Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein.
BACKGROUND
The causes of persistent bacteremia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) are poorly understood. This investigation examined potential associations between PB with key clinical features and several in vitro bacterial genotypic and phenotypic characteristics, in isolates from 1 institution.


METHODS
Pulsed-field gel electrophoresis (PFGE) relatedness, thrombin-induced platelet microbicidal protein (tPMP)-susceptibility phenotype, accessory gene regulator (agr) genotype and functionality (via delta-lysin production), and autolysis phenotypes were assessed in MRSA isolates from the bloodstream of 21 prospectively identified patients with PB (blood cultures positive after > or =7 days of therapy) and of 18 patients with resolving bacteremia (RB) (sterile blood cultures within the first 2-4 days of therapy) due to MRSA.


RESULTS
The 2 groups had comparable baseline characteristics but differed in their clinical courses (e.g., endocarditis was more frequent in patients with PB than in those with RB [43% vs. 0%, respectively; P=.0016]); isolates from patients with PB exhibited higher rates of (1) survival in vitro after exposure to tPMP (22.4+/-14.8% vs. 11.6+/-6.5%, respectively; P=.005); (2) defective delta-lysin production (71.4% vs. 38.9%, respectively; P=.057); (3) non-agr genotype II profile (100% vs. 77.8%, respectively; P=.037); and (4) overrepresentation of a specific PFGE genotype (85.7% vs. 44.4%, respectively; P=.015).


CONCLUSIONS
Isolates from patients with PB differed from those in patients with RB, in several in vitro characteristics. Further studies will be necessary to define how these factors might affect clinical outcome.
Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA. vance.fowler@duke.edu
Vance G
VG
Fowler
George
G
Sakoulas
Lauren M
LM
McIntyre
Venkata G
VG
Meka
Robert D
RD
Arbeit
Christopher H
CH
Cabell
Martin E
ME
Stryjewski
George M
GM
Eliopoulos
L Barth
LB
Reller
G Ralph
GR
Corey
Tiffanny
T
Jones
Natalie
N
Lucindo
Michael R
MR
Yeaman
Arnold S
AS
Bayer
D000900:Anti-Bacterial Agents / Q000276:immunology / Q000494:pharmacology; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D015373:Bacterial Typing Techniques; D018925:Chemokines / Q000276:immunology / Q000494:pharmacology*; D016172:DNA Fingerprinting; D004269:DNA, Bacterial / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D005838:Genotype; D006460:Hemolysin Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D016106:Methicillin Resistance; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D001620:beta-Thromboglobulin
C095698:Agr protein, Staphylococcus aureus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018925:Chemokines; D004269:DNA, Bacterial; D006460:Hemolysin Proteins; C061615:PPBP protein, human; D015534:Trans-Activators; D001620:beta-Thromboglobulin; C025651:CCCGGG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific