title: In vitro antimicrobial activity of GAR-936 tested against antibiotic-resistant gram-positive blood stream infection isolates and strains producing extended-spectrum beta-lactamases.
abstract: GAR-936, a new, semisynthetic glycylcycline, has shown good antibacterial activity against a wide range of clinically important Gram-positive and -negative aerobic bacteria including Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, most Enterobacteriaceae, Staphylococcus aureus and Enterococcus spp. The purpose of this study was to determine the activity of GAR-936 against a range of Gram-positive and -negative bloodstream isolates including many strains producing extended-spectrum beta-lactamases (ESBLs). Six hundred four bloodstream isolates of Gram-positive cocci collected as part of the SENTRY surveillance program were selected for their geographic diversity. GAR-936 was also tested against an additional 176 Gram-negative cocci isolates (Klebsiella pneumoniae, 98 strains; Escherichia coli, 78 strains), 96 of which were ESBL-producers. Broth microdilution testing was used to determine the susceptibility of the selected organisms and a range of comparator antimicrobial agents whose choice was based on their activities against the selected pathogens and included a mix of both newer and older agents. Presence of an ESBL-producing strain was confirmed using the clavulanate test. GAR-936 demonstrated impressive activity against all 604 strains of Gram-positive cocci, with an MIC range of <or=0.015-1 microg/mL, and MIC(90)s ranging from <or=0.05 microg/mL for S. pneumoniae to 0.25 for S. aureus and coagulase-negative staphylococci. MICs against the 176 Gram-negative isolates were higher (range 0.06-4 microg/mL), with MIC(90)s of 0.25-1 microg/mL. The activity of GAR-936 was relatively unaffected by the presence of ESBLs. The activity of GAR-936 was particularly impressive against Gram-positive cocci when compared against the test results for vancomycin and the newer antimicrobial agents, linezolid and quinupristin/dalfopristin. The MIC(90)s for GAR-936 were significantly lower than the comparator agents for all species tested with particularly impressive results against S. pneumoniae and enterococci.
authors.affiliation: University of Iowa College of Medicine, Iowa City, Iowa, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Biedenbach
authors.forename: M L
authors.initials: ML
authors.lastname: Beach
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D016983:Enterococcus / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013211:Staphylococcus aureus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013752:Tetracycline / Q000494:pharmacology; D000078304:Tigecycline; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D001618:beta-Lactamases; D013752:Tetracycline; D008911:Minocycline