Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Cefditoren pivoxil is an orally absorbed prodrug that is rapidly hydrolysed by intestinal esterases to the microbiologically active cephalosporin cefditoren. Cefditoren has a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including common respiratory and skin pathogens. Cefditoren has shown excellent in vitro activity against the Gram-positive pathogens penicillin-susceptible and -intermediate Streptococcus pneumoniae, S. pyogenes and methicillin-susceptible Staphylococcus aureus. Cefditoren was inactive against methicillin-resistant S. aureus. Of the important Gram-negative pathogens, cefditoren had potent antibacterial effects against beta-lactamase-positive and -negative Haemophilus influenzae, H. parainfluenzae and beta-lactamase-positive and -negative Moraxella catarrhalis. Cefditoren does not have antibacterial activity against Pseudomonas aeruginosa or atypical respiratory pathogens and has only variable activity against anaerobes. In healthy volunteers, single doses of cefditoren pivoxil 200 and 400mg achieved maximal plasma concentrations of 2.6 to 3.1 mg/L and 3.8 to 4.6 mg/L, respectively. Cefditoren penetrates rapidly into bronchopulmonary and tonsillar tissue as well as inflammatory and noninflammatory blister fluid. In two, randomised, double-blind trials involving patients with acute exacerbations of chronic bronchitis (AECB), cefditoren 200 and 400mg twice daily for 10 days produced clinical cure rates of 88 to 89% within 48 hours of treatment completion. Clinical cure rates in patients with AECB were similar to those of either clarithromycin 500mg twice daily or cefuroxime axetil 250mg twice daily. In patients with streptococcal pharyngitis, a 10-day course of cefditoren pivoxil 200mg twice daily produced clinical cure rates of 94% at 4 to 7 days after treatment, which were similar to those observed for phenoxymethylpenicillin potassium 250 mg four times daily. In uncomplicated skin and skin structure infections, a 10-day course of cefditoren pivoxil 200 or 400mg twice daily produced the same clinical cure rate of 89% within 48 hours of treatment completion. These cefditoren pivoxil dosage regimens were as effective as a 10-day course of either cefadroxil 500 mg twice daily or cefuroxime axetil 250mg twice daily in treating uncomplicated skin and skin structure infections, including those caused by S. aureus and S. pyogenes. The most common adverse events associated with therapeutic doses of cefditoren pivoxil are diarrhoea, nausea, headache, abdominal pain and vaginal candidiasis.
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PMID:Cefditoren pivoxil. 1181 76

The activity of cefditoren and six other cephalosporins was tested against 250 pneumococci, including strains resistant to macrolides and quinolones. Cefditoren gave the lowest MICs, with MIC(50) and MIC(90) values of < or =0.016/0.03, 0.125/0.5 and 0.5/2.0 mg/L for penicillin-susceptible, -intermediate and -resistant pneumococci, respectively. A time-kill study of 12 pneumococcal strains with varying drug susceptibilities showed that cefditoren, at 2 x MIC, gave 99% killing of all strains after 12 h, with 99.9% killing after 24 h. Other cephalosporins gave similar kill kinetics but at higher concentrations. Against 160 Haemophilus influenzae, cefditoren had the lowest MICs (MIC(50) and MIC(90) both < or =0.016 mg/L), irrespective of beta-lactamase production. Time-kill studies of cefditoren compared with five other oral cephalosporins showed that cefditoren, at 8 x MIC, was bactericidal against 8/9 strains and gave 90% killing of all strains at the MIC after 12 h. Activity was bactericidal (99.9% killing) after 24 h with all drugs tested. Multistep studies of four penicillin-susceptible, four penicillin-intermediate and four penicillin-resistant strains showed that cefditoren, co-amoxiclav and cefprozil did not select for resistant mutants after 50 subcultures, compared with cefuroxime and azithromycin, where resistant mutants were selected in two and nine strains, respectively. Single-step mutation studies showed that cefditoren, at the MIC, had the lowest frequency of spontaneous mutants compared with other drugs.
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PMID:Activity of cefditoren against respiratory pathogens. 1209 4

The minimum inhibitory concentrations (MICs) of 11 oral antibiotics were measured for 140 Streptococcus pneumoniae, 115 Haemophilus influenzae, and 46 Moraxella catarrhalis strains isolated from Japanese children. The antibiotics selected included a range of commonly prescribed agents together with a selection of new cefems and a penem. Cefditoren was most active against the highly penicillin resistant S. pneumoniae, beta-lactamase-producing H. influenzae and beta-lactamase-negative ampicillin-resistant H. influenzae. However, amoxycillin retained good activity against the penicillin-susceptible or -intermediately resistant S. pneumoniae (88.6%) and most of ampicillin-susceptible or -intermediately resistant H. influenzae (87.9%). We thus consider that amoxycillin remains a useful initial choice for the treatment of paediatric respiratory infections in Japan.
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PMID:Oral antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates from Japanese children. 1229 62

Cefditoren pivoxil, an oral third-generation cephalosporin, was approved by the Food and Drug Administration in September 2001. It has been used in Japan for several years. The greatest therapeutic potential of cefditoren appears to be its activity against gram-positive and gram-negative organisms causing respiratory tract infections and skin and skin-structure infections, such as Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Cefditoren is also effective against methicillin-susceptible strains of Staphylococcus aureus. Nevertheless, cefditoren has no activity against atypical pathogens, including Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella sp. Moreover, cefditoren does not inhibit Pseudomonas aeruginosa or Bacteroides fragilis. In virtually all studies, cefditoren has compared favorably against other orally administered antibiotics used against the most commonly isolated respiratory tract pathogens. Its side effect profile includes diarrhea, nausea, vomiting, headache, and dyspepsia. Cefditoren is indicated for treatment of mild-to-moderate acute exacerbations of chronic bronchitis, pharyngitis-tonsillitis, and uncomplicated skin and skin-structure infections caused by susceptible strains of organisms in adults and adolescents (> or = 12 yrs of age). Based on its reported antimicrobial activity, cefditoren has potential for empiric management of most commonly encountered respiratory tract infections. Additional studies will further define its role in clinical practice.
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PMID:Cefditoren, a new aminothiazolyl cephalosporin. 1238 78

Nasal sinusitis, tonsillitis, and pharyngolaryngitis typify upper respiratory tract infections, while bronchitis and pneumonia typify lower respiratory tract infections. Cases of paranasal sinusitis with severe suppuration are reportedly becoming less frequent, while those of chronic catarrhal paranasal sinusitis and edematous allergic paranasal sinusitis are becoming more so, The primary factor in paranasal sinusitis, a typical infectious disease encountered in otolaryngology, is bacterial infection. The main causative bacteria are Streptococcus pneumoniae, reported in 13.4% of cases, Haemophilus influenzae in 12.8% Moraxella catarrhalis in 5.5%, Staphylococcus aureus in 26.5%, Pseudomonas aeruginosa in 5.2%, and anaerobes. The incidence of strains resistant to antimicrobial agents has grown for S. pneumoniae, H. influenzae, and M. catarrhalis and decreased for S. aureus and P. aeruginosa. Acute exacerbation or severe suppuration in chronic paranasal sinusitis requires the administration of antimicrobial agents, with the same agent administered 2 weeks for maximal effect. First-line agents are AMPC/CVA, SBTPC, CDTR-PI, CFPN-PI, and GFLX for adults, with ASPC, SBPC, ACPC, CTRX, CMZ, FMOX, PAPM/BP, and MEPM injected in severe cases. Attention must be paid to strains that resist cephems and macrolides, such as PISP, PRSP, and BLNAR. In refractory chronic paranasal sinusitis, attention must also be paid to biofilms produced by S. aureus and P. aeruginosa. Suitable antimicrobial agents should be determined for treating of chronic paranasal sinusitis, in addition to the best procedure to ensure early recovery from inflammation, such as puncturing or irrigating the maxillary sinus, injecting a suitable agent, nebulization, and/or surgically widening the middle meatus.
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PMID:[Bacteria isolated from chronic upper and lower respiratory tract infections and the associated therapeutic strategies--in paranasal sinusitis]. 1651 20

In this study we evaluated the in vitro activities of cefditoren and 14 other comparator agents against 1025 isolates of major respiratory tract pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae and Staphylococcus aureus. Bacterial isolates were collected from 11 Asian countries. The majority of S. pneumoniae isolates (98.8%) were susceptible to cefditoren. The MIC(50) and MIC(90) values (minimum inhibitory concentrations for 50% and 90% of the organisms, respectively) of S. pneumoniae were <or=0.06 microg/mL and 1 microg/mL, respectively. These values were 2-32-fold lower than those of the other cephalosporins. Activity against S. pneumoniae was observed irrespective of penicillin or macrolide resistance. Cefditoren was also active against methicillin-susceptible S. aureus (100% susceptible; MIC(90)=1 microg/mL), H. influenzae (100% susceptible; MIC(90)<or=0.016 microg/mL) and M. catarrhalis (MIC(90)=0.016 microg/mL). However, the cefditoren MIC(90) of K. pneumoniae reached only 64 microg/mL (81.4% susceptible), which may be due to the high incidence of extended-spectrum beta-lactamases in Asian countries. Therefore, cefditoren should be considered as a therapeutic option for the treatment of respiratory tract infections in Asian countries.
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PMID:In vitro activity of cefditoren: antimicrobial efficacy against major respiratory pathogens from Asian countries. 1677 83

Cefditoren pivoxil, a new-third generation cephalosporin antibiotic that has recently been granted approval in Spain, shows important activity over a large part of the pathogens causing skin, soft tissue and respiratory tract infections, including Gram-negative and Gram-positive bacteria. Cefditoren has also been shown to be stable against hydrolysis by many common beta-lactamases. Data from in vitro studies and clinical trials show this antibiotic as an oral formulation with an intrinsic activity against Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae equivalent to that of other third-generation cephalosporins administered via parenteral, like cefotaxime or ceftriaxone, thereby placing its maximal benefits mainly in the treatment of ambulatory infections. This paper reviews the main characteristics of cefditoren pivoxil (spectrum of activity, chemical structure, mechanism of action, pharmacokinetics, adverse effects and clinical efficacy) and attempts to find its place in current antibiotic therapeutics.
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PMID:[Cefditoren pivoxil: A new oral cephalosporin for skin, soft tissue and respiratory tract infections]. 1709 91

The in vitro antibacterial activities of oral cephem antibiotics and ketolide telithromycin against major respiratory pathogens possessing beta-lactam-resistant mutations (within the pbp gene) and/or macrolide-resistant genes (erm and mef) were examined in clinical isolates collected at 66 institutes in all over the Japan between 2002 and 2003. Telithromycin showed the strongest antibacterial activity against methicillinsusceptible Staphylococcus aureus strains with and without macrolide-resistant genes, such as ermA or ermC gene. All the cephem antibiotics showed potent antibacterial activity against Streptococcus pyogenes, with minimum inhibitory concentrations (MICs) of 0.015 mg/L or lower. Cefdinir had a much higher MIC90 against genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) than cefditoren and cefcapene (8 mg/L cefdinir vs. 1 mg/L cefditoren and cefcapene). The majority of gPRSP harbored either ermB or mefA, and the antibacterial activity of telithromycin against these strains was decreased however some susceptibility was still sustained. Cefditoren exerted the strongest antibacterial activity against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, with an MIC90 of 0.5 mg/L. These results underline the importance of checking the susceptibility and selecting an appropriate antibiotic against target pathogens.
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PMID:In vitro activities of oral cephem and telithromycin against clinical isolates of major respiratory pathogens in Japan. 1729 46

Cefditoren is the active form of cefditoren pivoxil, an oral cephalosporin antibiotic used for the treatment of respiratory tract infections and otitis media caused by bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, and methicillin-susceptible strains of Staphylococcus aureus. Beta-lactam antibiotics, including cefditoren, target penicillin-binding proteins (PBPs), which are membrane-associated enzymes that play essential roles in the peptidoglycan biosynthetic process. To envision the binding of cefditoren to PBPs, we determined the crystal structure of a trypsin-digested form of PBP 2X from S. pneumoniae strain R6 complexed with cefditoren. There are two PBP 2X molecules (designated molecules 1 and 2) per asymmetric unit. The structure reveals that the orientation of Trp374 in each molecule changes in a different way upon the formation of the complex, but each forms a hydrophobic pocket. The methylthiazole group of the C-3 side chain of cefditoren fits into this binding pocket, which consists of residues His394, Trp374, and Thr526 in molecule 1 and residues His394, Asp375, and Thr526 in molecule 2. The formation of the complex is also accompanied by an induced-fit conformational change of the enzyme in the pocket to which the C-7 side chain of cefditoren binds. These features likely play a role in the high level of activity of cefditoren against S. pneumoniae.
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PMID:Crystal structure of cefditoren complexed with Streptococcus pneumoniae penicillin-binding protein 2X: structural basis for its high antimicrobial activity. 1772 58

Among orally administered cephalosporins, aminopenicillins (+/- clavulanate), and macrolides, cefditoren was the most potent agent against Haemophilus influenzae (MIC(50/90), < or =0.008/0.03 microg/mL; 316 isolates including 100 beta-lactamase-positive and 10 beta-lactamase-negative ampicillin-resistant [BLNAR]) and was 32-, 64-, and 512-fold more potent than cefdinir, cefuroxime, and cefprozil, respectively. Cefditoren (MIC(50), 0.03 microg/mL) was also > or =32-fold more active against BLNAR phenotypes, although newer macrolides provided complete coverage against these strains. All Moraxella catarrhalis isolates were inhibited by cefditoren (0.5 microg/mL), including beta-lactamase producers (MIC(50), 0.12 vs < or =0.008 microg/mL). Cefditoren retains potent activity against respiratory tract isolates in the United States, including those with resistance phenotypes.
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PMID:Antimicrobial activity of cefditoren tested against contemporary (2004-2006) isolates of Haemophilus influenzae and Moraxella catarrhalis responsible for community-acquired respiratory tract infections in the United States. 1835 94


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