Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency

Journal article

Rofael, S., Babe, C.L., Davrandi, M., Kondratiuk, A.L., Cleaver, L., Ahmed, N., Fullerton, C., McHugh, T. and Lowe, D.M. (2023). Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency. JAC-antimicrobial resistance. 5 (6), p. dlad135. https://doi.org/10.1093/jacamr/dlad135
AuthorsRofael, S., Babe, C.L., Davrandi, M., Kondratiuk, A.L., Cleaver, L., Ahmed, N., Fullerton, C., McHugh, T. and Lowe, D.M.
Abstract

Background
Antibody-deficient patients are at high risk of respiratory tract infections. Many therefore receive antibiotic prophylaxis and have access to antibiotics for self-administration in the event of breakthrough infections, which may increase antimicrobial resistance (AMR).

Objectives
To understand AMR in the respiratory tract of patients with antibody deficiency.

Methods
Sputum samples were collected from antibody-deficient patients in a cross-sectional and prospective study; bacteriology culture, 16S rRNA profiling and PCR detecting macrolide resistance genes were performed. Bacterial isolates were identified using MALDI-TOF, antimicrobial susceptibility was determined by disc diffusion and WGS of selected isolates was done using Illumina NextSeq with analysis for resistome and potential cross-transmission. Neutrophil elastase was measured by a ProteaseTag immunoassay.

Results
Three hundred and forty-three bacterial isolates from sputum of 43 patients were tested. Macrolide and tetracycline resistance were common (82% and 35% of isolates). erm(B) and mef(A) were the most frequent determinants of macrolide resistance. WGS revealed viridans streptococci as the source of AMR genes, of which 23% also carried conjugative plasmids linked with AMR genes and other mobile genetic elements. Phylogenetic analysis of Haemophilus influenzae isolates suggested possible transmission between patients attending clinic.

In the prospective study, a negative correlation between sputum neutrophil elastase concentration and Shannon entropy α-diversity (Spearman’s ρ = −0.306, P = 0.005) and a positive relationship with Berger–Parker dominance index (ρ = 0.502, P < 0.001) were found. Similar relationships were noted for the change in elastase concentration between consecutive samples, increases in elastase associating with reduced α-diversity.

Conclusions
Measures to limit antibiotic usage and spread of AMR should be implemented in immunodeficiency clinics. Sputum neutrophil elastase may be a useful marker to guide use of antibiotics for respiratory infection.

Year2023
JournalJAC-antimicrobial resistance
Journal citation5 (6), p. dlad135
PublisherOxford University Press (OUP)
ISSN2632-1823
Digital Object Identifier (DOI)https://doi.org/10.1093/jacamr/dlad135
Publication dates
Print14 Dec 2023
Publication process dates
Deposited03 Jan 2024
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