SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
In vitro synergy testing of daptomycin plus rifampin was performed against 24 unique isolates of Enterococcus faecium resistant to both linezolid and vancomycin. Synergy testing showed that 21/24 (88%) were synergistic and 3/24 (12%) were indifferent by the Etest method. Time-kill assays revealed synergy for 18/24 (75%) and indifference for 6/24 (25%).
In mice, vancomycin and linezolid treatment disrupted the anaerobic intestinal microflora, based on denaturing gradient gel electrophoresis analysis, and promoted colonization by Klebsiella pneumoniae and vancomycin-resistant enterococci. However, the effects varied depending on dose and duration of treatment. Daptomycin treatment did not disrupt the anaerobic microflora or promote either pathogen.
Daptomycin inhibited 67 of 70 clinical isolates of Bacillus species at < or =1 microg/ml and 100% of them at < or =2 microg/ml. It showed bactericidal activity similar to that of ciprofloxacin against vegetative cells but not against spores. For 2 strains, the ciprofloxacin MICs were >4 g/ml, and 10 strains were resistant to erythromycin.
The novel lipopeptide antibiotic A21978C complex is active against Gram-positive organisms. This complex consists of a common peptide nucleus with various lipid acyl groups at the N-terminus characteristic of each individual factor. The fatty acid acyl group is removed by incubation of the A21978C complex with Actinoplanes utahensis to give the peptide nucleus. This peptide nucleus has the same amino acid sequence as A21978C. New analogs of A21978C were synthesized by acylation of the N-terminus of a tert-butoxycarbonyl (tert-BOC)-protected nucleus and subsequent deprotection. 1H NMR showed that the newly introduced acyl group was at the desired N-terminus. Three major groups of analogs were synthesized bearing fatty acid acyl, amino-aroyl and extended peptide side chains. Each analog was evaluated for antimicrobial activity and acute toxicity. Of these analogs, the n-decanoyl analog of A21978C (LY146032) gave the best survival in the mouse acute toxicity test at a high dose of 1,000 mg/kg, iv and was chosen for further study. This analog has been named daptomycin.
Increasing antibiotic resistance of bacteria that infect prosthetic joints has stimulated interest in the incorporation of more effective antimicrobial agents into polymethylmethacrylate (PMMA). Vancomycin and daptomycin are effective against nearly all staphylococci and streptococci, and amikacin has a broader spectrum against gram-negative bacilli than do other aminoglycosides such as gentamicin. These three antibiotics maintained bioactivity after incorporation into several commonly used preparations of PMMA and eluted readily into the surrounding medium. Preparing PMMA under negative atmospheric pressure, which decreases porosity, caused a 50% reduction in antibiotic release; the addition of 25% dextran, which increases porosity, greatly facilitated elution of these antibiotics. Based on their broad antibacterial effect against gram-positive and gram-negative bacteria, inclusion of vancomycin and amikacin in PMMA merits clinical study. The addition of these antibiotics to PMMA, together with dextran, may be applicable when structural integrity is unimportant but a substantial local antimicrobial effect is desired, such as in the use of antibiotic-containing beads to treat osteomyelitis.
In vitro activity of the new cyclic lipopeptide LY 146032 (daptomycin, Eli Lilly) was evaluated against 67 clinical isolates of Staphylococcus aureus, 15 clinical isolates of S. epidermidis and 80 clinical isolates of Streptococcus faecalis. Activity was best against methicillin-resistant S. epidermidis (minimal inhibitory concentrations of LY 146032 0.25-0.5 mg/l). Minimal inhibitory concentrations and minimal bactericidal concentrations were of similar value. LY 146032 requires physiological concentrations of Ca++ ion for the expression of antibacterial activity. Results of the time-kill curves indicated that exposure to a concentration of the antibiotic equivalent to the minimal inhibitory concentration abolished recovery in the strains of S. aureus and S. epidermidis investigated. Response by S. faecalis was less predictable although most S. faecalis strains were killed in vitro by LY 146032 concentrations of less than or equal to 8 mg/l which is within the predicted clinically achievable range.
Explore the source record for details and available documents.
The in vitro activity of LY146032, a new peptolide antibiotic, was compared with those of vancomycin, teicoplanin, imipenem, amoxicillin and erythromycin. LY146032 inhibited 90% of Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-resistant isolates at less than or equal to 1 microgram/ml. Its activity was comparable to those of vancomycin and teicoplanin. MIC90s for the beta-hemolytic streptococci varied from 0.25 microgram/ml for group B streptococci to 4 micrograms/ml for some group C and F streptococci. MICs for Streptococcus faecalis were in the range of 0.5 to 8 micrograms/ml, and the MIC90 4 micrograms/ml, compared to 4 micrograms/ml for vancomycin and 1 microgram/ml for teicoplanin. For some viridans streptococci the MICs were 4 micrograms/ml, whereas Streptococcus pneumoniae were inhibited by 0.5 microgram/ml. Corynebacterium JK species were inhibited by 0.5 microgram/ml, similar to vancomycin, and Listeria monocytogenes by 4 micrograms/ml. Neisseria species, Haemophilus species and enteric species were not inhibited. Most MBCs were within two-fold of the respective MICs. After 14 days passage in sub-inhibitory concentrations of LY146032, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus faecalis showed minimal increase in MICs. The activity of LY146032 was increased by adding Ca2+ and was reduced in an anaerobic environment. Overall, LY146032 is an extremely interesting new agent that inhibits gram-positive species.
The in vitro activity of the new lipopeptide antibiotic LY146032 was generally four-fold greater (MIC 90 less than or equal to 0.5 microgram/ml) than that of vancomycin against methicillin-susceptible or methicillin-resistant Staphylococcus aureus and coagulase-negative species of Staphylococcus. Enterococci, Streptococcus bovis, group B and viridans streptococci, and Corynebacterium group J-K isolates were inhibited by less than or equal to 4 micrograms/ml of LY146032, which represented activity equivalent to or greater than that of vancomycin. Unlike vancomycin, LY146032 was bactericidal for Enterococcus faecalis, Enterococcus faecium and Listeria monocytogenes. Due to its bactericidal properties LY146032 appeared to represent an improvement over vancomycin and teicoplanin.
The in vitro activity of LY146032 was compared with those of seven other antimicrobial agents against gram-positive cocci. MICs of LY146032 were lowest for Streptococcus pneumoniae and methicillin-susceptible Staphylococcus epidermidis (0.25 mg/l). For methicillin-resistant Staphylococcus epidermidis and Staphylococcus aureus the MICs were 1 mg/l, for Enterococcus faecalis 2 mg/l and for Enterococcus faecium 4 mg/l. The activity of LY146032 was in general higher than that of vancomycin. Time-kill studies showed LY146032 had higher bactericidal activity than vancomycin against a methicillin-resistant Staphylococcus aureus strain, and bactericidal activity against Enterococcus faecalis and Enterococcus faecium.
The in vitro activity of LY146032, a new cyclic lipopeptide antibiotic, was compared with those of vancomycin, teicoplanin, and either oxacillin or ampicillin by determining agar dilution MIC values for 304 clinical gram-positive isolates. LY146032 had superior in vitro activity against oxacillin-resistant staphylococci when compared to vancomycin or teicoplanin. Against oxacillin-sensitive staphylococci, group JK-diphtheroids, streptococci, Listeria monocytogenes and Clostridium difficile, LY146032 was equally or less active than vancomycin, teicoplanin, or the penicillins tested. When tested by macrobroth dilution MIC/MBC, LY146032 showed good bactericidal activity against all organisms with the exception of Clostridium difficile.
LY264826 a new naturally occurring glycopeptide inhibited 90% of methicillin-susceptible and -resistant Staphylococcus aureus at 1 micrograms/ml. LY264826 had similar activity against methicillin-susceptible and -resistant coagulase-negative staphylococci. The LY264826 MIC90 for Streptococcus pyogenes was 0.25 microgram/ml, twofold more active than vancomycin and twofold less active than teicoplanin. LY264826 was eightfold more active than vancomycin and twofold more active than teicoplanin against enterococci. LY264826 inhibited Streptococcus pneumoniae at 0.25 microgram/ml and Listeria monocytogenes at 0.5 microgram/ml. Clostridium were inhibited by less than or equal to 0.25 microgram/ml of LY264826 and peptococci, peptostreptococci, and Fusobacterium were inhibited by less than 0.5 microgram/ml. Bacteroides species were LY284826 -resistant as were all Enterobacteriaceae, Flavobacterium, and Neisseria spp. Minimum bactericidal and inhibitory concentrations (MBCs and MICs) were within a dilution for S. aureus, S. pyogenes, and S. pneumoniae, but greater than or equal to 32-fold greater for enterococci.
Explore the source record for details and available documents.
An overview of the mechanism of action, dosing, clinical indications, and toxicities of the glycopeptide vancomycin is provided. Emerging gram-positive bacterial resistance to antimicrobials and its mechanisms are reviewed. Strategies to control emergence of resistance are proposed. Newer antimicrobial agents with activity against vancomycin-resistant organisms are now available and play a critical role in the treatment of life-threatening infections.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.