In essence, the reputation of vancomycin as a nephrotoxin is overstated, and it has not been demonstrated that maintaining vancomycin serum levels within certain ranges will prevent its nephrotoxic effects, when they do occur. Ototoxicity
Attempts to establish rates of vancomycin-induced ototoxicity are even more difficult due to the scarcity of quality evidence. The current consensus is that clearly related cases of vancomycin ototoxicity are rare. The association between vancomycin serum levels and ototoxicity is also uncertain. While cases of ototoxicity have been reported in patients whose vancomycin serum level exceeded 80 µg/mL, cases have been reported in patients with therapeutic levels, as well. Thus, whether therapeutic drug monitoring of vancomycin for the purpose of maintaining "therapeutic" levels will prevent ototoxicity also remains unproven. Interactions with other nephrotoxins
Another area of controversy and uncertainty concerns the question of whether, and if so, to what extent, vancomycin increases the toxicity of other nephrotoxins. Clinical studies have yielded variable results, but animal models indicate some increased nephrotoxic effect probably occurs when vancomycin is added to nephrotoxins such as aminoglycosides. However, a dose- or serum level-effect relationship has not been established. Dosing considerations
The recommended parenteral dosage in adults is 500 mg iv every 6 hours or 1000 mg every 12 hours, with modification to achieve a therapeutic range as needed. The recommended oral dosage in the treatment of antibiotic induced pseudomembranous enterocolitis is 125 to 500 mg every 6 hours for 7 to 10 days.
Early authors suggested peak levels of 30 to 40 mg/L and trough levels of 5 to 10 mg/L,
but current recommendations are that peak levels need not be measured and that trough levels of 10 to 15 mg/L or 15 to 20 mg/L, depending on the nature of the infection and the specific needs of the patient, may be appropriate. Using measured vancomycin concentrations to calculate doses optimizes therapy in patients with augmented renal clearance. Biosynthesis
Vancomycin is made by the soil bacterium Amycolatopsis orientalis. Vancomycin biosynthesis occurs primarily via three nonribosomal protein syntheses (NRPSs) VpsA, VpsB, and VpsC. The enzymes determine the amino acid sequence during its assembly through its 7 modules. Before vancomycin is assembled through NRPS, the non-proteinogenic amino acids are first synthesized. L-tyrosine is modified to become the β-hydroxytyrosine (β-HT) and 4-hydroxyphenylglycine (4-Hpg) residues. 3,5 dihydroxyphenylglycine ring (3,5-DPG) is derived from acetate. Nonribosomal peptide synthesis occurs through distinct modules that can load and extend the protein by one amino acid per module through the amide bond formation at the contact sites of the activating domains. Each module typically consists of an adenylation (A) domain, a peptidyl carrier protein (PCP) domain, and a condensation (C) domain. In the A domain, the specific amino acid is activated by converting into an aminoacyl adenylate enzyme complex attached to a 4phosphopantetheine cofactor by thioesterification The complex is then transferred to the PCP domain with the expulsion of AMP. The PCP domain uses the attached 4-phosphopantethein prosthetic group to load the growing peptide chain and their precursors.