Antibacterial therapy in ovine model of sepsis

Objective

Sepsis increases morbidity and mortality of burn victims with smoke inhalation. Since septic patients are usually on an antibiotic, we felt that antimicrobial therapy was appropriate to make our model clinically relevant. Because P. aeruginosa is a frequent cause of pneumonia/sepsis, we hypothesized that a combination of potent antipseudomonas antibiotics, such as ciprofloxacin and piperacillin, would improve the outcome of septic shock in sheep.

Methods

Sixteen sheep were surgically prepared for study. After a tracheotomy, acute lung injury/sepsis was induced by 48 breaths of cotton smoke inhalation and instillation of P. aeruginosa (2–5 × 10¹¹ CFU) into the lung. After the injury all sheep were awakened, mechanically ventilated, and resuscitated with Ringer's lactate solution. Animal groups: sham (n = 6, non-injured, nontreated); control (n = 5: injured, untreated); treated (n = 5: injured, treated with ciprofloxacin [0.4 g, every 12 hours] plus piperacillin [3 g, every 6 hours]). Antibiotics were intravenously administered starting 6 hours after the insult. The animals were sacrificed if they matched the termination criteria or survived over 96 hours. Statistical analysis was performed by ANOVA, significance was P < 0.05 *within group, ^†between groups. Data are the mean ± SEM.

Results

Cardiopulmonary variables were stable in the sham group and the survival rate was 100%. All injured sheep reached criteria for sepsis 6 hours postinjury. The mean survival time was significantly improved in the treatment group compared with the injured group (23 hours in control group vs 83 hours^† in treatment group). The control group showed a significant decrease in PaO₂/FiO₂ (P/F) ratio and mean arterial pressure (MAP, mmHg), left ventricular stroke work index (LVSWI, g × m m^-2 beat^-1), and systemic vascular resistance index (SVRI, dynes sec cm^-5 m^-2). The treatment group also showed a fall in the P/F ratio, MAP, LVSWI, and SVRI that was significantly improved after 18 hours compared with control (Table 1).

Table 1 abstract P97

Conclusion

The delayed therapy with ciprofloxacin and piperacillin was effective as a treatment strategy for P. aeruginosa-induced pneumonia/sepsis. This therapy increases the validity of our sepsis model.