Objective:

To report the off-label use of aztreonam-avibactam administered through outpatient parenteral antimicrobial therapy (OPAT) in a child with infectious pseudoarthrosis caused by NDM-producing *Klebsiella pneumoniae* and *Pseudomonas aeruginosa*.

Approach:

• Case Presentation: A 9-year-old Palestinian girl with multiple traumatic injuries from a bomb explosion developed persistent pain and drainage at a right tibial external-fixator site. Computed tomography showed distal tibial nonunion, and intraoperative bone cultures obtained after fixator removal grew *P aeruginosa* and ESBL- and NDM-producing *K pneumoniae*.
• Antimicrobial Treatment: Intravenous vancomycin was initiated empirically after bone sampling. Once culture and susceptibility results were available, treatment was changed to off-label aztreonam-avibactam because the *K pneumoniae* isolate was susceptible only to gentamicin and aztreonam-avibactam. The initial regimen provided 155 mg/kg/day of the aztreonam component every 6 hours as 3-hour intravenous infusions.
• OPAT Implementation: While awaiting repeat surgery for tibial malunion and persistent infection, the patient was discharged under hospital-at-home supervision. Caregivers received instruction in drug administration, intravenous-line care, recognition of warning signs, and replacement of elastomeric devices.
• Home Administration: Two 12-hour elastomeric pumps were used daily to provide continuous infusion. Each contained 1,500 mg of aztreonam and 500 mg of avibactam in normal saline and was replaced by the caregivers every 12 hours.

Key Findings:

• The patient remained afebrile and clinically stable and initially tolerated aztreonam-avibactam well.
• An alanine aminotransferase level of 110 U/L prompted temporary treatment interruption because of suspected hepatotoxicity. Liver enzyme levels normalized after 2 weeks, and OPAT was safely restarted.
• Definitive surgical management was completed without intraoperative complications.
• The patient completed a total of 6 weeks of aztreonam-avibactam therapy with good overall tolerability.
• Two months after treatment completion, she remained clinically stable, afebrile, and without signs or symptoms of persistent or recurrent infection.
• Home administration through elastomeric devices was feasible under monitoring, reduced hospitalization time, and supported family-centered care.

Interpretation:

This case supports the potential use of aztreonam-avibactam for selected pediatric osteoarticular infections caused by metallo-beta-lactamase-producing Gram-negative organisms when therapeutic alternatives are limited. It also demonstrates the feasibility of delivering prolonged aztreonam-avibactam through a monitored pediatric OPAT program. The transient liver-enzyme elevation underscores the importance of monitoring for possible hepatotoxicity during off-label treatment.

Limitations:

• This report describes a single patient and cannot establish comparative effectiveness, safety, or generalizability.
• Aztreonam-avibactam was used off-label and is not approved for pediatric use; its pediatric safety profile remains undefined.
• Therapeutic drug monitoring was not performed.
• Follow-up was limited to 2 months after treatment, preventing conclusions about long-term infection control or orthopedic outcomes.
• The dosing regimen was extrapolated from pediatric aztreonam prescribing recommendations rather than established pediatric aztreonam-avibactam dosing data.

Conclusion:

Off-label aztreonam-avibactam administered during hospitalization and through OPAT was feasible in this child with infectious pseudoarthrosis caused by NDM-producing *K pneumoniae* and *P aeruginosa*. Treatment was completed after temporary interruption for elevated liver enzymes, with no evidence of recurrent infection at short-term follow-up. Pediatric-specific studies are needed to define optimal dosing, safety, and long-term effectiveness.

Sources:

• Successful use of outpatient parenteral antimicrobial therapy (OPAT) aztreonam–avibactam in a pediatric case of an infectious pseudoarthrosis caused by NDM-producing Klebsiella pneumoniae and Pseudomonas aeruginosa