Non-lytic antibiotic treatment in community-acquired pneumococcal pneumonia does not attenuate inflammation: the PRISTINE trial

Groeneveld, Geert H; van der Reyden, Tanny J; Joosten, Simone A; Bootsma, Hester J; Cobbaert, Christa M; de Vries, Jutte J C; Kuijper, Ed J; van Dissel, Jaap T

Higher LTA concentrations in liquor in human patients with pneumococcal meningitis are associated with worse outcome. 40 In addition, in rabbits with pneumococcal meningitis, rifampicin reduces LTA release and the inflammatory response, and substantially improves survival. 13 Therefore, clinical trials with non-lytic antibiotics in pneumococcal meningitis should be developed. Rifampicin would be the antibiotic of choice, since it is most effective in killing S. pneumoniae while causing the least release of LTA per killed bacterial cell. 41 Unfortunately, we could not compare monotherapy of a nonlytic (rifampicin) antibiotic versus monotherapy of a lytic, b-lactam, antibiotic. This would be a highly relevant but different research question. The reasons for this are that the current Dutch guidelines for community-acquired pneumonia recommend b-lactam antibiotic (e.g. benzylpenicillin) treatment and the fact that rifampicin monotherapy may induce resistance during treatment. Therefore, it would have been unethical to withhold this first-line treatment from patients with community-acquired pneumonia. A significant difference in LTA release has been demonstrated in a rabbit model of S. pneumoniae meningitis, when comparing b-lactam monotherapy with rifampicin followed by b-lactam antibiotic therapy 6 h later. 42 In the rifampicin treatment group in our study, rifampicin was frequently (56%) given before b-lactam treatment, but with a median time frame of 5 min only (IQR " #10 to 60 min). Therefore, the antimicrobial killing of S. pneumonia in both groups might be primarily caused by the b-lactam (lytic) killing effect.