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)

Haemophilus influenzae was isolated from patients with respiratory tract infections in five centers in Saudi Arabia. All of the 129 isolates tested by MIC agar dilution were fully susceptible to ceftazidime and ciprofloxacin but 13.2% were resistant to ampicillin, 7% to tetracycline, 5.4% to chloramphenicol, 3.9% to roxithromycin, and 1.6% to amoxicillin/clavulanic acid. Seventeen (13.2%) of all isolates produced TEM-1 type beta-lactamase, the majority (82%) characterized as biotype I or II with 4 (23.5%) encapsulated and belonging to serotype b. There was a clear distinction between the prevalence of beta-lactamase production in hospital patients (26.3% of 19 isolates) compared with community based patients (10.9% of 110 isolates). In addition, we report an increase in the prevalence of beta-lactamase negative, ampicillin intermediate strains (BLNAI) compared to previous studies in this defined geographical region. Changes in the frequency and nature of antimicrobial resistance in common respiratory pathogens confirms the need to maintain surveillance.
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PMID:Antibiotic resistance and prevalence of beta-lactamase in Haemophilus influenzae isolates-a surveillance study of patients with respiratory infection in Saudi Arabia. 1072 63

beta-Lactamase production in Canadian isolates of Haemophilus influenzae has remained relatively constant (25-35%) over the last decade despite increasing cefaclor resistance (MIC >/= 32 mg/L). TEM (294/324, 90.7%) and ROB-1 (30/324, 9.3%) prevalence rates among 324 isolates of H. influenzae obtained from across Canada in 1997-1998 were similar (P > 0.05) to previously published reports. However, 66. 7% (26/39) of cefaclor-resistant isolates were ROB-1-positive (P < 0. 001) and the remaining four ROB-1-positive isolates were cefaclor-intermediate (MIC 16 mg/L). Susceptibilities to loracarbef (P < 0.001) and cefprozil were also reduced in the presence of ROB-1 while the activities of cefuroxime, cefotaxime, cefixime and imipenem were similar in both TEM- and ROB-1-positive solates.
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PMID:Presence of ROB-1 beta-lactamase correlates with cefaclor resistance among recent isolates of Haemophilus influenzae. 1083 42

Acidaminococcus fermentans belongs to the group of strictly anaerobic gram-negative cocci. All previously described Acidaminococcus strains are susceptible to beta-lactam antibiotics. An A. fermentans strain (RYC-MR95) resistant to penicillin and expanded-spectrum cephalosporin (amoxicillin and cefotaxime MICs, 64 microgram/ml) was isolated from a human perianal abscess. A fragment encoding a beta-lactamase from genomic DNA was cloned in Escherichia coli K-12 strain HB101, and the recombinant strain expressed resistance to amoxicillin (MIC, 1,024 microgram/ml) and cefotaxime (MIC, 4 microgram/ml). Clavulanic acid decreased the MICs to 8 and 0.03 microgram/ml, respectively. Analysis of the nucleotide sequence revealed a new class A beta-lactamase, ACI-1. In accordance with its biochemical properties, we propose to assign ACI-1 to functional group 2be. The ACI-1 enzyme (estimated pI 4.3) had <50% amino acid identity with any other class A beta-lactamases, the closest being ROB-1 from Haemophilus influenzae (44%). ACI-1 was closer to class A beta-lactamases from some gram-positive organisms (41 to 44% amino acid identity with Bacillus beta-lactamases) than to most class A enzymes from gram-negative organisms (TEM-1, 24.6%). The aci1 gene had a G+C content of 42.1%, in contrast with 56% G+C content for genomic DNA from A. fermentans, thus suggesting that aci1 may have been obtained by horizontal gene transfer.
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PMID:ACI-1 from Acidaminococcus fermentans: characterization of the first beta-lactamase in Anaerobic cocci. 1103 38

Respiratory infections are the most frequent reason for primary health care consultation. The main causes of respiratory tract infections in children are viruses and the most common types are upper respiratory tract infections: common cold, pharyngitis, otitis media and sinusitis. Pneumonia is much more serious. As well as viruses, bacteria are often involved in respiratory tract infections. Three bacterial species are most commonly isolated: Streptococcus pneumoniae, non-encapsulated Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. The most common bacterial cause of pharyngitis is Streptococcus pyogenes. Bacteria isolated from community-acquired infection usually are sensitive to the majority of suitable drugs, but during the past two decades, significant antibiotic resistance has emerged. Resistance to penicillins has spread among H. influenzae and S. pneumoniae. The mechanism of penicillin resistance in H. influenzae is mainly by production of beta-lactamases TEM-1 and ROB-1, whereas in S. pneumoniae resistance is an effect of the changes in penicillin binding proteins. Among respiratory pathogens, resistance to tetracyclines, macrolides, trimethoprim-sulphamethoxazole and fluoroquinolones has also appeared. Several mechanisms depending on changes in target, active efflux and modifying enzymes are involved.
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PMID:Epidemiological aspects of antibiotic resistance in respiratory pathogens. 1173 35

OBJECTIVE: The in vitro activity of apalcillin plus Ro 48-1220, a novel penam sulfone beta-lactamase inhibitor, was compared with apalcillin alone, piperacillin/tazobactam, ticarcillin/clavulanic acid, amoxicillin/clavulanic acid, imipenem, ceftazidime and cefepime. METHODS: Agar dilution and broth microdilution testing of 854 bacterial strains, subcultured from frozen stocks incubated for 24 h in 5% carbon dioxide, was carried out to determine the minimum bactericidal (MBC) and minimum inhibitory concentrations (MIC) of each of the study drugs in accordance with the NCCLS M26-T method. RESULTS: Apalcillin/Ro 48-1220 was active against all gram-negative aerobic and anaerobic isolates except Klebsiella oxytoca (MIC90 32 microg/mL). Among the Enterobacteriaceae, synergy for apalcillin/Ro 48-1220 (4 microg/mL fixed concentration) vs apalcillin alone was demonstrated for nearly all species when comparing MIC90 results. Apalcillin/Ro 48-1220 was highly potent against beta-lactamase-producing Moraxella catarrhalis, Haemophilus influenzae and Neisseria gonorrhoeae (MICs less-than-or-equal 1 microg/mL). However, much of this activity was due to the direct antimicrobial action of Ro 48-1220 alone (MICs less-than-or-equal 4 microg/mL). All Pseudomonas aeruginosa, Stenotrophomonas (Xanthomonas) maltophilia and Acinetobacter species were inhibited by apalcillin/Ro 48-1220 (MIC90 0.25 to 4 microg/mL). For the aerobic gram-positive organisms, none of the drugs tested were consistently effective against oxacillin-resistant staphylococci, Corynebacterium jeikeium and Enterococcus species other than E. faecalis. Apalcillin/Ro 48-1220 was as effective as piperacillin/tazobactam against Escherichia coli producing extended-spectrum TEM enzymes, but less active against isolates producing SHV-type beta-lactamases. When tested against 204 ceftazidime-, gentamicin- or fluoroquinolone-resistant organisms, 78%, 91% and 66% of strains, respectively, were susceptible to apalcillin/Ro 48-1220 (less-than-or-equal 16 microg/mL). CONCLUSIONS: Apalcillin/Ro 48-1220 is bactericidal with a modest inoculum effect; its wide spectrum of activity favors continued studies of spectrum, pharmacokinetics and in vivo efficacy.
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PMID:Comparative in vitro activity of apalcillin alone and combined with Ro 48-1220, a novel penam beta-lactamase inhibitor. 1186 35

OBJECTIVE: To ascertain the incidence of antibiotic resistance in Haemophilus influenzae in central Scotland and the beta-lactamases produced by these isolates. METHODS: A total of 213 H. influenzae isolates from four medical centers in Scotland [Aberdeen (n=58), Edinburgh (n=55), Glasgow (n=64) and Dundee (n=36)] were tested for susceptibility to a range of antimicrobials including beta-lactams, beta-lactam/beta-lactamase-inhibitor combinations, and a representative 4-quinolone, antifolate and macrolide. Susceptibility testing of the beta-lactam/beta-lactamase-inhibitor combination amoxicillin plus clavulanic acid was conducted at both 2:1 and 4:1 ratios and with clavulanic acid fixed at a concentration of 2 mg/L. Each strain was further investigated for the presence of beta-lactamase activity. RESULTS: Although the incidence of resistance to amoxicillin was 15%, in the presence of clavulanic acid, this resistance was reduced to 4.2%, 5.6% and 4.2% with the 2:1 ratio, 4:1 ratio and 2 mg/L fixed concentration, respectively. Sixteen percent of the isolates demonstrated immediate beta-lactamase production. Isoelectric focusing showed that 77.4%, 16.1% and 6.5% of the beta-lactamase-positive strains were found to contain TEM-1, VAT-1 and both TEM-1 and VAT-1 beta-lactamases, respectively. A further 29% of the strains were recognized as being beta-lactamase-positive after prolonged incubation with nitrocephin. CONCLUSIONS: This study suggests that current testing for beta-lactamases may underestimate the prevalence of beta-lactamase production in H. influenzae.
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PMID:Antibiotic susceptibilities of Haemophilus influenzae in central Scotland. 1186 52

We established breakpoints for differentiating ampicillin (ABPC)-susceptible strains from resistant strains among Haemophilus influenzae isolates according to susceptibility to various beta-lactam antibiotics, using a disc method. Susceptibility testing of isolates for 13 beta-lactam agents was followed by analysis of the resistance genes, using a polymerase chain reaction (PCR) to identify the TEM-1 beta-lactamase gene ( bla) and the ftsI gene encoding penicillin-binding protein (PBP) 3, which affects beta-lactam minimum inhibitory concentrations (MICs). A total of 228 H. influenzae isolates were classified into 114 beta-lactamase-negative, ABPC-susceptible (BLNAS) strains; 29 beta-lactamase-negative, ABPC-resistant (BLNAR) strains; 53 low-BLNAR strains with a low degree of ABPC resistance; 27 TEM-1-producing strains (BLPAR); and 5 strains with ftsI gene mutations in addition to TEM-1 production (BLPACR) according to the PCR results. To identify resistant strains by disc-method susceptibility testing, the zone of inhibition was measured for ABPC (10 microg/disc), cefaclor (30 microg/disc), cefpodoxime (10 microg/disc), and cefdinir (5 microg/disc) discs. Strains were identified as BLNAS without resistant genes when the diameter was > or =27 mm for the ABPC disc and > or =21 mm for the cefaclor disc. Other strains were identified as BLNAR when the diameter was < or =22 mm for the cefpodoxime disc and < or =17 mm for the cefdinir disc. Remaining strains were identified as low-BLNAR. These criteria differentiated resistance types with high accuracy. A discrepancy was noted between genetic results and disc-testing breakpoints for differentiating resistant from susceptible H. influenzae. A disc-testing breakpoint for cefditoren (5 microg/disc) was proposed, with the susceptibility statistically defined as a diameter of > or =24 mm, which corresponds to the breakpoint (1 microg/ml) of the microdilution method recommended by the Japanese Society of Chemotherapy.
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PMID:Differentiation of beta-lactamase-negative ampicillin-resistant Haemophilus influenzae from other H. influenzae strains by a disc method. 1195 20

Enzyme-catalyzed therapeutic activation (ECTA) is a novel prodrug strategy to overcome drug resistance resulting from enzyme overexpression. beta-Lactamase overexpression is a common mechanism of bacterial resistance to beta-lactam antibiotics. We present here the results for one of the beta-lactamase ECTA compounds, NB2001, which consists of the antibacterial agent triclosan in a prodrug form with a cephalosporin scaffold. Unlike conventional beta-lactam antibiotics, where hydrolysis of the beta-lactam ring inactivates the antibiotic, hydrolysis of NB2001 by beta-lactamase releases triclosan. Evidence supporting the proposed mechanism is as follows. (i) NB2001 is a substrate for TEM-1 beta-lactamase, forming triclosan with a second-order rate constant (k(cat)/K(m)) of greater than 77,000 M-1 s-1. (ii) Triclosan is detected in NB2001-treated, beta-lactamase-producing Escherichia coli but not in E. coli that does not express beta-lactamase. (iii) NB2001 activity against beta-lactamase-producing E. coli is decreased in the presence of the beta-lactamase inhibitor clavulanic acid. NB2001 was similar to or more potent than reference antibiotics against clinical isolates of Staphylococcus aureus (including MRSA), Staphylococcus epidermidis, Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis, Moraxella catarrhalis and Haemophilus influenzae. NB2001 is also active against Klebsiella pneumoniae, Enterobacter aerogenes, and Enterobacter cloacae. The results indicate that NB2001 is a potent, broad-spectrum antibacterial agent and demonstrate the potential of ECTA in overcoming beta-lactamase-mediated resistance.
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PMID:NB2001, a novel antibacterial agent with broad-spectrum activity and enhanced potency against beta-lactamase-producing strains. 1238 97

The extended-spectrum beta-lactamases (ESBLs) TEM-3, TEM-4 and TEM-5 were cloned into Haemophilus influenzae. These recombinant strains exhibited cefotaxime MICs of 0.5, 0.25 and 0.12 mg/L for TEM-3, -4 and -5, respectively, and the MIC of cefaclor was 4.0 mg/L. These MICs are higher than those of beta-lactamase-negative strains, or those producing simple wild-type TEM-1 beta-lactamase, but not high enough to be categorized as resistant according to the breakpoints of the NCCLS. The clones were also categorized as susceptible using NCCLS disc diffusion methodology and interpretive criteria. This study shows that current NCCLS susceptibility testing methods may have difficulty in detecting ESBLs if they were to occur in H. influenzae.
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PMID:Effect of extended-spectrum beta-lactamases on the susceptibility of Haemophilus influenzae to cephalosporins. 1249 85

The nasopharyngeal Haemophilus influenzae flora of healthy children under the age of 3 years attending day care centers in three distinct French geographic areas was analyzed by sampling during two periods, spring 1999 (May and June) and fall 1999 (November and December). The average carrier rate among 1,683 children was 40.9%. The prevalence of capsulated H. influenzae carriers was 0.4% for type f and 0.6% for type e. No type b strains were found among these children, of whom 98.5% had received one or more doses of anti-Haemophilus b vaccine. Among the strains, 44.5% were TEM-type beta-lactamase producers and nine (1.3%) were beta-lactamase-negative ampicillin-resistant strains. Pulsed-field gel electrophoresis restriction patterns showed a large diversity with 366 SmaI patterns from 663 strains. Among the strains isolated during a given period, 33% were isolated simultaneously in more than one area. In each area, depending on the sampling period, 68 to 72% of the strains had new pulsotypes and persistence of 28 to 32% of the strains was noted. For the 297 beta-lactamase-producing strains, 194 patterns were found. The genomic diversity of these strains was comparable to that of the whole set of strains and does not suggest a clonal diffusion. Among the beta-lactamase-producing strains isolated in November and December, depending on the area, 66 to 73% had new pulsotypes with persistence of only 27 to 33% of the strains. In any given geographic area, colonization by H. influenzae appears to be a dynamic process involving a high degree of genomic heterogeneity among the noncapsulated colonizing strains.
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PMID:Haemophilus influenzae carriage in children attending French day care centers: a molecular epidemiological study. 1268 58


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