TY - JOUR

T1 - Transmission and Antibiotic Resistance of Achromobacter in Cystic Fibrosis

AU - Gabrielaite, Migle

AU - Bartell, Jennifer A.

AU - Nørskov-Lauritsen, Niels

AU - Pressler, Tacjana

AU - Nielsen, Finn C.

AU - Johansen, Helle K.

AU - Marviga, Rasmus L.

PY - 2021

Y1 - 2021

N2 - Achromobacter 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 Achromobacter infections. We sequenced the genomes of 101 Achromobacter clinical isolates (identified as Achromobacter xylosoxidans 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 Achromobacter species-level typing and that the population of Achromobacter isolates was composed of five different species, among which A. xylosoxidans accounted for 52% of infections. Most patients were infected by unique Achromobacter clone types; nonetheless, suspected patient-to-patient transmission cases identified by shared clone types were observed in 35% (n = 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 Achromobacter species typing and identification of patient-to-patient transmission, which was revealed for Achromobacter ruhlandii, A. xylosoxidans, and, for the first time, Achromobacter insuavis. Furthermore, we show that the development of antibiotic resistance is associated with chronic Achromobacter infections. Our findings emphasize that transmission and antibiotic resistance should be considered in future treatment strategies.

AB - Achromobacter 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 Achromobacter infections. We sequenced the genomes of 101 Achromobacter clinical isolates (identified as Achromobacter xylosoxidans 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 Achromobacter species-level typing and that the population of Achromobacter isolates was composed of five different species, among which A. xylosoxidans accounted for 52% of infections. Most patients were infected by unique Achromobacter clone types; nonetheless, suspected patient-to-patient transmission cases identified by shared clone types were observed in 35% (n = 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 Achromobacter species typing and identification of patient-to-patient transmission, which was revealed for Achromobacter ruhlandii, A. xylosoxidans, and, for the first time, Achromobacter insuavis. Furthermore, we show that the development of antibiotic resistance is associated with chronic Achromobacter infections. Our findings emphasize that transmission and antibiotic resistance should be considered in future treatment strategies.

KW - Achromobacter

KW - Antibiotic resistance

KW - Cystic fibrosis airway infection

KW - Genetic epidemiology

KW - Genomics

KW - Pathogen transmission

KW - Phylogenetics

U2 - 10.1128/JCM.02911-20

DO - 10.1128/JCM.02911-20

M3 - Journal article

C2 - 33472899

AN - SCOPUS:85102923435

VL - 59

JO - Journal of Clinical Microbiology

JF - Journal of Clinical Microbiology

SN - 0095-1137

IS - 4

M1 - e02911-20

ER -