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- W3011486928 abstract "ABSTRACT KBP-7072 is a novel aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative multidrug resistant bacterial isolates and strains. A ntibacterial activity and the PK/PD relationship were assessed using in vivo infection models. Six to 8-week-old female CD-1 mice were randomized to oral KBP-7072, minocycline and vehicle in a Klebsiella pneumoniae murine model, and KBP-7072, linezolid and vehicle for a Streptococcus pneumoniae murine model. Each animal was inoculated with K. pneumoniae or S. pneumoniae placed on the tip of the nares. KBP-7072 and antibiotics were started 3 hours post inoculation and continued for 3 days for K. pneumoniae , and were started 18 hours post inoculation and continued for 3 days for S. pneumoniae . Animals were euthanized at 0 (control group), 24, 48 or 72 hours post final dose. In vivo efficacy and PK/PD parameters were determined in Staphylococcus aureus isolate (6424MRSA-363), K. pneumoniae isolate (6680kpn-522), and E. coli isolate (6691eco-558) murine thigh infection models. In vivo efficacy and PK/PD parameters ( f AUC/MIC, f C max /MIC and %T>MIC free ) were calculated. Respiratory infection occurred in all inoculated mice. KBP-7072 produced a significant ( p <0.05 to <0.001) dose-dependent decrease in colony forming units (CFUs) at all doses and a dose-dependent increase in survival rate ( p <0.001 vs. vehicle). The median survival in all KBP-7072-treated groups was significantly greater vs. comparators ( p <0.001). These results demonstrate potent in vivo efficacy for KBP-7072 and determined that the AUC/MIC parameter was optimal for assessing bacteriostatic and bactericidal effects of KBP-7072." @default.
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- W3011486928 date "2020-03-20" @default.
- W3011486928 modified "2023-10-04" @default.
- W3011486928 title "In VivoEfficacy and PK/PD Modeling of KBP-7072, An Aminomethylcycline Antibiotic, in Neutropenic Pneumonia and Thigh Infection Models" @default.
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- W3011486928 doi "https://doi.org/10.1101/2020.03.18.998112" @default.
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