Bacteremic Streptococcus pneumoniae
pneumonia is one of the most severe forms of invasive
pneumococcal disease (IPD) and with particularly high case-fatality rates among the elderly and individuals with comorbidities, exacerbated by rising antibiotic resistance and time to initiation of
therapy. Here, we examined the efficacy of the preclinical "vancapticin"
glycopeptide MCC5145 against fulminant
infection by S. pneumoniae serotype 2 strain D39 in a bioluminescent, neutropenic mouse model of bacteremic
pneumonia. MCC5145 is a semisynthetic
vancomycin derivative chemically modified at the C-terminus with a membrane-targeting motif designed to preferentially bind the anionic bacterial surface. We show that similar to
vancomycin, subcutaneous administration of MCC5145 to mice 1 day after intranasal
infection with a bioluminescent derivative of S. pneumoniae D39 elicited time and concentration-dependent reduction in total flux in the lungs and blood. Together, our finding supports the further development of MCC5145 as a potential new treatment option for
pneumonia and/or bacteremic
pneumonia in clinical settings, particularly for immunocompromised individuals. IMPORTANCE S. pneumoniae (the pneumococcus) causes severe community acquired lung and blood
infection, especially among the elderly and people with underlying medical conditions and/or weakened immune systems. The rising incidence of antibiotic resistance and delays between diagnosis of
infection and commencement of effective
therapy make treatment difficult and result in high mortality rates. In this work, we show that a new derivative (MCC5145) of an existing
antibiotic (
vancomycin) rapidly eradicated lethal pneumococcal challenge from the lungs and blood of mice with a suppressed immune system. Our findings support that MCC5145 is a promising option for the treatment of lung and blood
infections caused by the pneumococcus at point-of-care settings, particularly for the elderly and individuals with a weakened immune system.