Inhibiting PG signaling primes human whole blood to kill antibiotic-resistant bacteria. Healthy human peripheral blood was pre-incubated with/without penicillin and a pan EP/DP PG receptor antagonist targeted against EP₁, EP₂, EP₃-III, and DP₁ receptors as well as against individual PG receptors including EP4, DP1, and IP. Whole blood was then stimulated with either (A) serum-opsonized penicillin-susceptible (ST193) or (B) intermediate penicillin-resistant (ST199) S pneumonia for 1 hour. After which time, numbers of surviving S pneumoniae (cfu) were quantified 24 hours later on agar plates. Data were analyzed by one-way ANOVA and Bonferroni multiple comparison test. * values represent P < .05, ** values P < .01, and *** values P < .001.