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)

A high-density transposon mutagenesis strategy was applied to the Haemophilus influenzae genome to identify genes required for growth or viability. This analysis detected putative essential roles for the products of 259 ORFs of unknown function. Comparisons between complete genomes defined a subset of these proteins in H. influenzae having homologs in Mycobacterium tuberculosis that are absent in Saccharomyces cerevisiae, a distribution pattern that favors their use in development of antimicrobial therapeutics. Three genes within this set are essential for viability in other bacteria. Interfacing the set of essential gene products in H. influenzae with the distribution of homologs in other microorganisms can detect components of unrecognized cellular pathways essential in diverse bacteria. This genome-scale phenotypic analysis identifies potential roles for a large set of genes of unknown function.
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PMID:A genome-scale analysis for identification of genes required for growth or survival of Haemophilus influenzae. 1180 38

The in vitro antimicrobial activity of gatifloxacin against clinical isolates of pathogenic bacteria was evaluated. Minimum inhibitory concentrations of gatifloxacin, ofloxacin, ciprofloxacin, tosufloxacin, sparfloxacin, and rifampicin against 20 strains each of methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa, 18 strains of Enterobacter cloacae, 15 strains each of Streptococcus Pneumoniae and Moraxella catarrhalis, 12 strains of Haemophilus influenzae, 18 strains of Mycobacterium intracellulare, and 22 strains each of Mycobacterium tuberculosis and Mycobacterium avium were determined. The minimum inhibitory concentrations90's of gatifloxacin against the above species were 0.12, 8, <==0.06, 0.5, 2, 2, <==0.06, 0.39, 0.05, 0.013, 2, 0.5, and 4 &mgr;g/ml, respectively. Gatifloxacin was four times as active as ofloxacin against methicillin-susceptible and -resistant Staphylococcus aureus, and as active as ofloxacin against Enterobacteriaceae and Pseudomonas aeruginosa. Gatifloxacin was as active as tosufloxacin and sparfloxacin against Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. The antimycobacterial activity of gatifloxacin was similar to that of sparfloxacin. Five patients with chronic respiratory infections and one patient with acute pneumonia received 100-400 mg/day of gatifloxacin orally for 5-12 days (mean, 8.17 days). The clinical effects were excellent in one patient and good in five. One strain of Haemophilus influenzae was eradicated and one strain of Pseudomonas aeruginosa persisted after therapy. Adverse reactions were mild and improved after completion of therapy. In one patient with chronic bronchitis, the maximum sputum concentrations 2-4 h after oral administration of 150 mg of gatifloxacin on days 1 and 6 were 0.88 and 1.45 &mgr;g/ml, respectively, and in serum the values were 0.84 and 1.24 &mgr;g/ml, respectively. Thus it was found that gatifloxacin possesses potent activity against respiratory pathogens (including Mycobacteriaceae), and shows good penetration rate into sputum, and that it can be used as the drug of first choice in the treatment of respiratory tract infections.
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PMID:In vitro antimicrobial activity and penetration rate into sputum of gatifloxacin, a novel 6-fluoro-8-methoxy quinolone, and its therapeutic efficacy in respiratory infections. 1181 May 7

Antimicrobial resistance is reaching epidemic proportions. Bacteria have developed an impressive array of defenses to protect themselves against potent compounds. The widespread emergence of resistance has complicated the treatment of infections due to Staphylococcus, Streptococcus, Enterococcus, Neisseria, Haemophilus, gram-negative enteric bacilli, and Pseudomonas. Multidrug-resistant tuberculosis poses a grave public health problem, particularly among the homeless and those infected with HIV. HIV resistance to nucleoside analogs such as zidovudine is increasingly common and seriously threatens their clinical usefulness. It is apparent that simply producing new drugs is not a viable solution to the resistance crisis. Rational use of existing antimicrobial agents is vital, and combination regimens must be intelligently deployed. State-of-the-art molecular epidemiology will aid in the detection, analysis, and termination of resistance epidemics. Control of drug-resistant Mycobacterium tuberculosis will require appropriate initial treatment regimens, proper therapeutic modification using the latest susceptibility testing methods, and strong emphasis on measures ensuring compliance. HIV resistance is a challenging problem, and novel strategies will be necessary to combat it. Recognition that drug resistance among bacteria and viruses is a rapidly growing threat worldwide is an important first step toward finding effective long-term solutions.
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PMID:Will the Nineties Be the Decade We Lost the Battle Against Drug-Resistant Microbes? 1183 84

Antimicrobials show selective toxicity. Suitable targets for antimicrobials to act at include the bacterial cell wall, bacterial protein and folic acid synthesis, nucleic acid metabolism in bacteria and the bacterial cell membrane. Acquired antimicrobial resistance generally can be ascribed to one of five mechanisms. These are production of drug-inactivating enzymes, modification of an existing target, acquisition of a target by-pass system, reduced cell permeability and drug removal from the cell. Introduction of a new antimicrobial into clinical practice is usually followed by the rapid emergence of resistant strains of bacteria in some species that were initially susceptible. This has reduced the long-term therapeutic value of many antimicrobials. It used to be thought that antibacterial resistance was mainly a hospital problem but now it is also a major problem in the community. Organisms in which resistance is a particular problem in the community include members of the Enterobacteriaceae, including Salmonella spp. and Shigella spp., Mycobacterium tuberculosis, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria gonorrhoeae. Multi-resistant Gram-negative rods, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci are major causes of concern in the hospital setting. Prevalence of antibacterial resistance depends both on acquisition and spread. Decreasing inappropriate usage of antimicrobials should lessen the rate of acquisition, and spread can be minimised by sensible infection control measures.
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PMID:Mechanisms of antimicrobial resistance: their clinical relevance in the new millennium. 1189 25

Bacteriophage phiKZ is a giant virus that efficiently infects Pseudomonas aeruginosa strains pathogenic to human and, therefore, it is attractive for phage therapy. We present here the complete phiKZ genome sequence and a preliminary analysis of its genome structure. The 280,334 bp genome is a linear, circularly permutated and terminally redundant, A+T-rich double-stranded DNA molecule. The phiKZ DNA has no detectable sequence homology to other viruses and microorganisms, and it does not contain NotI, PstI, SacI, SmaI, XhoI, and XmaIII endonuclease restriction sites. The genome has 306 open reading frames (ORFs) varying in size from 50 to 2237 amino acid residues. According to the orientation of transcription, ORFs are apparently organized into clusters and most have a clockwise direction. The phiKZ genome also encodes six tRNAs specific for Met (AUG), Asn (AAC), Asp (GAC), Leu (TTA), Thr (ACA), and Pro (CCA). A putative promoter sequence containing a TATATTAC block was identified. Most potential stem-loop transcription terminators contain the tetranucleotide UUCG loops. Some genes may be assigned as phage-encoded RNA polymerase subunits. Only 59 phiKZ gene products exhibit similarity to proteins of known function from a diversity of organisms. Most of these conserved gene products, such as dihydrofolate reductase, ribonucleoside diphosphate reductase, thymidylate synthase, thymidylate kinase, and deoxycytidine triphosphate deaminase are involved in nucleotide metabolism. However, no virus-encoded DNA polymerase, DNA replication-associated proteins, or single-stranded DNA-binding protein were found based on amino acid homology, and they may therefore be strongly divergent from known homologous proteins. Fifteen phiKZ gene products show homology to proteins of pathogenic organisms, including Mycobacterium tuberculosis, Haemophilus influenzae, Listeria sp., Rickettsia prowazakeri, and Vibrio cholerae that must be considered before using this phage as a therapeutic agent. The phiKZ coat contains at least 40 polypeptides, and several proteins are cleaved during virus assembly in a way similar to phage T4. Eleven phiKZ-encoded polypeptides are related to proteins of other bacteriphages that infect a variety of hosts. Among these are four gene products that contain a putative intron-encoded endonuclease harboring the H-N-H motif common to many double-stranded DNA phages. These observations provide evidence that phages infecting diverse hosts have had access to a common genetic pool. However, limited homology on the DNA and protein levels indicates that bacteriophage phiKZ represents an evolutionary distinctive branch of the Myoviridae family.
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PMID:The genome of bacteriophage phiKZ of Pseudomonas aeruginosa. 1191 76

The polymerase chain reaction (PCR) offers a sensitive and specific way of detecting microbial DNA in clinical samples. The aims of the present study were to develop an assay, based on a single-tube, nested PCR, for identifying Brucella in samples of human blood and then to explore the use of this test in diagnosis. The primers chosen were derived from IS711, the insertion sequence gene found in all species of Brucella. The assay amplified a 52-bp final product which was detected colorimetrically. The PCR was sensitive and specific, giving positive reactions with 14 strains of Brucella from five species. The lower limit of detection in vitro was 30 organisms. There were no false-positive reactions either with a range of bacteria known to evoke serological cross-reactions with Brucella (Vibrio cholerae, Yersinia enterocolitica, Serratia marcescens, Haemophilus influenzae, Pseudomonas aeruginosa and Escherichia coli K12) or with organisms producing similar clinical syndromes (Mycobacterium tuberculosis and Salmonella typhi). The results of a preliminary field trial of the assay in Kuwait indicate that the assay may be a valuable technique in the diagnosis of human brucellosis, meriting further study with larger numbers of cases. All 28 subjects with brucellosis (diagnosed on the basis of typical clinical features and confirmed by positive serology and, in three cases, by positive blood cultures) were PCR-positive whereas 28 healthy controls and 28 patients with febrile illness attributable to infections other than brucellosis were PCR-negative.
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PMID:Single-tube, nested PCR for the diagnosis of human brucellosis in Kuwait. 1217 21

The parotid gland is the salivary gland most commonly affected by inflammation. The most common pathogens associated with acute bacterial parotitis are Staphylococcus aureus and anaerobic bacteria. The predominant anaerobes include gram-negative bacilli (including pigmented Prevotella and Porphyromonas spp.), Fusobacterium spp., and Peptostreptococcus spp. Streptococcus spp. (including S. pneumoniae) and gram-negative bacilli (including Escherichia coli) have also been reported. Gram-negative organisms are often seen in hospitalized patients. Organisms less frequently found are Arachnia, Haemophilus influenzae, Klebsiella pneumoniae, Salmonella spp., Pseudomonas aeruginosa, Treponema pallidum, cat-scratch bacillus, and Eikenella corrodens. Mycobacterium tuberculosis and atypical mycobacteria are rare causes of parotitis. Therapy includes maintenance of hydration and administration of parenteral antimicrobial therapy. Once an abscess has formed surgical drainage is required. The choice of antimicrobial depends on the etiologic agent. Maintenance of good oral hygiene, adequate hydration, and early and proper therapy of bacterial infection of the oropharynx may reduce the occurrence of suppurative parotitis.
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PMID:Acute bacterial suppurative parotitis: microbiology and management. 1254 18

The palladium-catalyzed cross-coupling reaction of 5-(tributylstannyl)isoindoline and its 1- and 3-methyl derivatives with 6-fluoro or 6-unsubstituted 7-bromo-1-cyclopropyl-8-methoxy (or difluoromethoxy)-4-oxoquinoline-3-carboxylate afforded the corresponding 1-cyclopropyl-7-(5-isoindolinyl)-4-oxoquinoline-3- carboxylic acids: 6-fluoro, 1a-7a and 6-nonfluoro, 1b-7b. The in vitro antibacterial spectra of the newly synthesized quinolones were mostly characterized by excellent Gram-positive activity against Staphylococcus aureus and Streptococcus pneumoniae including quinolone-resistant strains, and also by significant Gram-negative activity comparable to 7-(1-piperazinyl)fluoroquinolones. Comparative examinations of the in vitro antibacterial profiles and the in vivo toxicity in terms of intravenous lethality, micronuclei-inducing potential and convulsive activity provided 6-nonfluorinated 1-cyclopropyl-8-(difluoromethoxy)-7-(1-methylisoindolin-5-yl)-4- oxoquinoline-3-carboxylic acid [(+/-)-5b] as the candidate for evaluation of the stereoisomers. The enantiomers (R)-5b and (S)-5b were synthesized via the Suzuki coupling reaction of (R)- and (S)-1-methyl derivatives of 2-(triphenylmethyl)isoindolin-5-boronic acid with the corresponding 7-bromo-8-(difluoromethoxy)-4- oxoquinoline-3-carboxylate. The (R)-5b stereoisomer proved to be 2- to 4-fold more active than the (S)-5b stereoisomer against the organisms tested, with the exception of an equal potency observed with S. pneumoniae IID553 and Haemophilus influenzae ATCC49247. A noticeable in vitro antibacterial profile of (R)-5b was that it is 16- and 64-fold more active than levofloxacin (CAS 100986-85-4) and ciprofloxacin (CAS 86393-32-0), respectively, against Mycoplasma pneumoniae IID813 (MIC of 0.0313 microgram/ml), and 4-fold more active than ciprofloxacin and levofloxacin against Mycobacterium tuberculosis M-4 (MIC of 0.0313 microgram/ml). Additional studies indicate that (R)-5b (T-3811, CAS 194804-75-6) exhibits excellent antibacterial activity against a wide range of organisms including anaerobes and common respiratory pathogens, while demonstrating a high selectivity against the mammalian homolog topoisomerases. The methane-sulfonate of (R)-5b (T-3811ME, CAS 223652-90-2) is now undergoing clinical testings.
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PMID:Synthesis, antibacterial activity, and toxicity of 7-(isoindolin-5-yl)-4-oxoquinoline-3-carboxylic acids. Discovery of the novel des-F(6)-quinolone antibacterial agent garenoxacin (T-3811 or BMS-284756). 1257 31

This review describes the microbiology, diagnosis and management of suppurative thyroiditis (ST). Staphylococcus aureus, Streptococcus pyogenes, Streptococcus epidermidis, and Streptococcus pneumoniae, are the predominant aerobic isolates. The most common anaerobic bacteria are Gram-negative bacilli and Peptostreptococcus spp. Agents that are rarely recovered include Klebsiella spp., Haemophilus influenzae, Streptococcus viridans, Salmonella spp., Enterobacteriaceae, Mycobacterium tuberculosis, atypical mycobacteria, Aspergillus spp., Coccidioides immitis, Candida spp., Treponema pallidum, and Echinococcus spp. Viruses have been associated with subacute thyroiditis, and include measles, mumps, influenza, enterovirus Epstein-barr, adenovirus, echovirus, and St Louis encephalitis. Therapy includes administration of antibiotics effective against the causative pathogen(s). Proper selection of therapy can be guided by culture of the lesion. Surgical drainage may be necessary in case of suppuration.
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PMID:Microbiology and management of acute suppurative thyroiditis in children. 1269 45

Since community-acquired pneumonia (CAP) is a common disease with a high morbidity rate, it is important to obtain information concerning its etiology and susceptibility to antibiotics across different geographic areas. This study presents data obtained in 5 Latin American counties in the course of an international clinical trial that evaluated the efficacy and safety of treatment with either moxifloxacin or amoxicillin administered for 10 days to patients suspected of having CAP caused by a pneumococcal infection. Details are given of the pathogens identified, the patterns of sensitivity to antibiotics observed, and the clinical and microbiological results obtained.A total of 84 patients were studied, of whom 70 (83.3%) were evaluated at the end of the trial to determine the efficacy and safety of the treatment received. Gram-positive bacteria were found in samples from 29 patients (80.5%). The pathogen was Streptococcus pneumoniae in 28 of those cases (77.7%). Gram-negative bacteria were found in 7 patients (19.4%), the most common being Haemophilus influenzae in 3 patients (8.3%). The presence of atypical microorganisms was detected in 18 of the 70 patients (25%), mainly Mycobacterium pneumoniae (n=11), and in 6 cases (8.5%) the infection was mixed. Ten strains of S. pneumoniae (35.7%) were shown to be susceptible to penicillin, 2 (7.1%) were highly resistant, and 16 (57.1%) showed moderate resistance. The clinical success rate at the final visit after treatment was 94.1% for moxifloxacin and 91.7% for amoxicillin. The results of this trial demonstrate a high prevalence of S. pneumoniae with reduced susceptibility to penicillin in patients with CAP in Latin America. It also revealed a high incidence of atypical pathogens and mixed infection in 8.6% of patients. This information should be taken into account when establishing protocols for empirical treatment of CAP in Latin America.
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PMID:[A comparison of moxifloxacin and amoxicillin in the treatment of community-acquired pneumonia in Latin America: results of a multicenter clinical trial]. 1297 69


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