# Safety and Tolerability of Inhaled Aztreonam in Children and Adolescents: A Systematic Review and Meta-Analysis

## TL;DR

Inhaled aztreonam is generally safe for children and adolescents, with few serious side effects, though it may increase the risk of severe respiratory issues.

## Contribution

This study provides a systematic review and meta-analysis of inhaled aztreonam safety in pediatric populations, revealing its tolerability and risk profile.

## Key findings

- Inhaled aztreonam does not increase common adverse events like cough or headache compared to placebo or other antibiotics.
- It is associated with a higher risk of serious respiratory disorders (grade 3/4) but shows a protective effect against pulmonary function decline.
- Adverse events are mostly mild and manageable, with rare systemic effects.

## Abstract

What are the main findings?
Comparative analyses showed that inhaled aztreonam did not increase the risk of common adverse events (cough, dyspnea, fever, headache) compared with placebo or other inhaled antibiotics; however, serious grade 3/4 respiratory disorders were more frequent.A reduced risk of pulmonary function decline was observed in patients receiving inhaled aztreonam, with most adverse events being mild, manageable, and reversible.

Comparative analyses showed that inhaled aztreonam did not increase the risk of common adverse events (cough, dyspnea, fever, headache) compared with placebo or other inhaled antibiotics; however, serious grade 3/4 respiratory disorders were more frequent.

A reduced risk of pulmonary function decline was observed in patients receiving inhaled aztreonam, with most adverse events being mild, manageable, and reversible.

What is the implication of the main finding?
The overall tolerability and safety profiles support the use of inhaled aztreonam in children and adolescents with cystic fibrosis, provided that clinicians monitor for severe respiratory reactions and rare hepatotoxic effects.Future trials with larger sample sizes and longer follow-up should evaluate dosing strategies and investigate rare adverse events to refine risk–benefit assessments in pediatric populations.

The overall tolerability and safety profiles support the use of inhaled aztreonam in children and adolescents with cystic fibrosis, provided that clinicians monitor for severe respiratory reactions and rare hepatotoxic effects.

Future trials with larger sample sizes and longer follow-up should evaluate dosing strategies and investigate rare adverse events to refine risk–benefit assessments in pediatric populations.

Respiratory infections and chronic lung disease are major contributors to morbidity in children. Aztreonam lysine for inhalation (AZLI) delivers high local antibiotic concentrations while limiting systemic exposure; however, its safety in younger patients remains uncertain. This systematic review and meta-analysis searched MEDLINE, CENTRAL, and Google Scholar for randomized and observational studies reporting adverse events in children and adolescents (≤18 years) receiving AZLI, with no date limit. Fourteen studies were included. Most studies were moderate-to-high quality. Comparative analysis showed no clinically relevant increase in common adverse events relative to placebo or other inhaled antibiotics. The pooled relative risk for severe respiratory disorders (grade 3/4) was 1.65 (95% CI 1.07–2.57), suggesting a higher incidence of serious respiratory events, while a protective effect against decline in pulmonary function was observed (RR 0.70, 95% CI 0.54–0.90). Adverse events were generally mild; serious adverse events and hospitalizations were infrequent and comparable between groups. Cumulative prevalence estimates indicated that respiratory irritation occurred in 10–25% of patients, whereas systemic effects were uncommon. Overall, AZLI appears to have an acceptable tolerability and safety profile in children and adolescents, though careful monitoring is warranted, especially for severe respiratory events.