Transmission and Antibiotic Resistance of <i>Achromobacter</i> in Cystic Fibrosis

Abstract

<i>Achromobacter</i> species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen is associated with antibiotic resistance and more-severe disease outcomes. Nonetheless, little is known about the extent of transmission and antibiotic resistance development in <i>Achromobacter</i> infections. We sequenced the genomes of 101 <i>Achromobacter</i> clinical isolates (identified as <i>Achromobacter xylosoxidans</i> based on matrix-assister laser desorption ionization-time of flight [MALDI-TOF] or API N20 typing) collected from 51 patients with CF-the largest longitudinal data set to date. We performed phylogenetic analysis on the genomes and combined this with epidemiological and antibiotic resistance data to identify patient-to-patient transmission and the development of antibiotic resistance. We confirmed that the MALDI-TOF or API N20 method was not sufficient for <i>Achromobacter</i> species-level typing and that the population of <i>Achromobacter</i> isolates was composed of five different species, among which <i>A. xylosoxidans</i> accounted for 52% of infections. Most patients were infected by unique <i>Achromobacter</i> clone types; nonetheless, suspected patient-to-patient transmission cases identified by shared clone types were observed in 35% (<i>n</i> = 18) of patients. In 15 of 16 cases, the suspected transmissions were further supported by genome- or clinic visit-based epidemiological analysis. Finally, we found that resistance developed over time. We show that whole-genome sequencing (WGS) is essential for <i>Achromobacter</i> species typing and identification of patient-to-patient transmission, which was revealed for <i>Achromobacter ruhlandii</i>, <i>A. xylosoxidans</i>, and, for the first time, <i>Achromobacter insuavis</i> Furthermore, we show that the development of antibiotic resistance is associated with chronic <i>Achromobacter</i> infections. Our findings emphasize that transmission and antibiotic resistance should be considered in future treatment strategies.