samples were collected on a timed schedule in the 12 hours after the last dose of antibiotic. Antibiotic concentrations were measured by high performance liquid chromatography (HPLC). Results: Levels of antibiotic in respiratory samples were high and much beyond usual MIC of common gram negative bacteria. Concentration of instilled I was 4695 +/- 3580mcg/mL after 1h and, 4278 +/- 3104mcg/mL 2h after the last dose. These levels were much higher than those obtained when nebulized (76.1 +/- 72 mcg/mL 1h after last dose). With T we obtained comparable high concentrations on respiratory samples when nebulized (102 +/- 61 mcg/mL after 2h) or instilled (142 +/- 125 mcg/mL after 2h). No significant antibiotic absorption could be measured in serum.
Conclusion: Antibiotic instillation of Imipenem or Tobramycin achieves high concentrations in lower respiratory tract secretions and has a potential role in the treatment of mechanically ventilated patients with respiratory infections. Supported by grant FISS: 00/0283 2000-2002


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Citations should be made in the following way:
M. Adrover, J. R. Badia, D. Soy, M. Ferrer, A. Alarcón, N. Coromines, C. Codina, A. Torres (Barcelona, Spain). Pharmacokinetics of instilled versus nebulized tobramycin or Imipenem in mechanically ventilated ICU patients. Eur Respir J 2002; 20: Suppl. 38, 232

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