Counterpoint: Vancomycin and Staphylococcus aureus - An antibiotic enters obsolescence

Division of Infectious Disease and Geographic Medicine, Department of Medicine, Stanford University, CA, USA.
Clinical Infectious Diseases (Impact Factor: 9.42). 07/2007; 44(12):1543-8. DOI: 10.1086/518452
Source: PubMed

ABSTRACT The efficacy of vancomycin for the treatment of patients with infections due to Staphylococcus aureus is impaired by its poor tissue penetration and by its relatively weak antibacterial activity--an activity that is declining as S. aureus evolves. Neither dose escalation nor use of vancomycin in combination with other antibiotics that have antistaphylcoccal activity has been demonstrated to safely enhance its therapeutic efficacy. Although no clinical trials suggest superiority of vancomycin over any comparator, some have provided evidence of its inferiority. Strong consideration should be given to the use of alternative agents in the treatment of serious S. aureus infections.

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    • "Vancomycin, the most commonly used antibiotic in hospitalized patients with MRSA bacteremia, has several limitations [5], including the rise of strains with decreased susceptibility [6,7] or resistance [8,9] and suboptimal results for the treatment of patients with bacteremia due to methicillin-susceptible S. aureus (MSSA) [10,11]. Despite the dramatic consequences of SAB and the limitations of vancomycin, only one registrational, open-label, randomized clinical trial in patients with SAB has been conducted [12], and vancomycin remains first-line therapy for MRSA bacteremia in most settings [13]. "
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    ABSTRACT: Background Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality. Telavancin is a bactericidal lipoglycopeptide active against Gram-positive pathogens, including methicillin-resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2 trial in patients with uncomplicated S. aureus bacteremia. Methods Patients were randomized to either telavancin or standard therapy (vancomycin or anti-staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid complicated S. aureus bacteremia. The primary end point was clinical cure at 84 days. Results In total, 60 patients were randomized and 58 received ≥1 study medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy 16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar proportion of CE patients were cured in the telavancin (88%) and standard therapy (89%) groups. All patients with MRSA bacteremia were cured and one patient with MSSA bacteremia failed study treatment in each group. Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms. Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%). Conclusions This study suggests that telavancin may have utility for treatment of uncomplicated S. aureus bacteremia; additional studies are warranted. (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia (ASSURE); NCT00062647).
    BMC Infectious Diseases 05/2014; 14(1):289. DOI:10.1186/1471-2334-14-289 · 2.61 Impact Factor
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    • "In our patient's case, the S. aureus isolate showed a vancomycin MIC of 2 mg/mL which was considered to be perhaps less effective against serious methicillin resistance, or a " bridge too far " in that the doses required carried a significant risk of toxicity [14]. Guidelines therefore recommend therapy with alternative antimicrobials [16]. "
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    ABSTRACT: Large cardiac vegetation carries a poor prognosis and high mortality risk, especially if associated with methicillin-resistant Staphylococcus aureus (MRSA) infection. We share our experience of a rare and complicated large cardiac vegetation which had a favourable outcome with combination antibiotic treatment alone. A 35-year-old HIV-negative, HCV-positive male patient with a previous history of methicillin-susceptible S. aureus endocarditis showed MRSA mitral valve endocarditis with large vegetation, complicated by embolic stroke. The strain was soon identified by PCR but only after culture did the patient receive efficacious antibiotics. A combination of daptomycin plus trimethoprim/sulfamethoxazole (TMP/SMX) was administered for six weeks, followed by a high dosage of TMP/SMX for a further six weeks. Effectiveness of the treatment was demonstrated by the patient's clinical improvement and instrumental evidence of cardiac mitral vegetation clearance. Innovative antibiotic strategies in patient management are needed to fight Staphylococcus aureus endocarditis because strains show varying antimicrobial susceptibility patterns in different geographic areas. Timely initiation of targeted antimicrobial therapy remains a crucial step to reduce morbidity and mortality but culture is crucial for appropriate fine-tuning of antibiotic therapy.
    Le infezioni in medicina: rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive 03/2013; 21(1):41-5.
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    • "Additionally, surveillance studies report a consistent increase in mean MIC values for S. aureus isolates that are considered susceptible to vancomycin. This increase has been coined "MIC creep" [7]. The clinical significance of increasing MIC within the sensitive range was shown in a study comparing MIC and treatment outcome in patients receiving vancomycin treatment for MRSA bacteremia [8]. "
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    ABSTRACT: The rapid antibiotic resistance development has created a major demand for new antimicrobial agents that can combat resistant strains such as methicillin-resistant S. aureus (MRSA). Until a short time ago, the glycopeptide vancomycin was the only therapeutic choice in this situation. However, in recent years some newer agents with different mechanisms of actions have been added to the arsenal, and more are on the horizon. For a successful therapy it is of vital importance that these compounds are used judiciously and dosed appropriately. The present article reviews the pharmacokinetic properties of vancomycin, linezolid, tigecycline and daptomycin. The first major difference between these compounds is their oral bioavailability. Only linezolid can be administered orally, whereas vancomycin, daptomycin and tigecycline are limited to parenteral use. Once in the body, they show very different disposition. Daptomycin has a very small volume of distribution of 7L indicating very little tissue distribution whereas tigecycline has a very large volume of distribution of 350-500 L. Vancomycin and linezolid are in-between with volumes of distribution of approximately 30 and 50 L, close to total body water. However, studies have shown that linezolid shows better tissue penetration than vancomycin. Newer studies using microdialysis, a new technique that allows direct monitoring of unbound tissue levels, support this finding. As far as drug elimination, daptomycin and vancomycin are mainly eliminated into the urine and require dosing adjustments in renally impaired patients, whereas tigecycline is eliminated into the bile and linezolid is metabolized so that in renal patients no dosing adjustments are needed for these compounds. Although the elimination pathways are very different, the resulting half-lives of linezolid, vancomycin, and daptomycin are not greatly different and vary from 4-8 h. Tigecycline, however, has a much longer half-life of up to 1-2 days due to the slow redistribution from tissue binding sites.
    European journal of medical research 11/2010; 15(12):533-43. DOI:10.1186/2047-783X-15-12-533 · 1.40 Impact Factor
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