Impact of organism species on microbial eradication and development of resistance in severe gram-negative pneumonia

This study evaluated the species differences in microbiological outcomes of Gram-negative bacteria (GNB) causing severe pneumonia from the viewpoint of area under the concentration-time curve/MIC ratio (AUC/MIC). In total, 111 strains of GNB from 74 patients were analyzed. Overall, microbiological eradication was achieved in 88% of the cases with initial AUC/MIC≥119. However, relapse often occurred when resistance developed or AUC/MIC was <176. Pseudomonas aeruginosa and Enterobacter spp. were commonly involved in failed microbiological eradication and development of resistance. The AUC/MIC required for initial eradication of P. aeruginosa was much higher (478) and antibiotic resistance in P. aeruginosa and Enterobacter spp. occurred less frequently with combination therapy (10.0% vs. 67.7%). These data argue that target magnitudes of AUC/MIC to eradicate GNB differ by species. Since antibiotic resistance developed in some species of GNB despite high AUC/MIC, strategies to minimize development of resistance, including combination therapy, must be considered.