Antibiotic therapy and clinical outcomes of penicillin-susceptible Staphylococcus aureus (PSSA) bloodstream infection (BSI): a ten-year retrospective cohort study

In recent years, the incidence of penicillin-susceptible S. aureus (PSSA) bloodstream infection (BSI) has increased worldwide. However, the preferred antibiotic remains uncertain due to concerns of inducible resistance to benzylpenicillin. We compared outcomes associated with benzylpenicillin versus other antibiotics and investigated risk factors influencing treatment failure. Patients were grouped into benzylpenicillin and non-benzylpenicillin beta-lactam treatment groups (including anti-staphylococcal penicillins and cephalosporins). The primary outcome was overall treatment failure (30-day all-cause mortality and/or 90-day relapse). Of 335 patients, 74 (22.09%) received benzylpenicillin and 261 (77.91%) received a non-benzylpenicillin beta-lactam. While rates of overall treatment failure (13.51% vs. 17.24%; P = 0.45) and occurrence of adverse drug events (6.76% vs. 7.66%; P = 0.79) were comparable to non-benzylpenicillin beta-lactams, benzylpenicillin showed faster microbiological clearance [3.00 days (IQR, 2.00-4.00 days) vs. 4.00 days (IQR, 3.00-5.00 days); P = 0.03] and fewer persistent infections (22.97% vs. 36.02%; P = 0.04), suggesting potential to improve patient outcomes. We also found that unknown source (aOR 4.63, 95% CI 1.47-14.64; P < 0.01) was associated with treatment failure, while review by Infectious Disease (ID) specialists (aOR 0.30, 95% CI 0.12-0.73; P = 0.01) was protective, stressing the importance of early ID referral and thorough source identification. This study highlights benzylpenicillin as an effective treatment for PSSA BSI.