[7] Vancomycin is indicated for the treatment of serious, life-threatening infections by Gram-positive bacteria of both aerobic and anaerobic types[17] that are unresponsive to other antibiotics.

The minimum inhibitory concentration susceptibility data for a few medically significant bacteria are:[25] Common side effects associated with oral vancomycin administration (used to treat intestinal infections)[26] include: Serum vancomycin levels may be monitored in an effort to reduce side effects,[27] but the value of such monitoring has been questioned.

[14][32] Later trials using purer forms of vancomycin found nephrotoxicity is an infrequent adverse effect (0.1% to 1% of patients), but this is accentuated in the presence of aminoglycosides.

[33] Rare adverse effects associated with intravenous vancomycin (<0.1% of patients) include anaphylaxis, toxic epidermal necrolysis, erythema multiforme, superinfection, thrombocytopenia, neutropenia, leukopenia, tinnitus, dizziness and/or ototoxicity, and DRESS syndrome.

[34] Vancomycin can induce platelet-reactive antibodies in the patient, leading to severe thrombocytopenia and bleeding with florid petechial hemorrhages, ecchymoses, and wet purpura.

[35] Historically, vancomycin has been considered a nephrotoxic and ototoxic drug, based on numerous case reports in the medical literature following initial approval by the FDA in 1958.

[37] Concern for treatment failures prompted recommendations for higher dosing (troughs 15 to 20 μg/mL) for serious infection, and acute kidney injury (AKI) rates attributable to the vancomycin increased.

[39][40][41][42] Animal studies have demonstrated that higher doses and longer duration of vancomycin exposure correlates with increased histopathologic damage and elevations in urinary biomarkers of AKI.37-38[43] Damage is most prevalent at the proximal tubule, which is further supported by urinary biomarkers, such as kidney injury molecule-1 (KIM-1), clusterin, and osteopontin (OPN).

[45] The mechanisms underlying the pathogenesis of vancomycin nephrotoxicity are multifactorial but include interstitial nephritis, tubular injury due to oxidative stress, and cast formation.

[27] In children, concomitant administration of vancomycin and piperacillin/tazobactam has been associated with an elevated incidence of AKI relative to other antibiotic regimens.

Clinical studies have yielded various results, but animal models indicate that the nephrotoxic effect probably increases when vancomycin is added to nephrotoxins such as aminoglycosides.

The reaction usually appears within 4 to 10 min after the commencement or soon after the completion of an infusion and is characterized by flushing and/or an erythematous rash that affects the face, neck, and upper torso, attributed to the release of histamine from mast cells.

Dose optimization is achieved by therapeutic drug monitoring (TDM), which allows measurement of vancomycin levels in the blood.

TDM using area under the curve (AUC)-guided dosing, preferably with Bayesian forecasting, is recommended to ensure that the AUC0-24h/minimal inhibitory concentration (MIC) ratio is maintained above a certain threshold (400-600) associated with optimal efficacy.

[26] Plasma level monitoring of vancomycin is necessary due to the drug's biexponential distribution, intermediate hydrophilicity, and potential for ototoxicity and nephrotoxicity, especially in populations with poor renal function and/or increased propensity to bacterial infection.

In the A domain, the specific amino acid is activated by converting into an aminoacyl adenylate enzyme complex attached to a 4'-phosphopantetheine cofactor by thioesterification.

[citation needed] A set of NRPS enzymes (peptide synthase VpsA, VpsB, and VpsC) are responsible for assembling the heptapeptide.

[78] The cross-linked heptapeptide is then released by the action of the TE domain, and methyltransferase Vmt then N-methylates the terminal leucine residue.

[17] Specifically, vancomycin forms hydrogen bonds with the D-alanyl-D-alanine (D-Ala-D-Ala) peptide motif of the peptidoglycan precursor, a component of the bacterial cell wall.

That is why vancomycin is mainly used to treat infections caused by Gram-positive bacteria[18] (except some nongonococcal species of Neisseria).

The large hydrophilic molecule of vancomycin is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides.

[91][92] A few Gram-positive bacteria, such as Leuconostoc and Pediococcus, are intrinsically resistant to vancomycin, but they rarely cause disease in humans.

[94] Other Gram-positive bacteria with intrinsic resistance to vancomycin include Erysipelothrix rhusiopathiae, Weissella confusa, and Clostridium innocuum.

[95][96][97] Most Gram-negative bacteria are intrinsically resistant to vancomycin because their outer membranes are impermeable to large glycopeptide molecules[98] (with the exception of some non-gonococcal Neisseria species).

[108][109] In 2020 a team at the University Hospital Heidelberg (Germany) regained vancomycin's antibacterial power by modifying the molecule with a cationic oligopeptide.

Vancomycin was first isolated in 1953 by Edmund Kornfeld (working at Eli Lilly) from a bacteria in a soil sample collected from the interior jungles of Borneo by a missionary, William M.

[14] One quickly apparent advantage was that staphylococci did not develop significant resistance, despite serial passage in culture media containing vancomycin.

[32] Vancomycin never became the first-line treatment for S. aureus for several reasons: In 2004, Eli Lilly licensed Vancocin to ViroPharma in the U.S., Flynn Pharma in the UK, and Aspen Pharmacare in Australia.

The patent expired in the early 1980s, and the FDA authorized the sale of several generic versions in the U.S., including from manufacturers Bioniche Pharma, Baxter Healthcare, Sandoz, Akorn-Strides, and Hospira.

[114] The combination of vancomycin powder and povidone-iodine lavage may reduce the risk of periprosthetic joint infection in hip and knee arthroplasties.