Quantifying the matrix of relationships between reduced vancomycin susceptibility phenotypes and outcomes among patients with MRSA bloodstream infections treated with vancomycin .
OBJECTIVE
Several phenotypic characteristics of Staphylococcus aureus have been identified as aetiological factors responsible for adverse outcomes among patients receiving vancomycin. However, characterization of the outcomes associated with these reduced vancomycin susceptibility phenotypes (rVSPs) remains largely incomplete and it is unknown if these features contribute to deleterious treatment outcomes alone or in concert. This study described the interrelationship between rVSPs and assessed their individual and combined effects on outcomes among patients who received vancomycin for a methicillin-resistant S. aureus (MRSA) bloodstream infection.


METHODS
An observational study of adult, hospitalized patients with MRSA bloodstream infections who were treated with vancomycin between January 2005 and June 2009 was performed. The rVSPs evaluated included the following: (i) Etest MIC; (ii) broth microdilution MIC; (iii) MBC : MIC ratio; and (iv) heteroresistance to vancomycin by the Etest macromethod. Failure was defined as any of the following: (i) 30 day mortality; (ii) bacteraemia ≥ 7 days on therapy; or (iii) recurrence of MRSA bacteraemia within 60 days of therapy discontinuation.


RESULTS
During the study period, 184 cases met the study criteria and 41.3% met the failure criteria. There was a clear linear exposure-response relationship between the number of these phenotypic markers and outcomes. As the number of phenotypes escalated, the incidence of overall failure increased incrementally by 10%-18%.


CONCLUSIONS
The data suggest that rVSPs contribute to deleterious treatment outcomes in concert.
Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY, USA thomas.lodise@acphs.edu.
T P
TP
Lodise
Institute for Therapeutic Innovation, College of Medicine, University of Florida, 6550 Sanger Road, Lake Nona, FL, USA.
G L
GL
Drusano
University at Albany, State University of New York, Albany, 5 University Place, A217, Rensselaer, NY, USA.
V
V
Lazariu
Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY, USA.
N
N
El-Fawal
Albany Medical Center Hospital, Department of Pathology and Laboratory Medicine, 43 New Scotland Avenue, Albany, NY, USA.
A
A
Evans
Albany Medical Center Hospital, Department of Epidemiology, 43 New Scotland Avenue, Albany, NY, USA.
E
E
Graffunder
Albany Medical Center Hospital, Department of Pathology and Laboratory Medicine, 43 New Scotland Avenue, Albany, NY, USA.
K
K
Stellrecht
JMI Laboratories, 345 Beaver Kreek Ctr, Ste A, North Liberty, IA, USA.
R E
RE
Mendes
JMI Laboratories, 345 Beaver Kreek Ctr, Ste A, North Liberty, IA, USA.
R N
RN
Jones
Institute for Therapeutic Innovation, College of Medicine, University of Florida, 6550 Sanger Road, Lake Nona, FL, USA.
L
L
Cosler
University at Albany, State University of New York, Albany, 5 University Place, A217, Rensselaer, NY, USA.
L A
LA
McNutt
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D015331:Cohort Studies; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D016019:Survival Analysis; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use*; D055815:Young Adult
D000900:Anti-Bacterial Agents; D014640:Vancomycin
S. aureus; bacteraemia; methicillin-resistant Staphylococcus aureus