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

Infections caused by metallo-β-lactamase-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. We describe a case of mastoiditis with a retrotympanic abscess due to OXA-48- and 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). 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. 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. Serious infections caused by certain bacteria have become very difficult to treat. Some strains, such as Klebsiella pneumoniae that produce two enzymes called New Delhi metallo-β-lactamase and oxacillinase-48, can block the effect of almost all commonly used antibiotics. Because of this resistance, doctors have very few treatment options left, and patients may develop deep-seated infections that are hard to control. Aztreonam combined with avibactam is a new antibiotic pairing that can overcome this type of resistance. Aztreonam is not broken down by the New Delhi enzyme, and avibactam protects it from other enzymes. However, the usual way of giving this treatment can be complicated and can lead to unnecessary waste of the medication. In this study, we describe the case of a young man with a rare and severe ear and skull infection caused by these highly resistant bacteria. We used an alternative method of giving aztreonam and avibactam: we administered a full first dose and then provided the treatment continuously through an infusion pump. This approach aimed to keep the antibiotic level steady in the body and avoid wasting medication. We monitored the levels of both drugs in the patient’s blood and found that they stayed within the expected range. The patient improved without any side effects, and the infection resolved. This case shows that continuous infusion of aztreonam–avibactam may be an effective and practical treatment for severe infections caused by bacteria that resist most antibiotics. More research is needed to confirm these findings in larger groups of patients.