Combined antibiotic therapy improves survival in ovine septic shock

OBJECTIVE Sepsis increases morbidity and mortality of burn victims with smoke inhalation. Because P. aeruginosa is a frequent cause of pneumonia/sepsis, we hypothesized that combination of potent anti‐pseudomonas antibiotics, such as ciprofloxacin and piperacillin, would improve the outcome of septic shock in sheep. METHODS Sheep were surgically prepared for study. After a tracheotomy, acute lung injury was induced by cotton smoke and instillation of P. aeruginosa into lung. After the injury all sheep were awakened, mechanically ventilated, and resuscitated with Ringer's lactate solution. Animal groups: sham (n=6, non‐injured, non‐treated); injured (n=4: injured, untreated); treated (n=4: injured, treated with ciprofloxacin [0.4g, every 12 h] and piperacillin [3g, every 6h] 12h postinjury). RESULTS Sham animals survived 96h. All injured sheep reached criteria for sepsis and septic shock at 6h and 12h post‐injury, respectively. Mean survival time (mean±SEM) was 24±3 in injured group vs. 52±18 in treatment group. PaO 2 /FiO 2 was 69±10 in injured vs. 143±28 in treatment & MAP (mmHg) was 63±5 in injured vs. 71±10 in treatment at 18h post‐injury. We have also treated the sheep 6h post‐injury. Although the number of sheep in this group was only 2, both sheep survived 96h. CONCLUSIONS The combination antibacterial therapy may be effective treatment strategy for P. aeruginosa induced pneumonia/sepsis. Most septic patients are treated with antibiotics, so there also should be relevant models of sepsis. Support: NIH PO12GM066312, R01GM060688, Shriners of N. America #8450, #8954, #8820