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Experimental Severe Pseudomonas aeruginosa Pneumonia and Antibiotic Therapy in Piglets Receiving Mechanical Ventilation^*

^* From the División Neumonología (Drs. Luna, Baquero, and Gando), Centro Universitario de Cirugía Experimental (Drs. Patrón and Morato), Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica (Drs. Absi, Famiglietti, and Vay), and División Patología, Facultad de Medicina (Drs. Von Stecher, Agustí, and Torres), Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, Argentina; and Hospital Clínic de Barcelona (Dr. Sibila), Institut del Tòrax, Servicio de Neumología, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.

Correspondence to: Carlos M. Luna, MD, FCCP, Acevedo 1070, Banfield (1828), Buenos Aires, Argentina; e-mail: cymluna{at}advancedsl.com.ar

Abstract

Background: Little is known about the general and local consequences of severe pneumonia under mechanical ventilation (SPMV) and how these are resolved with antibiotic therapy (ABT).

Objectives: To investigate the physiologic, biological, microbiological, and pathologic changes produced by experimental SPMV in a porcine model, and to evaluate the effect of ABT.

Methods: Pseudomonas aeruginosa was inoculated in 12 large white-Landrace piglets receiving mechanical that were killed after 72 h if death did not occur before. Vital signs, serum and BAL cytokines, serum C-reactive protein (CRP), and graded postmortem lung pathology and cultures (blood and quantitative BAL and lung) were evaluated. Six piglets received inappropriate ABT (no ABT or ceftriaxone), and six piglets received appropriate ABT (ciprofloxacin).

Measurements and main results: Pathologic and microbiological evidence of infection were present in all the animals in both groups. SPMV produced significant oxygenation and lung compliance worsening, increased serum CRP, and reduced BAL fluid tumor necrosis factor (TNF)-. Arterial thrombosis in lung pathology was associated with higher temperature, hypoxemia and low lung compliance, higher initial serum CRP and TNF- concentrations, and increased serum interleukin (IL)-6 and BAL IL-6 and TNF-. Reduced ABT reduced body temperature and culture positivity.

Conclusions: This model resembles VAP and has been used for studying pulmonary infection and inflammation related to mechanical ventilation. ABT reduced fever and bacterial burden in SPMV but had no effect on cytokine or CRP concentrations, oxygenation, or lung mechanics. Pulmonary artery thrombosis was associated with worse response to infection.

Key Words: animal • antibiotic therapy • mechanical ventilation • Pseudomonas aeruginosa pneumonia