Aminoglycosides: Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.Gentamicins: A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Framycetin: A component of NEOMYCIN that is produced by Streptomyces fradiae. On hydrolysis it yields neamine and neobiosamine B. (From Merck Index, 11th ed)Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the PSEUDOMONAS species. It is a 10% component of the antibiotic complex, NEBRAMYCIN, produced by the same species.Amikacin: A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics.Kanamycin: Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.Netilmicin: Semisynthetic 1-N-ethyl derivative of SISOMYCIN, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity.Paromomycin: An oligosaccharide antibiotic produced by various STREPTOMYCES.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis.Dibekacin: Analog of KANAMYCIN with antitubercular as well as broad-spectrum antimicrobial properties.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Sisomicin: Antibiotic produced by Micromonospora inyoensis. It is closely related to gentamicin C1A, one of the components of the gentamicin complex (GENTAMICINS).Streptomycin: An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.Pseudomonas aeruginosa: A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.Ribostamycin: A broad-spectrum antimicrobial isolated from Streptomyces ribosifidicus.Kanamycin Kinase: A class of enzymes that inactivate aminocyclitol-aminoglycoside antibiotics (AMINOGLYCOSIDES) by regiospecific PHOSPHORYLATION of the 3' and/or 5' hydroxyl.Nebramycin: A complex of antibiotic substances produced by Streptomyces tenebrarius.Drug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Drug Resistance, Multiple, Bacterial: The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Enterobacteriaceae: A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock.beta-Lactams: Four-membered cyclic AMIDES, best known for the PENICILLINS based on a bicyclo-thiazolidine, as well as the CEPHALOSPORINS based on a bicyclo-thiazine, and including monocyclic MONOBACTAMS. The BETA-LACTAMASES hydrolyze the beta lactam ring, accounting for BETA-LACTAM RESISTANCE of infective bacteria.Acetyltransferases: Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1.Providencia: Gram-negative rods isolated from human urine and feces.Hygromycin B: Aminoglycoside produced by Streptomyces hygroscopicus. It is used as an anthelmintic against swine infections by large roundworms, nodular worms, and whipworms.Penicillins: A group of antibiotics that contain 6-aminopenicillanic acid with a side chain attached to the 6-amino group. The penicillin nucleus is the chief structural requirement for biological activity. The side-chain structure determines many of the antibacterial and pharmacological characteristics. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1065)Dihydrostreptomycin Sulfate: A semi-synthetic aminoglycoside antibiotic that is used in the treatment of TUBERCULOSIS.Mezlocillin: Semisynthetic ampicillin-derived acylureido penicillin. It has been proposed for infections with certain anaerobes and may be useful in inner ear, bile, and CNS infections.Enterobacteriaceae Infections: Infections with bacteria of the family ENTEROBACTERIACEAE.Butirosin Sulfate: A water-soluble aminoglycosidic antibiotic complex isolated from fermentation filtrates of Bacillus circulans. Two components (A and B) have been separated from the complex. Both are active against many gram-positive and some gram-negative bacteria.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Carbenicillin: Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function.Ear Diseases: Pathological processes of the ear, the hearing, and the equilibrium system of the body.Pseudomonas Infections: Infections with bacteria of the genus PSEUDOMONAS.Capreomycin: Cyclic peptide antibiotic similar to VIOMYCIN. It is produced by Streptomyces capreolus.beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Gram-Negative Bacterial Infections: Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method.Hearing Disorders: Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid.Bacterial Infections: Infections by bacteria, general or unspecified.Enterococcus faecalis: A species of gram-positive, coccoid bacteria commonly isolated from clinical specimens and the human intestinal tract. Most strains are nonhemolytic.Klebsiella pneumoniae: Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans.Bacteria: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.Codon, Nonsense: An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.Viomycin: A strongly basic peptide, antibiotic complex from several strains of Streptomyces. It is allergenic and toxic to kidneys and the labyrinth. Viomycin is used in tuberculosis as several different salts and in combination with other agents.Enterococcus: A genus of gram-positive, coccoid bacteria consisting of organisms causing variable hemolysis that are normal flora of the intestinal tract. Previously thought to be a member of the genus STREPTOCOCCUS, it is now recognized as a separate genus.Conjugation, Genetic: A parasexual process in BACTERIA; ALGAE; FUNGI; and ciliate EUKARYOTA for achieving exchange of chromosome material during fusion of two cells. In bacteria, this is a uni-directional transfer of genetic material; in protozoa it is a bi-directional exchange. In algae and fungi, it is a form of sexual reproduction, with the union of male and female gametes.Piperacillin: Semisynthetic, broad-spectrum, AMPICILLIN derived ureidopenicillin antibiotic proposed for PSEUDOMONAS infections. It is also used in combination with other antibiotics.Cross Infection: Any infection which a patient contracts in a health-care institution.Bacterial Proteins: Proteins found in any species of bacterium.Fluoroquinolones: A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.Serratia marcescens: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria found in soil, water, food, and clinical specimens. It is a prominent opportunistic pathogen for hospitalized patients.Tetracyclines: Closely congeneric derivatives of the polycyclic naphthacenecarboxamide. (Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1117)Ticarcillin: An antibiotic derived from penicillin similar to CARBENICILLIN in action.Serratia Infections: Infections with bacteria of the genus SERRATIA.Polymyxin B: A mixture of polymyxins B1 and B2, obtained from Bacillus polymyxa strains. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for infections with gram-negative organisms, but may be neurotoxic and nephrotoxic.Stria Vascularis: A layer of stratified EPITHELIUM forming the endolymphatic border of the cochlear duct at the lateral wall of the cochlea. Stria vascularis contains primarily three cell types (marginal, intermediate, and basal), and capillaries. The marginal cells directly facing the ENDOLYMPH are important in producing ion gradients and endochoclear potential.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.Salvia officinalis: A plant species of the Salvia genus known as a spice and medicinal plant.Ribosome Subunits, Small, Bacterial: The small subunit of eubacterial RIBOSOMES. It is composed of the 16S RIBOSOMAL RNA and about 23 different RIBOSOMAL PROTEINS.Endocarditis, Bacterial: Inflammation of the ENDOCARDIUM caused by BACTERIA that entered the bloodstream. The strains of bacteria vary with predisposing factors, such as CONGENITAL HEART DEFECTS; HEART VALVE DISEASES; HEART VALVE PROSTHESIS IMPLANTATION; or intravenous drug use.Methyltransferases: A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.R Factors: A class of plasmids that transfer antibiotic resistance from one bacterium to another by conjugation.Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to RISTOCETIN that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.Integrons: DNA elements that include the component genes and insertion site for a site-specific recombination system that enables them to capture mobile gene cassettes.Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.Lactams: Cyclic AMIDES formed from aminocarboxylic acids by the elimination of water. Lactims are the enol forms of lactams.Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Azlocillin: A semisynthetic ampicillin-derived acylureido penicillin.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Mentha: Mentha is a genus of the mint family (LAMIACEAE). It is known for species having characteristic flavor and aroma.Ceftazidime: Semisynthetic, broad-spectrum antibacterial derived from CEPHALORIDINE and used especially for Pseudomonas and other gram-negative infections in debilitated patients.Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.Carbapenems: A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. THIENAMYCINS are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain.Acinetobacter baumannii: A species of gram-negative, aerobic bacteria, commonly found in the clinical laboratory, and frequently resistant to common antibiotics.RNA, Ribosomal, 16S: Constituent of 30S subunit prokaryotic ribosomes containing 1600 nucleotides and 21 proteins. 16S rRNA is involved in initiation of polypeptide synthesis.Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are found on the skin and mucous membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals.Gram-Positive Bacterial Infections: Infections caused by bacteria that retain the crystal violet stain (positive) when treated by the gram-staining method.Klebsiella Infections: Infections with bacteria of the genus KLEBSIELLA.Acinetobacter Infections: Infections with bacteria of the genus ACINETOBACTER.Cefotaxime: Semisynthetic broad-spectrum cephalosporin.tRNA Methyltransferases: Enzymes that catalyze the S-adenosyl-L-methionine-dependent methylation of ribonucleotide bases within a transfer RNA molecule. EC 2.1.1.Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method.Acinetobacter: A genus of gram-negative bacteria of the family MORAXELLACEAE, found in soil and water and of uncertain pathogenicity.Codon, Terminator: Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids.Lateral Line System: Aquatic vertebrate sensory system in fish and amphibians. It is composed of sense organs (canal organs and pit organs) containing neuromasts (MECHANORECEPTORS) that detect water displacement caused by moving objects.Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment.Nucleotidyltransferases: A class of enzymes that transfers nucleotidyl residues. EC 2.7.7.Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.Norfloxacin: A synthetic fluoroquinolone (FLUOROQUINOLONES) with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin inhibits bacterial DNA GYRASE.Penicillin Resistance: Nonsusceptibility of an organism to the action of penicillins.beta-Lactam Resistance: Nonsusceptibility of bacteria to the action of the beta-lactam antibiotics. Mechanisms responsible for beta-lactam resistance may be degradation of antibiotics by BETA-LACTAMASES, failure of antibiotics to penetrate, or low-affinity binding of antibiotics to targets.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Cefoperazone: Semisynthetic broad-spectrum cephalosporin with a tetrazolyl moiety that is resistant to beta-lactamase. It has been proposed especially against Pseudomonas infections.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Proteus mirabilis: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is frequently isolated from clinical specimens. Its most common site of infection is the urinary tract.Enterobacter: Gram-negative gas-producing rods found in feces of humans and other animals, sewage, soil, water, and dairy products.Hearing Loss: A general term for the complete or partial loss of the ability to hear from one or both ears.Genes, Bacterial: The functional hereditary units of BACTERIA.Micromonospora: A genus of gram-positive bacteria that forms a branched mycelium. It commonly occurs as a saprophytic form in soil and aquatic environments.Fatty Alcohols: Usually high-molecular-weight, straight-chain primary alcohols, but can also range from as few as 4 carbons, derived from natural fats and oils, including lauryl, stearyl, oleyl, and linoleyl alcohols. They are used in pharmaceuticals, cosmetics, detergents, plastics, and lube oils and in textile manufacture. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with CILASTATIN, a renal dipeptidase inhibitor.Colony Count, Microbial: Enumeration by direct count of viable, isolated bacterial, archaeal, or fungal CELLS or SPORES capable of growth on solid CULTURE MEDIA. The method is used routinely by environmental microbiologists for quantifying organisms in AIR; FOOD; and WATER; by clinicians for measuring patients' microbial load; and in antimicrobial drug testing.Polymyxins: Basic lipopeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter.Amebicides: Agents which are destructive to amebae, especially the parasitic species causing AMEBIASIS in man and animal.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Hair Cells, Auditory: Sensory cells in the organ of Corti, characterized by their apical stereocilia (hair-like projections). The inner and outer hair cells, as defined by their proximity to the core of spongy bone (the modiolus), change morphologically along the COCHLEA. Towards the cochlear apex, the length of hair cell bodies and their apical STEREOCILIA increase, allowing differential responses to various frequencies of sound.Stenotrophomonas maltophilia: A species of STENOTROPHOMONAS, formerly called Xanthomonas maltophilia, which reduces nitrate. It is a cause of hospital-acquired ocular and lung infections, especially in those patients with cystic fibrosis and those who are immunosuppressed.Klebsiella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms arrange singly, in pairs, or short chains. This genus is commonly found in the intestinal tract and is an opportunistic pathogen that can give rise to bacteremia, pneumonia, urinary tract and several other types of human infection.4-Quinolones: QUINOLONES containing a 4-oxo (a carbonyl in the para position to the nitrogen). They inhibit the A subunit of DNA GYRASE and are used as antimicrobials. Second generation 4-quinolones are also substituted with a 1-piperazinyl group at the 7-position and a fluorine at the 6-position.Enoxacin: A broad-spectrum 6-fluoronaphthyridinone antibacterial agent that is structurally related to NALIDIXIC ACID.Xanthenes: Compounds with three aromatic rings in linear arrangement with an OXYGEN in the center ring.Serratia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in the natural environment (soil, water, and plant surfaces) or as an opportunistic human pathogen.RNA, Bacterial: Ribonucleic acid in bacteria having regulatory and catalytic roles as well as involvement in protein synthesis.Disk Diffusion Antimicrobial Tests: A method where a culturing surface inoculated with microbe is exposed to small disks containing known amounts of a chemical agent resulting in a zone of inhibition (usually in millimeters) of growth of the microbe corresponding to the susceptibility of the strain to the agent.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cephalothin: A cephalosporin antibiotic.

Selective inhibition of the bacterial peptidoglycan biosynthesis by the new types of liposidomycins. (1/2111)

We examined the inhibitory activity against bacterial peptidoglycan biosynthesis, mammalian glycoprotein biosynthesis and growth of BALB/3T3 cells of four different types of liposidomycins which have the structure with or without sulfate and/or 3-methylglutaric acid moieties. Liposidomycins inhibited peptidoglycan biosynthesis about 30 to 500 times more effectively than tunicamycin, whereas liposidomycins inhibited mammalian glycoprotein biosynthesis about 30 to 300 times less effectively than tunicamycin. When the cytotoxic effect of liposidomycins and tunicamycin on the growth of mammalian cells were compared, liposidomycins did not show toxicity against BALB/3T3 cell at 25 microg/ml, though tunicamycin inhibited cell growth by 50% at 0.05 microg/ml. On the basis of these results, it is concluded that liposidomycins are selective antibiotics showing highly specific inhibition toward bacterial peptidoglycan biosynthesis.  (+info)

RecA-Mediated gene conversion and aminoglycoside resistance in strains heterozygous for rRNA. (2/2111)

Clinical resistance to aminoglycosides in general is due to enzymatic drug modification. Mutational alterations of the small ribosomal subunit rRNA have recently been found to mediate acquired resistance in bacterial pathogens in vivo. In this study we investigated the effect of 16S rRNA heterozygosity (wild-type [wt] and mutant [mut] operons at position 1408 [1408wt/1408mut]) on aminoglycoside resistance. Using an integrative vector, we introduced a single copy of a mutated rRNA operon (1408 A-->G) into Mycobacterium smegmatis, which carries two chromosomal wild-type rRNA operons; the resultant transformants exhibited an aminoglycoside-sensitive phenotype. In contrast, introduction of the mutated rRNA operon into an M. smegmatis rrnB knockout strain carrying a single functional chromosomal wild-type rRNA operon resulted in aminoglycoside-resistant transformants. Subsequent analysis by DNA sequencing and RNase protection assays unexpectedly demonstrated a homozygous mutant genotype, rRNAmut/rRNAmut, in the resistant transformants. To investigate whether RecA-mediated gene conversion was responsible for the aminoglycoside-resistant phenotype in the rRNAwt/rRNAmut strains, recA mutant strains were generated by allelic exchange techniques. Transformation of the recA rrnB M. smegmatis mutant strains with an integrative vector expressing a mutated rRNA operon (Escherichia coli position 1408 A-->G) resulted in transformants with an aminoglycoside-sensitive phenotype. Subsequent analysis showed stable heterozygosity at 16S rRNA position 1408 with a single wild-type allele and a single resistant allele. These results demonstrate that rRNA-mediated mutational resistance to aminoglycosides is recessive.  (+info)

Optimizing aminoglycoside therapy for nosocomial pneumonia caused by gram-negative bacteria. (3/2111)

Nosocomial pneumonia is a notable cause of morbidity and mortality and leads to increases in lengths of hospital stays and institutional expenditures. Aminoglycosides are used to treat patients with these infections, but few data on the doses and schedules required to achieve optimal therapeutic outcomes exist. We analyzed aminoglycoside treatment data for 78 patients with nosocomial pneumonia to determine if optimization of aminoglycoside pharmacodynamic parameters results in a more rapid therapeutic response (defined by outcome and days to leukocyte count resolution and temperature resolution). Cox proportional hazards, Classification and Regression Tree (CART), and logistic regression analyses were applied to the data. By all analyses, the first measured maximum concentration of drug in serum (Cmax)/MIC predicted days to temperature resolution and the second measured Cmax/MIC predicted days to leukocyte count resolution. For days to temperature resolution and leukocyte count resolution, CART analyses produced breakpoints, with an 89% success rate at 7 days of therapy for a Cmax/MIC of > 4.7 and an 86% success rate at 7 days of therapy for a Cmax/MIC of > 4.5, respectively. Logistic regression analyses predicted a 90% probability of temperature resolution and leukocyte count resolution by day 7 if a Cmax/MIC of > or = 10 is achieved within the first 48 h of aminoglycoside therapy. Aggressive aminoglycoside dosing immediately followed by individualized pharmacokinetic monitoring would ensure that Cmax/MIC targets are achieved early in therapy. This would increase the probability of a rapid therapeutic response for pneumonia caused by gram-negative bacteria and potentially decreasing durations of parenteral antibiotic therapy, lengths of hospitalization, and institutional expenditures, a situation in which both the patient and the institution benefit.  (+info)

Efficacy of ampicillin plus ceftriaxone in treatment of experimental endocarditis due to Enterococcus faecalis strains highly resistant to aminoglycosides. (4/2111)

The purpose of this work was to evaluate the in vitro possibilities of ampicillin-ceftriaxone combinations for 10 Enterococcus faecalis strains with high-level resistance to aminoglycosides (HLRAg) and to assess the efficacy of ampicillin plus ceftriaxone, both administered with humanlike pharmacokinetics, for the treatment of experimental endocarditis due to HLRAg E. faecalis. A reduction of 1 to 4 dilutions in MICs of ampicillin was obtained when ampicillin was combined with a fixed subinhibitory ceftriaxone concentration of 4 micrograms/ml. This potentiating effect was also observed by the double disk method with all 10 strains. Time-kill studies performed with 1 and 2 micrograms of ampicillin alone per ml or in combination with 5, 10, 20, 40, and 60 micrograms of ceftriaxone per ml showed a > or = 2 log10 reduction in CFU per milliliter with respect to ampicillin alone and to the initial inoculum for all 10 E. faecalis strains studied. This effect was obtained for seven strains with the combination of 2 micrograms of ampicillin per ml plus 10 micrograms of ceftriaxone per ml and for six strains with 5 micrograms of ceftriaxone per ml. Animals with catheter-induced endocarditis were infected intravenously with 10(8) CFU of E. faecalis V48 or 10(5) CFU of E. faecalis V45 and were treated for 3 days with humanlike pharmacokinetics of 2 g of ampicillin every 4 h, alone or combined with 2 g of ceftriaxone every 12 h. The levels in serum and the pharmacokinetic parameters of the humanlike pharmacokinetics of ampicillin or ceftriaxone in rabbits were similar to those found in humans treated with 2 g of ampicillin or ceftriaxone intravenously. Results of the therapy for experimental endocarditis caused by E. faecalis V48 or V45 showed that the residual bacterial titers in aortic valve vegetations were significantly lower in the animals treated with the combinations of ampicillin plus ceftriaxone than in those treated with ampicillin alone (P < 0.001). The combination of ampicillin and ceftriaxone showed in vitro and in vivo synergism against HLRAg E. faecalis.  (+info)

Arginine-aminoglycoside conjugates that bind to HIV transactivation responsive element RNA in vitro. (5/2111)

HIV gene expression is crucially dependent on binding of the viral Tat protein to the transactivation RNA response element. A number of synthetic Tat-transactivation responsive element interaction inhibitors of peptide/peptoid nature were described as potential antiviral drug prototypes. We present a new class of peptidomimetic inhibitors, conjugates of L-arginine with aminoglycosides. Using a gel-shift assay and affinity chromatography on an L-arginine column we found that these compounds bind specifically to the transactivation responsive element RNA in vitro with Kd values in the range of 20-400 nM, which is comparable to the Kd of native Tat bound to the transactivation responsive element (10-12 nM). Confocal microscopy studies demonstrated that fluorescein-labelled conjugate penetrates into live cells. High affinity to the transactivation responsive element, low toxicity, and relative simplicity of synthesis make these compounds attractive candidates for antiviral drug design.  (+info)

The therapeutic monitoring of antimicrobial agents. (6/2111)

AIMS: To review the basis and optimal use of therapeutic drug monitoring of antimicrobial agents. METHODS: Antimicrobial agents for which a reasonable case exists for therapeutic drug monitoring were reviewed under the following headings: pharmacokinetics, why monitor, therapeutic range, individualisation of therapy, sampling times, methods of analysis, interpretative problems and cost-effectiveness of monitoring. RESULTS: There is a strong historical case for monitoring aminoglycosides. The recent move to once-daily dosing means that criteria for therapeutic drug monitoring need to be redefined. Vancomycin has been monitored routinely but many questions remain about the most appropriate approach to this. A case can be made for monitoring teicoplanin, flucytosine and itraconazole in certain circumstances. CONCLUSIONS: The approach to monitoring aminoglycosides needs to be redefined in the light of once-daily dosing. It is premature to suggest that less stringent monitoring is necessary as toxicity remains a problem with these drugs. The ideal method of monitoring vancomycin remains to be defined although a reasonable case exists for measuring trough concentrations, mainly to ensure efficacy. Teicoplanin is monitored occasionally to ensure efficacy while flucytosine is monitored occasionally to avoid high concentrations associated with toxicity. Itraconazole has various pharmacokinetic problems and monitoring has been suggested to ensure that adequate concentrations are achieved.  (+info)

Recovery of the vestibulocolic reflex after aminoglycoside ototoxicity in domestic chickens. (7/2111)

Avian auditory and vestibular hair cells regenerate after damage by ototoxic drugs, but until recently there was little evidence that regenerated vestibular hair cells function normally. In an earlier study we showed that the vestibuloocular reflex (VOR) is eliminated with aminoglycoside antibiotic treatment and recovers as hair cells regenerate. The VOR, which stabilizes the eye in the head, is an open-loop system that is thought to depend largely on regularly firing afferents. Recovery of the VOR is highly correlated with the regeneration of type I hair cells. In contrast, the vestibulocolic reflex (VCR), which stabilizes the head in space, is a closed-loop, negative-feedback system that seems to depend more on irregularly firing afferent input and is thought to be subserved by different circuitry than the VOR. We examined whether this different reflex also of vestibular origin would show similar recovery after hair cell regeneration. Lesions of the vestibular hair cells of 10-day-old chicks were created by a 5-day course of streptomycin sulfate. One day after completion of streptomycin treatment there was no measurable VCR gain, and total hair cell density was approximately 35% of that in untreated, age-matched controls. At 2 wk postlesion there was significant recovery of the VCR; at this time two subjects showed VCR gains within the range of control chicks. At 3 wk postlesion all subjects showed VCR gains and phase shifts within the normal range. These data show that the VCR recovers before the VOR. Unlike VOR gain, recovering VCR gain correlates equally well with the density of regenerating type I and type II vestibular hair cells, except at high frequencies. Several factors other than hair cell regeneration, such as length of stereocilia, reafferentation of hair cells, and compensation involving central neural pathways, may be involved in behavioral recovery. Our data suggest that one or more of these factors differentially affect the recovery of these two vestibular reflexes.  (+info)

Antibiotic penetrance of ascitic fluid in dogs. (8/2111)

Antibiotic concentrations in ascitic fluid after parenteral therapy may be important in the treatment of peritonitis. We have created ascites in dogs by partial ligation of the inferior vena cava. Ascitic fluid volume was measured at the time each antibiotic was administered. Nine antibiotics were studied in the same three dogs. Antibiotic concentration in ascitic fluid was found to vary inversely with ascites volume. Percentage of penetration (ratio of ascites peak to serum peak x100) ranged from 5.8 to 65% among the drugs studied. Only metronidazole showed a statistically significant higher percentage of penetration than other antimicrobials. Concentrations in ascitic fluid after single doses of cephalothin (15 mg/kg) and the aminoglycosides (2 mg/kg, gentamicin and tobramycin; 7.5 mg/kg, amikacin and kanamycin) did not exceed the minimum inhibitory concentration of many gram-negative rods and may justify the use of higher than usual initial parenteral doses, or possibly initial intraperitoneal administration in seriously ill patients.  (+info)

  • Advances that open new avenues in developing aminoglycosideantibiotics During the last twenty years, there have been numerous advances inthe understanding of the chemistry, biochemistry, and recognitionof aminoglycosides. (
  • Aminoglycoside , any of several natural and semisynthetic compounds that are used to treat bacterial diseases . (
  • Aminoglycosides are selectively active against oxygen-dependent (aerobic), gram-negative bacterial cells, since these cells possess the chemical characteristics that attract aminoglycosides and the specific transport mechanisms that facilitate the uptake of the drugs into the cells. (
  • Once inside bacterial cells, aminoglycosides exert their effects by binding to ribosomes , organelles that are fundamental to protein synthesis. (
  • The bacterial cell-killing effect of aminoglycosides is concentration-dependent, with high concentrations of drug having high rates of bacterial killing. (
  • The aminoglycosides also have a post-antibiotic effect, in which bacterial cell killing continues for a brief period of time after the blood plasma concentration of the antibiotic has fallen below the so-called minimal inhibitory concentration (the smallest amount of drug necessary to induce cell-killing effects). (
  • The inhibition of protein synthesis is mediated through aminoglycosides' energy-dependent, sometimes irreversible binding, to the cytosolic, membrane-associated bacterial ribosome (image at right). (
  • Aminoglycosides first cross bacterial cell walls-lipopolysaccharide in gram-negative bacteria-and cell membranes, where they are actively transported. (
  • functional integrity of the bacterial cell membrane" can be lost, later in time courses of aminoglycoside exposure and transport. (
  • Aminoglycosides are used to treat bacterial infections. (
  • Because treatment of enterococcal endocarditis requires prolonged use of a potentially nephrotoxic and ototoxic aminoglycoside plus a bacterial cell wall-active drug (eg, penicillin, vancomycin ) to achieve bactericidal synergy, the choice of aminoglycoside must be based on special in vitro susceptibility testing. (
  • Multivariate discriminant analysis was performed on data for 50 consecutive hemodialysis patients who had received aminoglycoside treatment because of severe bacterial infections. (
  • We attempt to present and discuss these developments, not to ascertain whether there is a likelihood that new molecules or effective means to avoid bacterial resistance and drug-induced toxicity will eventually reach the clinical arena, but to foster continuing research on aminoglycosides and to make the clinician aware of the pertinent progress made in this area. (
  • Aminoglycosides act primarily by impairing bacterial protein synthesis through binding to prokaryotic ribosomes. (
  • The research group led by Dr. Seiichi Nishizawa and Dr. Yusuke Sato (Department of Chemistry, Graduate School of Science) has reported a novel small ligand, ATMND-C2-NH2 that has the tightest binding affinity for the bacterial A-site among the non-aminoglycoside ligands. (
  • The three classes of enzymes which inactivate aminoglycosides and lead to bacterial resistance are reviewed. (
  • Here, we use explicit solvent molecular dynamics (MD) simulations to map ions (NH 4 + , K + ) and water binding sites of a free bacterial A-site and their aminoglycoside complexes. (
  • Although the ototoxic effects of aminoglycosides are well documented, this class of drugs is still widely used today. (
  • Of all ototoxic drugs, the aminoglycosides are the most vestibulotoxic, although they vary greatly in their differential effects on the vestibular and cochlear systems. (
  • More frequent aminoglycoside monitoring may be performed for people with impaired kidney function (renal insufficiency) and for people who have an increased risk of toxic side effects, such as those taking other drugs known to adversely affect hearing and the kidneys (ototoxic or nephrotoxic). (
  • Therapeutic use of aminoglycosides is problematic, because these drugs are also nephrotoxic and ototoxic. (
  • Aminoglycosides are primarily used to combat infections due to aerobic, Gram-negative bacteria. (
  • Aminoglycosides are ineffective against anaerobic bacteria (bacteria that cannot grow in the presence of oxygen), viruses, and fungi. (
  • Aminoglycosides that are derived from bacteria of the Streptomyces genus are named with the suffix -mycin, whereas those that are derived from Micromonospora are named with the suffix -micin. (
  • Aminoglycosides display concentration-dependent bactericidal activity against "most gram-negative aerobic and facultative anaerobic bacilli" but not against gram-negative anaerobes and most gram-positive bacteria. (
  • Aminoglycoside resistance in bacteria can be acquired by several mechanisms, including drug modification, target alteration, reduced uptake and increased efflux. (
  • Bacteria take up aminoglycosides by oxygen-dependent process → inactive against anaerobes. (
  • Active export of cations out of the cytosol hyperpolarizes bacteria, and induces an electrophoretic driving force that promotes the entry of cationic aminoglycosides. (
  • Our data establish the hybrid ribosome approach as an excellent model to study the mechanisms of mutation- and aminoglycoside- mediated dysfunction of the mitochondrial ribosome and to address issues of species-specific drug action in bacteria. (
  • All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis. (
  • In the inhaled form, for pulmonary infections as in cystic fibrosis patients, aminoglycosides do not cause hearing loss because they are not absorbed into the blood stream. (
  • To better understand the mechanisms that contribute to aminoglycoside toxicity, David Raible's lab at the University of Washington imaged fluorescently-labeled aminoglycosides in the hair cells of live zebrafish. (
  • These findings provide structural and functional insights into aminoglycoside-induced impacts on the eukaryotic ribosome and implicate pleiotropic mechanisms of action beyond decoding. (
  • According to recent studies, these cells have a repertoire of molecular responses to aminoglycoside exposure that engages multiple neuroprotective mechanisms. (
  • The structure explains binding of diverse aminoglycosides to the ribosome, their specific activity against prokaryotic organisms, and various resistance mechanisms, and provides insight into ribosome function. (
  • Within 20 minutes, the diffuse signal decreases as aminoglycosides merge into puncta, indicating their uptake into lysosomes. (
  • We propose that TRPV4 has a role in aminoglycoside uptake and retention in the cochlea. (
  • Both persephone mutant and DIDS-treated wild-type larvae show reduced uptake of labeled aminoglycosides. (
  • Aminoglycoside interactions and impacts on the eukaryotic ribosome. (
  • However, the sites of interaction of aminoglycosides with the eukaryotic ribosome and their modes of action in eukaryotic translation remain largely unexplored. (
  • Here, we use the combination of X-ray crystallography and single-molecule FRET analysis to reveal the interactions of distinct classes of aminoglycosides with the 80S eukaryotic ribosome. (
  • The distinct impacts of the aminoglycosides examined suggest that their chemical composition and distinct modes of interaction with the ribosome influence PTC read-through efficiency. (
  • Aminoglycosides target the decoding center of the 80S ribosome in a different ways. (
  • Aminoglycoside-induced proteinuria may result from general renal damage or may reflect alterations in specific steps in the renal handling of proteins. (
  • Acute renal toxicity is largely reversible because kidney tubule cells can proliferate and replace cells lost to aminoglycoside toxicity ( Mingeot-Leclercq and Tulkens, 1999 ). (
  • Prematurity/immaturity Reproduction: prematurity / dysmaturity - premature or young neonatal foals particularly with hypoxia, azotemia and septicemia, have larger aminoglycoside clearance times due to renal hypoperfusion and decreased GFR. (
  • Stereotypically, aminoglycoside toxicity results in non-oliguric renal failure which more often than not recovers (after a few weeks) once the drug is withdrawn. (
  • The approval of ZEMDRI was supported in part by data from the EPIC (Evaluating Plazomicin In cUTI) clinical trial, which was the first randomized controlled study of once-daily aminoglycoside therapy for the treatment of cUTI, including pyelonephritis. (
  • Conclusions: A once daily aminoglycoside regimen is now used in the majority of UK CF Centres. (
  • The amount of an aminoglycoside given per dose depends on a variety of factors, including kidney function, other drugs the person may be taking, age, and weight. (
  • Kinetic parameters such as the half-life (t 1/2 ), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. (
  • These key structural features are also found in the rev -binding site of human immunodeficiency virus type 1 (HIV-1) ( 10 , 110 ), but aminoglycosides are unlikely to become anti-HIV drugs, as was originally hoped ( 116 ), without thorough chemical optimization and/or screening ( 51 , 78 ) because of their lack of specificity. (
  • The aminoglycosides are amongst the most well-known nephrotoxic drugs. (
  • drug design strategies involving aminoglycosides and related drugs. (
  • However, in primary fibroblasts from a Cercopithecidae species, aminoglycosides do not impair cell growth, respiratory complex IV activity and quantity or the mitochondrial protein synthesis. (
  • The propensity of aminoglycosides to induce miscoding errors that suppress the termination of protein synthesis supports their potential as therapeutic interventions in human diseases associated with premature termination codons (PTCs). (
  • In this work, we used the zebrafish lateral line system to monitor the dynamic behavior of mitochondrial and cytoplasmic oxidation occurring within the same dying hair cell following exposure to aminoglycosides. (
  • To identify pharmacological blockers of aminoglycoside entry, it is important to understand how cells take up aminoglycosides. (
  • The nucleotides responsible for aminoglycoside binding form an asymmetrical internal loop caused by noncanonical base pairs ( 23 , 67 ). (
  • APH(2″) enzymes display differential preferences between ATP or GTP as the phosphate donor, with aminoglycoside 2″-phosphotransferase IVa (APH(2″)-IVa) being a member that utilizes both nucleotides at comparable efficiencies. (
  • Steady state kinetic studies, as well as sequence and structural comparisons with members of the APH(2″) subfamily and other aminoglycoside kinases, rationalize the different substrate preferences for these enzymes. (
  • Comparisons of the amino acid sequences of 49 aminoglycoside-modifying enzymes have revealed new insights into the evolution and relatedness of these proteins. (
  • As knowledge of the molecular structure of these enzymes increases, progress can be made in our understanding of how resistance to new aminoglycosides emerges. (
  • Tests that evaluate kidney function, such as a creatinine test , are often performed at regular intervals during treatment with aminoglycosides. (
  • The report then estimates 2017-2022 market development trends of Aminoglycoside industry. (
  • The worldwide market for Aminoglycosides is expected to grow at a CAGR of roughly xx% over the next five years, will reach xx million US$ in 2023, from xx million US$ in 2017, according to a new GIR (Global Info Research) study. (
  • Herein, we report on the detection of various aminoglycosides, by exploiting their ability to aggregate gold nanoparticles. (
  • A murine thigh-infection model was used to determine the effect of certain host- and drug-related factors on the duration of the in-vivo postantibiotic effect (PAE) observed with aminoglycosides against Gram-negative bacilli. (
  • The basic chemical structure required for both potency and the spectrum of antimicrobial activity of aminoglycosides is that of one or several aminated sugars joined in glycosidic linkages to a dibasic cyclitol. (