Tiseo Giusy, Giordano Cesira, Leonildi Alessandro, Riccardi Niccolò, Galfo Valentina, Limongi Federica, Nicastro Manuela, Barnini Simona, Falcone Marco
Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.
Microbiology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
JAC Antimicrob Resist. 2023 Jun 14;5(3):dlad078. doi: 10.1093/jacamr/dlad078. eCollection 2023 Jun.
Carbapenem-resistant (CRAB) infections are associated with high mortality rates. The optimal treatment regimen for CRAB has not been defined. Cefiderocol has been recently introduced in the armamentarium against CRAB but there is concern about treatment-emergent resistance. Since mortality rates in CRAB infections remain high, further antibiotic options are needed.
We report a case of severe infection by CRAB resistant to both colistin and cefiderocol treated with sulbactam/durlobactam and describe the molecular features of the strain. Susceptibility to cefiderocol was detected by disc diffusion according to EUCAST breakpoints. Susceptibility to sulbactam/durlobactam was determined by Etest according to preliminary breakpoints provided by Entasis Therapeutics. Whole Genome Sequencing (WGS) of the CRAB isolate was performed.
A burn patient with ventilator-associated pneumonia by CRAB resistant to colistin and cefiderocol received sulbactam/durlobactam as compassionate use. She was alive after 30 days from the end of therapy. Complete microbiological eradication of CRAB was achieved. The isolate harboured , and . A missense mutation in PBP3 was detected. The isolate harboured a mutation in the TonB-dependent siderophore receptor gene that showed a frameshift mutation causing a premature stop codon (K384fs). Moreover, the gene, which is orthologous to , was interrupted by a transposon insertion P635-IS (IS family).
Further treatment options for severe infections by CRAB resistant to all available antibiotics are urgently needed. Sulbactam/durlobactam may be a future option against MDR .
耐碳青霉烯类鲍曼不动杆菌（CRAB）感染与高死亡率相关。CRAB的最佳治疗方案尚未确定。头孢地尔最近已被纳入抗CRAB的药物库，但人们担心会出现治疗后耐药性。由于CRAB感染的死亡率仍然很高，因此需要更多的抗生素选择。
我们报告了1例对黏菌素和头孢地尔均耐药的CRAB严重感染病例，该病例接受了舒巴坦/度洛巴坦治疗，并描述了该菌株的分子特征。根据欧盟CAST标准，通过纸片扩散法检测对头孢地尔的敏感性。根据Entasis Therapeutics提供的初步标准，通过Etest法测定对舒巴坦/度洛巴坦的敏感性。对CRAB分离株进行全基因组测序（WGS）。
1例因CRAB导致呼吸机相关性肺炎的烧伤患者，对黏菌素和头孢地尔耐药，接受了舒巴坦/度洛巴坦的同情用药治疗。治疗结束30天后她仍然存活。实现了CRAB的完全微生物清除。分离株携带 、 和 。检测到PBP3基因存在错义突变。分离株在TonB依赖性铁载体受体基因 中发生突变，表现为移码突变，导致提前出现终止密码子（K384fs）。此外，与 直系同源的 基因被转座子插入P635-IS（IS家族）中断。
迫切需要针对对所有可用抗生素均耐药的CRAB严重感染的进一步治疗选择。舒巴坦/度洛巴坦可能是未来对抗多重耐药菌的一种选择。
