Rofael, Sylvia;
Leboreiro Babe, Clara;
Davrandi, Mehmet;
Kondratiuk, Alexandra L;
Cleaver, Leanne;
Ahmed, Naseem;
Atkinson, Claire;
... Lowe, David M; + view all
(2023)
Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency.
JAC-Antimicrobial Resistance
, 5
(6)
, Article dlad135. 10.1093/jacamr/dlad135.
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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.
Type: | Article |
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Title: | Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency |
Location: | England |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1093/jacamr/dlad135 |
Publisher version: | https://doi.org/10.1093/jacamr/dlad135 |
Language: | English |
Additional information: | © The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10184388 |
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