Vancomycin MIC Does Not Predict 90-Day Mortality, Readmission, or Recurrence in a Prospective Cohort of Adults with Staphylococcus aureus Bacteremia

Abstract

Staphylococcus aureus is a leading cause of bacteremia (1, 2). Even when an individual is appropriately treated, the risk of mortality from S. aureus bacteremia (SAB) is 20 to 40% per episode (3-8). Furthermore, the morbidity from SAB is striking, with 10 to 15% of episodes being complicated by endocarditis or a risk of metastatic disease elsewhere in the body (9, 10). The financial consequences of SAB are also significant, with health care costs ranging from $12,078 to $25,573 per episode of SAB (11-13). Typically, SAB is treated with narrow-spectrum beta-lactam antibiotics for methicillin-susceptible S. aureus (MSSA) isolates and the glycopeptide antibiotic vancomycin for methicillin-resistant S. aureus (MRSA) isolates (14-17). Isolates with vancomycin MICs of Յ2 g/ml are considered susceptible, those with MICs of 4 to 8 g/ml are considered intermediately resistant, and those with MICs of Ͼ8 g/ml are designated resistant (18). The question of whether infection by S. aureus strains with vancomycin MICs of 2 g/ml is associated with worse outcomes has been a topic of much research, although a consensus has not been reached. Compared with research methods such as Epsilometer testing (Etest) or broth microdilution (BMD), automated MIC measurements can be off by 1 dilution in either direction (e.g., a value of 2 g/ml could mean 1 or 4 g/ml if repeated) (19,20), which adds to the deliberation over interpreting study results, although consistency between BMD and Etest results can also vary. In addition, most studies have focused on MRSA, but the role of vancomycin MIC in MSSA infection has not been fully evaluated. A number of studies, including systematic reviews and meta-analyses, have demonstrated increased mortality in the setting of SAB with vancomycin MICs of Ն2.0 g/ml (21-28). Conversely, others have shown an increased risk of mortality in individuals with MICs of Ͻ2.0 g/ml (29-32). In spite of these data, the majority of studies have failed to show any significant increase in the risk of mortality attributable to vancomycin MIC (5,26,. A recent rigorous meta-analysis failed to demonstrate increased 30-day or in-hospital mortality attributable to vancomycin MIC, irrespective of the MIC cutoff that was chosen (1.5, 2.0, 4.0, or 8.0 g/ml) (5). Although valuable, meta-analyses are lim-

Early Administration of Adjuvant β‐Lactam Therapy in Combination with Vancomycin among Patients with Methicillin‐Resistant Staphylococcus aureus Bloodstream Infection: A Retrospective, Multicenter Analysis

“…In addition, a recent cohort study of Danish patients with community‐acquired S. aureus bloodstream infection found patients with chronic heart failure had a higher rate of 90‐day mortality compared to those without chronic heart failure; however, the proportion of patients with MRSA in this study was extremely low, making direct comparisons difficult . Notably, vancomycin MIC had no impact on clinical outcome, which is consistent with two recently published studies …”

“…28 Notably, vancomycin MIC had no impact on clinical outcome, which is consistent with two recently published studies. 29,30 It is possible that b-lactam therapy, particularly piperacillin-tazobactam, in combination with vancomycin leads to higher frequency of nephrotoxicity compared to vancomycin alone. [31][32][33] The majority of patients in COMBO received piperacillin-tazobactam.…”

Reduced Vancomycin Susceptibility of Methicillin-Susceptible Staphylococcus aureus Has No Significant Impact on Mortality but Results in an Increase in Complicated Infection

“…Regarding mortality effect, some prior studies on the relationship between vancomycin MIC and outcomes in MSSA BSI have found an increased mortality risk (19,20) associated with MICs Ն 2 mg/liter, however other recent studies have failed to demonstrate a statistically significant difference in death rates (2,23,26). A metaanalysis looking at effect of vancomycin MIC on mortality in S. aureus bacteremia failed to show a significant difference in 30-day mortality rates in SAB across a range of vancomycin MIC cutoffs (21).…”

“…The RVS phenotype in MSSA infection has recently been studied for its effect on clinical outcome. In particular, it has been linked to increased risk of mortality in some studies, although other analyses have failed to show robust associations with clinical outcome (15,(17)(18)(19)(20)(21)(22)(23).…”

Ceftaroline-Resistant, Daptomycin-Tolerant, and Heterogeneous Vancomycin-Intermediate Methicillin-Resistant Staphylococcus aureus Causing Infective Endocarditis

“…Whether this was the cause or an effect of treatment failure is uncertain, particularly given that the patient with ventilator-associated pneumonia caused by a virtually identical isolate with a vancomycin MIC of 2 g/ml responded to vancomycin. The importance of vancomycin MICs of Ͼ1 mg/ml as a predictor of treatment failure (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) has been hotly debated. In neither of these cases was the MIC a particularly good predictor.…”