Limitations of Vancomycin in the Management of Resistant Staphylococcal Infections

Clinical Infectious Diseases, Sep 2007

Vancomycin is effective against methicillin-resistant Staphylococcus aureus and has been widely used in the past few years. However, several recent reports have highlighted the limitations of vancomycin, and its role in the management of serious infections is now being reconsidered. Vancomycin treatment failure rates are associated with an increase in the minimum inhibitory concentration as well as a decrease in the rate of bacterial killing. The intrinsic limitations of vancomycin also include poor tissue penetration, particularly in the lung; relatively slow bacterial killing; and the potential for toxicity. In addition, intermediate-level vancomycin resistance has emerged among staphylococci, as have rare cases of fully resistant strains. Because of these problems, when using vancomycin, it is probably prudent to carefully establish the diagnosis, test for antimicrobial susceptibility, and monitor serum trough concentrations to ensure adequate dosing.

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Limitations of Vancomycin in the Management of Resistant Staphylococcal Infections

Limitations of Vancomycin • CID Limitations of Vancomycin in the Management of Resistant Staphylococcal Infections Marin H. Kollef () 0 0 Medical Intensive Care Unit and Respiratory Care Services, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine and Barnes-Jewish Hospital , St. Louis, Missouri Vancomycin is effective against methicillin-resistant Staphylococcus aureus and has been widely used in the past few years. However, several recent reports have highlighted the limitations of vancomycin, and its role in the management of serious infections is now being reconsidered. Vancomycin treatment failure rates are associated with an increase in the minimum inhibitory concentration as well as a decrease in the rate of bacterial killing. The intrinsic limitations of vancomycin also include poor tissue penetration, particularly in the lung; relatively slow bacterial killing; and the potential for toxicity. In addition, intermediate-level vancomycin resistance has emerged among staphylococci, as have rare cases of fully resistant strains. Because of these problems, when using vancomycin, it is probably prudent to carefully establish the diagnosis, test for antimicrobial susceptibility, and monitor serum trough concentrations to ensure adequate dosing. - CLINICAL RESPONSE TO VANCOMYCIN Vancomycin failure rates among patients with endocarditis, bacteremia, or bacteremic pneumonia due to methicillin-susceptible Staphylococcus aureus (MSSA) or MRSA have been published since 1977, and they have ranged from 37%, as noted in the first published report, to as high as 50% [2]. Nafcillin was used as a comparator in several of studies of vancomycin failure. In 1990, Small and Chambers [3] found a vancomycin failure rate of 38% in a series of 13 patients with endocarditis due to MSSA, and they contrasted this finding with a reported failure rate of only 1.4% with nafcillin. In a 1997 study of MSSA endocarditis, failure rates of 50% with vancomycin and 26% with nafcillin were reported [4]. A 2003 study of bacteremia also showed a higher failure rate with vancomycin than with nafcillin (20% vs. 4%, respectively) [5]. Moreover, therapy with vancomycin (vs. nafcillin) was significantly associated with relapse. Two studies have evaluated the performance of vancomycin in patients with staphylococcal bacteremic pneumonia [6, 7]. In the first study, Gonzalez et al. [6] prospectively studied all patients at their institution who had bacteremic pneumonia due to S. aureus during an outbreak of MRSA infections, comparing the outcomes of infections due to MRSA (n p 32) with those of infections due to MSSA (n p 54). Although the mortality and complication rates were not statistically significantly different for patients with MRSA infections versus those with MSSA infections, the mortality rate was significantly higher among patients with MSSA infections who received vancomycin than among those who received cloxacillin (41% vs. 0%; P ! .01). Furthermore, multivariate analysis of all cases showed a correlation between mortality and vancomycin treatment (odds ratio [OR], 14), whereas mortality was even higher when vancomycin treatment was used in patients with respiratory distress (OR, 38.46) [6]. In the second study [7], which included 60 patients with confirmed nosocomial bacteremic pneumonia due to staphylococcal infection, 70% of infections were due to methicillin-resistant strains. The rate of infectionrelated deaths was high (∼40%) and was greater among patients who received empirical treatment with vancomycin than among those who received empirical treatment with a b-lactam (50% vs. 28% for patients with MSSA infections; 46% vs. 25% for patients with MRSA infections); however, this difference did not achieve statistical significance [7]. The authors noted that their findings might have been partially explained by the fact that patients receiving b-lactam agents were younger and had lower Acute Physiology and Chronic Health Evaluation II scores, but they also suggested that the relatively slow activity of vancomycin may have been associated with a higher rate of treatment failure. These findings suggest that vancomycin failure rates may be even higher as the proportion of resistant isolates increases. Decreasing vancomycin bactericidal activity and fluctuating MICs compound the problem in invasive S. aureus infections [8]. In addition, an in vitro study evaluating the effect of several antibiotics (vancomycin, nafcillin, clindamycin, and linezolid) showed that antibiotics have differing effects on the expression of toxins by staphylococci [9]. Both MSSA and MRSA strains were isolated from patients and were cultured in the presence of the 4 antibiotics. Assays were then performed to analyze the expression of Panton-Valentine leukocidin, a-hemolysin, and toxic shock syndrome toxin–1. The results showed that, although clindamycin and linezolid markedly suppressed the formation of toxins (by su (...truncated)


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Marin H. Kollef. Limitations of Vancomycin in the Management of Resistant Staphylococcal Infections, Clinical Infectious Diseases, 2007, pp. S191-S195, 45/Supplement 3, DOI: 10.1086/519470