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Expert Review of Anti-infective Therapy Dec 2008The appearance and dissemination of vancomycin resistance among clinically important Gram-positive bacteria was an important watershed in antimicrobial resistance trends... (Review)
Review
The appearance and dissemination of vancomycin resistance among clinically important Gram-positive bacteria was an important watershed in antimicrobial resistance trends that drastically narrows therapeutic options, particularly among the enterococci. Clinical resistance despite apparent susceptibility has also become an increasingly recognized issue with vancomycin treatment of methicillin-resistant Staphylococcus aureus pneumonia and endocarditis, which may be, in part, due to vancomycin-heteroresistant strains. The newly developed glycopeptides telavancin, dalbavancin and oritavancin have superior in vitro activity, enhanced bactericidality and unique pharmacokinetic properties compared with vancomycin and teicoplanin. Current clinical trial data show noninferiority to vancomycin or standard-of-care antistaphylococcal therapy for complicated skin-skin structure infections, and acceptable safety profiles. Although promising, whether or not these new compounds are clinically efficacious for the true therapeutic deficits created by in vitro and clinical vancomycin resistance is yet to be determined.
Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Glycopeptides; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Vancomycin; Vancomycin Resistance
PubMed: 19053904
DOI: 10.1586/14787210.6.6.917 -
Clinical Pharmacokinetics Apr 1995Renewed interest in vancomycin over the past decade has led to an abundance of data concerning the pharmacokinetics of vancomycin, and its dosage selection and... (Review)
Review
Renewed interest in vancomycin over the past decade has led to an abundance of data concerning the pharmacokinetics of vancomycin, and its dosage selection and concentration-response relationships. No definitive data exist that correlate vancomycin serum concentrations with clinical outcomes. However, inconsistencies in sampling times for peak serum concentrations and differences in infusion times make interpreting vancomycin serum concentrations difficult. Furthermore, the evidence implicating vancomycin as a cause of oto- or nephrotoxicity is circumstantial, and these adverse effects may occur only in high-risk populations. Owing to the variability in its dose-serum concentration relationship and multicompartmental pharmacokinetics, several methodologies have been developed for instituting and adjusting vancomycin dosages. Nomograms rely on a fixed volume of distribution and the relationship between vancomycin clearance and creatinine clearance. Since both of these factors may be altered in certain populations, dosage methodologies (both traditional and Bayesian) that use population- or patient-specific pharmacokinetic data perform better than standard nomograms for initiating vancomycin therapy. Controversy still exists as to whether a 1- or a 2-compartment model is more appropriate for making dosage adjustments; however, steady-state rather than non-steady-state vancomycin serum concentrations should be used for dosage adjustments. Certain pathophysiological states such as age, bodyweight and renal function contribute to altered pharmacokinetics and may alter the design of the dosage regimen. Since no definitive relationship exists between vancomycin serum concentrations and either clinical outcome or adverse effects, considerable controversy surrounds the utility of monitoring serum vancomycin concentrations. Therefore, routine vancomycin serum concentration monitoring may be warranted only in specific populations, such as patients receiving concurrent aminoglycoside therapy or those receiving higher than usual dosages of vancomycin, patients undergoing haemodialysis and patients with rapidly changing renal function.
Topics: Dose-Response Relationship, Drug; Drug Monitoring; Humans; Vancomycin
PubMed: 7648760
DOI: 10.2165/00003088-199528040-00005 -
Journal of the American Chemical Society Sep 2020A next-generation total synthesis of vancomycin aglycon is detailed that was achieved in 17 steps (longest linear sequence, LLS) from the constituent amino acid subunits...
A next-generation total synthesis of vancomycin aglycon is detailed that was achieved in 17 steps (longest linear sequence, LLS) from the constituent amino acid subunits with kinetically controlled diastereoselective introduction of all three elements of atropisomerism. In addition to new syntheses of three of the seven amino acid subunits, highlights of the approach include a ligand-controlled atroposelective one-pot Miyaura borylation-Suzuki coupling sequence for introduction of the AB biaryl axis of chirality (>20:1 dr), an essentially instantaneous and scalable macrolactamization of the AB ring system nearly free of competitive epimerization (>30:1 dr), and two room-temperature atroposelective intramolecular SAr cyclizations for sequential CD (8:1 dr) and DE ring closures (14:1 dr) that benefit from both preorganization by the preformed AB ring system and subtle substituent effects. Combined with a protecting group free two-step enzymatic glycosylation of vancomycin aglycon, this provides a 19-step total synthesis of vancomycin. The approach paves the way for large-scale synthetic preparation of pocket-modified vancomycin analogues that directly address the underlying mechanism of resistance to vancomycin.
Topics: Anti-Bacterial Agents; Crystallography, X-Ray; Models, Molecular; Molecular Structure; Stereoisomerism; Vancomycin
PubMed: 32885969
DOI: 10.1021/jacs.0c07433 -
Clinical Infectious Diseases : An... Jul 2011
Topics: Administration, Oral; Anti-Infective Agents; Clostridioides difficile; Clostridium Infections; Humans; Metronidazole; Treatment Outcome; Vancomycin
PubMed: 21690636
DOI: 10.1093/cid/cir311 -
Lancet (London, England) Mar 1985
Topics: Bacterial Infections; Humans; Vancomycin
PubMed: 2858624
DOI: No ID Found -
Drug Intelligence & Clinical Pharmacy Oct 1986Vancomycin is an effective and widely used antistaphylococcal antibiotic. Despite several decades of use, however, our knowledge of the toxicologic and pharmacokinetic...
Vancomycin is an effective and widely used antistaphylococcal antibiotic. Despite several decades of use, however, our knowledge of the toxicologic and pharmacokinetic properties of vancomycin remains incomplete. This review summarizes current information regarding the adverse reactions and pharmacokinetics of vancomycin. Although there have been reports of side effects with vancomycin, these effects tend to be infrequent, easily managed, and reversible. Several methods for adjustment of vancomycin therapy have been recommended. The relationship between serum concentrations of vancomycin and the occurrence of ototoxicity or nephrotoxicity has not been well established. However, because of large interpatient variations in pharmacokinetic parameters, it seems preferable to individualize vancomycin therapy based on serum concentration data.
Topics: Adult; Drug Administration Schedule; Half-Life; Humans; Kinetics; Vancomycin
PubMed: 3769763
DOI: 10.1177/106002808602001003 -
Journal of Chromatography. A May 2008This review discusses the use of vancomycin-related substances as potential chiral stationary phase that can be used as a packing material for the enantioselective... (Review)
Review
This review discusses the use of vancomycin-related substances as potential chiral stationary phase that can be used as a packing material for the enantioselective separation of various racemic compounds in various modalities including HPLC, CE and also as chiral mobile phase additives. The chiral recognition mechanisms involved including the role of dimerization are presented.
Topics: Chromatography, High Pressure Liquid; Dimerization; Electrophoresis, Capillary; Stereoisomerism; Vancomycin
PubMed: 17950744
DOI: 10.1016/j.chroma.2007.09.060 -
Journal of Clinical Pharmacy and... Feb 1995The glycopeptide antibiotics vancomycin and teicoplanin have similar mechanisms of action on bacterial cell wall synthesis. Their spectra of activity are limited to... (Review)
Review
The glycopeptide antibiotics vancomycin and teicoplanin have similar mechanisms of action on bacterial cell wall synthesis. Their spectra of activity are limited to Gram-positive bacteria, with the degree of bactericidal activity depending on the species of micro-organism. Staphylococcus aureus, Staphylococcus epidermis, enterococci and Clostridium difficile are generally sensitive, including methicillin-resistant strains of S. aureus and S. epidermidis. Glycopeptide resistance has recently emerged in staphylococci and enterococci. Vancomycin has a shorter half-life than teicoplanin and requires multiple dosing to maintain adequate serum levels. It can only be given by prolonged intravenous infusion over 1 h. In contrast, the pharmacokinetics of teicoplanin allow for once-daily dosing, either by rapid intravenous infusion or by the intramuscular route. The latter offers reliable absorption for patients with limited venous access and is also of benefit for out-patient therapy. Teicoplanin is a safer drug than vancomycin. It is associated with a lower incidence of nephrotoxicity or ototoxicity. Compared to vancomycin, the availability of the intramuscular route and the absence of a requirement for routine serum monitoring, together with the reduced need to treat drug-related side-effects make teicoplanin more cost-effective. It is as effective as vancomycin for most indications, is safe, easy to administer and an important agent for treating Gram-positive infections. Its role in hospitals is likely to increase if the price of drug acquisition is kept low.
Topics: Cell Wall; Cost-Benefit Analysis; Drug Resistance, Microbial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Half-Life; Humans; Teicoplanin; Vancomycin
PubMed: 7775615
DOI: 10.1111/j.1365-2710.1995.tb00619.x -
Bioorganic & Medicinal Chemistry Letters Jun 2021Over 60-year clinical use of vancomycin led to the emergence of vancomycin-resistant bacteria and threatened our health. To combat vancomycin-resistant strains, numerous...
Over 60-year clinical use of vancomycin led to the emergence of vancomycin-resistant bacteria and threatened our health. To combat vancomycin-resistant strains, numerous vancomycin analogues were developed, such as Telavancin, Oritavancin and Dalbavancin. Extra structures embedded on C-terminus has been proved to be an effective strategy to promote antibacterial activity of vancomycin against vancomycin-resistant strains. Here, we reported a facile strategy, inspired by native chemical ligation, for vancomycin C-terminus functionalization and derivatization. The introduction of C-terminal hydrazide on vancomycin not only provided us an accessible method for C-terminus functionalization through carbonyl azide and thioester, also acted as an efficient site for vancomycin structure modifications. Based on hydrazide-vancomycin, we effectively conjugated cysteine and cysteine containing peptides onto vancomycin C-terminus, and two fluorescent FITC-vancomycin were prepared through Cys-Maleimide conjugation. Meanwhile, we introduced lipophilic structures onto vancomycin C-terminus via the hydrazide moiety. The obtained vancomycin derivatives were evaluated against both Gram-positive and negative bacteria strains.
Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Humans; Hydrazines; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Vancomycin; Vancomycin-Resistant Staphylococcus aureus
PubMed: 33839255
DOI: 10.1016/j.bmcl.2021.128027 -
The Journal of Antimicrobial... Aug 1995
Review
Topics: Anti-Bacterial Agents; Bacterial Infections; Humans; Vancomycin
PubMed: 8522457
DOI: 10.1093/jac/36.2.279