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)

Thiamphenicol-glycinate-acetylcysteinate (TGA; CAS 20192-91-0) is widely used for the treatment of infections of varied aetiology. The aim of this study was to compare the antibacterial activity of thiamphenicol-glycinate (TG; CAS 15318-45-3), TGA, amoxicillin (CAS 61336-70-7) plus clavulanic acid (CAS 58001-44-8), azithromycin (CAS 83905-01-5) and ceftriaxone (CAS 104376-79-6). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined against Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae according to the National Committee for Clinical Laboratory Standards (NCCLS) methods. The effects of changes in assay conditions were also examined. The activity of TG and TGA was similar to that of amoxicillin plus clavulanic acid, with the exception of methicillin resistant S. aureus. Azithromycin and ceftriaxone were characterised by a limited activity against gram-positive cocci and methicillin resistant and cefinase-positive S. aureus, respectively. TG and TGA are characterized by a wide spectrum of activity, comparable to that of recent commercialized antibiotics for treatment of respiratory tract infections.
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PMID:Comparative in vitro activity of thiamphenicol-glycinate and thiamphenicol-glycinate-acetylcysteinate and other antimicrobials against respiratory pathogens. 1136 73

We measured the susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several currently approved antimicrobial agents by two different methods. We also measured the susceptibility of isolates to seven fluoroquinolones. Beta-lactamase was produced by 123/566 (21.7%) of H. influenzae isolates compared with 178/200 (89%) of M. catarrhalis isolates. For S. pneumoniae 83/374 (22.2%) isolates were penicillin resistant and of these 2.1% (8/374) showed high level resistance (MIC > or = 2 mg/l). Regardless of methodology, all fluoroquinolones were highly active against H. influenzae (MIC(90) < or = 0.031 mg/l) and M. catarrhalis (MIC(90) < or = 0.064 mg/l) isolates. Susceptibility of H. influenzae to cefuroxime and amoxycillin/clavulanic acid was 99-100% whereas 84-85.5% were susceptible to cefaclor and cefprozil. Azithromycin susceptibility ranged from 82.6 to 99.2% depending on the method. M. catarrhalis isolates were uniformly susceptible to all agents tested except amoxycillin. Cross-resistance in S. pneumoniae to all non-quinolone agents was concurrent with increasing penicillin resistance as shown by increasing MIC90 values. For the fluoroquinolones tested, the rank order of potency based on MIC(90) values was as follows: gemifloxacin (0.031-0.063 mg/l), trovafloxacin (0.125 mg/l), moxifloxacin (0.125-0.25 mg/l), grepafloxacin (0.125-0.25 mg/l), gatifloxacin (0.5 mg/l), levofloxacin (1 mg/l) and ciprofloxacin (2 mg/l). Our study confirms either a high or increasing prevalence of antimicrobial resistant respiratory pathogens in Canada and also compares the new and old fluoroquinolones and their potential role as therapy for community-acquired infections. The prevalence of beta-lactamase positive H. influenzae may have decreased from levels reported in previous studies.
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PMID:Susceptibility of Canadian isolates of Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae to oral antimicrobial agents. 1139 15

Azithromycin (Zithromac), a 15-membered ring macrolide antibacterial agent, was approved to be manufactured in Japan in March 2000. It showed good in vitro and/or in vivo antibacterial activities against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Peptostreptococcus micros, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydia pneumoniae. Its activity against H. influenzae was particularly more potent than that of currently used macrolide antibacterial agents. After oral administration to patients, azithromycin was readily absorbed and became widely distributed throughout the body, achieving higher concentrations in tissues and phagocytic cells than in serum or plasma. Its distribution into phagocytes was as high as more than 10 times that of erythromycin, and azithromycin was readily released from phagocytes in the presence of S. aureus. In experimentally infected mice, the concentration of azithromycin was higher in infected tissues than in uninfected tissues, which indicated that azithromycin was selectively delivered to infected tissues by migrating phagocytes. These pharmacological and pharmacokinetic properties were reflected in good clinical results for the treatment of respiratory infections and other infections with once daily dosing for 3 days.
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PMID:[Pharmacological and pharmacokinetic properties of azithromycin (Zithromac), a novel 15-membered ring macrolide antibacterial agent]. 1141 44

Azithromycin is an azalide with potent activity against Haemophilus influenzae including ampicillin-resistant strains. We evaluated the efficacy of azithromycin, clarithromycin and three beta -lactams when used for 1 day only and for 3 days for the treatment of a murine model of bronchopneumonia, using three strains of H. influenzae, two of which were ampicillin resistant. MICs of azithromycin (1-2 mg/L) and clarithromycin (4-8 mg/L) were similar for the three strains. The MICs of cefdinir and cefcapene for beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae were 32 times higher than those for beta-lactamase-positive ampicillin-resistant and ampicillin-susceptible strains. The viable counts in the infected tissues of azithromycin-treated mice with bronchopneumonia caused by the susceptible strain TUM8, beta-lactamase-positive strain TUH36 and BLNAR strain TUH267 were less than the counts obtained with the other antibiotics used, irrespective of MIC. At a dose of 50 mg/kg, the area under the concentration curve and the half-life of azithromycin in the lungs were respectively three times higher and six times longer than those of clarithromycin. Our results indicate that azithromycin may be useful for both ampicillin-susceptible and ampicillin-resistant bronchopneumonial infections caused by H. influenzae.
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PMID:Efficacy of azithromycin, clarithromycin and beta-lactam agents against experimentally induced bronchopneumonia caused by Haemophilus influenzae in mice. 1153 11

The azalide antibiotic azithromycin and the newer macrolides, such as clarithromycin, dirithromycin and roxithromycin, can be regarded as 'advanced-generation' macrolides compared with erythromycin, the first macrolide used clinically as an antibiotic. Their pharmacokinetics are characterized by a combination of low serum concentrations, high tissue concentrations and, in the case of azithromycin, an extended tissue elimination half-life. Azithromycin is particularly noted for high and prolonged concentrations at the site of infection. This allows once-daily dosing for 3 days in the treatment of respiratory tract infections, in contrast to longer dosage periods required for erythromycin, clarithromycin, roxithromycin and agents belonging to other classes of antibiotics. The spectrum of activity of the advanced-generation macrolides comprises Gram-positive, atypical and upper respiratory anaerobic pathogens. Azithromycin and the active metabolite of clarithromycin also demonstrate activity against community-acquired Gram-negative organisms, such as Haemophilus influenzae. Advanced-generation macrolides, and in particular azithromycin, are highly concentrated within polymorphonuclear leucocytes, which gravitate by chemotactic mechanisms to sites of infection. Following phagocytosis of the pathogens at the infection site, they are exposed to very high, and sometimes cidal, intracellular concentrations of antibacterial agent. Pharmacodynamic models and susceptibility breakpoints derived from studies with other classes of drugs, such as the beta-lactams and aminoglycosides, do not adequately explain the clinical utility of antibacterial agents that achieve high intracellular concentrations. In the case of azithromycin, attention should focus on tissue pharmacokinetic and pharmacodynamic concepts.
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PMID:Advanced-generation macrolides: tissue-directed antibiotics. 1157 89

A minority of patients with upper respiratory tract infections (URTI) have a bacterial infection and may benefit from antibiotherapy. In previous investigations we showed that in patients suffering from acute rhinosinusitis associated with the presence of Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis in their nasopharygeal secretions, resolution of symptoms was significantly improved by antibiotic treatment. The present analysis was performed to determine whether specific clinical symptoms or signs observed during careful endoscopic examination of the nasal cavities could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis infected with pathogenic bacteria. Detailed clinical histories were obtained and medical examinations performed in 265 patients (138 females, 127 males; mean age 35 years) presenting with a < 4-week history of URTI symptoms but who did not require immediate antibiotic therapy for severe rhinosinusitis. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae and M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Azithromycin (500 mg/day for 3 days; n = 133) or placebo (n = 132) were randomly given to all patients in a double-blind manner. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms significantly associated in a multivariate model with the presence of bacteria included colored nasal discharge (p < 0.003), facial pain (p < 0.032) and radiologically determined maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening > 10 mm) (p < 0.001). This best predictive model had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. In the group of patients with positive bacterial cultures, resolution of symptoms at Day 7 was observed in 73% of patients treated with azithromycin and in 47% of patients in the placebo group (p < 0.007). We conclude that signs and symptoms of acute rhinosinusitis in patients with mild-to-moderate clinical presentations are poor predictors of the presence of bacteria.
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PMID:Symptoms and clinical and radiological signs predicting the presence of pathogenic bacteria in acute rhinosinusitis. 1193 12

Azithromycin is an important antibiotic for the treatment of several different Gram-positive and Gram-negative bacterial infections. Erythromycin and clarithromycin are less useful antibiotics against Gram-negative infections. This difference in inhibitory activity was explored by comparing the effects of azithromycin and erythromycin on cellular functions in Haemophilus influenzae cells. Effects of both antibiotics on translation, cell viability, and growth rates have been measured. An IC(50) of 0.4 microg/ml was found for the effects of azithromycin on each of these processes. For erythromycin, an IC(50) of 1.5 microg/ml was observed, indicating a fourfold lower sensitivity of the organisms to this compound. The features of a second target for macrolide antibiotic inhibition in H. influenzae cells have also been examined. Inhibition of the synthesis of the large 50S ribosomal subunit was measured. Subunit formation was prevented in a concentration dependent fashion, with azithromycin showing a ninefold greater effect on this process compared with erythromycin. Synthesis of the 30S ribosomal subunit was not effected. Pulse and chase labeling kinetics confirmed the slower synthesis rate of the 50S particle in the presence of each antibiotic. The results are discussed in terms of the stronger effect of azithromycin on ribosome biosynthesis in this organism.
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PMID:Inhibition of 50S ribosomal subunit assembly in Haemophilus influenzae cells by azithromycin and erythromycin. 1200 Sep 92

A multi-center surveillance study was conducted in Thailand during 1999-2000 to determine antimicrobial susceptibilities among the respiratory pathogens Streptococcus pneumoniae (n = 206), Haemophilus influenzae (n = 305), and Moraxella catarrhalis (n = 39). Of the S. pneumoniae isolates collected, 33.5% were penicillin-susceptible, 27.2% intermediate and 39.3% resistant. Expectedly, resistance rates to beta-lactams were higher among penicillin-resistant (ceftriaxone, 14.8%; amoxicillin-clavulanate, 42.0%; cefuroxime, 100%) than penicillin-susceptible (ceftriaxone, 0%; amoxicillin-clavulanate, 0%; cefuroxime, 0%) isolates. Likewise, azithromycin and clarithromycin resistances were 4.3% and 5.8% among penicillin-susceptible isolates, and 77.8% and 95.1% among penicillin-resistant isolates. All S. pneumoniae remained susceptible to vancomycin and 99.5% were susceptible to levofloxacin. Multidrug resistance (resistance to >3 antimicrobial classes) was present in 25.2% of pneumococcal isolates (n = 52), with resistance to azithromycin, penicillin and trimethoprim-sulfamethoxazole the most common phenotype (40/52 isolates; 77.0%). Among the isolates of H. influenzae, the prevalence of beta-lactamase production was 45.2%. All isolates of H. influenzae were susceptible to amoxicillin-clavulanate, azithromycin, ceftriaxone, cefuroxime and levofloxacin while 49.5% were resistant to trimethoprim-sulfamethoxazole. All 39 isolates of M. catarrhalis produced beta-lactamase. Azithromycin (MIC90, < or = 0.03 microg/ml) and levofloxacin (MIC90, 0.03 microg/ml) were the most active agents tested against M. catarrhalis. The results of this study may serve as a baseline for future studies to monitor antimicrobial susceptibilities among respiratory pathogens in Thailand.
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PMID:Antimicrobial resistance among respiratory pathogens collected in Thailand during 1999-2000. 1201 69

Treatment of acute otitis media (AOM) with azithromycin results in apparent clinical success, but tympanocentesis performed 4 to 6 days after initiation of therapy in children with nontypeable Haemophilus influenzae (NTHI) recovered from initial middle ear cultures demonstrates persistence of infection in more than 50% of episodes. We sought to determine the effect of azithromycin at different doses on the density of middle ear infection due to NTHI to provide additional understanding of this dichotomy between clinical and microbiologic outcome measures in AOM. In a chinchilla model of experimental otitis media (EOM), animals treated with placebo were compared to animals receiving a single daily dose 30 or 120 mg of azithromycin per kg of body weight per day for 5 days. Microbiologic outcome was assessed by obtaining quantitative cultures from the middle ear during a 5-day course and for 1 week following therapy. Azithromycin concentrations were measured to ascertain whether a concentration-dependent effect was present. Azithromycin at 30 and 120 mg/kg/day demonstrated a dose-dependent effect on the quantitative assessment of middle ear infection due to NTHI. A 30-mg/kg dose of azithromycin daily resulted in levels in serum and areas under the serum concentration-time curve at 24 h comparable to published data obtained with children given azithromycin at 5 to 10 mg/kg in multiday regimens. Increased doses of azithromycin (120 mg/kg) achieved 2.5- to 4-fold-higher levels in serum and 3- to 6-fold-higher total levels and levels in extracellular middle ear fluid as well as more rapid reduction in bacterial density and a greater proportion of middle ears with complete sterilization than either placebo or the 30-mg/kg/day regimen.
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PMID:Experimental acute otitis media due to nontypeable Haemophilus influenzae: comparison of high and low azithromycin doses with placebo. 1206 74

The MIC at which 50% of strains are inhibited (MIC(50)) and the MIC(90) of GW 773546, a novel macrolide, were 1.0 and 2.0 microg/ml, respectively, for 223 beta-lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae strains. The MIC(50)s and MIC(90)s of GW 708408, a second novel macrolide, and telithromycin, an established ketolide, were 2.0 and 4.0 microg/ml, respectively, while the MIC(50) and MIC(90) of azithromycin were 1.0 and 2.0 microg/ml, respectively. The MIC(50) and MIC(90) of erythromycin were 4.0 and 8.0 microg/ml, respectively; and those of clarithromycin were 4.0 and 16.0 microg/ml, respectively. All compounds except telithromycin were bactericidal (99.9% killing) against nine strains at two times the MIC after 24 h. Telithromycin was bactericidal against eight of the nine strains. In addition, both novel macrolides and telithromycin at two times the MIC showed 99% killing of all nine strains after 12 h and 90% killing of all strains after 6 h. After 24 h, all drugs were bactericidal against four to seven strains when they were tested at the MIC. Ten of 11 strains tested by multistep selection analysis yielded resistant clones after 14 to 43 passages with erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50 passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to 41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins and 23S rRNA were detected in resistant strains selected with all compounds, with alterations in the L22 protein predominating. Single-step resistance selection studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 x 10(-9) to 2.2 x 10(-6) with GW 773546, 1.5 x 10(-9) to 6.0 x 10(-4) with GW 708408, and 7.1 x 10(-9) to 3.8 x 10(-4) with telithromycin, whereas the frequencies were 1.3 x 10(-9) to 6.0 x 10(-4) with erythromycin and azithromycin and 2.0 x 10(-9) to 2.0 x 10(-3) with clarithromycin. Alterations in the L22 protein (which were predominant) and the L4 protein were present in mutants selected by the single-step selection process. The postantibiotic effects of GW 773546, GW 708408, and telithromycin for seven H. influenzae strains were 6.6 h (range, 5.2 to 8.8 h), 4.7 h (range, 2.6 to 6.9 h), and 6.4 h (range, 3.8 to 9.7 h), respectively. The results of in vitro studies obtained with both novel macrolides were similar to those obtained with telithromycin and better than those obtained with older macrolides.
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PMID:Activities of two novel macrolides, GW 773546 and GW 708408, compared with those of telithromycin, erythromycin, azithromycin, and clarithromycin against Haemophilus influenzae. 1550 29


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