Continuous Infusion of Aztreonam–Avibactam After High Loading Dose for an Infection Caused by an OXA-48- and NDM-1-Co-producing ST147 Klebsiella pneumoniae

Abstract

Introduction: Infections caused by metallo-βlactamase-producing Enterobacterales offer limited therapeutic options. Aztreonam–avibactam (ATM-AVI) provides a promising alternative, but its approved intermittent regimen is complex and can lead to substantial drug waste. Methods: We describe a case of mastoiditis with a retrotympanic abscess due to OXA-48and NDM-1-producing Klebsiella pneumoniae, managed with continuous infusion (CI) of ATM-AVI after a full-vial loading dose, supported by therapeutic drug monitoring (TDM) and whole-genome sequencing (EPISEQ CS V2.0, bioMérieux). Results: A 35-year-old man previously treated abroad for meningitis and brain abscesses presented with residual deep-seated infection caused by OXA-48-and NDM-1-producing K. pneumoniae. After initial treatment with ceftazidime–avibactam plus aztreonam, therapy was switched to ATM-AVI using a full-vial loading dose followed by CI. TDM demonstrated sustained plasma levels of both drugs, and the patient improved without adverse events. Conclusion: CI of ATM-AVI following a high loading dose was feasible, safe, and allowed optimized pharmacokinetic/pharmacodynamic (PK/PD) exposure while preventing drug wastage. Larger studies are warranted to determine the clinical utility of CI ATM-AVI across different MIC ranges.