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)

We questioned whether the penicillin binding protein (PBP) profiles of representative strains from the 19 species varied within the genus Haemophilus and whether these profiles would be of taxonomic value. Seventeen of the 19 representative strains studied had distinct PBP profiles; only those of H. avium and H. paragallinarum were identical. The data support the inclusion of H. aegyptius in the genus as a species related to but separate from H. influenzae and could not exclude H. somnus, H. agni, and H. equigenitalis from the genus. Comparative PBP analysis within the genus Haemophilus may therefore be useful taxonomically.
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PMID:The penicillin binding proteins of the genus Haemophilus. 326 61

The susceptibility of 554 recent clinical isolates and known resistant bacterial strains to the new monocyclic beta-lactam Ro 17-2301 were studied and compared to that to other beta-lactams (including aztreonam and temocillin) and gentamicin. Ro 17-2301 had a high degree of activity against the Enterobacteriaceae (MIC90 less than or equal to 0.25 mg/l) being similar or slightly more active than aztreonam and ceftazidime. Strains of Acinetobacter spp. (MIC90 16 mg/l). Haemophilus influenzae strains (including beta-lactamase producers) were more susceptible (MIC90 0.5 mg/l) than those of Neisseria gonorrhoeae (MIC90 4 mg/l); against these latter two groups of isolates aztreonam was more active (MIC90 0.12 mg/l). Both aztreonam and Ro 17-2301 had little activity against Gram-positive cocci with the exception of Streptococcus pneumoniae for which the MIC90 of RO 17-2301 was 16 mg/l. Ro 17-2301 had modest activity against Bacteroides fragilis. The MBC of Ro 17-2301 was very similar to the MIC and the addition of human serum had little effect on the amount of the compound. The mean serum protein binding was 26.3%. A study of the penicillin binding protein affinity of Ro 17-2301 in a strain of Escherichia coli showed PBP 3 to be the primary target. The morphological response to exposure to Ro 17-2301 was filamentation followed by lysis after prolonged exposure.
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PMID:The in-vitro activity of Ro 17-2301, a new monobactam, compared with other antimicrobial agents. 398 Mar 9

ABT-773 is a novel ketolide effective against antibacterial-resistant respiratory tract pathogens. The pharmacokinetic profile of ABT-773 was studied in rats and consisted of a mean peak concentration in plasma of 1.07 microg/ml and an area under the concentration-time curve (AUC) of 12.03 microg. h/ml when the compound was delivered at a dose of 25 mg/kg of body weight. It concentrated in rat lung tissue, with a lung tissue-to-plasma ratio of 29 based on the AUC. In acute systemic infections in mice, ABT-773 showed efficacy against macrolide-susceptible strains of Staphylococcus aureus, Streptococcus pneumoniae, S. pyogenes, and Listeria monocytogenes. Additionally, ABT-773 improved the survival of mice infected with resistant S. pneumoniae containing either the ermB gene, the mefE gene, or altered penicillin binding protein genes. In a rat lung model of infection, ABT-773 demonstrated 50% effective doses lower than those of comparator macrolides when evaluated against the following strains of S. pneumoniae: a macrolide-lincosamide-streptogramin B-susceptible strain, an ermB strain, and an mefE strain. ABT-773 was also effective against Haemophilus influenzae lung infections in rats. Thus, ABT-773 may prove to be a useful new antibacterial agent for the treatment of respiratory tract infections.
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PMID:Efficacies of ABT-773, a new ketolide, against experimental bacterial infections. 1150 33

Cefditoren, a broad-spectrum orally administered cephalosporin ester, has documented in vitro efficacy against many Gram-positive and -negative pathogens and stability against clinically important beta-lactamases. We have reviewed the microbiology and the pharmacokinetic/pharmacodynamic literature regarding the spectrum and potency of this newer agent against the major etiologic agents of community-acquired respiratory infection, (Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis), as well as the Enterobacteriaceae and non-enteric Gram-negative bacilli, staphylococci, and other aerobic and anaerobic Gram-positive cocci. The level of cefditoren activity against S. pneumoniae (MIC(90,) 0.5 microg/mL) was superior to all marketed oral cephalosporins and at least equal to amoxicillin +/- clavulanate. H. influenzae (MIC(90,) 0.016-0.03 microg/mL) and M. catarrhalis (MIC(90,) 0.06-0.5 microg/mL) were also very susceptible to cefditoren. In contrast to cefixime and ceftibuten, cefditoren was active against oxacillin-susceptible staphylococci (MIC(90,) < or = 1 microg/mL) at a level comparable to cefuroxime axetil, cefaclor or cefprozil. Enterococci, Pseudomonas aeruginosa and most anaerobes (Gram-negative) were not cefditoren-susceptible, but most Enterobacteriaceae, beta-haemolytic and viridans group streptococci were highly susceptible. Furthermore, an overview of key in vitro susceptibility testing methods and issues including disk diffusion testing and Etest (AB BIODISK, Solna, Sweden) method accuracy, interpretive criteria, and pharmacodynamic considerations for the selection of a breakpoint concentration are provided. The rapid bactericidal nature of the antibacterial activity of cefditoren, its post antibiotic effect, penicillin binding protein targets, and extent of beta-lactamase stability are all favorable qualities. In conclusion, this orally administered (BID) beta-lactam possesses promise for use against commonly isolated problematic respiratory tract pathogens such as penicillin-non-susceptible pneumococci and beta-lactamase-positive M. catarrhalis or H. influenzae. Success in the clinical trials will further define the role of cefditoren in this era of emerging resistant bacterial pathogens.
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PMID:Cefditoren in vitro activity and spectrum: a review of international studies using reference methods. 1168 8

Between September 1999 and August 2001, we studied serotypes to capsular antigen, beta-lactamase production, mutation of penicillin binding protein (PBP) genes by PCR method, and antimicrobial susceptibilities of 13 strains of Haemophilus influenzae isolated from spinal fluid or blood in children. Diseases of patients were meningitis in 11, pneumonia in 1, and laryngitis in 1. The age range of the patients was from 26 days to 5 years. The serotypes of all strains were b. Four of the 13 strains were beta-lactamase-positive. The mutation of genes of pbp3 was revealed from 4 isolates and 2 of the strains were beta-lactamase-positive. MICs of ampicillin to beta-lactamase-negative strains ranged from 0.125 to 1 microgram/ml and those to beta-lactamase-positive were more than 32 micrograms/ml. MICs of 2 strains of beta-lactamase-negative and mutation-positive were 0.5 and 1 microgram/ml. The excellent active antimicrobials in our study was cefotaxime (MIC90 0.06 microgram/ml), meropenem (MIC90 0.125 microgram/ml), ceftazidime (MIC90 0.25 microgram/ml), and cefepime (MIC90 0.25 microgram/ml).
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PMID:[Mutation of penicillin-binding protein genes and antimicrobial susceptibility of Haemophilus influenzae isolated from spinal fluid or blood in children]. 1203 27

The sequences of the ftsI gene, encoding the transpeptidase domain of penicillin binding protein (PBP) 3A and/or PBP 3B, which are involved in septal peptidoglycan synthesis, were determined for 108 clinical strains of Haemophilus influenzae with reduced susceptibility to beta-lactam antibiotics with or without beta-lactamase production and were compared to those of the ampicillin-susceptible Rd strain and ampicillin-susceptible clinical isolates. The sequences have 18 different mutation patterns and were classified into two groups on the basis of amino acid substitutions deduced from the nucleotide sequences located between bp 960 and 1618 of the ftsI gene. In group I strains (n = 7), His-517 was substituted for Arg-517. In group II strains (n = 101), Lys-526 was substituted for Asn-526. In subgroup IIa (n = 5; H. influenzae ATCC 49247), the only observed substitution was Lys-526 for Asn-526; in subgroup IIb (n = 56), Val-502 was substituted for Ala-502 (n = 13), along with several other substitutions: Asn-350 for Asp-350 (n = 15), Asn-350 for Asp-350 and Glu-490 for Gly-490 (n = 14), and Asn-350 for Asp-350 and Ser-437 for Ala-437 (n = 5). In subgroup IIc (n = 25), Thr-502 was substituted for Ala-502. In subgroup IId, Val-449 was substituted for Ile-449 (n = 15). The MICs of beta-lactam antibiotics for the 108 strains were to 8 to 16 times the MICs for susceptible strains. The strains, isolated from both adults and children, were analyzed for genetic relationship by pulsed-field gel electrophoresis and by determination of ftsI sequence phylogeny. Both analyses revealed the lack of clonality and the heterogeneity of the strains, but some clusters suggest the spread and/or persistence of a limited number of strains of the same pulsotype and pattern of amino acid substitutions. Reduced susceptibility to beta-lactam, brought about by mutations of the ftsI gene, is becoming a frequent phenomenon, affecting both strains that produce beta-lactamase and those that do not. The level of resistance remains low but opens the way to greater resistance in the future.
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PMID:Diversity of beta-lactam resistance-conferring amino acid substitutions in penicillin-binding protein 3 of Haemophilus influenzae. 1206 76

The penicillin binding protein (PBP) genes dacA, dacB and ftsI from 14 cefuroxime-resistant (CXM(R)) isolates and three clinical isolates with low CXM MIC for non-beta-lactamase-producing Haemophilus influenzae type b were molecularly characterized. One strain, 5788, was used to transform H. influenzae Rd to CXM(R) for direct comparison of the pbps in the same genetic background. No obvious mutations in the dacA and dacB gene products could be associated with CXM(R). One amino acid substitution in the ftsI gene product in particular, S357N, could give rise to CXM(R). Sequence analysis from the CXM(R) transformants also implicated FtsI; in this case, the substitutions were V511A and R517H. To verify S357N substitution, the protein sequence of H. influenzae FtsI was threaded through the S. pneumoniae PBP 2X structure giving an average root mean square deviation of the alpha-carbon chains of 0.5 A. The S357N substitution alters both the residue size and charge. One explanation for the contribution of S357N to CXM(R) is that the asparagine side-chain produces unfavourable steric hindrance with the side chain of Val-362 changing the torsion angles of the asparagine residue, which in turn may influence the position of the loop V362-P366 adjacent to the active site. Whilst other groups have examined the contribution of H. influenzae PBPs in ampicillin resistance, this is the first report analysing their role in CXM(R).
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PMID:Cefuroxime resistance in non-beta-lactamase Haemophilus influenzae is linked to mutations in ftsI. 1261 52

The roles of beta-lactamase and alterations in penicillin-binding protein in the development of amoxicillin and amoxicillin/clavulanate resistance in two beta-lactamase-positive, amoxicillin/clavulanate-resistant (BLPACR) strains of Haemophilus influenzae were investigated. Seven beta-lactamase-negative, ampicillin-resistant (BLNAR) strains were also studied for comparison of their resistance mechanisms. All strains had been recovered from patients in Japan. The TEM type beta-lactamase of the two BLPACR strains had 100% homology with the amino acid sequences of published TEM-1 beta-lactamase, showing that amoxicillin/clavulanate resistance was not associated with mutations in this beta-lactamase. However, these strains, as well as the seven BLNAR strains, had multiple mutations in ftsI, which encodes penicillin binding protein 3 (PBP3). The transformation of H. influenzae Rd strain with amplified ftsI genes from two BLPACR and two BLNAR strains enabled the selection of amoxicillin/clavulanate-resistant transformants with the same mutations as their parent strains. We concluded that amoxicillin/clavulanate resistance in the two BLPACR strains was due to changes in PBP3. The possibility of the presence of an extended spectrum beta-lactamase was excluded in the BLPACR strains studied.
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PMID:Contribution of beta-lactamase and PBP amino acid substitutions to amoxicillin/clavulanate resistance in beta-lactamase-positive, amoxicillin/clavulanate-resistant Haemophilus influenzae. 1458 54

Between April 2001 and March 2003, we studied minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 7 strains of Streptococcus pneumoniae and 8 strains of Haemophilus influenzae isolated from children with meningitis. The age range of the patients was from 4 months to 5 years. Susceptibilities of ampicillin (ABPC), cefotaxime (CTX), panipenem (PAPM), and vancomycin (VCM) in S. pneumoniae and those of ABPC, CTX, ceftriaxone (CTRX), and meropenem (MEPM) in H. influenzae were measured. MICs of ABPC, CTX, PAPM, and VCM to S. pneumoniae were < or = 0.06-2, < or = 0.06-0.5, < or = 0.06, and 0.25-0.5 microgram/ml and MICs of ABPC, CTX, CTRX, and MEPM to H. influenzae were 0.12-64, < or = 0.06-0.5, < or = 0.06-0.12, and < or = 0.06-0.25 microgram/ml, respectively. In 5 of all strains, difference between MIC and MBC to ABPC was observed. Four strains out of them had mutations of penicillin binding protein genes measured by PCR methods.
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PMID:[Antimicrobial susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae isolated from children with meningitis]. 1510 92

Haemophilus influenzae is a major community-acquired pathogen causing significant morbidity and mortality worldwide. Meningitis and bacteremia due to type b strains occur in areas where the protein-conjugated type b vaccine is not in use, whereas nontypeable strains are major causes of otitis media, sinusitis, acute exacerbations of chronic bronchitis, and pneumonia. Antibiotic resistance in this organism is more diverse and widespread than is commonly appreciated. Intrinsic efflux resistance mechanisms limit the activity of the macrolides, azalides, and ketolides. beta-Lactamase production is highly prevalent worldwide and is associated with resistance to ampicillin and amoxicillin. Strains with alterations in penicillin binding proteins, particularly PBP3 (beta-lactamase negative ampicillin resistant and beta-lactamase positive amoxicillin-clavulanate resistant), are increasing in prevalence, particularly in Japan, with increasing resistance to ampicillin, amoxicillin, amoxicillin-clavulanate, and many cephalosporins, limiting the efficacy of expanded-spectrum cephalosporins against meningitis and of many oral cephalosporins against other diseases. Most strains remain susceptible to the carbapenems, which are not affected by penicillin binding protein changes, and the quinolones. The activity of many oral agents is limited by pharmacokinetics achieved with administration by this route, and the susceptibility of isolates based on pharmacokinetic and pharmacodynamic parameters is reviewed.
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PMID:Antimicrobial resistance in Haemophilus influenzae. 1742 89


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