More Evidence of Vancomycin Impotence
Abstract & Commentary
By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
Source: Stryjewski ME, et al. Use of Vancomycin or First-Generation Cephalosporins for the Treatment of Hemodialysis-Dependent Patients with Methicillin-Susceptible Staphylococcus aureus Bacteremia. Clin Infect Dis. 2007; 44:190-196.
Synopsis: Vancomycin was inferior to cefazolin in the treatment of MSSA bacteremia in chronic hemodialysis patients in a retrospective study.
A number of retrospective studies have provided evidence that, relative to therapy with semisynthetic penicillins such as nafcillin, vancomycin is inferior in the treatment of bactermic infections due to methicillin-susceptible Staphylococcus aureus (MSSA). Vancomycin, however, continues to be used in the treatment of MSSA infections in patients with beta lactam allergies and, often, because of the convenience of infrequent dosing in patients requiring dialysis. In patients with non-life-threatening penicillin allergies, cephalosporins are often used as an alternative to semisynthetic penicillins. Stryjewski et al have now retrospectively examined the efficacy of vancomycin relative to that of a first-generation cephalosporin, cefazolin, in the treatment of 123 adults at the Duke University Medical Center with MSSA bacteremia who were receiving chronic hemodialysis.
Vancomycin therapy was initiated with a 15 mg/kg loading dose, followed by a 500 mg dose after each high-flux dialysis, while cefazolin was given as a 2-gram or 3-gram dose, depending upon whether the next dialysis was scheduled to occur in 2 or 3 days, respectively. Vancomycin recipients were younger (51 years vs 57 years) and also had a significantly higher incidence of the presence of meta-static complications of their infections at the initiation of therapy (36.7% vs 11.7%). Despite this imbalance favoring vancomycin, treatment failure, defined as death or recurrent infection, nonetheless, occurred significantly more frequently in vancomycin recipients (24 of 77; 31.2%) than cefazolin recipients (6 of 46; 13.0%; P = 0.02). Among those treated with vancomycin and for whom the data was available, the median vancomycin serum trough concentration was 13.7 mcg/ml in those who were successfully treated with this glycopeptide antibiotic and 16.8 mcg/ml in those who failed therapy. None of the isolates had a vancomycin MIC > 2 mcg/ml; most were 1 mcg/ml. Hemodialysis access was removed in 67.7% of vancomycin recipients and 75.6% of those treated with cefazolin. Multivariate analysis identified retention of dialysis access and treatment with vancomycin as significant independent risk factors for treatment failure.
Commentary
The role of vancomycin in the treatment of serious infections due to S. aureus has been called into serious question. In the case of MSSA infections, the evidence of inferiority vancomycin, relative to beta-lactam therapy, has, in my opinion, achieved critical mass. In addition to this report by Stryjewski and colleagues, eg, Chang and colleagues have reported their prospective observational experience indicating that, relative to treatment with nafcillin, vancomycin therapy was associated with a significantly greater risk of persistent bacteremia and/or relapse.1
These results are particularly interesting because of previously identified deficiencies of cefazolin as an antistaphylococcal antibiotic. The efficacy of cefazolin in the treatment of MSSA infections may be less than that of nafcillin, particularly with MSSA isolates that produce type A-lactamase, which is capable of rapid hydrolysis of cefazolin, especially when a high inoculum of organisms is present.2 The relative inefficacy of vancomycin is thus thrown into even higher relief when the problems with cefazolin are considered.
The role of vancomycin in the treatment of MRSA infections is also questionable,3 with increasing evidence of diminished efficacy as the susceptibility of this organism diminishes, as evidenced by "MIC creep." Thus, vancomycin may be in the twilight of its career as an antistaphylococcal agent.
References
- Chang FY, et al. Staphylococcus aureus Bacteremia: Recurrence and the Impact of Antibiotic Treatment in A Prospective Multicenter Study. Medicine. 2003;82:333-339.
- Nannini EC, et al. Relapse of Type A Lactamase-Producing Staphylococcus aureus Native Valve Endocarditis During Cefazolin Therapy: Revisiting the Issue. Clin Infect Dis. 2003;37:1194-1198.
- Deresinski S. Vancomycin: Does It Still Have a Role as an Antistaphylococcal Agent? Expert review of anti-infective therapy, in press.
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