Re-evaluation of penicillin and ceftriaxone MIC results to predict susceptibility to the oral cephalosporin, cefpodoxime, in <i>Streptococcus pneumoniae</i> clinical isolates from the United States according to CLSI guidelines (2019–2021)

Clinical and Laboratory Standards Institute (CLSI) M100Ed24 (2024) states that <i>Streptococcus pneumoniae</i> susceptible to oral penicillin can be considered susceptible to various β-lactams, including oral cephalosporins. However, surrogacy guidance is not available for isolates nonsusceptible to oral penicillin. Instead, such isolates require specific MIC testing and interpretations for reporting susceptibility to oral cephalosporins, for which susceptibility testing is limited in most automated systems, and consequently restricts information pertaining to oral cephalosporins at an individual institution. This study evaluated the ability of the penicillin breakpoints to predict cefpodoxime and ceftriaxone susceptibilities against a recent collection of <i>S. pneumoniae</i> from United States hospitals according to CLSI guidelines. The susceptible breakpoint for oral penicillin (≤0.06 mg/L) predicted susceptibility to cefpodoxime and ceftriaxone. However, when isolates were nonsusceptible to oral penicillin (MIC, >0.06 mg/L), susceptibility to cefpodoxime could not be predicted due to a low categorical agreement (CA) (78.4%). Parenteral penicillin breakpoints also could not predict cefpodoxime susceptibility due to the elevated number of very major errors and a CA of 76.8%; however, these breakpoints could still be used as a surrogate marker to predict ceftriaxone susceptibility. Finally, ceftriaxone could be used for surrogate testing of cefpodoxime by applying breakpoints (≤0.25 mg/L for susceptible; 0.5 mg/L for intermediate; ≥1 mg/L for resistant) lower than the current clinical cutoffs. These analyses showed that isolates nonsusceptible to oral penicillin cannot be considered susceptible to cefpodoxime, and caution should be used when prescribing oral cephalosporins for the empiric treatment of community-acquired bacterial pneumonia.IMPORTANCESusceptibility results to oral cephalosporins are rarely available to guide therapy due to the limited number of drugs evaluated on common automated antimicrobial susceptibility testing (AST) systems (i.e., Vitek 2, MicroScan, and Phoenix). In addition, disk diffusion methods for determining <i>Streptococcus pneumoniae</i> susceptibility to β-lactam agents are not reliable, and a quantitative method, such as broth microdilution or gradient strips, is required. In addition, the epidemiology and serotypes of <i>S. pneumoniae</i> are constantly evolving; therefore, this work provides a re-evaluation of surrogacy testing for β-lactam agents against <i>S. pneumoniae</i> recently recovered from United States laboratories. The data provide the possible use of ceftriaxone MIC for determining cefpodoxime susceptibility. This should be of interest to microbiology laboratories and the scientific community.