FIGURE 43–8 Schematic of a bacterial cell wall and normal synthesis of cell wall peptidoglycan via transpeptidation; M, N-acetylmuramic acid; Glc, glucose; NAcGlc or G, N-acetylglucosamine. Vancomycin binds the D-Alanine D-Alanine (D-Ala D-Ala) terminus of the amino acid peptide, inhibiting cross-linkage of the cell wall.
strains (MIC ≥ 16 mcg/mL), which have acquired the enterococcal resistance determinants. The underlying mechanism for reduced vancomycin susceptibility in vancomycin-intermediate strains (MIC = 4–8 mcg/mL) of S aureus is not fully known. However, these strains have altered cell wall metabolism that results in a thickened cell wall with increased numbers of d-Ala-d-Ala residues, which serve as dead-end binding sites for vancomycin. Vancomycin is sequestered within the cell wall by these false targets and may be unable to reach its site of action.
Vancomycin is bactericidal for Gram-positive bacteria in concentrations of 0.5–10 mcg/mL. Most pathogenic staphylococci, including those producing β-lactamase and those resistant to nafcillin and methicillin, are killed by 2 mcg/mL or less. Vancomycin kills staphylococci relatively slowly and only if cells are actively dividing; the rate is less than that of the penicillins both in vitro and in vivo. Vancomycin is synergistic in vitro with gentamicin and streptomycin against Enterococcus faecium and Enterococcus faecalis strains that do not exhibit high levels of aminoglycoside resistance. Vancomycin is active against many Gram-positive anaerobes including C difficile.
Vancomycin is poorly absorbed from the intestinal tract and is administered orally only for the treatment of colitis caused by C difficile. Parenteral doses must be administered intravenously. A 1-hour intravenous infusion of 1 g produces blood levels of 15–30 mcg/mL for 1–2 hours. The drug is widely distributed in the body including adipose tissue. Cerebrospinal fluid levels 7–30% of simultaneous serum concentrations are achieved if there is meningeal inflammation. Ninety percent of the drug is excreted by glomerular filtration. In the presence of renal insufficiency, striking accumulation may occur (Table 43–2). In functionally anephric patients, the half-life of vancomycin is 6–10 days. A significant amount of vancomycin is removed during a standard hemodialysis run using a high-flux membrane.