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

Sylvia Rofael; Clara Leboreiro Babe; Mehmet Davrandi; Alexandra L Kondratiuk; Leanne Cleaver; Naseem Ahmed; Claire Atkinson; Timothy McHugh; David M Lowe

doi:10.1093/jacamr/dlad135

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

JAC Antimicrob Resist. 2023 Dec 14;5(6):dlad135. doi: 10.1093/jacamr/dlad135. eCollection 2023 Dec.

Authors

Sylvia Rofael^{1

2}, Clara Leboreiro Babe¹, Mehmet Davrandi¹, Alexandra L Kondratiuk³, Leanne Cleaver⁴, Naseem Ahmed¹, Claire Atkinson^{3

5}, Timothy McHugh¹, David M Lowe^{3

6}

Affiliations

¹ Centre for Clinical Microbiology, University College London, Royal Free Campus, Pond Street, London, UK.
² Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
³ Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, Pears Building, Rowland Hill Street, London, UK.
⁴ Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, Guy's Campus, King's College London, London, UK.
⁵ Cancer Biology and Therapy Research Group, Divisionof Human Sciences, School of Applied Sciences, London South Bank University, London, UK.
⁶ Department of Clinical Immunology, Royal Free London NHS Foundation Trust, Pond Street, London, UK.

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.