Extended-spectrum β-lactamases’ (ESBLs) production is the main resistance mechanism to third-generation cephalosporins (TGCs) in gram-negative bacilli. In Argentina, there is a high prevalence of cefotaximase-type ESBLs (CTX-M). For this reason, dissociated resistance phenotype (DRP) displaying a profile of resistance to cefotaxime (CTX) and susceptibility to ceftazidime (CAZ) might be detected. The aims of this study were to determine the prevalence of DRP in Enterobacterales clinical isolates, to characterize the mechanisms responsible for this phenotype and to evaluate the in vitro behaviour against different antibiotics. Sixty Enterobacterales resistant to any TGC were studied, and among them, 25% displayed a DRP. The β-lactamases associated with DRP were 5/11 CTX-M-2, 4/11 CTX-M-14, 1/11 CTX-M-15 and 1/11 CMY-2 in E. coli, 2/3 CTX-M-2 and 1/3 CMY-2 in P. mirabilis and 1/1 CTX-M-14 in K. pneumoniae. Furthermore, CTX-M-2 and CTX-M-14 were related with DRP in both wild-type isolates and the corresponding transconjugants. Time-kill experiments showed CAZ bactericidal activity on CTX-M-2-and CTX-M-14-producing strains and bacterial regrowth in those CMY-2 producers. An opposite behaviour was evident when cefepime (FEP) was used. However, CAZ and gentamicin combination showed a synergistic effect against the CMY-2 producers. We concluded that Enterobacterales with DRP responded differently to CAZ or FEP depending on the type of β-lactamase they possess, suggesting that these cephalosporins could be a therapeutic option. Therefore, the characterization of the involved resistance mechanism might contribute to define the appropriate antibiotic treatment.

超广谱β-内酰胺酶（ESBLs）的产生是革兰氏阴性杆菌对第三代头孢菌素（TGCs）的主要耐药机制。在阿根廷，头孢噻肟酶型 ESBL (CTX-M) 的流行率很高。因此，可能会检测到显示对头孢噻肟 (CTX) 耐药和对头孢他啶 (CAZ) 易感性的解离耐药表型 (DRP)。本研究的目的是确定 肠杆菌属 临床分离株中 DRP 的流行率，表征导致这种表型的机制，并评估针对不同抗生素的体外行为。六十种肠杆菌 研究了对任何 TGC 具有抗性，其中 25% 显示出 DRP。与 DRP 相关的 β-内酰胺酶在大肠杆菌中为 5/11 CTX-M-2、4/11 CTX-M-14、1/11 CTX-M-15 和 1/11 CMY-  2，2/3 CTX -M-2 和 1/3 CMY-2 在 奇异变形杆菌中，1/1 CTX-M-14 在 肺炎克雷伯菌中。此外，CTX-M-2 和 CTX-M-14 在野生型分离株和相应的转导结合物中都与 DRP 相关。计时杀灭实验表明，CAZ 对产生 CTX-M-2 和 CTX-M-14 的菌株具有杀菌活性，并且在这些 CMY-2 生产者中细菌再生。当使用头孢吡肟 (FEP) 时，相反的行为是明显的。然而，CAZ 和庆大霉素组合对 CMY-2 生产者显示出协同作用。我们得出结论， 肠杆菌 DRP 对 CAZ 或 FEP 的反应取决于它们所拥有的 β-内酰胺酶的类型，这表明这些头孢菌素可能是一种治疗选择。因此，相关耐药机制的表征可能有助于确定适当的抗生素治疗。