Counterpoint: Vancomycin and Staphylococcus aureus--an antibiotic enters obsolescence.
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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ABSTRACT: Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA] strains). As colistin-induced vancomycin tolerance is reversible, it may not be detected by routine sensitivity testing and may be responsible for treatment failure at vancomycin doses expected to be clinically effective based on such routine testing. IMPORTANCE : Commonly, antibiotic resistance is associated with permanent genetic changes, such as point mutations or acquisition of resistance genes. We show that phenotypic resistance can arise where changes in gene expression result in tolerance to an antibiotic without any accompanying genetic changes. Specifically, methicillin-resistant Staphylococcus aureus (MRSA) behaves like vancomycin-intermediate S. aureus (VISA) upon exposure to colistin, which is currently used against infections by Gram-negative bacteria. Vancomycin is a last-resort drug for treatment of serious S. aureus infections, and VISA is associated with poor clinical prognosis. Phenotypic and reversible resistance will not be revealed by standard susceptibility testing and may underlie treatment failure. Copyright © 2015 Haaber et al.mBio 01/2015; 6(1):e02268-14. DOI:10.1128/mBio.02268-14 · 6.88 Impact Factor
Journal of the American College of Surgeons 11/2014; DOI:10.1016/j.jamcollsurg.2014.02.039 · 4.45 Impact Factor
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ABSTRACT: Telavancin was the first marketed lipoglycopeptide. Although licensed in Europe in 2011 for the treatment of nosocomial pneumonia caused by meticillin-resistant Staphylococcus aureus (MRSA), it did not become clinically available until March 2014. Given the limited clinical experience with telavancin in Europe, this review provides an overview of its antimicrobial and clinical activity as well as its position among today's antimicrobials, with particular focus on the implications of its licensing requirements. Telavancin has potent in vitro activity against isolates of Gram-positive pathogens, including MRSA and glycopeptide-intermediate S. aureus strains. In addition, at clinically attainable doses telavancin inhibits Gram-positive isolates of antibiotic-resistant strains from biofilm models. The in vitro potency of telavancin has been corroborated in the clinical setting. Comparative clinical studies of telavancin demonstrate non-inferiority compared with vancomycin in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for telavancin-treated patients with monomicrobial S. aureus infection, including isolates with reduced vancomycin susceptibility. These studies also demonstrate an overall similar safety profile for telavancin and vancomycin, although importantly, patients with moderate-to-severe renal impairment at baseline are at greater risk for mortality with telavancin and this feature must be taken into account when selecting patients for its usage. In Europe, telavancin is a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. For example, it should be considered in such patients when vancomycin and linezolid are not suitable and where renal function permitsInternational Journal of Antimicrobial Agents 12/2014; DOI:10.1016/j.ijantimicag.2014.12.006 · 4.26 Impact Factor