# Ceftazidime–avibactam for multidrug and pandrug-resistant gram-negative infections in critically Ill children: a single-center pediatric ıntensive care experience

## TL;DR

Ceftazidime–avibactam showed promising results in treating drug-resistant bacterial infections in critically ill children, with most patients showing improvement.

## Contribution

The study provides real-world evidence of ceftazidime–avibactam's effectiveness in critically ill pediatric patients with limited treatment options.

## Key findings

- Microbiological clearance was observed in 85.7% of patients with available data.
- Clinical improvement was noted in most critically ill children despite prior antibiotic exposure.
- Resistance emerged in one patient, emphasizing the need for close monitoring during treatment.

## Abstract

Carbapenem-resistant multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative infections represent a critical therapeutic challenge in pediatric intensive care units (PICUs), where effective treatment options are extremely limited. This study aimed to describe the real-world clinical outcomes and safety of ceftazidime–avibactam (CZA) in critically ill children with MDR/PDR infections. We conducted a retrospective observational study of pediatric patients aged 1 month to 18 years who received CZA for microbiologically confirmed MDR or PDR Gram-negative infections in a tertiary PICU between February 2021 and January 2025. Twenty-one critically ill children (median age 55 months, IQR 11–126) were included; two-thirds had underlying chronic conditions and 23.8% were immunosuppressed. Klebsiella pneumoniae was the predominant pathogen (85.7%). Microbiological clearance in follow-up cultures was observed in 85.7% of patients with available microbiological data, and clinical improvement was noted in most patients in this critically ill population. Infection-related mortality was 19% and was primarily associated with host-related factors, including younger age and immunosuppression. Resistance emergence during therapy was observed in one patient. Such resistance development during CZA treatment has been reported rarely in the literature and may involve mechanisms such as mutations in carbapenemase enzymes or alterations in bacterial permeability. In our study, resistance was detected during ongoing therapy in a single patient with Klebsiella pneumoniae, highlighting the importance of close microbiological monitoring in critically ill patients receiving prolonged treatment.

Conclusion: CZA was used as a salvage treatment in critically ill children with MDR and PDR Gram-negative infections, with favorable clinical and microbiological outcomes observed. These real-world data support its cautious incorporation into pediatric antimicrobial stewardship strategies in PICU settings.

What is Known:• Ceftazidime–avibactam is a promising agent against carbapenem-resistant Enterobacterales in adults.• Pediatric data remain limited, especially in critically ill children with MDR or PDR infections.What is New:• Ceftazidime–avibactam was used as salvage therapy for multidrug- and pandrug-resistant Gram-negative infections in critically ill children.• Clinical and microbiological response was achieved in a high-risk PICU population despite prolonged hospitalization and extensive prior antibiotic exposure.

What is Known:

• Ceftazidime–avibactam is a promising agent against carbapenem-resistant Enterobacterales in adults.

• Pediatric data remain limited, especially in critically ill children with MDR or PDR infections.

What is New:

• Ceftazidime–avibactam was used as salvage therapy for multidrug- and pandrug-resistant Gram-negative infections in critically ill children.

• Clinical and microbiological response was achieved in a high-risk PICU population despite prolonged hospitalization and extensive prior antibiotic exposure.