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)

Norfloxacin is a synthetic antibiotic belonging to the fluoroquinolone class. At present, an oral formulation is available and indicated for the treatment of urinary tract infections. Because of the properties of norfloxacin, a 0.3% norfloxacin ophtalmic solution may be used by ophtalmologists. The molecular target of norfloxacin is DNA gyrase that regulates DNA replication. Norfloxacin is a broad spectrum antibiotic. A flurin atome in position 6 is responsible for the broad spectrum of activity as compared with the first generation quinolones. MICs of norfloxacin against Haemophilus influenzae, Neisseria gonorrhoeae, Staphylococcus aureus, Pseudomonas aeruginosa, and enterbacteriaceae are low or intermediate. Norfloxacin is a bactericidal drug of which MBCs are equivalent to or twice as high as MICs against the majority of organisms. The proportion of norfloxacin resistant strains is limited and, at present, no plasmid resistance has been observed. This explains the activity of norfloxacin against clinical isolates whose drug resistance is plasmid-mediated. Norfloxacin resistance is chromosomic, but the mutation rate is low. There is no cross-resistance between quinolones and other classes of drug, with the exception of drug resistance related to changes in the bacterial outer membrane proteins. A low decrease in norfloxacin susceptibility is observed in case of resistance to first generation quinolones. The above-mentioned properties make norfloxacin in ophtalmic solution a first line drug for treatment of superficial ocular infections and a second line drug for treatment of infections due to organisms resistant to other drugs.
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PMID:[Norfloxacin: a broad-spectrum quinolone for superficial eye infections]. 223 90

Fluoroquinolones are antibiotics that act principally on DNA gyrase. At the moment, resistance to these antibiotics is purely chromosome-mediated. As regards pharmacokinetics, these compounds have a high bioavailability and penetrate extremely well into tissues and cells. Therapeutic concentrations are obtained in bronchial mucosa and lung tissue. In severe lower respiratory tract infections fluoroquinolones must be given in combination with other antibiotics to prevent the emergence of resistant mutants. The indications of fluoroquinolones in lower respiratory tract infections depend on their antibacterial spectrum. They are particularly useful in the treatment of infections caused by methicillin-sensitive or resistant staphylococci, Pseudomonas spp. (notably in cystic fibrosis) and intracellular organisms. They are not indicated for streptococcal infections, notably those due to Streptococcus pneumoniae, and for anaerobic infections. Fluoroquinolones are currently used mainly in hospital-acquired lower respiratory tract infections, in infected cystic fibrosis and in some acute episodes of chronic bronchitis since they are active against Haemophilus influenzae and Branhamella catarrhalis.
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PMID:[Fluoroquinolones: pharmacology, antibacterial spectrum and indications in pneumology]. 266 44

The in-vitro and in-vivo antibacterial activities of fleroxacin were compared with those of other new quinolones including NY-198. Fleroxacin showed potent activity against most members of the Enterobacteriaceae, Neisseria gonorrhoeae and Haemophilus influenzae, and good activity against Pseudomonas aeruginosa and staphylococci. Against these bacteria, the activity of fleroxacin was roughly comparable to that of norfloxacin, enoxacin, NY-198, and ofloxacin, but slightly less than that of ciprofloxacin. Fleroxacin strongly inhibited DNA supercoiling activity of DNA gyrase purified from Escherichia coli which may explain its high antibacterial activity. The protective effects of a single oral dose of fleroxacin in mice were greater than those of norfloxacin and comparable to or greater than that of ciprofloxacin, ofloxacin and NY-198 against systemic infections with Staphylococcus aureus, Esch. coli and Ps. aeruginosa, and Serratia marcescens.
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PMID:In-vitro and in-vivo antibacterial activity of fleroxacin, a new fluorinated quinolone. 284 4

The antibacterial activity of ofloxacin against Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Branhamella catarrhalis, and Neisseria gonorrhoeae was comparable to norfloxacin and enoxacin, and far exceeded the activity of pipemidic acid and nalidixic acid. The activity of ofloxacin was two to eight times less than that of ciprofloxacin. Ofloxacin was more active against Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Acinetobacter spp., Legionella spp., and Bacteroides fragilis, than norfloxacin, enoxacin, pipemidic acid and nalidixic acid, and the activity of ofloxacin was comparable to that of ciprofloxacin. Ofloxacin was two to seven times more effective than norfloxacin in systemic infections in mice with S. aureus, Escherichia coli, Serratia marcescens and P. aeruginosa. Ofloxacin strongly inhibited DNA supercoiling activity of DNA gyrase purified from E. coli KL-16. There is a parallel relationship between antibacterial activity of ofloxacin and its inhibitory action against DNA gyrases from ofloxacin-susceptible and ofloxacin-resistant clinical isolates of E. coli. These results indicate that the high bactericidal action of ofloxacin and the related new quinolone agents can be explained by their potent inhibitory activities against DNA gyrase in bacterial cells.
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PMID:Antibacterial activity of ofloxacin and its mode of action. 302 66

Structural modification of the so-called 'first-generation' or 'urinary' quinolones has led to a considerable increase in their intrinsic antibacterial activity, together with marked changes in the pharmacokinetic properties. Tissue penetration is the most notable change, and the newer quinolones are comparable with the newer broad spectrum beta-lactams in their clinical spectrum of activity. Marketed compounds in the 4-quinolones group include pefloxacin, ofloxacin, enoxacin, ciprofloxacin and norfloxacin; many more compounds are in various stages of research and development. The 4-quinolones act by inhibition of bacterial DNA gyrase, a process which is pH and concentration dependent. The bactericidal activity can be partly abolished if protein synthesis is inhibited by chloramphenicol, or if RNA synthesis is inhibited by rifampicin (rifampin). The antibacterial spectrum of activity includes methicillin- and gentamicin-resistant staphylococci, multiresistant non-fermenters, all Enterobacteriaceae, Legionella, Neisseria species, Branhamella and Haemophilus influenzae. With the exception of norfloxacin, which is only 30 to 40% bioavailable from the oral route, the 4-quinolones are 80 to 100% bioavailable, absorption occurring within 1 to 3 hours. Food does not significantly alter Cmax, AUC or elimination half-life, although tmax, may be increased. The 4-quinolones are widely distributed throughout the body, with volumes of distribution greater than 1.5 L/kg. Protein binding is less than 30% in most cases. Penetration into most tissues is good. With the exception of ofloxacin and lomefloxacin (NY 198), which are metabolically stable, metabolism of the 4-quinolones occurs primarily at the C7 position in the piperazinyl ring. Biotransformation is extensive (85%) with pefloxacin, medium (25 to 40%) with ciprofloxacin and enoxacin, and low (less than 20%) with norfloxacin. Elimination half-lives vary between 3 and 5 hours (ciprofloxacin) and 8 to 14 hours (pefloxacin). Biliary concentrations of the 4-quinolones are 2 to 10 times greater than those in serum or plasma, with several compounds undergoing enterohepatic circulation. There is some evidence that ciprofloxacin, norfloxacin, ofloxacin and enoxacin have an active renal tubular excretion pathway. In impaired renal function, reduction of the glomerular filtration rate below 30 ml/min (1.8 L/h) is associated with an increase in elimination half-life and AUC, and a decrease in renal and total clearance of the 4-quinolones, and a decrease in 24-hour urinary recovery.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of the newer antibacterial 4-quinolones. 328 49

Ciprofloxacin is a new fluoroquinolone that is highly active against many diverse microorganisms. At concentrations of less than 1 microgram/mL it is active against most gram-negative bacteria, including Enterobacteriaceae, Haemophilus, Neisseria, and other Pasteurellaceae, Vibrionaceae, and various species of Pseudomonas and Acinetobacter. Most staphylococci, including strains resistant to methicillin, are also susceptible to ciprofloxacin. Streptococci are not highly susceptible to ciprofloxacin, and obligate anaerobes are generally resistant to this and other quinolones. Ciprofloxacin, like other quinolones, inhibits DNA gyrase, but its bactericidal effects are not completely reversible by inhibitors of protein or RNA synthesis. Thus, unlike many other quinolones, ciprofloxacin may have multiple lethal effects. Resistance is less readily selected in vitro by ciprofloxacin than by nalidixic acid, and single-step mutants usually remain susceptible to clinically achievable concentrations. Resistance mediated by mutations in genes altering DNA gyrase and expression of outer membrane proteins has been described for ciprofloxacin and other quinolones. The antimicrobial spectrum and potency of ciprofloxacin, coupled with its rapid bactericidal effects, make this fluoroquinolone a promising new antimicrobial agent.
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PMID:Ciprofloxacin: in vitro activity, mechanism of action, and resistance. 329 57

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of ciprofloxacin and norfloxacin are reviewed, and mechanisms of antimicrobial resistance and drug and laboratory interactions are described. Norfloxacin is the first antimicrobial in the fluoroquinolone class to be marketed in the United States; ciprofloxacin is under investigation in clinical trials. The fluoroquinolones are structurally related to nalidixic acid. The activity and spectrum are enhanced by the addition of 6-fluoro and 7-piperazino substituents. Quinolone antimicrobials appear to inhibit DNA gyrase, an enzyme specific and essential for all bacteria, as their primary mechanism of action. As a result, DNA synthesis is inhibited. Ciprofloxacin and norfloxacin are active against gram-negative enteric bacteria, Pseudomonas aeruginosa, Haemophilus influenzae, and Neisseria gonorrhoeae. Ciprofloxacin has good activity against Staphylcoccus spp., including methicillin-resistant Staph. aureus. Norfloxacin generally is less potent than ciprofloxacin, particularly against Ps. aeruginosa and Staph. aureus. Peak concentrations occur about one to two hours after an oral administration of either drug. Both drugs are widely distributed in body fluids and tissues and are eliminated by renal excretion, metabolism, and biliary excretion. Dosage reductions are required in severe renal dysfunction. Ciprofloxacin and norfloxacin are effective agents for treating urinary-tract infections, including infections caused by Ps. aeruginosa. The recommended dosage of norfloxacin for urinary-tract infections in adults is 400 mg orally every 12 hours; the drug should be given for 7 to 10 days in uncomplicated infections and for 10 to 21 days in complicated ones. The fluoroquinolones may be useful for treating chronic bacterial prostatitis. Ciprofloxacin is potentially useful for treating sexually transmitted diseases. Ciprofloxacin is active against N. gonorrhoeae, including beta-lactamase-producing strains and strains that are resistant to tetracycline, and Chlamydia spp. Use of ciprofloxacin for treating gastrointestinal infections and for selective decontamination of the gastrointestinal tract is promising. In open studies, ciprofloxacin has been effective against a variety of infections caused by susceptible organisms. Resistance to ciprofloxacin has developed during treatment of infections caused by Ps. aeruginosa, Staph. aureus, and Serratia marcescens. The most frequently reported adverse effects of either drug are gastrointestinal complaints, headache, and dizziness.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ciprofloxacin and norfloxacin, two fluoroquinolone antimicrobials. 331 72

The in vitro activity of the new fluoroquinolone HSR-903 was compared with those of ciprofloxacin, lomefloxacin, sparfloxacin, and levofloxacin. HSR-903 inhibited 90% of methicillin-susceptible and -resistant Staphylococcus aureus (MRSA) clinical isolates at 0.78 and 1.56 microg/ml, respectively, and its activity against MRSA was 16-fold higher than those of sparfloxacin and levofloxacin and 64-fold higher than that of ciprofloxacin. The MICs at which 90% of the isolates are inhibited (MIC90s) of HSR-903 for Streptococcus pyogenes and penicillin G-susceptible and -resistant Streptococcus pneumoniae (PRSP) were 0.10, 0.05, and 0.05 microg/ml, respectively. Against PRSP, the activity of HSR-903 was 4-fold higher than that of sparfloxacin and 32- to 256-fold higher than those of the other quinolones. The MIC90 of HSR-903 for Enterococcus faecalis was 0.20 microg/ml, and HSR-903 was more active than the other quinolones against enterococci. The activity of HSR-903 against members of the family Enterobacteriaceae and Pseudomonas aeruginosa was roughly similar to that of ciprofloxacin and greater than those of the other quinolones. Against Haemophilus influenzae, Moraxella catarrhalis, and Helicobacter pylori, HSR-903 was the most potent of the quinolones tested. The activity of HSR-903 was not affected by the medium, the inoculum size, or the addition of serum, but decreased under acidic conditions, as did those of the other quinolones tested. HSR-903 exhibited rapid bactericidal action and had a good postantibiotic effect on S. aureus and P. aeruginosa. HSR-903 inhibited supercoiling by DNA gyrase from Escherichia coli, but it was much less active against human topoisomerase II.
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PMID:In vitro activity of HSR-903, a new quinolone. 917 93

The responses of Haemophilus influenzae to DNA gyrase inhibitors were analyzed at the transcriptional and the translational level. High-density microarrays based on the genomic sequence were used to monitor the expression levels of >80% of the genes in this bacterium. In parallel the proteins were analyzed by two-dimensional electrophoresis. DNA gyrase inhibitors of two different functional classes were used. Novobiocin, as a representative of one class, inhibits the ATPase activity of the enzyme, thereby indirectly changing the degree of DNA supercoiling. Ciprofloxacin, a representative of the second class, obstructs supercoiling by inhibiting the DNA cleavage-resealing reaction. Our results clearly show that different responses can be observed. Treatment with the ATPase inhibitor Novobiocin changed the expression rates of many genes, reflecting the fact that the initiation of transcription for many genes is sensitive to DNA supercoiling. Ciprofloxacin mainly stimulated the expression of DNA repair systems as a response to the DNA damage caused by the stable ternary complexes. In addition, changed expression levels were also observed for some genes coding for proteins either annotated as "unknown function" or "hypothetical" or for proteins not directly involved in DNA topology or repair.
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PMID:Gene expression changes triggered by exposure of Haemophilus influenzae to novobiocin or ciprofloxacin: combined transcription and translation analysis. 1115 10

We investigated the in vitro and in vivo antibacterial activities of pazufloxacin mesilate (PZFX mesilate), a new injectable quinolone, and obtained the following results. 1) The MIC50 and MIC90 values of PZFX against clinically isolated Gram-positive and -negative bacteria, ranged from 0.0125 to 12.5 micrograms/ml and 0.025 to 100 micrograms/ml, respectively. PZFX showed broad spectrum activity. The antibacterial activities of PZFX against quinolone-susceptible, methicillin-resistant Staphylococcus aureus, beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae, extended spectrum beta-lactamase possessing Klebsiella pneumoniae and imipenem/cilastatine (IPM/CS)-resistant Pseudomonas aeruginosa were superior to those of ceftazidime (CAZ), ceftriaxone, IPM/CS, meropenem and panipenem/betamipron. 2) PZFX showed superior bactericidal activity against S. aureus, Escherichia coli, Proteus mirabilis, Serratia marcescens and P. aeruginosa to those of CAZ and IPM/CS after treatment for 15 minutes at the drug concentration equivalent to that in human serum at clinical dose to be continued for 15 minutes. 3) CAZ and IPM/CS had no bactericidal activity at the 16 times of MIC against P. aeruginosa in human polymorphonuclear leucocytes, while PZFX exhibited potent bactericidal activity in a dose-dependent manner against such bacteria. 4) PZFX inhibited both DNA gyrase and topoisomerase IV from S. aureus at nearly the same level. PZFX showed poor inhibitory activity against topoisomerase II from human placenta and showed high selectivity to bacterial topoisomerase. 5) PZFX mesilate showed superior therapeutic activity to that of CAZ with following infection model caused by S. aureus and P. aeruginosa or each; systemic infection with cyclophosphamide-treated mice, systemic infection in mice with high challenge doses, CMC pouch infection in rat, and calculus infection in rat bladder. 6) Intravenous administration of PZFX with high plasma concentration just after administration, showed more excellent therapeutic effect against the rat intraperitoneal infection, than p.o. and s.c. administration.
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PMID:[In vitro and in vivo antibacterial activities of pazufloxacin mesilate, a new injectable quinolone]. 1237 71


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