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      In vitro activity of tigecycline, a new glycylcycline, tested against 1,326 clinical bacterial strains isolated from Latin America

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          Abstract

          The in vitro activity of tigecycline (former GAR-936), a new semisynthetic tetracycline, was evaluated in comparison with tetracycline and other antimicrobial agents. MATERIAL AND METHODS: A total of 1,326 contemporary clinical isolates collected from the Latin American region were collected in 2000-2002 period and tested with microdilution broth according to the CLSI guidelines. The bacterial pathogens evaluated included Staphylococcus aureus (505), Streptococcus pneumoniae (269), coagulase-negative staphylococci (CoNS; 227), Haemophilus influenzae (129), Enterococcus spp. (80), Moraxella catarrhalis (54), beta-haemolytic streptococci (28), viridans group streptococci (26), and Neisseria meningitidis (8) RESULTS:Tigecycline demonstrated excellent activity against all Gram-positive cocci, with 90% of penicillin-resistant S. pneumoniae strains being inhibited at 0.12 µg/mL, while the same isolates had an MIC90 of > 16 µg/mL for tetracycline. All Enterococcus spp. were inhibited at 0.25 µg/mL of tigecycline. Tigecycline (MIC50, 0.25 µg/mL) was eight-fold more potent than minocycline (MIC50, 2 µg/mL) against oxacillin-resistant S. aureus (ORSA); all ORSA were inhibited at < 2 µg/mL of tigecycline. Tigecycline demonstrated excellent activity (MIC50, 0.5 µg/mL) against CoNS with reduced susceptibility to teicoplanin (MIC, 16 µg/mL). Tigecycline also showed high potency against respiratory pathogens such as M. catarrhalis (MIC50, 0.12 µg/mL) and H. influenzae (MIC50, 0.5 µg/mL). No tigecycline resistant isolates were detected when the proposed susceptible breakpoints (< 4 µg/mL) was applied. CONCLUSIONS: This results indicate that tigecycline has potent in vitro activity against clinically important pathogenic bacteria, including Gram-positive isolates resistant to both tetracycline and minocycline.

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          Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance.

          Tetracycline has been a widely used antibiotic because of its low toxicity and broad spectrum of activity. However, its clinical usefulness has been declining because of the appearance of an increasing number of tetracycline-resistant isolates of clinically important bacteria. Two types of resistance mechanisms predominate: tetracycline efflux and ribosomal protection. A third mechanism of resistance, tetracycline modification, has been identified, but its clinical relevance is still unclear. For some tetracycline resistance genes, expression is regulated. In efflux genes found in gram-negative enteric bacteria, regulation is via a repressor that interacts with tetracycline. Gram-positive efflux genes appear to be regulated by an attenuation mechanism. Recently it was reported that at least one of the ribosome protection genes is regulated by attenuation. Tetracycline resistance genes are often found on transmissible elements. Efflux resistance genes are generally found on plasmids, whereas genes involved in ribosome protection have been found on both plasmids and self-transmissible chromosomal elements (conjugative transposons). One class of conjugative transposon, originally found in streptococci, can transfer itself from streptococci to a variety of recipients, including other gram-positive bacteria, gram-negative bacteria, and mycoplasmas. Another class of conjugative transposons has been found in the Bacteroides group. An unusual feature of the Bacteroides elements is that their transfer is enhanced by preexposure to tetracycline. Thus, tetracycline has the double effect of selecting for recipients that acquire a resistance gene and stimulating transfer of the gene.
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            Tetracyclines, molecular and clinical aspects.

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              Comparison of the in vitro activity of the glycylcycline tigecycline (formerly GAR-936) with those of tetracycline, minocycline, and doxycycline against isolates of nontuberculous mycobacteria.

              We compared the in vitro activity of the glycylcycline tigecycline (formerly GAR-936) with those of tetracycline, doxycycline, and minocycline by broth microdilution against 76 isolates belonging to seven species of rapidly growing mycobacteria (RGM) and 45 isolates belonging to five species of slowly growing nontuberculous mycobacteria (NTM). By using a resistance breakpoint of >4 micro g/ml for tigecycline and >8 micro g/ml for tetracycline, all RGM were highly susceptible to tigecycline, with inhibition of 50% of isolates at < or =0.12 micro g/ml and inhibition of 90% of isolates at 0.25 micro g/ml for Mycobacterium abscessus and inhibition of both 50 and 90% of isolates at < or =0.12 micro g/ml for M. chelonae and the M. fortuitum group. The MICs of tigecycline were the same for tetracycline-resistant and -susceptible strains, and RGM isolates were 4- to 11-fold more susceptible to tigecycline than to the tetracyclines. In contrast, no slowly growing NTM were susceptible to tigecycline, and isolates of M. marinum and M. kansasii were less susceptible to this agent than to minocycline. This new antimicrobial offers exciting therapeutic potential for the RGM, especially for isolates of the M. chelonae-M. abscessus group, against which the activities of the currently available drugs are limited.
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                Author and article information

                Journal
                bjid
                Brazilian Journal of Infectious Diseases
                Braz J Infect Dis
                Brazilian Society of Infectious Diseases (Salvador, BA, Brazil )
                1413-8670
                1678-4391
                October 2005
                : 9
                : 5
                : 348-356
                Affiliations
                [01] orgnameFederal University of São Paulo orgdiv1Division of Infectious Diseases
                [02] São Paulo orgnameDepartment of Medicine Brazil
                [03] North Liberty IA orgnameThe JMI Laboratories USA
                Article
                S1413-86702005000500001 S1413-8670(05)00900501
                10.1590/S1413-86702005000500001
                77d573b9-c2eb-4732-b295-6ea9d88bc8fb

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 17 May 2005
                : 27 September 2005
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 19, Pages: 9
                Product

                SciELO Brazil

                Categories
                Original Papers

                Latin America and SENTRY,tigecycline,Antimicrobial susceptibility

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