Whole-genome sequence-informed MALDI-TOF MS diagnostics reveal importance of Klebsiella oxytoca group in invasive infections: a retrospective clinical study
Autor:innen
Cuenod, Aline
Wüthrich, Daniel
Seth-Smith, Helena
Ott, Chantal
Gehringer, Christian
Foucaul, Frederic
Mouchet, Roxanne
Kassim, Ali
Revathi, Gunturu
Vogt, Deborah
Autor:in (Körperschaft)
Publikationsdatum
2021
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Genome Medicine
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
Ausgabe / Nummer
150
Seiten / Dauer
Patentnummer
Verlag / Herausgebende Institution
Springer
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Background
Klebsiella spp. are opportunistic pathogens which can cause severe infections, are often multi-drug resistant and are a common cause of hospital-acquired infections. Multiple new Klebsiella species have recently been described, yet their clinical impact and antibiotic resistance profiles are largely unknown. We aimed to explore Klebsiella group- and species-specific clinical impact, antimicrobial resistance (AMR) and virulence.
Methods
We analysed whole-genome sequence data of a diverse selection of Klebsiella spp. isolates and identified resistance and virulence factors. Using the genomes of 3594 Klebsiella isolates, we predicted the masses of 56 ribosomal subunit proteins and identified species-specific marker masses. We then re-analysed over 22,000 Matrix-Assisted Laser Desorption Ionization - Time Of Flight (MALDI-TOF) mass spectra routinely acquired at eight healthcare institutions in four countries looking for these species-specific markers. Analyses of clinical and microbiological endpoints from a subset of 957 patients with infections from Klebsiella species were performed using generalized linear mixed-effects models.
Results
Our comparative genomic analysis shows group- and species-specific trends in accessory genome composition. With the identified species-specific marker masses, eight Klebsiella species can be distinguished using MALDI-TOF MS. We identified K. pneumoniae (71.2%; n = 12,523), K. quasipneumoniae (3.3%; n = 575), K. variicola (9.8%; n = 1717), “K. quasivariicola” (0.3%; n = 52), K. oxytoca (8.2%; n = 1445), K. michiganensis (4.8%; n = 836), K. grimontii (2.4%; n = 425) and K. huaxensis (0.1%; n = 12). Isolates belonging to the K. oxytoca group, which includes the species K. oxytoca, K. michiganensis and K. grimontii, were less often resistant to 4th-generation cephalosporins than isolates of the K. pneumoniae group, which includes the species K. pneumoniae, K. quasipneumoniae, K. variicola and “K. quasivariicola” (odds ratio = 0.17, p < 0.001, 95% confidence interval [0.09,0.28]). Within the K. pneumoniae group, isolates identified as K. pneumoniae were more often resistant to 4th-generation cephalosporins than K. variicola isolates (odds ratio = 2.61, p = 0.003, 95% confidence interval [1.38,5.06]). K. oxytoca group isolates were found to be more likely associated with invasive infection to primary sterile sites than K. pneumoniae group isolates (odds ratio = 2.39, p = 0.0044, 95% confidence interval [1.05,5.53]).
Conclusions
Currently misdiagnosed Klebsiella spp. can be distinguished using a ribosomal marker-based approach for MALDI-TOF MS. Klebsiella groups and species differed in AMR profiles, and in their association with invasive infection, highlighting the importance for species identification to enable effective treatment options.
Schlagwörter
MALDI-TOF MS, Klebsiella spp., Invasive infections, Antimicrobial resistance, Species identification
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1756-994X
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Gold
Lizenz
Zitation
CUENOD, Aline, Daniel WÜTHRICH, Helena SETH-SMITH, Chantal OTT, Christian GEHRINGER, Frederic FOUCAUL, Roxanne MOUCHET, Ali KASSIM, Gunturu REVATHI, Deborah VOGT, Stefanie VON FELTEN, Stefano BASSETTI, Sarah TSCHUDIN-SUTTER, Timm HETTICH, Götz SCHLOTTERBECK, Christina HOMBERGER, Carlo CASANOVA, Jakob MORAN-GILAD, Orli SAGI, Belen RODRIGUEZ-SANCHEZ, Franco MÜLLER, Martina AERNI, Valeria GAIA, Helke VAN DESSEL, Greetje KAMPINGA, Claudia MÜLLER, Claudia DAUBENBERGER, Valentin PFLÜGER und Adrian EGLI, 2021. Whole-genome sequence-informed MALDI-TOF MS diagnostics reveal importance of Klebsiella oxytoca group in invasive infections: a retrospective clinical study. Genome Medicine. 2021. Nr. 150. DOI 10.1186/s13073-021-00960-5. Verfügbar unter: https://doi.org/10.26041/fhnw-4144