(973) Inhaled Versus IV Tobramycin for Empiric Gram-Negative Coverage in Ventilator-Associated PNA

Introduction: Broad spectrum antibiotics are necessary for treatment of ventilator-associated pneumonia (VAP) in critically ill patients. The use of aerosolized antibiotics may theoretically provide higher localized antimicrobial concentrations while decreasing systemic exposure and drug toxicities, but there is a lack of consistent data to support their empiric use. This study aims to compare clinical outcomes between patients receiving empiric inhaled (INHt) versus intravenous (IVt) tobramycin in combination with antipseudomonal antibiotics for treatment of VAP.

Methods: This single-health system, retrospective, cohort study included adult patients admitted to an ICU who received INHt or IVt in combination with IV antipseudomonal therapy for treatment of VAP. The primary outcome compared rates of treatment success between patients who received INHt vs IVt as empiric therapy. Secondary outcomes included 72-hr treatment success, incidence of acute kidney injury, change in modified SOFA (mSOFA) from baseline to end-of-therapy (EOT), ICU length of stay (LOS), hospital LOS, and all-cause mortality.

Results: A total of 40 patients were included in the analysis (INHt n=28; IVt n= 12). There was no significant difference in EOT treatment success (INHt 67.9% vs IVt 91.7%; p=0.231). There were no significant differences in 72-hour treatment success (INHt 85.7% vs IVt 100%; p=0.297), incidence of acute kidney injury (INHt 14.3% vs IVt 8.3%; p>0.99), hospital LOS (INHt 23 days [17-39.7] vs IVt 32.5 days [22.8-46]; p=0.125), ventilator duration (INHt 22.5 days [11.8-31] vs IVt 18.5 days [10.3-32.8]; p=0.745), or all-cause mortality (INHt 9% vs IVt 3%; p=0.725) between cohorts. The mSOFA significantly decreased from baseline to EOT in each group (INHt baseline 6.5 [5.0-9.0] vs INHt EOT 4.5 [2.3-7.0]; p< 0.001; IVt baseline 8.0 [5.3-9.8] vs IVt EOT 4.5 [2.0-6.0]; p=0.004), although comparisons of change in mSOFA from baseline to EOT was not significant when compared between cohorts (INHt -3.5 [-4.8 to -0.5] vs IVt -2.0 [-3.0 to -1.0]; p=0.139).

Conclusions: There was no significant difference in treatment success between INHt and IVt for empiric treatment of VAP. Further research is warranted to establish the role of aerosolized antibiotics in the treatment of VAP.