Silent evolution: β-lactam resistance acquisition in a virulent Salmonella enterica paratyphi B during systemic...

The emergence of antimicrobial resistance during therapy is often monitored solely at the site of clinically apparent infection, potentially overlooking cryptic evolution in unexamined anatomical reservoirs. We report a case of acute cholecystitis caused by a virulent Salmonella enterica serovar Paratyphi B. While the bile isolate was susceptible to β-lactams, a fecal isolate obtained on day 7 of otherwise successful systemic therapy harbored an IncI1-ST1 plasmid encoding bla_CTX-M-14, conferring extended-spectrum β-lactamase resistance. Whole-genome sequencing confirmed the isolates were clonal (eight single-nucleotide polymorphisms apart). This case demonstrates "silent evolution" of resistance within the intestinal reservoir during effective treatment of the site of clinically apparent infection. It provides direct clinical evidence that therapeutic success can mask the concurrent development of resistance in secondary sites, a phenomenon that likely leads to a significant underestimation of intrahost resistance evolution.