A Critical Review of Cephalexin and Cefadroxil for the Treatment of Acute Uncomplicated Lower Urinary Tract Infection in the Era of "Bad Bugs, Few Drugs".

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 the available antibiotic armamentarium.  This review examines the historical clinical trials and experimental studies of cephalexin and cefadroxil, particularly through the modern lens of pharmacokinetics/pharmacodynamics (PK/PD), to better appreciate the efficacy of these drugs 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 beta-lactamase-producing (ESBL) Enterobacteriaceae comparable to many traditionally first-line agents.  Cephalexin can be conveniently administered as 500 mg twice or thrice daily, similar to cefadroxil (500 mg twice daily); therefore, either agent may be used as a fluoroquinolone-sparing alternative. Cephalexin may be the more practical choice for many clinicians because reliable antimicrobial susceptibility test interpretative criteria (STIC) are provided by CLSI, USCAST, and the European Committee on Antimicrobial Susceptibility Testing (EUCAST), whereas direct cefadroxil STIC is offered only by EUCAST.