Escherichia coli producing AmpC DHA-1 bacteraemia in neutropenic leukemic patient: continuous infusion ceftazidime/avibactam as a carbapenem sparing regimen

TL;DR

A neutropenic patient with a drug-resistant E. coli infection was successfully treated with ceftazidime/avibactam using continuous infusion and drug monitoring.

Contribution

Demonstrates successful carbapenem-sparing treatment of AmpC-producing E. coli in a high-risk patient using continuous infusion and therapeutic drug monitoring.

Findings

Ceftazidime/avibactam achieved therapeutic plasma concentrations and cleared the infection in a neutropenic patient.

Genomic analysis identified multiple resistance genes and virulence factors in the E. coli isolate.

Early switch to CZA may have preserved microbiota and prevented secondary carbapenem-resistant infection.

Abstract

Escherichia coli 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 E. coli 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 (blaDHA-1, qnrB4, mphA, dfrA7) and virulence factors, with the isolate identified as E. coli ST442, serotype O174:H9. The early switch from meropenem to CZA may have contributed to microbiota preservation and prevented subsequent infection by carbapenemase-producing Klebsiella pneumoniae, 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 E. coli 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.

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