title: Efficacy profiles of daptomycin for treatment of invasive and noninvasive pulmonary infections with Streptococcus pneumoniae.
abstract: 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.
authors.affiliation: Clinic for Pulmonary Medicine, Department of Experimental Lung Research, Hannover School of Medicine, Hannover 30625, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Henken
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bohling
authors.forename: Jens
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: A David
authors.initials: AD
authors.lastname: Ogunniyi
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.forename: Vyvyan C
authors.initials: VC
authors.lastname: Salisbury
authors.forename: Dirk
authors.initials: D
authors.lastname: Wedekind
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Bode-Böger
authors.forename: Thomas
authors.initials: T
authors.lastname: Welsh
authors.forename: Franz C
authors.initials: FC
authors.lastname: Bange
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Maus
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D017576:Daptomycin