Interleukin (IL)-1β and IL-10 Host Responses in Patients With Staphylococcus aureus Bacteremia Determined by Antimicrobial Therapy

Background. Patient interleukin (IL)-1 beta and IL-10 responses early in Staphylococcus aureus bacteremia (SaB) are associated with bacteremia duration and mortality. We hypothesized that these responses vary depending on antimicrobial therapy, with particular interest in whether the superiority of beta-lactams links to key cytokine pathways. Methods. Three medical centers included 59 patients with SaB (47 methicillin-resistant S. aureus [MRSA], 12 methicillinsensitive S. aureus [MSSA]) from 2015-2017. In the first 48 hours, patients were treated with either a beta-lactam (n = 24), including oxacillin, cefazolin, or ceftaroline, or a glyco-/lipopeptide (n = 35), that is, vancomycin or daptomycin. Patient sera from days 1, 3, and 7 were assayed for IL-1 beta and IL-10 by enzyme-linked immunosorbent assay and compared using the Mann-Whitney U test. Results. On presentation, IL-10 was elevated in mortality (P =.008) and persistent bacteremia (P =.034), while no difference occurred in IL-1 beta. Regarding treatment groups, IL-1 beta and IL-10 were similar prior to receiving antibiotic. Patients treated with beta-lactam had higher IL-1 beta on days 3 (median +5.6 pg/mL; P =.007) and 7 (+10.9 pg/mL; P =.016). Ex vivo, addition of the IL-1 receptor antagonist anakinra to whole blood reduced staphylococcal killing, supporting an IL-1 beta functional significance in SaB clearance. beta-lactam-treated patients had sharper declines in IL-10 than vancomycin or daptomycin-treated patients over 7 days. Conclusions. These data underscore the importance of beta-lactams for SaB, including consideration that the adjunctive role of beta-lactams for MRSA in select patients helps elicit favorable host cytokine responses.