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Limited established treatment options exist for the treatment of serious, invasive infections caused by multidrug-resistant Staphylococcus aureus, most notably nosocomially acquired methicillin-resistant S. aureus (MRSA). Although vancomycin represents the gold standard for therapy of such invasive infections, reports of increasing in vitro resistance to vancomycin, combined with reports of clinical failures (with this and other anti-staphylococcal agents), underscore the need for alternative therapies. Older agents with favorable in vitro activity available in both oral and intravenous close forms include trimethoprim-sulfamelhoxazole and clindamycin. Limited clinical data exist to support their routine use as initial therapy in the treatment of invasive disease. However, these and other options (e.g., tetracyclines) are being reexplored in the setting of increasing concern over MRSA acquired in the community setting. Newer treatment options for MRSA include linezolid, quinupristin-dalfopristin, daptomycin, and tigecycline. With the exception of linezolid, these newer agents require intravenous administration. Combination therapy may be considered in select invasive diseases refractory to standard monotherapies. These diseases include infections such as endocarditis, meningilis, and prosthetic device infections. Additional alternatives to vancomycin are under clinical investigation. Those in later stages of development include oritavancin, dalbavancin, telavancin, and ceftobiprole. [ABSTRACT FROM AUTHOR]

Tigecycline for treatment of multidrug-resistant gram-negative bacteria in transplant recipient patients: Challenges of antimicrobial susceptibility testing Keywords: CLSI; EUCAST; MIC breakpoints; multidrug-resistant bacteria; tigecycline; treatment EN CLSI EUCAST MIC breakpoints multidrug-resistant bacteria tigecycline treatment 1 2 2 04/17/20 20200401 NES 200401 To the Editor, With the widespread of multidrug-resistant gram-negative bacteria, organ transplant recipients become highly vulnerable to these pathogens because they often undergo complex surgery and they also receive immunosuppressive therapy, increasing risk of infection.[1] Consequently, the hospital length of stay and hospitalization costs for transplant recipients who get infected with these multidrug-resistant bacteria have increased.[1] Thus, there is a high-priority requisite for active antimicrobial agents against those bacteria such as tigecycline. Effectiveness of tigecycline in the treatment of infections caused by carbapenem-resistant gram-negative bacteria in pediatric liver transplant recipients: A retrospective study. [Extracted from the article]

Tigecycline is the first commercially available member of the glycylcyclines, a new class of antimicrobial agents. The glycylcyclines are derivatives of the tetracycline antibiotics, with structural modifications that allow for potent gram-positive, gram-negative, and anaerobic activity, including certain multidrug-resistant strains. The enhanced activity can be attributed to stronger binding affinity and enhanced protection against several mechanisms of resistance that affect other antibiotic classes such as tetracyclines. Tigecycline exhibits generally bacteriostatic action by reversibly binding to the 30S ribosomal subunit and inhibiting protein translation. In vitro activity has been demonstrated against multidrug-resistant gram-positive pathogens including methicillin-resistant and glycopeptide-intermediate and -resistant Staphylococcus aureus, as well as vancomycin-resistant enterococci. Multidrug-resistant gram-negative pathogens, such as Acinctobacter baumannii and extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Eschcrichia coli, are typically highly susceptible to tigecycline. The drug also has displayed significant activity against many clinically important anaerobic organisms. This agent demonstrates a predictable pharmacokinetic profile and minimal drug interactions, and is generally well tolerated, with nausea being the most common adverse event. It was approved in June 2005 for the treatment of complicated skin and skin structure infections (SSSIs) and complicated intraabdominal infections. Currently, a limited number of broad-spectrum antimicrobials are available to combat multidrug-resistant organisms. The addition of new agents is essential to limiting the spread of these pathogens and improving outcomes in patients with these types of infections. Tigecycline has demonstrated promising results in initial in vitro and clinical studies for SSSIs and complicated intraabdominal infections; however further clinical experience will clarify its role as a broad-spectrum agent. [ABSTRACT FROM AUTHOR]

The advent of mutidrug-resistant gram-positive aerobes such as Staphylococcus aurcus. Streptococcus pneumoniae, and the enterococci, which are resistant to β-lactams, vancomycin, and a host of other commonly used antimicrobials, has complicated our approach to antibiotic therapy. Despite marketing of the first oxazolidinone, linezolid, and the streptogramin combination, quinupristin-dalfopristin, an urgent need exists for more agents to combat these pathogens. Two such agents, the glycopeptide oritavancin (LY333328) and the glycylcycline tigecycline (GAR-936), arc in phase III clinical trials. These agents, which require parenteral administration. exhibit substantial in vitro activity against a variety of gram-positive aerobes and anaerobes, including the multidrug-resistant organisms listed previously. Only tigecycline demonstrates useful activity against gram-negative organisms. Combination therapy of these agents with ampicillin or aminoglycosides frequently leads to synergistic in vitro activity against multidrug-resistant staphylococci and streptococci. These agents are also active in a variety of animal models of systemic and localized infections. Few published efficacy and tolerability data arc available in humans. If controlled clinical trial data verify these agents' efficacy and tolerability, both drugs should become welcome additions to the available antimicrobials. However, restricting their use to the treatment of infections caused by bacteria resistant to other antimicrobials, especially multidrug-resistant staphylococci and streptococci, may prolong their clinical utility by retarding the development of resistance. Careful surveillance of bacterial sensitivity to these agents should be undertaken to assist clinicians in the decision whether or not 10 use these agents empirically to treat infections caused by suspected multidrug-resistant gram-positive pathogens. [ABSTRACT FROM AUTHOR]