Giuliano S, Piccirilli A, Angelini J, Patriarca F, Fanin R, Martini L, Semenzin T, Fanin M, Lanini S, Bonomo R A, Perilli M, Tascini C
Infectious Diseases Clinic, Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC), Udine, Italy.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
JAC Antimicrob Resist. 2025 Jun 18;7(3):dlaf109. doi: 10.1093/jacamr/dlaf109. eCollection 2025 Jun.
resistant to third-generation cephalosporins, primarily due to the production of ESBLs and AmpC β-lactamases, poses a significant therapeutic challenge, particularly in immunocompromised patients. Ceftazidime/avibactam (CZA) has emerged as a potential carbapenem-sparing option, though data on its efficacy against AmpC-producing Enterobacterales remain limited.
We report a case of bloodstream infection (BSI) caused by an strain harbouring the plasmid-mediated AmpC enzyme DHA-1 in a neutropenic patient following allogeneic haematopoietic stem cell transplantation. The strain was characterized via whole-genome sequencing and conjugation assays. Therapeutic drug monitoring (TDM) was used to guide a continuous infusion CZA regimen in the context of augmented renal clearance (ARC).
The patient responded favourably to CZA therapy (2.5 g every 8 h via continuous infusion for 9 days), with rapid microbiological clearance and clinical improvement. TDM confirmed therapeutic plasma concentrations of both ceftazidime (29.57 mg/L) and avibactam (5.52 mg/L). Genomic analysis revealed multiple resistance genes (, , , ) and virulence factors, with the isolate identified as ST442, serotype O174:H9. The early switch from meropenem to CZA may have contributed to microbiota preservation and prevented subsequent infection by carbapenemase-producing , for which the patient was colonized.
This case illustrates the clinical utility of a carbapenem-sparing strategy guided by TDM in a high-risk, ARC patient with an AmpC-producing BSI. Continuous infusion CZA achieved pharmacokinetic/pharmacodynamic targets associated with therapeutic success, offering a promising alternative to carbapenems while mitigating the risk of resistance development and microbiota disruption.
对第三代头孢菌素耐药,主要是由于超广谱β-内酰胺酶(ESBLs)和AmpCβ-内酰胺酶的产生,这构成了重大的治疗挑战,尤其是在免疫功能低下的患者中。头孢他啶/阿维巴坦(CZA)已成为一种潜在的碳青霉烯类药物节省方案,尽管其对产AmpC肠杆菌科细菌疗效的数据仍然有限。
我们报告了1例异基因造血干细胞移植后的中性粒细胞减少患者发生血流感染(BSI),病原体为携带质粒介导的AmpC酶DHA-1的菌株。通过全基因组测序和接合试验对该菌株进行了鉴定。在肾清除率增加(ARC)的情况下,采用治疗药物监测(TDM)来指导CZA持续静脉输注方案。
患者对CZA治疗反应良好(每8小时持续静脉输注2.5 g,共9天),微生物学快速清除,临床症状改善。TDM证实头孢他啶(29.57 mg/L)和阿维巴坦(5.52 mg/L)的血浆浓度均达到治疗水平。基因组分析揭示了多个耐药基因(、、、)和毒力因子,该分离株被鉴定为ST442,血清型O174:H9。早期从美罗培南转换为CZA可能有助于维持微生物群,并预防随后由产碳青霉烯酶的细菌引起的感染,该患者已被该菌定植。
本病例说明了在1例产AmpC细菌引起BSI的高危ARC患者中,TDM指导的碳青霉烯类药物节省策略的临床应用价值。持续静脉输注CZA达到了与治疗成功相关的药代动力学/药效学目标,为碳青霉烯类药物提供了一种有前景的替代方案,同时降低了耐药性产生和微生物群破坏的风险。