LAUSR

First-generation oral cephalosporins (cephalexin and cefadroxil) have traditionally been considered second-line treatment options for uncomplicated lower urinary tract infections (uLUTIs).  However, in the current age of "bad bugs, few drugs" where there are increasingly limited oral options against resistant Enterobacteriaceae, there is an urgent need to rethink how best to utilize our available antibiotic armamentarium.  In this review, we examine the historical clinical trials and experimental studies of cephalexin and cefadroxil particularly through the modern lens of pharmacokinetics-pharmacodynamics (PK/PD) to better appreciate their efficacy in uLUTIs.  Furthermore, newer cefazolin-cephalexin surrogate testing as recommended by the Clinical and Laboratory Standards Institute (CLSI) and the United States Committee on Antimicrobial Susceptibility Testing (USCAST) has recategorized cephalexin in many instances from resistant to susceptible.  We conclude that cephalexin and cefadroxil have very good early bacteriological and clinical cures in uLUTIs due to non-extended-spectrum β-lactamase-producing (ESBL) Enterobacteriaceae comparable to many traditionally first-line agents.  It is possible to conveniently administer cephalexin as 500mg twice or thrice daily, similar to cefadroxil 500mg twice daily, which conceivably could allow either agent to be deployed as a fluoroquinolone-sparing alternative. However, cephalexin may be the more practical choice for many as reliable antimicrobial susceptibility test interpretative criteria (STIC) are provided by CLSI, USCAST, and the European Committee on Antimicrobial Susceptibility Testing (EUCAST), whereas direct cefadroxil SITC is offered only by EUCAST.