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Query: UNIPROT:O75191 (H. influenzae)
 4,961 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (the latter including paediatric patients), skin and soft tissues (again including paediatric patients), in uncomplicated urethritis/cervicitis associated with N. gonorrhoeae, Chlamydia trachomatis or U. urealyticum and in the treatment of early Lyme disease. Azithromycin was as effective as erythromycin and other commonly used drugs including clarithromycin, beta-lactams (penicillins and cephalosporins), and quinolone and tetracycline antibiotics in some of the above infections. Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to therapy with azithromycin (as is the case with erythromycin) indicating the need for physician vigilance, although it should be noted that azithromycin is of equivalent efficacy to amoxicillin in the treatment of such patients. In the therapy of urethritis/cervicitis associated with C. trachomatis, N. gonorrhoea or U. urealyticum, a single dose azithromycin regimen offers a distinct advantage over currently available pharmacological options, while providing effective therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy. 128 May 67

Azithromycin contains an aza-methyl substitution in the 15-membered aglycone ring and as such it is the prototype antibiotic of the azalide class, similar in mechanism of activity to the macrolides. It demonstrates a broad spectrum of activity against many aerobic and anaerobic Gram-positive species, and also inhibits a number of important aerobic and anaerobic Gram-negative bacteria. Significantly, azithromycin shows good activity against Haemophilus influenzae, an organism against which older macrolide antibiotics have proved disappointing. It is highly effective in inhibiting clinically significant intracellular pathogens such as Chlamydia trachomatis and Legionella. Bactericidal activity is seen for certain streptococci and for H. influenzae. Closely linked with azithromycin's microbiologic activity are its novel pharmacokinetics. Azithromycin moves rapidly from blood to tissue compartments where it remains for prolonged periods. Although serum concentrations remain low, the levels attained in the tissues (often greater than 2 mg/kg) are higher than the minimum inhibitory concentration for many common pathogens, and delivery of drug to infection sites by phagocytic cells contributes to these concentrations. This penetration into eukaryotic and prokaryotic cells may be responsible for azithromycin's expanded spectrum of activity, particularly against intracellular organisms. The use of antibiotic blood levels as breakpoints for susceptibility would appear to be inappropriate in the case of azalides. Rather, levels of drug at the tissue site of infection should be considered as guides to predicting efficacy. The in vitro activity of azithromycin, together with its unique tissue pharmacodynamics, define an agent that should demonstrate utility in infections of the respiratory tract, skin and skin structures, and certain sexually transmitted diseases.
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PMID:Clinical microbiology of azithromycin. 165 36

Azithromycin is a new azalide antibiotic with structural modifications that confer to the molecule acid stability, extension of antibacterial spectrum that includes important Gram-negative pathogens, long elimination half-life, and tendency to concentrate into various tissues where it persists for extended periods of time. The existence and length of a post-antibiotic effect (PAE), an important parameter for the characterization of new antibiotic molecules, has not yet been evaluated for this agent. In this study the PAE of azithromycin was assessed against representative respiratory pathogens included in the in vitro antimicrobial activity of the drug. The results obtained indicate that azithromycin produce a significant PAE on all Gram-positive and Gram-negative bacteria tested, resulting in an average value of 3.5 h for both S. pyogenes and S. pneumoniae, 3 h for B. catarrhalis and H. influenzae, and 2 h for Klebsiella spp. These findings support previous reports underlining the remarkable in vitro activity of azithromycin against H. influenzae, a pathogen poorly susceptible to the classical macrolides. Furthermore, the present demonstration of the existence of a long PAE of azithromycin against other Gram-positive and Gram-negative bacteria extends the pharmacokinetic advantages of the drug and strongly supports the application of this azalide in the therapy of respiratory infections.
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PMID:Post-antibiotic effect of azithromycin on respiratory tract pathogens. 196 17

The in-vitro activities of azithromycin and erythromycin were compared against 689 clinical isolates, including Gram-positive cocci, Haemophilus influenzae, and anaerobes. Of the 100 methicillin-susceptible isolates of Staphylococcus aureus tested, 77% were susceptible to 1 mg/l azithromycin and 0.5 mg/l erythromycin, whereas 22% were resistant to 32 mg/l of both compounds. All methicillin-resistant S. aureus isolates were highly resistant to both macrolides (MIC greater than 64 mg/l). Coagulase-negative staphylococci showed a wide range of susceptibilities to both compounds; MIC50 values for azithromycin and erythromycin for all isolates were 0.5 and 0.25 mg/l, respectively. With the exception of enterococci, both macrolides showed similar activity against streptococci; MIC90 values for both group A and group B streptococci were 0.03 and 0.06 mg/l for erythromycin and azithromycin, respectively. Azithromycin was less active than erythromycin against enterococci, with mode MICs of 4.0 and 1.0 mg/l, respectively; about 20% of isolates were highly resistant to both compounds. Azithromycin was substantially more active than erythromycin against H. influenzae; 41% of isolates were inhibited by 0.5 mg/l azithromycin and all isolates were inhibited by 2 mg/l. The MIC90 for erythromycin was 8 mg/l; 36% of isolates required concentrations of greater than or equal to 4 mg/l for inhibition. The anaerobic bacteria tested showed similar susceptibility to both azithromycin and erythromycin.
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PMID:Comparative in-vitro activity of azithromycin and erythromycin against Gram-positive cocci, Haemophilus influenzae and anaerobes. 215 33

Macrolide antibiotics, commonly used in upper and lower respiratory tract infections, are inconsistently active against Haemophilus influenzae. The new azalide, azithromycin, was compared with erythromycin and roxithromycin against this pathogen. Azithromycin (MIC range 0.06-1 mg/l) was four to eight times more potent than erythromycin (MIC range 0.5-8 mg/l) and roxithromycin (MIC range 0.5-16 mg/l). At 1 mg/l, 100% of the strains of H. influenzae were inhibited by azithromycin compared with 16% with erythromycin and 5% with roxithromycin. Azithromycin exhibited a rapid bactericidal effect, with a 99.9% kill at 4 h. The MBC was equal to or up to four-times greater than the MIC.
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PMID:Bacteriostatic and bactericidal activity of azithromycin against Haemophilus influenzae. 215 34

Azithromycin (CP-62,993), a new acid-stable 15-membered-ring macrolide, was well absorbed following oral administration in mice, rats, dogs, and cynomolgus monkeys. This compound exhibited a uniformly long elimination half-life and was distributed exceptionally well into all tissues. This extravascular penetration of azithromycin was demonstrated by tissue/plasma area-under-the-curve ratios ranging from 13.6 to 137 compared with ratios for erythromycin of 3.1 to 11.6. The significance of these pharmacokinetic advantages of azithromycin over erythromycin was shown through efficacy in a series of animal infection models. Azithromycin was orally effective in treating middle ear infections induced in gerbils by transbulla challenges with amoxicillin-resistant Haemophilus influenzae or susceptible Streptococcus pneumoniae; erythromycin failed and cefaclor was only marginally active against the H. influenzae challenge. Azithromycin was equivalent to cefaclor and erythromycin against Streptococcus pneumoniae. In mouse models, the new macrolide was 10-fold more potent than erythromycin and four other antibiotics against an anaerobic infection produced by Fusobacterium necrophorum. Similarly, azithromycin was effective against established tissue infections induced by Salmonella enteritidis (liver and spleen) and Staphylococcus aureus (thigh muscle); erythromycin failed against both infections. The oral and subcutaneous activities of azithromycin, erythromycin, and cefaclor were similar against acute systemic infections produced by Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, or S. aureus, whereas azithromycin was more potent than erythromycin and cefaclor against the intracellular pathogen Listeria monocytogenes. The pharmacokinetic advantage of azithromycin over erythromycin in half-life was clearly demonstrated in prophylactic treatment of an acute mouse model of S. aureus infection. These properties of azithromycin strongly support the further evaluation of this new macrolide for use in community-acquired infections of skin or soft tissue and respiratory diseases.
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PMID:Pharmacokinetic and in vivo studies with azithromycin (CP-62,993), a new macrolide with an extended half-life and excellent tissue distribution. 283 Aug 41

Azithromycin is a new macrolide which accumulates in high concentrations in human phagocytes. The cellular to extracellular ratio (C/E) of azithromycin concentrations (fixed extracellular concentration 1 mg/L) in human polymorphonuclear leucocytes (PMN) were significantly affected by small increases in the environmental temperature (C/E 20.3 +/- 2 and 59.4 +/- 6 at 37 degrees C and 40 degrees C, respectively). PMN-associated azithromycin was not affected by the presence of different concentrations of human serum. The intracellular accumulation of azithromycin decreased slightly (C/E approximately 5) when cells were activated with PMA or opsonized with zymosan. The phagocytosis of opsonized Staphylococcus aureus or Haemophilus influenzae, however, slightly increased the intracellular concentrations of azithromycin. At different extracellular concentrations, azithromycin did not affect the production of hydrogen peroxide and superoxide radicals by PMN. The intracellular survival of H. influenzae in human PMN was abolished in the presence of concentrations higher than 0.125 mg/L of azithromycin. Under the same experimental conditions, however, azithromycin did not show any intracellular activity against S. aureus.
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PMID:Factors affecting the intracellular accumulation and activity of azithromycin. 776 86

Azithromycin and clarithromycin are alternatives to conventional macrolides in the routine treatment of many dermatologic, upper respiratory, and lower respiratory tract infections. In this role as alternative therapy, they are better tolerated, less toxic, and more convenient to take, although at a greater cost to the patient. This dosing convenience is an important consideration for the clinician; as shown by Nelson, patient compliance ranges from 95% with once-daily dosing to 58% with four-times-a-day dosing. Thus, less frequent dosing with both drugs as well as the shorter course of therapy possible with azithromycin may be therapeutically advantageous. In addition to their role as alternatives to conventional macrolide therapy, azithromycin and clarithromycin extend the spectrum of macrolides and offer new therapeutic options for H. influenzae, MAC in AIDS, MOTT, and leprosy. Finally, experimental therapy may extend their use for additional opportunistic infections, such as toxoplasmosis and cryptosporidiosis.
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PMID:Azithromycin and clarithromycin. 779 24

Some recently marketed macrolide antimicrobial agents possess physiochemical, antimicrobial, and pharmacokinetic advantages that enable their wider clinical use against Haemophilus influenzae infections. A five-laboratory study assessed the validity of existing or proposed azithromycin, clarithromycin, and erythromycin interpretive criteria for tests with H. influenzae isolates. National Committee for Clinical Laboratory Standards (NCCLS) methods, criteria, and quality-control guidelines were used. A total of 350 H. influenzae strains were processed, including fresh clinical isolates (250 strains) and replicate tests of 100 stock cultures sampling strains isolated from 1984 to 91. Azithromycin interpretive criteria (susceptible at < or = 4 micrograms/ml, > or = 12 mm) produced a 99.8% absolute agreement between the minimum inhibitory concentrations and disk diffusion results (0.2% false-susceptible error). Clarithromycin breakpoint criteria (susceptible at < or = 8 micrograms/ml, > or = 13 mm; and resistant at > or = 32 micrograms/ml, < or = 10 mm) produced high minor interpretive error, but < or = 1% combined false-susceptible and false-resistant discrepancies. Erythromycin interpretive guidelines were initially proposed for susceptible at < or = 0.5 microgram/ml, > or = 26 mm. This categorizes nearly all H. influenzae strains as resistant to this older macrolide. The NCCLS should consider the proposed erythromycin criteria for publication in appropriate tables, and a class drug should also be selected (azithromycin) that would best predict macrolide-class susceptibility for those agents indicated by the US Food and Drug Administration for H. influenzae infection chemotherapy (azithromycin and clarithromycin). No serious interpretive problems were observed with the current NCCLS criteria using Haemophilus test medium.
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PMID:Validation of NCCLS macrolide (azithromycin, clarithromycin, and erythromycin) interpretive criteria for Haemophilus influenzae tested with the Haemophilus test medium. National Committee for Clinical Laboratory Standards. 792 21

Clinical efficacy of azithromycin and erythromycin was compared in an open trial in 32 and 18 patients with acute sinusitis respectively. The following pathogens were isolated: Haemophilus influenzae (29.8 per cent), Streptococcus pneumoniae (19.1 per cent), Staphylococcus aureus (10.6 per cent), Streptococcus faecalis (8.5 per cent) and other microbes (8.5 per cent). Azithromycin was administered in a dose of 500 mg on day 1. During the following 4 days it was administered in a dose of 250 mg. Erythromycin was administered in a dose of 500 mg 4 times a day for 8 to 10 days. 91.2 per cent of the aerobic microflora were sensitive to azitromycin and 85.3 per cent were sensitive to erythromycin. One of 14 strains of H. influenzae proved to be resistant to azithromycin, 3 strains were resistant to erythromycin. Complete recovery was stated in 90.6 per cent of the cases treated with azithromycin and 66.7 per cent of the cases treated with erythromycin.
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PMID:[Comparative clinical effectiveness and tolerance of azithromycin (sumamed) and erythromycin in patients with sinusitis]. 806 Jan 76


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