Scientific Publications by FDA Staff

Antimicrob Agents Chemother 2015 Sep;59(9):5435-44

An in vitro combined antibiotic/antibody treatment eliminates toxicity from Shiga toxin-producing E. coli.

Skinner C, Zhang G, Patfield S, He X

Treating Shiga toxin-producing Escherichia coli (STEC) gastrointestinal infections is a difficult endeavor. The utility of antibiotics as an STEC treatment is controversial since antibiotic resistance among STEC isolates is widespread and certain antibiotics dramatically increase expression of Shiga toxin (Stx), one of the most important virulence factors in STEC. Stx contributes to life-threatening hemolytic uremic syndrome (HUS), which develops in a considerable portion of patients with STEC infections. Understanding the antibiotic resistance profiles of STEC isolates and the Stx induction potential of promising antibiotics are essential in evaluating any antibiotic treatment of STEC. In this study, forty-two O157:H7 and non-O157 STEC (including the "big six") isolates were evaluated for their resistance against 22 antibiotics using an antibiotic array. Tigecycline inhibited the growth of all the tested STEC isolates, and also inhibited production of Stx, Stx2 in particular. In combination with neutralizing antibodies to Stx1 and Stx2, the tigecycline/antibody treatment fully protected Vero cells from Stx toxicity, even when the STEC bacteria and Vero cells were co-cultured together. The combination of an antibiotic like tigecycline with neutralizing antibodies presents a promising strategy for future STEC treatments.