1453. Cephalexin and Cefadroxil Are Not Therapeutic Equivalents for Uncomplicated Cystitis (uUTI): Further Analysis of Cefazolin Surrogate Susceptibility Testing Criteria

BACKGROUND: Cephalexin (CLEX) and cefadroxil are first-generation oral cephalosporins (OC’s) with similar antimicrobial spectrums, side-effects, and high urine concentrations; and are US-FDA approved for uUTI. Some stewardship programs are replacing CLEX (4 × daily) with cefadroxil (2 × daily) for dosing convenience. The US Committee on Antimicrobial Susceptibility Testing (USCAST) and CLSI recommend a cefazolin (CZOL) UTI surrogate breakpoint (≤16 mg/L; ≥15 mm) to predict susceptibility (S) for 7 OC’s against indicated Enterobacteriaceae. Direct cefadroxil antimicrobial S testing (AST) does not exist in US breakpoint interpretive documents, limiting specific results. METHODS: We reanalyzed and compared the CZOL surrogate testing for cefadroxil, CLEX and 5 other OC’s using AST data previously reported (Schuetz et al., 2013; IHMA). Broth microdilution AST was used against 205 isolates: E. coli (92; 40% with β-lactamase), K. pneumoniae (62), P. mirabilis (31; 10% with β-lactamase), and other enteric bacilli (20). A CZOL surrogate S breakpoint (≤16 mg/L) was used to infer S for OC’s. RESULTS: CZOL X cefadroxil cross-S accuracy rate was only 91.6% (unacceptable; < 95%) and the false resistance was 1.0% (acceptable). Cross-S accuracy was ≥ 97.0% for all tested OC’s except cefadroxil and cephradine (80.1%). CZOL spectrum vs. tested, indicated species (81.0%) was essentially identical for CLEX, cefprozil, cefaclor and loracarbef (80.0–81.0%). In contrast, cefdinir, cefpodoxime, and cefuroxime axetil S rates were underestimated 5.3 to 10.7% by the surrogate test. CLSI and USCAST did not list cefadroxil or cephradine for CZOL surrogate uUTI prediction; however the current (2019) US-FDA website document states “cefadroxil may be deduced from testing CZOL” regardless of clinical indication. CONCLUSION: Cefadroxil -S for guiding uUTI therapy cannot be accurately predicted by CZOL results at ≤16 mg/L (unacceptable surrogate accuracy and compromised spectrum/potency). Furthermore, direct cefadroxil AST does not exist in United States due to lack of breakpoint criteria (CLSI, USCAST) and reagent materials (MIC products or disks). CLEX or other OC’s remain preferred, more active (table) uUTI treatment choices having quality direct or surrogate AST guidances. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures.