ly-146032 and Pneumococcal-Infections

Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to approximately 70% or approximately 60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Daptomycin; Disease Models, Animal; Mice; Mice, Inbred C57BL; Pneumococcal Infections; Pneumonia, Pneumococcal; Sepsis; Streptococcus pneumoniae

This study aimed to evaluate the antimicrobial susceptibility profiles of 364 Streptococcus pneumoniae isolates and studied the genotypes of S. pneumoniae with high level beta-lactam resistance in Taiwan. Clonal complexes related to Spain(23F)-1, Taiwan(19F)-14, and Taiwan(23F)-15 were responsible for the spread of isolates with high beta-lactam resistance.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Genotype; Humans; Microbial Sensitivity Tests; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; Taiwan