Zidovudine in synergistic combination with nitrofurantoin or omadacycline: and in murine urinary tract or lung infection evaluation against multidrug-resistant .
Ping Tian: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China. ORCID
Qing-Qing Li: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Ming-Juan Guo: Department of Hepatology, The First Affiliated Hospital of Jilin University, Changchun, China.
Yun-Zhu Zhu: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Rong-Qing Zhu: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Ya-Qin Guo: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Yi Yang: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Yan-Yan Liu: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Liang Yu: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China. ORCID
Ya-Sheng Li: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China. ORCID
Jia-Bin Li: Department of Infectious Diseases & Anhui Center for Surveillance of Bacterial Resistance, The First Affiliated Hospital of Anhui Medical University, Hefei, China. ORCID
Limited treatment options and multidrug-resistant (MDR) present a significant therapeutic challenge, underscoring the need for novel approaches. Drug repurposing is a promising tool for augmenting the activity of many antibiotics. This study aimed to identify novel synergistic drug combinations against based on drug repurposing. We used the clinically isolated GN 172867 MDR strain of to determine the reversal resistance activity of zidovudine (AZT). The combined effects of AZT and various antibiotics, including nitrofurantoin (NIT) and omadacycline (OMC), were examined using the checkerboard method, growth curves, and crystal violet assays to assess biofilms. An combination activity testing was carried out in 12 isolates of murine urinary tract and lung infection models were used to evaluate the therapeutic effects of AZT + NIT and AZT + OMC, respectively. The fractional inhibitory concentration index and growth curve demonstrated that AZT synergized with NIT or OMC against strains. In addition, AZT + NIT inhibited biofilm formation and cleared mature biofilms. , compared with untreated GN 172867-infected mice, AZT + NIT and AZT + OMC treatment decreased colony counts in multiple tissues ( < 0.05) and pathological scores in the bladder and kidneys ( < 0.05) and increased the survival rate by 60% ( < 0.05). This study evaluated the combination of AZT and antibiotics to treat drug-resistant infections and found novel drug combinations for the treatment of acute urinary tract infections. These findings suggest that AZT may exert significant anti-resistance activity.
