Abstract
Treatment failure in biofilm-associated bacterial infections is an important healthcare issue. In vitro studies and mouse models suggest that bacteria enter a slow-growing/non-growing state that results in transient tolerance to antibiotics in the absence of a specific resistance mechanism. However, little clinical confirmation of antibiotic tolerant bacteria in patients exists. In this study we investigate a Staphylococcus epidermidis pacemaker-associated endocarditis, in a patient who developed a break-through bacteremia despite taking antibiotics to which the S. epidermidis isolate is fully susceptible in vitro. Characterization of the clinical S. epidermidis isolates reveals in-host evolution over the 16-week infection period, resulting in increased antibiotic tolerance of the entire population due to a prolonged lag time until growth resumption and a reduced growth rate. Furthermore, we observe adaptation towards an increased biofilm formation capacity and genetic diversification of the S. epidermidis isolates within the patient.
Publication types
-
Case Reports
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Anti-Bacterial Agents / pharmacology*
-
Bacteremia / drug therapy
-
Bacteremia / microbiology*
-
Bacteremia / pathology
-
Bacterial Proteins / genetics
-
Bacterial Proteins / metabolism
-
Biofilms / drug effects
-
Biofilms / growth & development
-
Drug Resistance, Multiple / genetics*
-
Drug Tolerance / genetics
-
Endocarditis / drug therapy
-
Endocarditis / microbiology*
-
Endocarditis / pathology
-
Evolution, Molecular
-
Fluoroquinolones / pharmacology
-
Glycopeptides / pharmacology
-
Host-Pathogen Interactions / genetics*
-
Humans
-
INDEL Mutation
-
Male
-
Microbial Sensitivity Tests
-
Pacemaker, Artificial / microbiology
-
Peptides, Cyclic / pharmacology
-
Phylogeny
-
Polymorphism, Single Nucleotide
-
Staphylococcal Infections / drug therapy
-
Staphylococcal Infections / microbiology*
-
Staphylococcal Infections / pathology
-
Staphylococcus epidermidis / drug effects
-
Staphylococcus epidermidis / genetics*
-
Staphylococcus epidermidis / growth & development
-
Staphylococcus epidermidis / isolation & purification
-
beta-Lactams / pharmacology
Substances
-
Anti-Bacterial Agents
-
Bacterial Proteins
-
Fluoroquinolones
-
Glycopeptides
-
Peptides, Cyclic
-
beta-Lactams