Mendes Rodrigo E, Pierce Jessica V, Wright Kelly, Huband Michael D, Castanheira Mariana
Element Iowa City (JMI Laboratories), North Liberty, Iowa, USA.
Paratek Pharmaceuticals, King of Prussia, Pennsylvania, USA.
J Clin Microbiol. 2025 Jun 24:e0002725. doi: 10.1128/jcm.00027-25.
Clinical and Laboratory Standards Institute (CLSI) M100Ed24 (2024) states that 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 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 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 are constantly evolving; therefore, this work provides a re-evaluation of surrogacy testing for β-lactam agents against 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.
临床和实验室标准协会（CLSI）M100Ed24（2024）指出，对口服青霉素敏感的菌株可被视为对包括口服头孢菌素在内的各种β-内酰胺类药物敏感。然而，对于对口服青霉素不敏感的分离株，尚无替代指导意见。相反，此类分离株需要进行特定的最低抑菌浓度（MIC）检测和解读，以报告对口服头孢菌素的敏感性，而在大多数自动化系统中，敏感性检测有限，因此限制了单个机构中与口服头孢菌素相关的信息。本研究根据CLSI指南，评估了青霉素断点预测头孢泊肟和头孢曲松对近期从美国医院收集的菌株敏感性的能力。口服青霉素的敏感断点（≤0.06 mg/L）可预测对头孢泊肟和头孢曲松的敏感性。然而，当分离株对口服青霉素不敏感（MIC>0.06 mg/L）时，由于分类一致性（CA）较低（78.4%），无法预测对头孢泊肟的敏感性。由于极重大错误数量增加且CA为76.8%，胃肠外青霉素断点也无法预测头孢泊肟的敏感性；然而，这些断点仍可作为预测头孢曲松敏感性的替代标志物。最后，通过应用低于当前临床临界值的断点（敏感为≤0.25 mg/L；中介为0.5 mg/L；耐药为≥1 mg/L），头孢曲松可用于头孢泊肟的替代检测。这些分析表明，对口服青霉素不敏感的分离株不能被视为对头孢泊肟敏感，在为社区获得性细菌性肺炎的经验性治疗开具口服头孢菌素时应谨慎。重要性由于常见自动化抗菌药物敏感性检测（AST）系统（即Vitek 2、MicroScan和Phoenix）上评估的药物数量有限，很少有口服头孢菌素的敏感性结果可用于指导治疗。此外，用于确定对β-内酰胺类药物敏感性的纸片扩散法不可靠，需要定量方法，如肉汤微量稀释法或梯度条法。此外，肺炎链球菌的流行病学和血清型在不断演变；因此，这项工作对近期从美国实验室分离出的肺炎链球菌针对β-内酰胺类药物的替代检测进行了重新评估。这些数据提供了利用头孢曲松MIC来确定头孢泊肟敏感性的可能性。这应该会引起微生物学实验室和科学界的兴趣。
