Relationship between sputum bacterial load and lung function in children with cystic fibrosis receiving tobramycin - 01/04/25

Doi : 10.1016/j.rmed.2025.108042

Kiera Harwood ^a,^b,^⁎ , Stephen Duffull ^c, Tony Lai ^d,^e, Alice Lei ^b, Sarah Manning ^f, Casey Pell ^g, Sarath Ranganathan ^a,^h,ⁱ, Phil Robinson ^a,^h,ⁱ, Geraint Rogers ^f,^j, Indy Sandaradura ^d,^e, Catherine Satzke ^a,^g,^k, Shivanthan Shanthikumar ^a,^h,ⁱ, Steven Taylor ^f,^j, Amanda Gwee ^a,^b,^l
^a Department of Paediatrics, The University of Melbourne, Parkville, Australia
^b Antimicrobials Group, Murdoch Children's Research Institute, Parkville, Australia
^c Certara, New Jersey, United States
^d The Children's Hospital at Westmead, Sydney, Australia
^e University of Sydney, Sydney, Australia
^f Microbiome and Host Health, South Australian Health and Medical Research Institute, South Australia, Australia
^g Translational Microbiology Group, Murdoch Children's Research Institute, Parkville, Australia
^h Department of Respiratory and Sleep Medicine, Royal Children's Hospital, Parkville, Australia
ⁱ Respiratory Diseases Group, Murdoch Children's Research Institute, Parkville, Australia
^j Infection and Immunity, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, Australia
^k Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, Australia
^l Department of General Medicine and Infectious Diseases, Royal Children's Hospital, Parkville, Australia

^⁎Corresponding author. Department of Paediatrics, The University of Melbourne, Parkville, Australia.Department of PaediatricsThe University of MelbourneParkvilleAustralia

Abstract

Background

Chronic pulmonary infection with pathogens such as Pseudomonas aeruginosa is associated with lung function decline and increased mortality in people with cystic fibrosis (CF). The relationship between sputum bacterial load and the severity of pulmonary exacerbations remains unclear. This study aimed to explore the relationship between sputum bacterial load and clinical response to antibiotic treatment of pulmonary exacerbations in children with CF.

Methods

Multicentre prospective longitudinal study of children with CF receiving IV tobramycin for a pulmonary exacerbation who had prior isolation of Gram-negative bacteria and able to expectorate sputum. Lung function (FEV₁) and sputum bacterial load were assessed. Bacterial load was performed using quantitative PCR on either intact (live) bacterial cells or all bacterial DNA (live + dead) and targeted either P. aeruginosa only or all bacteria.

Results

Twelve children (14 admissions) were enrolled and each provided ≥2 sputum samples; 11 children (13 admissions) also had ≥2 FEV₁ measurements. In 10 admissions where FEV₁ improved, five showed a reduction in all live bacteria, with a median reduction by 8.65 × 10⁶ copies/g (73 % reduction). Live P. aeruginosa was detected in 8/10 children and in seven, a median reduction of 2.99 × 10⁷ copies/g (90 % reduction) was observed. Improved FEV₁ correlated with greater reductions in live + dead P. aeruginosa (ρ = −0.63, p = 0.04).

Conclusion

A greater reduction in total sputum P. aeruginosa bacterial load (live + dead) was associated with improved lung function (FEV₁) in children with CF receiving tobramycin.

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Highlights

•	Tobramycin is commonly used for pulmonary exacerbations in cystic fibrosis.
•	The link between sputum bacterial load and clinical response to therapy is unclear.
•	A reduction in sputum P. aeruginosa load correlated with improved lung function.
•	CFTR modulators (LUM/IVA, TEZ/IVA) did not affect sputum bacterial load.

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Keywords : Microbiome, Lung, Exacerbation, Antibiotics

Plan

Introduction

Methods

Patients and data collection

Sputum bacterial load

Tobramycin AUC_24,ss and P. aeruginosa MIC calculations

Statistical analysis

Results

Cohort characteristics and antibiotic dosing details

Relationship between initial FEV₁ and initial sputum bacterial load

Relationship between the change in FEV₁ and change in sputum bacterial load

Relationship between tobramycin AUC_24,ss, sputum bacterial load and FEV₁

Influence of other CF-associated pathogens

Discussion

CRediT authorship contribution statement

Funding

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Article 108042- avril 2025 Retour au numéro

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Relationship between sputum bacterial load and lung function in children with cystic fibrosis receiving tobramycin - 01/04/25

Abstract

Background

Methods

Results

Conclusion

Highlights

Plan

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