Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro activity of ABT-773 was evaluated against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates. ABT-773 was the most active antimicrobial tested against S. pneumoniae. ABT-773 and azithromycin were equivalent in activity against H. influenzae and M. catarrhalis and more active than either clarithromycin or erythromycin.
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PMID:In vitro activity of ABT-773, a new ketolide, against recent clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 1063 82

The activity of the ketolide ABT-773 against Haemophilus and Moraxella was compared to those of 11 other agents. Against 210 Haemophilus influenzae strains (39.0% beta-lactamase positive), microbroth dilution tests showed that azithromycin and ABT-773 had the lowest MICs (0.5 to 4.0 and 1.0 to 8.0 microg/ml, respectively), followed by clarithromycin and roxithromycin (4.0 to >32.0 microg/ml). Of the beta-lactams, ceftriaxone had the lowest MICs (</=0.004 to 0.016 microg/ml), followed by cefixime and cefpodoxime (0.008 to 0.125 and </=0.125 to 0.25 microg/ml, respectively), amoxicillin-clavulanate (0.125 to 4.0 microg/ml), and cefuroxime (0. 25 to 8.0 microg/ml). Amoxicillin was only active against beta-lactamase-negative strains, and cefprozil had the highest MICs of all oral cephalosporins tested (0.5 to >32.0 microg/ml). Against 50 Moraxella catarrhalis strains, all of the compounds except amoxicillin and cefprozil were active. Time-kill studies against 10 H. influenzae strains showed that ABT-773, at two times the MIC, was bactericidal against 9 of 10 strains, with 99% killing of all strains at the MIC after 24 h; at 12 h, ABT-773 gave 90% killing of all strains at two times the MIC. At 3 and 6 h, killing by ABT-773 was slower, with 99.9% killing of four strains at two times the MIC after 6 h. Similar results were found for azithromycin, with slightly slower killing by erythromycin, clarithromycin, and roxithromycin, especially at earlier times. beta-Lactams were bactericidal against 8 to 10 strains at two times the MIC after 24 h, with slower killing at earlier time periods. Most compounds gave good killing of five M. catarrhalis strains, with beta-lactams killing more rapidly than other drugs. ABT-773 and azithromycin gave the longest postantibiotic effects (PAEs) of the ketolide-macrolide-azalide group tested (4.4 to >8.0 h), followed by clarithromycin, erythromycin, and roxithromycin. beta-Lactam PAEs were similar and shorter than those of the ketolide-macrolide-azalide group for all strains tested.
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PMID:Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 compared to their susceptibilities to 11 other agents. 1112 Sep 46

CHANGING RESISTANCE OF GRAM-POSITIVE COCCI: Several new families of antibiotics are under development in response to the changing resistance of Gram-positive cocci. Linezolide, the leading member of the oxazolidinone family and telithromycin and ABT-773, leading members of the ketolide family have reached an advanced stage of development. INHIBITION OF PROTEIN SYNTHESIS: Oxazolidinones and ketolides inhibit protein synthesis at different levels. Oxazolidinones inhibit formation of the 70S initiation complex and ketolides block the protein elongation step by inhibiting peptidyl transferase. MECHANISMS OF RESISTANCE: To date, no cross resistance of linezolide with other antibiotic families used for the treatment of Gram-positive bacteria has been observed. It is quite difficult to obtain resistant mutants in the laboratory but two point mutations on the 23S ribosome fraction have been described in vivo. Resistance of Gram-positive cocci to macrolides occur via mechanisms altering the target (methylation of 23S rRNA or ribosome protein mutations) or via mechanisms involving active efflux. LINEZOLIDE: Linezolide is highly active in vitro against meticillin-resistant Staphylococcus aureus (MRSA), against Streptococcus including resistant pneumococcal strains, and against glycopeptide-resistant E. faecium and E. faecalis strains. TELITHROMYCIN AND ABT-773: These ketolides are active against Streptococcus and Pneumococcus strains exhibiting erythromycin-inducible resistance and resistance by active efflux. In addition, these antibiotics are highly active against other bacteria causing respiratory tract infections (Moraxella and Haemophilus), anaerobic germs and intracellular germs (Legionella).
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PMID:[Ketolides and oxazolidinones. Mechanisms of action and antibacterial spectrum]. 1115 36

The antimicrobial activity of ABT-773, a novel ketolide, was tested against 618 Gram-positive strains collected from various surveillance programmes between 1997 and 2000. ABT-773 has potent activity against Streptococcus pneumoniae (MIC90, < or = 0.03-0.12 mg/l), beta-haemolytic streptococci (MIC90, < or = 0.03 mg/l) and viridans group streptococci (MIC90, < or = 0.03 mg/l), including erythromycin-resistant strains. In contrast, ABT-773 was less active against erythromycin-resistant Staphylococcus aureus (31% susceptible at < or = 0.25 mg/l), coagulase-negative staphylococci (41% susceptible) and enterococci (30% susceptible). Haemophilus influenzae (MIC90, 4 mg/l) was less inhibited by the two ketolides tested, and ABT-773 was generally two- to fourfold more potent than telithromycin. The ketolides appear to have potential clinical use against some Gram-positive species resistant to macrolides.
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PMID:Comparative antimicrobial activity of ABT-773, a novel ketolide, tested against drug-resistant Gram-positive cocci and Haemophilus influenzae. 1139 14

ABT-773, a novel ketolide, was compared to erythromycin, azithromycin, clarithromycin, ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, and gemifloxacin against antibiotic-resistant strains recently isolated from patients with respiratory tract infections. MICs were determined by agar dilution using standard NCCLS methodology. ABT-773 (MIC(90) 0.06 mg/L) was more active than the macrolides (MIC(90) > or = 2 mg/L) and fluoroquinolones (MIC(90) > or = 0.5 mg/L) against penicillin-resistant Streptococcus pneumoniae. The fluoroquinolones were the most active agents tested against beta-lactamase-positive Haemophilus influenzae (MIC(90) < or = 0.01-0.06 mg/L), against which ABT-773 (MIC(90) 4 mg/L) was comparable to azithromycin and two- and four-fold more active than erythromycin and clarithromycin, respectively. Against beta-lactamase positive Moraxella catarrhalis, the activity of ABT-773 (MIC(90) 0.06 mg/L) was comparable to gemifloxacin, trovafloxacin, levofloxacin, and ciprofloxacin (MIC(90) 0.03-0.06 mg/L) and 4- to eightfold greater than that of clarithromycin, gatifloxacin, and erythromycin. These data suggest ABT-773 could be a valuable compound for the treatment of respiratory tract infections, including those resistant to usual oral therapy.
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PMID:In vitro activity of ABT-773 versus macrolides and quinolones against resistant respiratory tract pathogens. 1144 61

The comparative in vitro activities of ABT-773 against 207 aerobic and 162 anaerobic antral sinus puncture isolates showed that erythromycin-resistant pneumococcal strains were susceptible to ABT-773 (< or =0.125 microg/ml); the MIC at which 90% of the isolates tested were inhibited for Haemophilus influenzae and other Haemophilus spp. was 4 microg/ml; and all Moraxella spp. and beta-lactamase-producing Prevotella species strains were inhibited by < or =0.125 microg/ml. Among the anaerobes tested, only fusobacteria (45%) required > or =4 microg of ABT-773/ml for inhibition. ABT-773 may offer a therapeutic alternative for sinus infections.
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PMID:In vitro activities of ABT-773, a new ketolide, against aerobic and anaerobic pathogens isolated from antral sinus puncture specimens from patients with sinusitis. 1145 98

ABT-773 is a novel ketolide effective against antibacterial-resistant respiratory tract pathogens. The pharmacokinetic profile of ABT-773 was studied in rats and consisted of a mean peak concentration in plasma of 1.07 microg/ml and an area under the concentration-time curve (AUC) of 12.03 microg. h/ml when the compound was delivered at a dose of 25 mg/kg of body weight. It concentrated in rat lung tissue, with a lung tissue-to-plasma ratio of 29 based on the AUC. In acute systemic infections in mice, ABT-773 showed efficacy against macrolide-susceptible strains of Staphylococcus aureus, Streptococcus pneumoniae, S. pyogenes, and Listeria monocytogenes. Additionally, ABT-773 improved the survival of mice infected with resistant S. pneumoniae containing either the ermB gene, the mefE gene, or altered penicillin binding protein genes. In a rat lung model of infection, ABT-773 demonstrated 50% effective doses lower than those of comparator macrolides when evaluated against the following strains of S. pneumoniae: a macrolide-lincosamide-streptogramin B-susceptible strain, an ermB strain, and an mefE strain. ABT-773 was also effective against Haemophilus influenzae lung infections in rats. Thus, ABT-773 may prove to be a useful new antibacterial agent for the treatment of respiratory tract infections.
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PMID:Efficacies of ABT-773, a new ketolide, against experimental bacterial infections. 1150 33

The in vitro activities of ABT-773, azithromycin, erythromycin, and clindamycin were compared by testing 1,223 clinical isolates selected to represent different species and phenotypes. ABT-773 was particularly potent against staphylococci (the MIC at which 90% of the strains tested were inhibited [MIC(90)] was < or =0.06 microg/ml), including all strains that were macrolide resistant but clindamycin susceptible. Streptococcus pneumoniae and other streptococci were inhibited by low concentrations of ABT-773, and that included most erythromycin-resistant strains. Against Haemophilus influenzae, ABT-773 and azithromycin were similar in their antibacterial potency (MIC(90), 4.0 and 2.0 microg/ml, respectively).
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PMID:In vitro activity of the ketolide ABT-773. 1155 91

This study determined the postantibiotic effect (PAE) of ABT-773 versus that of amoxicillin-clavulanate against clinical isolates of Streptococcus pneumoniae and Haemophilus influenzae. The PAEs of ABT-773 and amoxicillin-clavulanate ranged from 2.3 to 6.0 h and 0 to 2.2 h against S. pneumoniae and from 2.7 to 9.1 h and 0 to 0.8 h against H. influenzae, respectively.
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PMID:Postantibiotic effects of ABT-773 and amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae. 1170 52

Attempts were made to select mutants on agar media containing the new ketolide ABT-773, erythromycin or rifampicin, at concentrations above the MICs, from Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae, including erythromycin-resistant strains. ABT-773 did not select for mutants in four strains, whereas in eight strains the frequencies at 72 h were < or = 10(-9). ABT-773 MICs were 0.015-4 mg/L for mutants, except those selected from inducible Erm(A) S. aureus. Mutants selected on ABT-773 or erythromycin were cross-resistant to ABT-773, erythromycin and, sometimes, clindamycin. The susceptibility profiles indicate that different mutations were selected and that ABT-773 and erythromycin may interact with the ribosome differently.
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PMID:Comparison of selection for mutants with reduced susceptibility to ABT-773, erythromycin and rifampicin in respiratory tract pathogens. 1200 79


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