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Rapid resistance development to three antistaphylococcal therapies in antibiotic-tolerant staphylococcus aureus bacteremia.
- Source :
-
PloS one [PLoS One] 2021 Oct 20; Vol. 16 (10), pp. e0258592. Date of Electronic Publication: 2021 Oct 20 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Aged
Aminoacyltransferases genetics
Anti-Bacterial Agents classification
Anti-Bacterial Agents therapeutic use
Bacteremia drug therapy
Evolution, Molecular
Humans
Male
Methicillin-Resistant Staphylococcus aureus drug effects
Methicillin-Resistant Staphylococcus aureus genetics
Methicillin-Resistant Staphylococcus aureus isolation & purification
Microbial Sensitivity Tests
Microbial Viability drug effects
Mutation
Staphylococcal Infections drug therapy
Transcription Factors genetics
Anti-Bacterial Agents pharmacology
Bacteremia microbiology
Bacterial Proteins genetics
Drug Resistance, Multiple, Bacterial
Methicillin-Resistant Staphylococcus aureus growth & development
Staphylococcal Infections microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 16
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 34669727
- Full Text :
- https://doi.org/10.1371/journal.pone.0258592