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)

Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has demonstrated activity against a variety of bacterial pathogens, including resistant isolates, during preclinical studies. In vitro activities of tigecycline and comparators were tested against 11,859 recent (2000 and 2002) bacterial strains recovered from patients in 29 countries with community-acquired respiratory tract disease (3,317 gram-positive and -negative strains) and skin and soft tissue infections (8,542 gram-positive strains). All oxacillin-susceptible and -resistant Staphylococcus aureus (5,077 strains; tigecycline MIC(90), 0.5 microg/mL) and coagulase-negative staphylococci (1,432 strains; MIC(90), 0.5 microg/mL), penicillin-susceptible and -resistant Streptococcus pneumoniae (1,585 strains; MIC(90), < or =0.25 microg/mL), viridans group streptococci (212 strains; MIC(90), < or =0.25-0.5 microg/mL), vancomycin-susceptible and -resistant enterococci (1,416 strains; MIC(90), 0.25-0.5 microg/mL), beta-haemolytic streptococci (405 strains; MIC(90), < or =0.25 microg/mL), beta-lactamase positive and negative Haemophilus influenzae (1,220 strains; MIC(90), 1 microg/mL), Moraxella catarrhalis (495 strains; MIC(90), 0.25 microg/mL), and Neisseria meningitidis (17 strains; MIC(90), < or =0.12 microg/mL) were inhibited by 2 microg/mL or less of tigecycline. Whereas potency of tetracycline and doxycycline markedly dropped in various resistant organism subsets, tigecycline was unaffected with an overall MIC(90) of 0.5 microg/mL. These findings confirm that tigecycline maintains a truly broad spectrum like the tetracycline class while enhancing potency. It also incorporates stability to the commonly occurring tetracycline resistance mechanisms, making it an attractive candidate for continued clinical development against pathogens causing serious community-acquired respiratory tract infections, as well as cutaneous infections.
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PMID:In vitro activity of tigecycline (GAR-936) tested against 11,859 recent clinical isolates associated with community-acquired respiratory tract and gram-positive cutaneous infections. 1524 11

To evaluate the in vitro activity of tigecycline, the minimum inhibitory concentrations (MICs) of tigecycline against 1,201 strains of recent clinical isolates from 10 hospitals in Shanghai, China were determined and compared with selected comparators. Results showed that tigecycline had broad-spectrum antimicrobial activity. It was highly active against Gram-positive cocci, including methicillin-resistant Staphylococcus spp., penicillin-intermediate Streptococcus pneumoniae, Enterococcus faecalis and E. faecium. Tigecycline also had good activity against most strains of Enterobacteriaceae, Haemophilus influenzae, Neisseria gonorrhoeae, and Moraxella catarrhalis. However, it was poorly active against Acinetobacter baumannii and Pseudomonas aeruginosa. Tigecycline was highly active against anaerobic Gram-positive cocci such as Peptococcus spp. The in vitro activity of tigecycline was significantly better than that of minocycline and tetracycline. It was as active as or slightly more active than vancomycin and teicoplanin in the activity against resistant aerobic Gram-positive cocci. Tigecycline was bactericidal against all Gram-positive cocci tested except Enterococcus spp. Inoculum size but not pH of medium or concentration of human serum in broth had significant effect on the in vitro activity of tigecycline. Aged media (48-72 hours after preparation) used in the test and specific resistance problem in China may have some effects on MIC values of tigecycline.
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PMID:In vitro activities of tigecycline against clinical isolates from Shanghai, China. 1558

Antimicrobial resistance is an increasing public health concern, all the more as it is concurrently accompanied by limited antimicrobial drugs development, especially broad-spectrum antibiotics. Tigecycline, the first in the novel glycylcycline class to undergo clinical development, showed extensive in vitro activity against a broad range of Gram positive aerobes, among which Staphylococcus aureus, Streptococcus pneumoniae, and Gram negative pathogens, such as Haemophilus influenzae and enterobacteriae, despite these germs resistance to beta-lactams, vancomycin, and a number of other common antibiotics. Tigecycline is also active against some anaerobes. Data obtained in phase II clinical trials have shown good tolerance and efficacy of tigecycline administered by intravenous infusion in the treatment of complicated skin and skin structure infections and intra-abdominal infections. Should these results be confirmed by phase III clinical trials, tigecycline would provide a new option in the ongoing fight against resistant pathogens, which would usefully add to the present antibacterial armamentarium, particularly in severe or hospital treated infections.
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PMID:[Tigecycline: a new antibiotic in ongoing clinical development]. 1578 Aug 94

The steady-state serum and intrapulmonary pharmacokinetic and pharmacodynamic parameters of tigecycline were determined after intravenous administration in 30 subjects. Tigecycline was administered as a 100mg loading dose followed by six 50mg doses given every 12h and was measured using HPLC/mass spectrometry. Ratios of tigecycline maximum serum concentration and area under the serum concentration-time curve to 90%-minimum inhibitory concentrations (C(max)/MIC(90); AUC/MIC(90)), and percentage time above MIC(90) were calculated for common respiratory pathogens (Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae, Moraxella catarrhalis and Haemophilus influenzae). The C(max) (mean+/-S.D.), AUC and half-life for serum were 0.72+/-0.24 microg/mL, 1.73+/-0.64 microg*h/mL and 15.0+/-1.10h; for lung epithelial lining fluid (ELF) the values were 0.37 microg/mL, 2.28 microg*h/mL and 39.1h; and for alveolar cells (AC) were 15.2 microg/mL, 134 microg*h/mL and 23.7h. Tigecycline was concentrated in AC: C(max)/MIC(90) ratios ranged from 30.4 (H. influenzae) to 507 (S. pneumoniae); AUC/MIC(90) ratios ranged from 268 (H. influenzae) to 4467 (S. pneumoniae); and percentage dose interval above MIC(90) was 100% for the five respiratory pathogens. The C(max)/MIC(90), AUC/MIC(90) ratios, T>MIC(90) and extended serum and intrapulmonary half-lives following the regimen used in this study are favourable for the treatment of tigecycline-susceptible pulmonary infections.
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PMID:Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline. 1588 87

The Tigecycline Evaluation and Surveillance Trial (TEST Program) determined the in vitro activity of tigecycline over a large population of organisms from geographically diverse sites. Tigecycline was compared to amikacin, ampicillin, amoxicillin/clavulanic acid, imipenem, cefepime, ceftazidime, ceftriaxone, levofloxacin, minocycline, piperacillin/tazobactam, linezolid, penicillin, and vancomycin against 3989 commonly encountered clinical Gram-negative and Gram-positive pathogens collected from sites in the United States during 2004. The tigecycline activity was equivalent to imipenem against Enterobacteriaceae. Tigecycline inhibited extended-spectrum beta-lactamase and AmpC phenotypes at MIC90 values (minimum inhibitory concentration) of < or =2 microg/mL. In vitro results for tigecycline were similar to other broad-spectrum antimicrobial agents against nonfermenters with MIC90 results of 2 microg/mL against Acinetobacter spp. and >16 microg/mL against Pseudomonas aeruginosa. Tigecycline demonstrated potent activity against Staphylococcus aureus (MIC90, 0.25 microg/mL) and enterococci (MIC90, 0.12 microg/mL) regardless of methicillin or vancomycin susceptibility. Tigecycline MIC values were unaffected by penicillin nonsusceptibility and beta-lactamase production among fastidious respiratory pathogens (Streptococcus pneumoniae [MIC90, 0.5 microg/mL] and Haemophilus influenzae [MIC90, 0.25 microg/mL]). Tigecycline offers excellent activity against most of the commonly encountered nosocomial and community-acquired bacterial pathogens.
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PMID:In vitro activity of tigecycline against 3989 Gram-negative and Gram-positive clinical isolates from the United States Tigecycline Evaluation and Surveillance Trial (TEST Program; 2004). 1610 61

Emerging antimicrobial resistance among respiratory tract pathogens has created a critical need for development of new antimicrobial agents that are not affected by the commonly occurring genetic resistance mechanisms. Tigecycline, a novel broad-spectrum parenteral glycylcycline, has been shown to be active against many of Gram-positive, Gram-negative, atypical, and anaerobic organisms, including strains highly resistant to commonly prescribed antimicrobials and was recently approved by the US Food and Drug Administration for treating infections of skin and skin structures, and for intra-abdominal infections. In this study, tigecycline spectrum and potency were evaluated against a global collection of pathogens (2000-2004) recovered from community-acquired respiratory infections (7580 strains) or from hospitalized patients with pneumonia (3183 strains). Among community-acquired infections, the ranking pathogens were Haemophilus influenzae (52.9%; 21% ampicillin-resistant), Streptococcus pneumoniae (39.2%; 23.7% penicillin-nonsusceptible), and Moraxella catarrhalis (7.9%). Tigecycline displayed potent activity by inhibiting 100% of the 3 species at clinically achievable concentrations (2, 1, and 0.5 microg/mL, respectively). The 10 most prevalent pathogens producing 94.3% of pneumonias in hospitalized patients were Staphylococcus aureus (48.5% of strains; 49.4% oxacillin-resistant), Pseudomonas aeruginosa (15.6%), Klebsiella spp. (5.6%), S. pneumoniae (4.6%), Acinetobacter spp. (4.5%), Enterobacter spp. (4.0%), Escherichia coli (3.8%), Serratia marcescens (2.5%), Enterococcus spp. (2.3%), Stenotrophomonas maltophilia (1.8%), and beta-hemolytic streptococci (1.1%). At a concentration of 4 microg/mL, tigecycline inhibited >96% of these pathogens (exception, P. aeruginosa). S. aureus was readily inhibited by tigecycline (MIC50 and MIC90, 0.25 and 0.5 microg/mL, respectively) with all strains inhibited at < or =1 microg/mL. Streptococci recovered from hospitalized patients (beta-hemolytic and S. pneumoniae) were also very susceptible to tigecycline with the highest MIC being 0.12 microg/mL. All E. coli (including 13.3% with an extended-spectrum beta-lactamase [ESBL] phenotype) were inhibited by < or =1 microg/mL, and all Klebsiella (25.8% ESBL phenotype) and Enterobacter spp. plus 97.0% of Serratia spp. were inhibited by < or =4 microg/mL. Tigecycline was also active against Acinetobacter spp. and S. maltophilia strains (MIC50 and MIC90, 1 and 4 microg/mL, respectively). Further clinical studies should consider the role that tigecycline may play in the therapy for severe respiratory tract infections, both of nosocomial and community origin.
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PMID:Antimicrobial activity of tigecycline tested against organisms causing community-acquired respiratory tract infection and nosocomial pneumonia. 1610 63

Tigecycline, a new glycylcycline antibiotic, has shown promising in vitro activity against many common pathogens, including multidrug-resistant strains. To determine the activity of tigecycline against a broad range of pathogens from diverse populations and geographic areas, the Tigecycline Evaluation and Surveillance Trial (TEST Program) commenced in 2003. This study evaluated the activity of tigecycline and commonly used antimicrobials against 6792 clinical isolates from 40 study centers in 11 countries. Tigecycline was the most active agent tested against Gram-positive facultative species including multidrug-resistant strains. MIC90 results (microg/mL) for tigecycline against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were 0.12, 0.12, 0.25, and 0.25 microg/mL, respectively. Tigecycline was active against Enterobacteriaceae with an MIC90 of 1 microg/mL. Haemophilus influenzae was very susceptible to tigecycline with an MIC90 of only 0.25 microg/mL. Pseudomonas aeruginosa was the least susceptible organism tested against tigecycline. Tigecycline appears to be a promising new glycylcycline agent for the treatment of many types of pathogens with varying resistance phenotypes.
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PMID:In vitro activity of tigecycline against 6792 Gram-negative and Gram-positive clinical isolates from the global Tigecycline Evaluation and Surveillance Trial (TEST Program, 2004). 1610 67

In vitro activities of tigecycline were compared with 15 other comparator agents against recent clinical isolates of respiratory pathogens (623 Streptococcus pneumoniae, 105 Staphylococcus aureus, 92 Klebsiella pneumoniae, and 84 Haemophilus influenzae isolates) collected from 11 Asian countries. All isolates of S. pneumoniae from Asian countries were susceptible to tigecycline regardless of penicillin susceptibility with MIC90 of <or=0.06 mg/L. Both methicillin-resistant and methicillin-susceptible S. aureus isolates were susceptible to tigecycline with very low MIC90 values (0.25 and 0.12 mg/L, respectively). Tigecycline was also active against K. pneumoniae (98.9% susceptible; MIC50, 1 mg/L; MIC90, 2 mg/L) including 10 extended-spectrum beta-lactamase-producing isolates and H. influenzae (100% susceptible; MIC50 and MIC90, 0.12 mg/L) from Korea. Data confirmed that tigecycline has an excellent in vitro activity against drug-resistant clinical isolates of respiratory pathogens from Asian countries.
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PMID:Antimicrobial activity of tigecycline against recent isolates of respiratory pathogens from Asian countries. 1663 37

The in vitro spectra of activity of tigecycline and tetracycline were determined for 2,490 bacterial isolates representing 50 different species or phenotypic groups. All isolates were tested simultaneously by broth microdilution using freshly prepared Mueller-Hinton broth and by disk diffusion. Portions of these data were submitted to the Food and Drug Administration (FDA) in support of the sponsor's application for new drug approval. In a separate study, MIC and disk diffusion quality control ranges were determined. The tigecycline MICs at which 50%/90% of bacteria were inhibited were (in microg/ml) as follows: for Streptococcus spp., 0.06/0.12; for Moraxella catarrhalis, 0.06/0.12; for Staphylococcus spp., 0.12/0.25; for Enterococcus spp., 0.12/0.25; for Listeria monocytogenes, 0.12/0.12; for Neisseria meningitidis, 0.12/0.25; for Haemophilus spp., 0.25/0.5; for Enterobacteriaceae, 0.05/2.0; for non-Enterobacteriaceae, 0.5/8.0. Tigecycline was consistently more potent than tetracycline against all species studied. The data from this study confirm the FDA-approved MIC and disk diffusion breakpoints for tigecycline for Streptococcus spp. other than Streptococcus pneumoniae, enterococci, and Enterobacteriaceae. Provisional breakpoints for Haemophilus spp. and S. pneumoniae are proposed based on the data from this study. The following MIC and/or disk diffusion quality control ranges are proposed: Staphylococcus aureus ATCC 29213, 0.03 to 0.25 microg/ml; S. aureus ATCC 25923, 20 to 25 mm; Escherichia coli ATCC 25922, 0.03 to 0.25 microg/ml and 20 to 27 mm; Pseudomonas aeruginosa ATCC 27853, 9 to 13 mm, Enterococcus faecalis ATCC 29212, 0.03 to 0.12 microg/ml; S. pneumoniae ATCC 49619, 0.015 to 0.12 microg/ml and 23 to 29 mm; Haemophilus influenzae ATCC 49247, 0.06 to 0.5 microg/ml and 23 to 31 mm; and Neisseria gonorrhoeae ATCC 49226, 30 to 40 mm.
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PMID:Comparative in vitro antimicrobial activity of tigecycline, a new glycylcycline compound, in freshly prepared medium and quality control. 1749 17

Tigecycline, the 9-t-butylglycylamino derivative of minocycline is the first commercially available glycylcycline exhibiting an extended spectrum of antibacterial activity due to its capacity to evade the tetracycline ribosomal and efflux resistance mechanisms. We conducted a collaborative in vitro study determining the activity of tigecycline compared to 14 antimicrobials against clinically relevant isolates obtained from adult patients hospitalized in 9 Argentinean institutions. Minimum inhibitory concentrations (MICs) were determined by the reference broth microdilution method. The number of isolates and MICs 50/90 (mg/L) for tigecycline were the following: Acinetobacter spp. 132 (0.5/1); Escherichia coli 220 (0.12/0.25); Klebsiella spp. 220 (0.5/1), Enterobacter spp. 205 (0.5/1); Serratia spp. 84 (0.5/2); Haemophilus influenzae 96 (0.25/0.5); Staphylococcus aureus 223 (0.12/0.25); Streptococcus pneumoniae 98 (<or= 0.25/1); S. agalactiae 51 (0.5/0.5); Enterococcus spp. 104 (0.06/0.12); Pseudomonas aeruginosa 169 (8/16). We conclude that tigecycline is a promising drug for the treatment of infections in hospitalized patients in Argentina.
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PMID:Comparative in vitro activity of tigecycline against aerobic and facultative isolates recovered from hospitalized patients: an Argentinean multicenter study. 1807 2


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