Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clavulanic acid, Z-(2R,5R)-3-(beta-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo-[3,2,0] heptane-2-carboxylic acid, has been shown to be an effective inhibitor of the beta-lactamases of the Richmond types II, III, IV, and V. Inhibition is a time-dependent reaction and is irreversible. Clavulanic acid had poor antibacterial activity against Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa, with minimal inhibitory levels greater than 25 mug/ml. It did inhibit the majority of Neisseria gonorrhoeae at 0.1 mug/ml and Haemophilus influenzae at 6.3 mug/ml. Clavulanic acid acted synergistically with penicillins and cephalosporins to inhibit beta-lactamase-producing S. aureus and Enterobacteriaceae. Clavulanic acid combined with ampicillin inhibited beta-lactamase-producing N. gonorrhoeae, H. influenzae, Escherichia coli, Salmonella typhi, and Shigella sonnei.
 ...
PMID:Clavulanic acid, a novel inhibitor of beta-lactamases. 31 Feb 79

A total of 818 clinical bacterial isolates were tested for the production of beta-lactamase by rapid chromogenic cephalosporin method and for the susceptibility to ticarcillin alone and in combination with clavulanic acid (2 micrograms/mL) by agar dilution method. These included 83 strains of methicillin-sensitive Staphylococcus aureus (MSSA), 31 of methicillin-resistant S. aureus (MRSA), 49 of Neisseria gonorrhoeae, 58 of Haemophilus influenzae, 112 of Escherichia coli, 118 of Klebsiella pneumoniae, 58 of Proteus mirabilis, 30 of Proteus vulgaris, 60 of Serratia marcescens, 113 of Enterobacter cloacae, 60 of Pseudomonas aeruginosa and 46 of Bacteroides fragilis. The results revealed that 46.6% of P. mirabilis, 53.4% of H. influenzae, 57.1% of N. gonorrhoeae, 80% of P. vulgaris, 83.9% of MRSA, 85.6% of MSSA, 87.5% of E. coli, 91.7% of S. marcescens, 95.7% of B. fragilis, 98.2% of E. cloacae, and 100% of K. pneumoniae and P. aeruginosa strains produced beta-lactamase. In general, beta-lactamase nonproducers were more susceptible to ticarcillin than beta-lactamase producers. The ranges of minimum inhibitory concentrations (MICs) of ticarcillin for beta-lactamase nonproducers of MSSA, MRSA, H. influenzae, E. coli, P. vulgaris, S. marcescens, E. cloacae, B. fragilis and beta-lactamase producers of MSSA, H. influenzae strains were all within the in vitro susceptible range. The presence of clavulanic acid resulted in a significant enhancement of the antibacterial activity of ticarcillin against beta-lactamase producers of MRSA, N. gonorrhoeae, E. coli, K. pneumoniae, P. mirabilis, P. vulgaris and B. fragilis strains. Clavulanic acid had no synergistic activity for ticarcillin against S. marcescens, P. aeruginosa and E. cloacae.
 ...
PMID:In vitro antibacterial activities of ticarcillin alone and ticarcillin plus clavulanic acid against beta-lactamase producing and non-producing microorganisms. 134

beta-Lactamases have been known since the early 1940s when they were recognized as a major mechanism of resistance in Staphylococcus aureus. The synthesis of semisynthetic penicillins provided agents that overcame the resistance of staphylococci, but as gram-negative bacteria became increasingly important as the cause of infections, plasmid-mediated beta-lactamases were recognized in the Enterobacteriaceae, Haemophilus, and chromosomally mediated beta-lactamases in Klebsiella, and Bacteroides were found to be the mechanism of resistance of these species to ampicillin and related penicillins. Two approaches to the problem have been developed. One is to make stable compounds. This has been possible in the cephalosporin family. The other method has been to find inhibitors of beta-lactamases. Clavulanate is a beta-lactamase inhibitor that, in combination with amoxicillin, allows the combination to inhibit many of the organisms that are resistant to amoxicillin. Similarly, clavulanate has been combined with ticarcillin to provide a parenteral agent to inhibit beta-lactamase-producing bacteria and retain activity against Pseudomonas. Sulbactam has been combined with ampicillin. The combination of suicide inhibitors with other beta-lactams has provided agents that inhibit many of the bacteria present in mixed cutaneous infections. Clinical studies have established the efficacy of the clavulanate-amoxicillin and clavulanate-ticarcillin combinations in skin and skin-structure infections. These agents offer an alternative to other drugs when treating cutaneous infections.
 ...
PMID:Beta-lactamases, beta-lactamase inhibitors, and skin and skin-structure infections. 218 13

Resistance of many species of bacteria to beta-lactam antibiotics is mediated via inactivation by beta-lactamase. Beta-lactamase inhibitors irreversibly bind to beta-lactamases and thus can prevent the destruction of active beta-lactam antibiotics. In the United States three beta-lactam-antibiotic/beta-lactam-inhibitor combinations are commercially available--the orally absorbed amoxicillin/clavulanic acid (A/C), the parenteral formulations of ampicillin/sulbactam (A/S) and ticarcillin/clavulanate (T/C). In a multicenter study that focused on T/C, the in vitro activity of amoxicillin (AMOX), ampicillin (AMP) and ticarcillin (TIC) against Neisseria gonorrhoeae and Haemophilus influenzae was obliterated when beta-lactamase-positive strains were tested, but all tested strains were susceptible to the antibiotics in combination with their respective beta-lactamase inhibitors. Clavulanic acid improved the activity of TIC against most species of Enterobacteriaceae but not against those Enterobacteriaceae that elaborate type I beta-lactamase or against non-Enterobacteriaceae gram-negative bacilli (except for Pseudomonas maltophilia). Staphylococci are generally beta-lactamase positive and considered resistant to AMP and TIC, but greater than 99% of 1,137 Staphylococcus aureus isolates and 92% of coagulase-negative staphylococcal isolates were susceptible to T/C, with comparable figures obtained for A/C and A/S. The activity of TIC against Bacteroides fragilis was improved up to 64-fold by clavulanic acid, with a definite but less pronounced effect on the non-fragilis Bacteroides species. Ninety-seven percent of strains of other anaerobic genera were susceptible to both TIC and T/C.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Implications of beta-lactamase-inhibitor combinations. 231 14

The in vitro activities of ticarcillin, piperacillin, clavulanic acid, tazobactam, ticarcillin-clavulanate, and piperacillin-tazobactam against 819 bacterial isolates were compared. The two beta-lactamase inhibitors, clavulanic acid and tazobactam, had little useful antibacterial activity but enhanced the activities of the penicillins against beta-lactamase-producing strains of Haemophilus influenzae, Branhamella catarrhalis, and methicillin-susceptible Staphylococcus aureus; all strains were susceptible to both combinations. Both enzyme inhibitors also enhanced the activities of the penicillins against most strains of Escherichia coli, Klebsiella spp., Citrobacter diversus, Proteus spp., Providencia spp., and Bacteroides spp. and against occasional strains of Citrobacter freundii, Enterobacter spp., and Serratia marcescens. Clavulanic acid frequently enhanced the activity of ticarcillin against Xanthomonas maltophilia, and tazobactam frequently enhanced the activity of piperacillin against Morganella morganii. Enhancement was observed primarily with strains relatively resistant to the penicillins. In general, clavulanic acid was more effective than tazobactam in enhancing penicillin activity against Klebsiella spp., C. diversus, X. maltophilia, and Bacteroides spp., whereas tazobactam was more effective against Escherichia coli and Proteeae. There was little or no enhancement of activity against Enterococcus faecalis, Aeromonas hydrophila, Pseudomonas aeruginosa, Pseudomonas cepacia, or Acinetobacter anitratus. Clavulanic acid occasionally antagonized the activity of ticarcillin against ticarcillin-susceptible members of the family Enterobacteriaceae, but those strains were still considered susceptible to the combination. Tazobactam never antagonized the activity of piperacillin. In a direct comparison of the activities of ticarcillin-clavulanate and piperacillin-tazobactam, the two were equally active against H. influenzae, B. catarrhalis, and S. aureus; the latter was more active against E. faecalis. For relatively susceptible strains of members of the family Enterobacteriaceae, neither combination was predictably more active than the other, but relatively resistant strains were generally more susceptible to piperacillin-tazobactam. Piperacillin-tazobactam was more active than ticarcillin-clavulanate against A. hydrophila, P. aeruginosa, and P. cepacia, similar in activity against A. anitratus, and less active against X. maltophilia and Bacteroides spp.
 ...
PMID:Comparative in vitro activities of piperacillin-tazobactam and ticarcillin-clavulanate. 255 4

Clavulanic acid is known to potentiate the activity of amoxycillin and ticarcillin against beta-lactamase-producing Bacteroides species. In order to assess the usefulness of the clavulanate antibiotics in mixed infections with aerobes and anaerobes, artificially associated cultures of clinically significant Bacteroides species and facultative anaerobes (Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Enterococcus faecalis, Staphylococcus spp. and Streptococcus spp.) were tested. The minimal bactericidal concentrations (MBC) of amoxycillin and ticarcillin, singly and in combination with clavulanate, were determined for the individual species in the associated culture and for the associated culture as a whole. In the absence of clavulanate, association experiments showed that the MBCs of susceptible strains increased in the presence of beta-lactamase-producing species, whereas the addition of clavulanate to the test systems led to MBCs which were mostly comparable to values as determined in single strain testing.
 ...
PMID:Efficacy of clavulanate-potentiated antibiotics against Bacteroides species and artificially associated cultures of aerobes and anaerobes. 260 20

beta-Lactamases constitute the major defense mechanism of pathogenic bacteria against beta-lactam antibiotics. When the beta-lactam ring of this antibiotic class is hydrolyzed, antimicrobial activity is destroyed. Although beta-lactamases have been identified with clinical failures for over 40 years, enzymes with various abilities to hydrolyze specific penicillins or cephalosporins are appearing more frequently in clinical isolates. One approach to counteracting this resistance mechanism has been through the development of beta-lactamase inactivators. beta-Lactamase inhibitors include clavulanic acid and sulbactam, molecules with minimal antibiotic activity. However, when combined with safe and efficacious penicillins or cephalosporins, these inhibitors can serve to protect the familiar beta-lactam antibiotics from hydrolysis by penicillinases or broad-spectrum beta-lactamases. Both of these molecules eventually inactivate the target enzymes permanently. Although clavulanic acid exhibits more potent inhibitory activity than sulbactam, especially against the TEM-type broad-spectrum beta-lactamases, the spectrum of inhibitory activities are very similar. Neither of these inhibitors acts as a good inhibitor of the cephalosporinases. Clavulanic acid has been most frequently combined with amoxicillin in the orally active Augmentin and with ticarcillin in the parenteral beta-lactam combination Timentin. Sulbactam has been used primarily to protect ampicillin from enzymatic hydrolysis. Sulbactam has been used either in the orally absorbed prodrug form as sultamicillin or as the injectable combination ampicillin-sulbactam. Synergy has been demonstrated for these combinations for most members of the Enterobacteriaceae, although those organisms that produce cephalosporinases are not well inhibited. Synergy has also been observed for Neisseria gonorrhoeae, Haemophilus influenzae, penicillinase-producing Staphylococcus aureus, and anaerobic organisms. These antibiotic combinations have been used clinically to treat urinary tract infections, bone and soft-tissue infections, gonorrhea, respiratory infections, and otitis media. Gastrointestinal side effects have been reported for Augmentin and sultamicillin; most side effects with these agents have been mild. Although combination therapy with beta-lactamase inactivators has been used successfully, the problem of resistance development to two agents must be considered. Induction of cephalosporinases can occur with clavulanic acid. Permeability mutants could arise, especially with added pressure from a second beta-lactam.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Beta-lactamase inhibitors from laboratory to clinic. 306 Feb 40

The in vitro activity of amoxicillin in the presence of clavulanic acid against clinical isolates of Haemophilus influenzae and Branhamella catarrhalis was assessed in comparison with ampicillin, amoxicillin, cefaclor and erythromycin. The isolates were selected so as to yield equal numbers of beta-lactamase producing and non-beta-lactamase producing strains of the two species. MICs obtained by agar dilution indicated that amoxicillin in the presence of clavulanic acid was the most active of the drugs tested. Clavulanic acid potentiated the activity of amoxicillin against beta-lactamase-producing strains of both Haemophilus influenzae and Branhamella catarrhalis. Further studies on a few strains of each species revealed that the beta-lactamase of Haemophilus influenzae (TEM-1) rapidly inactivated ampicillin and slowly inactivated cefaclor but not cefuroxime. The Branhamella catarrhalis enzyme rapidly inactivated cefaclor, ampicillin and to some extent cefuroxime. Clavulanic acid afforded protection against the beta-lactamase action of both species when beta-lactam antibiotics were added to bacterial cultures.
 ...
PMID:In vitro activity of amoxicillin plus clavulanic acid against Haemophilus influenzae and Branhamella catarrhalis. 349 74

Patients with purulent meningitis received amoxicillin-clavulanic acid (200/20 mg/kg [body weight] per day). Clavulanic acid levels in cerebrospinal fluid were less than or equal to 0.05 micrograms/ml in 5 of 18 samples and ranged from 0.1 to 0.8 micrograms/ml in the others. Of 12 cerebrospinal fluid samples tested, 10 lacked bactericidal activity in vitro against a beta-lactamase-producing strain of Haemophilus influenzae.
 ...
PMID:Bactericidal activity against Haemophilus influenzae of cerebrospinal fluid of patients given amoxicillin-clavulanic acid. 350 42

The in-vitro activity of ticarcillin with and without clavulanic acid was investigated against 285 freshly isolated clinical strains of Gram-positive and Gram-negative bacteria by the agar-dilution technique on Mueller-Hinton-agar. Clavulanic acid had an excellent or moderate potentiating effect on the in-vitro activity of ticarcillin against staphylococci, Escherichia coli, Klebsiella spp., Enterobacter aerogenes, Proteus mirabilis, Citrobacter spp., Acinetobacter, Haemophilus influenzae and Bacteroides spp. No effect was seen against enterococci, indole-positive Proteus spp., Ent. cloacae, Serratia marcescens and Pseudomonas aeruginosa. The effect of clavulanic acid was dose- and inoculum-dependent.
 ...
PMID:In-vitro activity of ticarcillin with and without clavulanic acid against clinical isolates of gram-positive and gram-negative bacteria. 363 25


1 2 Next >>