Abstract
ObjectivesTo investigate the efficacy of zidovudine in combination with carbapenems against NDM-1-producing Enterobacteriaceae.MethodsMICs were determined using the broth microdilution method. The combinatory effects of zidovudine and carbapenems were examined using the chequerboard method and time–kill analysis.ResultsWe found that the NDM-1-producing strains were resistant to all carbapenems tested. FIC index from chequerboard assay demonstrated that zidovudine synergized with carbapenems against all the NDM-1 strains. Time–kill analysis demonstrated significant synergistic activity when a low level of zidovudine was combined with meropenem.ConclusionsZidovudine in combination with carbapenems produced synergistic activity against NDM-1 Enterobacteriaceae strains in vitro.
Highlights
Carbapenemase-producing Enterobacteriaceae (CPE) strains are associated with a reported mortality rate of up to 40%–50% in those patients who are infected.[1]
The rapid emergence of CPE, which are often resistant to many other antibiotics, has left the world with colistin as the last-resort treatment option, colistin is associated with both nephrotoxic and neurotoxic side effects.[2]
We showed that zidovudine (30-azido-30-deoxythymidine, previously known as azidothymidine) boosted the activity of colistin both in vitro and in vivo against multiple strains of resistant Enterobacteriaceae that produced ESBLs or NDM-1 or carried the mobilized colistin resistance gene.[3]
Summary
Carbapenemase-producing Enterobacteriaceae (CPE) strains are associated with a reported mortality rate of up to 40%–50% in those patients who are infected.[1] The rapid emergence of CPE, which are often resistant to many other antibiotics, has left the world with colistin as the last-resort treatment option, colistin is associated with both nephrotoxic and neurotoxic side effects.[2] it is crucial to boost the effectiveness of carbapenems against CPE. We showed that zidovudine (30-azido-30-deoxythymidine, previously known as azidothymidine) boosted the activity of colistin both in vitro and in vivo against multiple strains of resistant Enterobacteriaceae that produced ESBLs or NDM-1 or carried the mobilized colistin resistance (mcr) gene.[3] Zidovudine is an antiretroviral drug that is used in combination with other antivirals to prevent and treat HIV/AIDS It inhibits viral reverse transcriptase and was the first effective treatment for HIV/AIDS.[4] Synergy between zidovudine and other non-polymyxin antibiotics has not been published previously
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