Efficacy of Zidovudine-Amikacin Combination Therapy and in a Rat Tissue Cage Infection Model against Amikacin-Resistant, Multidrug-Resistant .

Multidrug-resistant (MDR) infections have become an urgent global threat to public health. The aim of this study was to evaluate the efficacy of zidovudine-amikacin combination therapy and . Molecular characteristics and antibiotic resistance profiles of 53 amikacin-resistant MDR, extensively drug-resistant (XDR), or pan-drug-resistant (PDR) clinical isolates were examined via PCR and susceptibility testing. Checkerboard assays were performed for these 53 isolates to assess synergistic effects of the zidovudine-amikacin combination, and static time-kill experiments were performed for four XDR or PDR isolates. A Galleria mellonella model and a rat tissue cage infection model were established to assess synergistic effects. The gene was detected in 25 (47.2%) isolates, followed by in 5 (9.4%) isolates, in 27 (50.9%) isolates, and in 3 (5.8%) isolates. Checkerboard assays showed the synergy of this combination against 38 (71.7%) isolates. The time-kill assays further confirmed that zidovudine strongly synergized with amikacin against four XDR or PDR isolates. The Galleria mellonella model study showed that the survival benefit of zidovudine-amikacin combination therapy was significantly better than that of monotherapy for those four isolates. Furthermore, the rat tissue cage infection model study showed that zidovudine-amikacin combination therapy displayed more potent bactericidal activity than monotherapy after 3 and 7 days of treatment for the above four isolates. Our data support the idea that the zidovudine-amikacin combination could be a plausible alternative therapy against infections with amikacin-resistant MDR , especially with XDR and PDR . Our study revealed for the first time that the zidovudine-amikacin combination shows a significant bactericidal effect against amikacin-resistant MDR, XDR, and PDR . Second, using and approaches, our study showed that zidovudine strongly synergized with amikacin against amikacin-resistant MDR isolates. Most importantly, with regard to survival benefit, pharmacokinetics, and bactericidal effects, our experiment demonstrated the effectiveness of zidovudine-amikacin.