Emergence of a dalbavancin induced glycopeptide/lipoglycopeptide non-susceptible Staphylococcus aureus during treatment of a cardiac device-related endocarditis
Standard
Emergence of a dalbavancin induced glycopeptide/lipoglycopeptide non-susceptible Staphylococcus aureus during treatment of a cardiac device-related endocarditis. / Kussmann, Manuel; Karer, Matthias; Obermueller, Markus; Schmidt, Katy; Barousch, Wolfgang; Moser, Doris; Nehr, Marion; Ramharter, Michael; Poeppl, Wolfgang; Makristathis, Athanasios; Winkler, Stefan; Thalhammer, Florian; Burgmann, Heinz; Lagler, Heimo.
In: EMERG MICROBES INFEC, Vol. 7, No. 1, 05.12.2018, p. 202.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Emergence of a dalbavancin induced glycopeptide/lipoglycopeptide non-susceptible Staphylococcus aureus during treatment of a cardiac device-related endocarditis
AU - Kussmann, Manuel
AU - Karer, Matthias
AU - Obermueller, Markus
AU - Schmidt, Katy
AU - Barousch, Wolfgang
AU - Moser, Doris
AU - Nehr, Marion
AU - Ramharter, Michael
AU - Poeppl, Wolfgang
AU - Makristathis, Athanasios
AU - Winkler, Stefan
AU - Thalhammer, Florian
AU - Burgmann, Heinz
AU - Lagler, Heimo
PY - 2018/12/5
Y1 - 2018/12/5
N2 - In the present study, we demonstrated the emergence of dalbavancin non-susceptible and teicoplanin-resistant Staphylococcus aureus small colony variants which were selected in vivo through long-term treatment with dalbavancin. A 36-year-old man presented with a cardiac device-related S. aureus endocarditis and received long-term therapy with dalbavancin. Consecutively, two glycopeptide/lipoglycopeptide susceptible and two non-susceptible S. aureus isolates were obtained from blood cultures and the explanted pacemaker wire. The isolates were characterized by: standard typing methods, antimicrobial susceptibility testing, auxotrophic profiling, proliferation assays, scanning and transmission electron microscopy, as well as whole genome sequencing. The isolated SCVs demonstrated a vancomycin-susceptible but dalbavancin non-susceptible and teicoplanin-resistant phenotype whereof the respective MICs of the last isolate were 16- and 84-fold higher than the susceptible strains. All four strains were indistinguishable or at least closely related by standard typing methods (spa, MLST, and PFGE), and whole genome sequencing revealed only eight sequence variants. A consecutive increase in cell wall thickness (up to 2.1-fold), an impaired cell separation with incomplete or multiple cross walls and significantly reduced growth rates were observed in the present study. Therefore, the mutations in pbp2 and the DHH domain of GdpP were identified as the most probable candidates due to their implication in the biosynthesis and metabolism of the staphylococcal cell wall. For the first time, we demonstrated in vivo induced dalbavancin non-susceptible/teicoplanin resistant, but vancomycin and daptomycin susceptible S. aureus SCVs without lipopeptide or glycopeptide pretreatment, thus, indicating the emergence of a novel lipoglycopeptide resistance mechanism.
AB - In the present study, we demonstrated the emergence of dalbavancin non-susceptible and teicoplanin-resistant Staphylococcus aureus small colony variants which were selected in vivo through long-term treatment with dalbavancin. A 36-year-old man presented with a cardiac device-related S. aureus endocarditis and received long-term therapy with dalbavancin. Consecutively, two glycopeptide/lipoglycopeptide susceptible and two non-susceptible S. aureus isolates were obtained from blood cultures and the explanted pacemaker wire. The isolates were characterized by: standard typing methods, antimicrobial susceptibility testing, auxotrophic profiling, proliferation assays, scanning and transmission electron microscopy, as well as whole genome sequencing. The isolated SCVs demonstrated a vancomycin-susceptible but dalbavancin non-susceptible and teicoplanin-resistant phenotype whereof the respective MICs of the last isolate were 16- and 84-fold higher than the susceptible strains. All four strains were indistinguishable or at least closely related by standard typing methods (spa, MLST, and PFGE), and whole genome sequencing revealed only eight sequence variants. A consecutive increase in cell wall thickness (up to 2.1-fold), an impaired cell separation with incomplete or multiple cross walls and significantly reduced growth rates were observed in the present study. Therefore, the mutations in pbp2 and the DHH domain of GdpP were identified as the most probable candidates due to their implication in the biosynthesis and metabolism of the staphylococcal cell wall. For the first time, we demonstrated in vivo induced dalbavancin non-susceptible/teicoplanin resistant, but vancomycin and daptomycin susceptible S. aureus SCVs without lipopeptide or glycopeptide pretreatment, thus, indicating the emergence of a novel lipoglycopeptide resistance mechanism.
KW - Adult
KW - Anti-Bacterial Agents/pharmacology
KW - Bacterial Typing Techniques
KW - Daptomycin/pharmacology
KW - Endocarditis/drug therapy
KW - Humans
KW - Lipoglycopeptides
KW - Male
KW - Microbial Sensitivity Tests
KW - Multilocus Sequence Typing
KW - Pacemaker, Artificial/microbiology
KW - Prosthesis-Related Infections/microbiology
KW - Staphylococcal Infections/complications
KW - Staphylococcus aureus/drug effects
KW - Teicoplanin/analogs & derivatives
KW - Vancomycin/pharmacology
KW - Whole Genome Sequencing
U2 - 10.1038/s41426-018-0205-z
DO - 10.1038/s41426-018-0205-z
M3 - SCORING: Journal article
C2 - 30514923
VL - 7
SP - 202
JO - EMERG MICROBES INFEC
JF - EMERG MICROBES INFEC
SN - 2222-1751
IS - 1
ER -
