In vitro activities of nucleoside analog antiviral agents against salmonellae

Abstract

Zidovudine (ZDV) has antibacterial activity against many members of the family Enterobacteriaceae, including ,ug/ml) and ddl (MIC50, 8 ,ug/ml; MIC range, 2 to 125 jg/ml) had concentration-dependent activity. Anti-SabnoneUla activity was not observed for ddC or ACV. Nine Escherichia coli blood isolates were inhibited by ZDV (MIC50, 0.125 ,ug/ml; MIC range, 0.031 to 1 ,ug/ml) to a greater degree than they were by ddl (MIC50, 62.5 ,ug/ml; MIC range, 31 to >62.5 ,ug/ml). Inoculum size affected susceptibility to ZDV and ddI for Salmonela and E. coli isolates. Resistance to ZDV or to ddl could be induced in vitro in SalmoneUa isolates, but cross-resistance was not observed. These results indicate that at concentrations achieved during the treatment of HIV infection, ZDV has activity against nontyphoidal salmonellae, although resistance can develop. ddI, ddC, and ACV at currently used dosages would not be expected to be effective in the prevention or treatment of Salmonella infections.

Screening under infection-relevant conditions reveals chemical sensitivity in multidrug resistant invasive non-typhoidal Salmonella (iNTS)

“…This finding aligns with previous data indicating AZT and other nucleoside analogs act as prodrugs that require phosphorylation by endogenous kinases. AZT can be phosphorylated by thymidine kinase into its 5’-mono-, -di-, and -triphosphate derivatives (29), and only AZT-triphosphate can be incorporated into growing DNA chains to terminate chain elongation (30). To confirm these results, we transferred the tdk E168* nonsense mutation into a wild-type ST313 iNTS background by allelic replacement and also generated a Δ tdk mutant and tested the susceptibility of these strains to AZT.…”

Screening under infection-relevant conditions reveals chemical sensitivity in multidrug resistant invasive non-typhoidal Salmonella (iNTS)

“…AZT can be phosphorylated by thymidine kinase into its 5 0 -mono-, -di-, and -triphosphate derivatives, 31 and only AZT-triphosphate can be incorporated into growing DNA chains to terminate chain elongation. 32 To confirm these results, we transferred the tdk E168 Ã nonsense mutation into a wild-type ST313 iNTS background by allelic replacement and also generated a Dtdk mutant and tested the susceptibility of these mutant strains to AZT. Both the tdk E168 Ã and Dtdk strains were resistant to AZT activity relative to wild-type ST313, with a 4500-fold shift in MIC (Fig.…”

Recovery of uncommon bacteria from blood: association with neoplastic disease.

“…However, with the advent of zidovudine therapy, the frequency of these Salmonella bacteremias appears to have declined. Sperber et al (290) have reported that this drug inhibits Salmonella spp. at clinically achievable levels.…”