Optimizing the Clinical Use of Vancomycin

Abstract

Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of >400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of >400 for a MIC of <1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated. Vancomycin has traditionally been used as a first-line agent for treating methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive beta-lactam-resistant bacteria (1), which are frequent etiologies of severe health-related infections (2, 3).Although the effectiveness of vancomycin is supported by more than 5 decades of use and multiple studies, the clinical and microbiological scenario in which it is used is always changing. Attaining an appropriate dosage of vancomycin for S. aureus infections might be difficult due to the clinical impact of the creep in the MIC of vancomycin and heteroresistance among MRSA strains, or due to complex pharmacokinetic and pharmacodynamic (PK/PD) situations. In this context, the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) introduced a practice guideline in 2009 (4), marking a milestone in vancomycin therapy. However, several questions, such as the optimal dosing in some special clinical situations (e.g., with renal replacement therapies or in burn patients or obese patients), the role of continuous infusion, or the renal toxicity when the suggested vancomycin serum levels are achieved, remain unanswered. The present review mainly focuses on these issues. VANCOMYCIN PHARMACODYNAMICS AND ITS IMPLICATIONS FOR DRUG MONITORINGThe killing effect of vancomycin is characterized by a slow mode of action and is further hampered by a large bacterial inoculum, a stationary growth phase, and anaerobic conditions (5, 6). Although several pharmacodynamic parameters have been proposed to determine vancomycin activity, data from experimental and clinical studies have selected the area under the curve (AUC)/ MIC ratio as the best parameter to predict the...

Staphylococcus aureus: Overview of Bacteriology, Clinical Diseases, Epidemiology, Antibiotic Resistance and Therapeutic Approach

“…The emergence and increased incidence of hVISA and VISA has limited the therapeutic use of vancomycin in the treatment of MRSA infections in hospital. However, by optimizing the dose regimen and drug delivery, thereby, achieving the desired blood plasma concentration which would give the clinical efficacy is the way forward in preserving the clinical utility of vancomycin [88,89].…”

Cobalt(III)‐Catalyzed C−H Amidation of Dehydroalanine for the Site‐Selective Structural Diversification of Thiostrepton

“…Many analogs demonstrated activity within 2–5 times the MICs observed for 1 (Table , bolded entries). Importantly, except for 4 g , all compounds were generally competitive with vancomycin, a potent compound currently used for treating bacterial infections . Only VSE E. faecium showed consistent vulnerability to vancomycin over the derivatives of 1 .…”

Cobalt(III)‐Catalyzed C−H Amidation of Dehydroalanine for the Site‐Selective Structural Diversification of Thiostrepton

“…Importantly,e xcept for 4g,a ll compounds were generally competitive with vancomycin, ap otent compound currently used for treating bacterial infections. [19] Only VSE E. faecium showed consistent vulnerability to vancomycin over the derivatives of 1.T he most active analogs,i ncluding 2c, 4a,a nd 4c,p ossessed relatively nonpolar amides.I nc ontrast, compounds with the smallest alkyl (2g,h)o rapolar carbohydrate group (4g)h ad the poorest activity.…”