Effect of High Blood Glucose Level on the Antimicrobial Activity of Daptomycin against Staphylococcus aureus in Streptozotocin-Induced Diabetic Mice

• Published in: Japanese Journal of Infectious Diseases Vol. 73; no. 3; pp. 205 - 209
• Main Authors: Kondo, Takayuki, Hagihara, Mao, Esaka, Yukihiro, Yamamoto, Takuhei, Uno, Bunji, Yamagishi, Yuka, Mikamo, Hiroshige
• Format: Journal Article
• Language: English
• Published: Japan National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee 29-05-2020; Japan Science and Technology Agency
• Subjects: Animal models; Animals; Anti-Bacterial Agents - therapeutic use; Antimicrobial activity; Blood; Blood glucose; Computer simulation; Daptomycin; Daptomycin - therapeutic use; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Disease Models, Animal; Drug resistance; Female; Glucose; High performance liquid chromatography; Hyperglycemia; Hyperglycemia - complications; Infections; Levels; Liquid chromatography; Methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Neutropenia - chemically induced; Neutropenia - microbiology; Penicillin; Specific Pathogen-Free Organisms; Staphylococcal Infections - drug therapy; Staphylococcus aureus; Staphylococcus infections; Streptozocin; Thigh; tissue penetration; tissue penetration; hyperglycemia; diabetes mellitus; Staphylococcus aureus; Daptomycin
• ISSN: 1344-6304; 1884-2836
• DOI: 10.7883/yoken.JJID.2019.457

Daptomycin is active against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), demonstrating efficacy in the treatment of infections in diabetic patients. However, daptomycin degrades in 5% glucose solution, and data on the efficacy of daptomycin in hyperglycemic patients are limited. Therefore, we investigated the effect of high levels of blood glucose on the efficacy and concentration of daptomycin. The efficacy of simulated human exposure to daptomycin against S. aureus was compared in a neutropenic murine thigh model, with and without hyperglycemia. A clinically isolated MRSA strain and S. aureus ATCC25923 standard strain were used. Daptomycin concentrations, in the serum and at the infected site, were preliminarily analyzed using the high-performance liquid chromatography assay. Even in hyperglycemic mice, the mean concentration of daptomycin in hyperglycemic mice was equivalent to that in untreated mice within the physiological blood glucose levels. Additionally, the efficacy of daptomycin against MRSA was equal to that observed in the untreated and hyperglycemic mice. Based on similar studies using S. aureus ATCC25923, the efficacy in hyperglycemic mice was equal to or greater than that observed in untreated mice. In conclusion, daptomycin is an alternative therapeutic option in diabetic mice with serious staphylococcal infections, regardless of blood glucose control in this animal model.