Case report links off-label aztreonam–avibactam to clinical improvement in extremely preterm infant with NDM-producing Klebsiella pneumoniae

A retrospective single-patient case report described an extremely preterm male infant with life-threatening NDM-producing, carbapenem-resistant Klebsiella pneumoniae infection who improved after receiving off-label intravenous aztreonam–avibactam alongside surgical source control and other antimicrobial therapy. The infant was born at 24+2 weeks of gestation with a birth weight of 530 g and was treated at West China Second University Hospital of Sichuan University in Chengdu, China. His course included sepsis, pulmonary hemorrhage, disseminated intravascular coagulation, necrotizing enterocolitis, appendiceal perforation and suspected necrotizing fasciitis.

The infant initially received conventional mechanical ventilation and empirical ampicillin plus ceftazidime after an early episode of Escherichia coli bacteremia. On day 41 of life, while enteral feeding had been advanced to 60 mL/kg/day, he developed pulmonary hemorrhage and disseminated intravascular coagulation with scattered ecchymoses. His white blood cell count reached 2.5 × 10⁹/L, platelet count 29 × 10⁹/L and hemoglobin level 89 g/L. Blood metagenomic next-generation sequencing detected K. pneumoniae with 10 reads, and a rectal swab was positive for carbapenem-resistant K. pneumoniae.

Clinicians changed treatment to polymyxin B, administered with a loading dose of 25,000 IU/kg, equivalent to 2.5 mg/kg, followed by 15,000 IU/kg, or 1.5 mg/kg, every 12 hours, together with aztreonam at 30 mg/kg every 8 hours. Procalcitonin declined to a nadir of 0.25 ng/mL, but the pancytopenia did not improve substantially. On day 56, at a weight of 1.41 kg, the infant developed progressive abdominal distension, gastric retention, fever up to 37.7 °C, abdominal tenderness and absent bowel sounds, with fresh blood detected on digital rectal examination. His white blood cell count was 1.2 × 10⁹/L, C-reactive protein was 31.8 mg/L and procalcitonin was 7.13 ng/mL.

Imaging showed ascites and pneumatosis intestinalis. Exploratory laparotomy confirmed neonatal necrotizing enterocolitis with appendiceal perforation. Surgeons performed partial resection of necrotic bowel, appendectomy and terminal ileostomy. Postoperative blood mNGS detected K. pneumoniae with high confidence at 3,087 species-specific reads, while ascitic-fluid mNGS detected the organism at 259,429 reads. Ascitic-fluid testing also identified the NDM β-lactamase gene with 101 reads, SHV with 40 reads, APH(3′)-Ia with three reads and tet(A) with three reads. Enterococcus faecium was detected with moderate confidence at nine reads, although blood and ascitic-fluid cultures were negative.

After surgery, the infant received vancomycin at 15 mg/kg every 8 hours in combination with polymyxin B and aztreonam. Low-molecular-weight heparin was also used for thromboprophylaxis under an institutional protocol for critically ill neonates with infectious peritonitis. By day 60, erythema, swelling and progressive dark discoloration had developed over the anterior chest, abdominal wall and right lower limb. The right leg became indurated and tense while the dorsalis pedis artery remained palpable. With C-reactive protein at 13.3 mg/L and persistently low platelets, the lesions raised concern for sepsis-associated skin involvement and possible necrotizing fasciitis. Necrotizing fasciitis remained a suspected diagnosis because it was not confirmed surgically and the lesions resolved with antibiotic therapy alone.

Following multidisciplinary review, a risk-benefit assessment and guardian consent, the clinicians replaced aztreonam with off-label aztreonam–avibactam at 40 mg/kg every 8 hours, comprising aztreonam at 30 mg/kg and avibactam at 10 mg/kg, with each dose infused over three hours. Linezolid at 10 mg/kg every eight hours was added for Gram-positive coverage. On day 64 of life—the fourth day of aztreonam–avibactam therapy—the infant showed marked improvement, including substantial resolution of ecchymoses and abdominal distension, recovery of bowel sounds and a decline in C-reactive protein to 3.7 mg/L.

On day 66, the sixth day of treatment, blood mNGS was negative, linezolid was discontinued and enteral feeding was restarted. By day 70, the tenth treatment day, the ecchymoses and right-leg induration had completely resolved, enteral nutrition was advancing smoothly and C-reactive protein had fallen to 0.6 mg/L. Aztreonam–avibactam was continued for 24 days through day 84 because of the complicated intra-abdominal infection. No dose adjustment was required, and the clinicians identified no adverse events considered attributable to aztreonam–avibactam. The infant transitioned to non-invasive ventilation on day 84, reached full enteral feeding with stable weight gain by day 89 and was discharged after 117 days of hospitalization weighing 2,320 g.

Aztreonam–avibactam combines aztreonam, a monobactam stable against metallo-β-lactamase hydrolysis, with avibactam, which inhibits class A, C and some class D serine β-lactamases and can protect aztreonam from degradation by co-produced enzymes. The report states that the combination was approved in China on 30 June 2025 for complicated intra-abdominal infections and hospital-acquired pneumonia, including ventilator-associated pneumonia, in adults with limited or no alternative options, but had no approved neonatal indication. A phase IIa pediatric trial involving neonates and infants younger than nine months had been initiated in 2024 to provide pharmacokinetic and safety data.

The case has important limitations. The neonatal dose was selected through multidisciplinary consultation and extrapolation from standard neonatal aztreonam dosing, without systematic pharmacokinetic assessment or therapeutic drug monitoring, so optimal pharmacokinetic and pharmacodynamic targets were not established. Pathogen identification relied primarily on mNGS because cultures were negative, and standardized surveillance after treatment withdrawal was not performed to confirm durable pathogen clearance. Concomitant vancomycin, linezolid and surgery also limit attribution of the improvement to aztreonam–avibactam alone. As a retrospective single-patient report without a comparison group, the findings document an observed clinical response and apparent tolerability in one extremely preterm infant, but do not establish the regimen’s efficacy or support broad neonatal recommendations. Prospective pharmacokinetic, safety and efficacy data are needed to define its role in critically ill neonates.

Subject of Research: Off-label aztreonam–avibactam salvage treatment of NDM-producing Klebsiella pneumoniae in an extremely preterm infant

Article Title: From sepsis to necrotizing enterocolitis with appendiceal perforation: a case report of successful salvage therapy with aztreonam–avibactam in an extremely preterm infant with NDM-producing Klebsiella pneumoniae

Article References: He, Y., Huang, J., Du, B., Chen, Z., Huang, L., Shi, J., Zhang, M., Zhang, L., & Tang, J. (2026). From sepsis to necrotizing enterocolitis with appendiceal perforation: a case report of successful salvage therapy with aztreonam–avibactam in an extremely preterm infant with NDM-producing Klebsiella pneumoniae. Frontiers in Pharmacology, 17, Article 1919037. https://doi.org/10.3389/fphar.2026.1919037

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1919037

Keywords: aztreonam–avibactam, NDM-producing Klebsiella pneumoniae, extremely preterm infant, salvage therapy, neonatal sepsis, necrotizing enterocolitis, appendiceal perforation, metagenomic sequencing, case report, surgical source control, sepsis, necrotizing