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.
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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)