Streptococcus pneumoniae
PharmacologyIn Vivo Pharmacodynamic Target Assessment of Antofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in a Neutropenic Murine Pneumonia ModelWe determined in vivo efficacy and target PK/PD exposures of antofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in the murine pneumonia model. The mean plasma free drug area under the concentration-time curve/MIC (fAUC/MIC) targets associated with stasis and 1-...
Experimental TherapeuticsA Choline-Recognizing Monomeric Lysin, ClyJ-3m, Shows Elevated Activity against Streptococcus pneumoniaeStreptococcus pneumoniae is a leading pathogen for bacterial pneumonia, which can be treated with bacteriophage lysins harboring a conserved choline binding module (CBM). Such lysins regularly function as choline-recognizing dimers. Previously, we reported a pneumococcus-specific lysin ClyJ comprising the binding domain from the putative endolysin gp20 from the ...
Editor's Pick Challenging Clinical Case in Antimicrobial ResistanceEmergence of Ceftriaxone Resistance during a Case of Pneumococcal Meningitis with Fatal EvolutionWe report a case of a 62-year-old man treated for Streptococcus pneumoniae meningitis by ceftriaxone and dexamethasone. After neurological improvement, neurological degradation by vasculitis occurred, despite effective concentrations of ceftriaxone in the serum and cerebrospinal fluid (CSF). S. pneumoniae...
Experimental TherapeuticsLinker Editing of Pneumococcal Lysin ClyJ Conveys Improved Bactericidal ActivityStreptococcus pneumoniae is a leading human pathogen uniquely characterized by choline moieties on the bacterial surface. Our previous work reported a pneumococcus-specific chimeric lysin, ClyJ, which combines the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) enzymatically active domain (EAD) from the PlyC lysin and the cell wall binding domain (CBD)...
Clinical TherapeuticsEffects of Delayed Antibiotic Therapy on Outcomes in Children with Streptococcus pneumoniae Sepsis...Delayed antimicrobial therapy is associated with poor outcomes in sepsis, but the optimal antibiotic administration time remains unclear. We aimed to investigate the effects of the time of antimicrobial administration on outcomes and evaluate an optimal empirical antibiotic administration time window for children with Streptococcus pneumoniae sepsis.
Mechanisms of ResistancePenicillin-Binding Protein Typing, Antibiotic Resistance Gene Identification, and Molecular Phylogenetic Analysis of Meropenem-Resistant Streptococcus pneumoniae Serotype 19A-CC3111 Strains in JapanSince the introduction of pneumococcal conjugate vaccines, the prevalence of non-meropenem-susceptible pneumococci has been increasing in Japan. In an earlier study, we demonstrated that multidrug-resistant serotype 15A-ST63 in Japan has a specific pbp1a sequence (pbp1a-13) that could promote meropenem resistance. To trace the origin of pbp1a, we analyzed isolates of serotype 19A-CC3111, which is the most...
Mechanisms of ResistanceReactive Oxygen Species Production Is a Major Factor Directing the Postantibiotic Effect of Fluoroquinolones in Streptococcus pneumoniaeWe studied the molecular mechanisms involved in the postantibiotic effect of the fluoroquinolones levofloxacin and moxifloxacin in Streptococcus pneumoniae. Wild-type strain R6 had postantibiotic effects of 2.05 ± 0.10 h (mean ± standard deviation [SD]) and 3.23 ± 0.45 h at 2.5× and 10× MIC of levofloxacin, respectively. Moxifloxacin exhibited lower effects of 0.87 ±...
PharmacologyPharmacokinetic/Pharmacodynamic Evaluation of Solithromycin against Streptococcus pneumoniae Using Data from a Neutropenic Murine Lung Infection ModelSolithromycin (CEM-101) is a novel fluoroketolide antimicrobial agent with activity against typical and atypical pathogens associated with community-acquired bacterial pneumonia. Using a neutropenic murine lung infection model, the objectives of this study were to identify the pharmacokinetic/pharmacodynamic (PK/PD) index most closely associated with efficacy and the magnitude of such indices associated with solithromycin efficacy...
Experimental TherapeuticsCombining Ceftriaxone with Doxycycline and Daptomycin Reduces Mortality, Neuroinflammation, Brain Damage, and Hearing Loss in Infant Rat Pneumococcal MeningitisDespite appropriate antibiotic therapy, pneumococcal meningitis (PM) is associated with a case fatality rate of up to 30% in high-income countries. Survivors often suffer from severe lifelong disabilities.
Mechanisms of ResistanceGain- and Loss-of-Function Screens Coupled to Next-Generation Sequencing for Antibiotic Mode of Action and Resistance Studies in Streptococcus pneumoniaeTwo whole-genome screening approaches are described for studying the mode of action and the mechanisms of resistance to trimethoprim (TMP) in the Gram-positive Streptococcus pneumoniae. The gain-of-function approach (Int-Seq) relies on a genomic library of DNA fragments integrated into a fucose-inducible cassette.