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)

Tazobactam (YTR 830), a new beta-lactamase inhibitor, was evaluated for its effect in combination with piperacillin, a broad spectrum, but beta-lactamase sensitive, penicillin, against 14 common bacteria. A total of 1,086 clinical isolates from different clinical specimens were tested for beta-lactamase production by the rapid chromogenic cephalosporin method. Their susceptibilities to piperacillin alone and in combination with tazobactam in a ratio of 8:1 by the agar dilution method were evaluated. The percentage of beta-lactamase producing strains ranged from 14.5% to 100% in these tested species. In general, the beta-lactamase producers were more resistant to piperacillin than the beta-lactamase nonproducers with higher minimal inhibitory concentrations (MICs). For the beta-lactamase producers, tazobactam decreased the MICs of piperacillin prominently in methicillin-resistant Staphylococcus aureus, Neisseria gonorrhoeae, Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Morganella morganii, Salmonella species and Bacteroides fragilis, with a 4-fold or greater decrease in MIC50, MIC90 and the geometric mean of MIC. For Serratia marcescens and Pseudomonas aeruginosa, the MICs did not change after adding tazobactam. For other species, there was a moderate decrease in MICs. We conclude that tazobactam is an effective beta-lactamase inhibitor for increasing the antimicrobial activity of piperacillin against beta-lactamase producing strains of many species of bacteria.
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PMID:Antimicrobial activities of piperacillin alone and in combination with tazobactam against beta-lactamase-producing bacteria. 168 75

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.
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PMID:Comparative in vitro activities of piperacillin-tazobactam and ticarcillin-clavulanate. 255 4

The combination of piperacillin and the beta-lactamase inhibitor tazobactam (formerly YTR 830) was studied to determine optimal disk concentrations and dilution testing conditions. In addition, the potency of the combination was compared to that of piperacillin alone. The spectrum of piperacillin was greatly expanded by the addition to tazobactam principally against beta-lactamase producing strains of Haemophilus influenzae, Escherichia coli, Morganella morganii, Proteus vulgaris, Providencia stuartii, Shigella spp., Neisseria gonorrhoeae, and Staphylococcus spp. Tazobactam was active alone against Branhamella catarrhalis (minimum inhibitory concentration [MIC] 50, less than or equal to 1 microgram/ml), gonococci (MIC 50, 0.5-4 micrograms/ml), and N. meningitidis (MIC 50, less than or equal to 1 microgram/ml). Studies with beta-lactamase-producing type strains showed tazobactam to have high affinity for plasmid-mediated enzymes (TEM-1 and 2, SHV-1, HMS-1, and some CARB or OXA types) and not chromosomal beta-lactamases. Piperacillin/tazobactam inhibited 93% of fluoro-quinolone resistant strains at less than or equal to 64/8 micrograms/ml but failed to suppress the growth of 15 strains producing stably depressed cephalosporinases. Comparisons of piperacillin/tazobactam results determined with 100/10-, 100/20-, and 100/30-micrograms disks established the 100/10-micrograms disk as most usable. Among five different MIC combinations the ratio of eight parts piperacillin to one part tazobactam or fixed concentration tests at greater than or equal to 4 micrograms tazobactam/ml were preferred, each producing very low occurrences (less than or equal to 1.6%) of false-resistance or -susceptibility when compared to disk test results. MICs determined by agar and broth microdilution methods were essentially the same. The recommended breakpoints for piperacillin/tazobactam MICs were identical to those now found in the NCCLS susceptibility testing standards with the following exceptions: (1) for tests with H. influenzae and Staphylococcus spp.--susceptible at greater than or equal to 21 mm (MIC less than or equal to 16/2 micrograms/ml) and resistant less than or equal to 20 mm (MIC less or equal to 32/4 micrograms/ml); and (2) all remaining nonspeudomonas isolates would be interpreted by the NCCLS piperacillin enteric bacilli susceptibility criteria. This newer beta-lactamase inhibitor combination appears to be worthy of further in vivo trials guided by these or similar tentative in vitro susceptibility testing parameters.
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PMID:Studies to optimize the in vitro testing of piperacillin combined with tazobactam (YTR 830). 256 Apr 22

Classification schemes for gram-negative beta-lactamases are presented, mechanisms by which beta-lactamases inactivate beta-lactam antibiotics are reviewed, and methods for assessing the efficiency of beta-lactamase inhibitors are evaluated. Beta-lactamases are commonly produced by Staphylococcus species, the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter species, and some anaerobes. Currently available beta-lactamase inhibitors are thought to be "suicide inhibitors" that form stable complexes between the bacterial beta-lactamase and the beta-lactamase inhibitor in a multistep chemical reaction. Each step can be quantitated; however, the overall process is difficult to measure. Thus, a comparative evaluation of commercially available beta-lactamase inhibitors is extremely difficult and must be done under standardized test conditions. In general, sulbactam, clavulanate, and tazobactam are all potent inhibitors of staphylococcal penicillinase; chromosomal beta-lactamases produced by Bacteroides species, Proteus vulgaris, Haemophilus influenzae, Neisseria gonorrhoeae; and type IV enzymes of Klebsiella species. Although sulbactam possesses activity against TEM-1 and TEM-2 beta-lactamases, it does not have reliable activity against SHV-1 beta-lactamases. Clavulanate and tazobactam are potent inhibitors of both TEM and SHV-1 beta-lactamases. P. aeruginosa and some Enterobacteriaceae produce an inducible, extremely potent, broad-spectrum enzyme (type I beta-lactamase). Tazobactam is the only currently available. beta-lactamase inhibitor with activity against type I beta-lactamases; however, some enzymes are not inhibited by tazobactam.
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PMID:Combination beta-lactam and beta-lactamase-inhibitor products: antimicrobial activity and efficiency of enzyme inhibition. 760 85

The in-vitro activities of piperacillin plus tazobactam at ratios of 4:1, 8:1 and 16:1 were determined against 952 non-copy clinical aerobic bacterial isolates collected from 20 UK centres. Tazobactam enhanced the activity of piperacillin against Enterobacteriaceae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis. No enhancement was noted for Pseudomonas aeruginosa, other Pseudomonas spp., streptococci and enterococci. For 95.6% of strains MICs were either the same or only one two-fold dilution different with all the three ratios of tazobactam, and for most of the remaining strains the piperacillin MIC was lowest with the highest proportion of the tazobactam (4:1). The percentage of strains which remained resistant was also lowest with the 4:1 ratio. Regression analysis of MICs versus inhibition zone size with a variety of disc strengths tested on DST agar indicated that for Enterobacteriaceae, and H. influenzae 30 +4 micrograms, and 5 +1 microgram piperacillin/tazobactam discs gave the most reliable results. However, for S. aureus no disc gave good discrimination. Zone sizes obtained on DST and Iso-Sensitest agar were similar, with 96.1% of 1450 paired tests showing agreement to within 3 mm.
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PMID:The activity of piperacillin/tazobactam against clinical isolates collected in 20 UK centres and the design of a disc test for susceptibility testing. 822 17

Twenty-nine British and Irish hospitals each collected up to 300 bacterial isolates from in-patients. The organisms were identified by an appropriate API system or, for staphylococci, by their Gram and coagulase reactions. Disc susceptibility tests were performed. Isolates that gave zones < or = 25 mm to piperacillin/tazobactam (75 micrograms + 10 micrograms) discs were sent to a central laboratory for re-examination and determination of MIC, together with a sample of the more susceptible organisms. Results were evaluated for 6724 isolates. Over 95% of the isolates of Escherichia coli, klebsiellae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus, Moraxella and Bacteriodes, spp. streptococci, pneumococci and Enterococcus faecalis were susceptible to piperacillin/tazobactam (defined as giving a zone > or = 22 mm to a 75 micrograms + 10 micrograms disc), as were 86% of Acinetobacter spp. and 82% of the Citrobacter, Enterobacter, Morganella and Serratia group. Tazobactam particularly extended the activity of piperacillin against E. coli isolates (96% susceptible cf. 61% to piperacillin alone) klebsiellae (95% cf. 70%), P. mirabilis (99% cf. 86%), and Acinetobacter spp. (86% cf. 53%). Occasional (18%) resistance in Enterobacter, Serratia and Citrobacger spp. was probably caused by stable depression of Class I beta-lactamases, which are inhibited poorly by tazobactam. High resistance frequencies (> 25%) were found for Enterococcus faecium and Xanthomonas maltophilia. Tazobactam potentiated piperacillin against beta-lactamase-producing methicillin-susceptible Staphylococcus aureus, but the mode inhibition zone of piperacillin/tazobactam discs was only 26 mm, compared to 38 mm for beta-lactamase-negative isolates. Nevertheless, fewer than 5% of the enzyme producers appeared resistant to 8 + 4 mg/L piperacillin/tazobactam in MIC tests. Similar behaviour was noted for coagulase-negative staphylococci. Amongst the eleven comparator drugs, ceftazidime, gentamicin and ciprofloxacin were as active as piperacillin/tazobactam against most enterobacteria. However, Acinetobacter and Bacteroides spp. and enterococci were resistant to ceftazidime, and Bacteroides spp., enterococci, pneumococci and other streptococci were inherently resistant to ciprofloxacin and gentamicin. Cefuroxime, ampicillin and co-amoxiclav had narrower spectra. Only imipenem showed a consistently wider spectrum and lower frequency of resistance than piperacillin/tazobactam.
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PMID:Multicentre survey of the comparative in-vitro activity of piperacillin/tazobactam against bacteria from hospitalized patients in the British Isles. 822 27

Among 325 fresh isolates of bacteria from 153 hospital patients with serious infections, 142 were susceptible to piperacillin, 129 were resistant and a further 54 exhibited a marked inoculum effect. Tazobactam restored the susceptibility of resistant isolates of Staphylococcus aureus and Staphylococcus epidermidis (except methicillin-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Acinetobacter spp. and Bacteroides fragilis. Among 87 Enterobacteriaceae that were resistant to piperacillin, or showed an inoculum effect, 78 (89%) were restored to susceptibility by tazobactam. Pseudomonas spp. resistant to piperacillin were mostly resistant to the combination.
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PMID:Susceptibility survey of piperacillin alone and in the presence of tazobactam. 838 53

Inhibitor combinations provide one strategy to overcome beta-lactamase-mediated resistance. Their success depends, obviously, on the inhibitor being able to bind and inactivate the beta-lactamase molecules. Clavulanate, sulbactam and tazobactam are irreversible inactivators of many beta-lactamases, forming covalent complexes which resist hydrolysis. 'Suicide' kinetics are seen with some, but not all, enzymes. All three compounds inactivate staphylococcal penicillinase, the chromosomal beta-lactamases of Proteus vulgaris and Bacteroides spp., and the Class IV beta-lactamases present in some klebsiellae. Tazobactam, but not the other compounds, has moderate activity against some Class I (AmpC) chromosomal beta-lactamases, notably that of Morganella morganii, but not that of Enterobacter cloacae. Both clavulanate and tazobactam are strong inhibitors of the widely distributed TEM and SHV plasmid-mediated beta-lactamases; sulbactam is a weaker inhibitor. Other factors, aside from the affinity of the inhibitor for the enzyme, co-determine the success or failure of inhibition. Potentiation is most readily achieved if little enzyme is produced, and if the organism is very permeable to the inhibitor. Thus, resistance to inhibitor combinations is rare in strains of Haemophilus influenzae and Neisseria gonorrhoeae that produce TEM-beta-lactamase, but is commoner in enterobacteria that produce this enzyme, since these are less permeable and sometimes manufacture very large amounts of enzyme. The partner beta-lactam agent is also important. Irrespective of the inhibitor used, piperacillin is easier to protect against TEM beta-lactamases and the M. morganii Class I enzyme than are ampicillin, amoxycillin or ticarcillin. This may relate to the lower affinity of piperacillin for these enzymes, or to its greater affinity for the bacterial penicillin-binding proteins. Finally, pH can affect the degree of inhibition achieved with sulphones for some beta-lactamases, notably TEM-1.
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PMID:Determinants of the activity of beta-lactamase inhibitor combinations. 844 36

Tazobactam is a new, irreversible inhibitor of bacterial beta-lactamases of staphylococci, plasmid-mediated beta-lactamases of the TEM and SHV types found in Escherichia coli and Klebsiella species and beta-lactamases of anerobes such as Bacteroides species. Its combination with piperacillin, a broad spectrum ureido-penicillin, would be expected to improve the activity of piperacillin against staphylococci, TEM and SHV beta-lactamase producing Gram negative bacteria and anerobes. Minimal inhibitory concentrations (MIC) of piperacillin/tazobactam were determined for 1952 individual patient isolates of Gram positive and negative bacteria causing significant infections and compared with MIC values for cefotaxime, ceftazidime, ciprofloxacin, imipenem, ticarcillin/clavulanic acid. MICs were determined by agar dilution (NCCLS 1990 and 1992). Piperacillin/tazobactam had excellent activity against methicillin susceptible staphylococci, Streptococcus pneumoniae, Haemophilus influenzae, enterococci and organisms of the Bacteroides fragilis group. It was also active against the majority of Enterobacteriaceae and Pseudomonas aeruginosa isolates tested. It was not active against extended spectrum beta-lactamase (ESBL) producing Klebsiella species and some high level TEM and SHV beta-lactamase producing E. coli and Klebsiella species. Activity against Gram negative organisms capable of producing chromosomally mediated beta-lactamases was good, since in most organisms tested, the enzymes were not induced in sufficient quantities to cause antibiotic resistance. However some Enterobacter species were derepressed hyperproducing mutants; these isolates showed resistance to piperacillin/tazobactam since tazobactam does not inhibit these Class I beta lactamases. Activity was superior to ticarcillin/clavulanic acid for Gram negative rods. Imipenem was the most active agent against ESBL producing Klebsiella species. Piperacillin/tazobactam has a suitable spectrum of activity in vitro to suggest its use in monotherapy of mixed anerobic infections, mixed respiratory infections such as aspiration pneumonia and, in combination with an aminoglycoside, it would provide Gram positive as well as Gram negative cover of febrile episodes in immunosuppressed patients.
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PMID:An evaluation of the in vitro activity of piperacillin/tazobactam. 874 25

We aimed to prospectively evaluate the clinical and bacteriological effects of piperacillin in children with pneumonia. Twenty-eight patients (6 months to 5 years of age) with pneumonia were treated with piperacillin. In the same period, 95 strains of Haemophilus influenzae and 41 strains of Streptococcus pneumoniae were isolated in our department and the minimum inhibitory concentration (MIC) of piperacillin was determined. The clinical efficacy of piperacillin was excellent in 4 cases, good in 23, and fair in 1; the response rate was 96.4% (27/28). Among the isolates from our department, there were 4 strains (9.8%) of penicillin-susceptible S. pneumoniae (PSSP), 32 strains (78.0%) of penicillin-intermediate-resistant S. pneumoniae (PISP), and 5 strains (12.2%) of penicillin-resistant S. pneumoniae (PRSP). Against S. pneumoniae, the MIC50 and MIC90 for piperacillin were 0.5 microg/ml and 2 microg/ml, respectively. Panipenem showed the best results, followed by piperacillin, ampicillin, and flomoxef. Among the isolates from our department, there were 51 strains (53.7%) of beta-lactamase-negative ampicillin-susceptible H. influenzae, 42 strains (44.2%) of beta-lactamase-negative ampicillin-resistant H. influenzae, 1 strain (1.1%) of beta-lactamase-positive ampicillin-resistant H. influenzae, and 1 strain (1.1%) of beta-lactamase-positive amoxicillin-clavulanic acid-resistant H. influenzae. The MIC50 and MIC90 for piperacillin against H. influenzae were 0.0625 microg/ml and 0.125 microg/ml, respectively. Tazobactam/piperacillin and piperacillin showed the best results, followed by panipenem, ampicillin, and flomoxef. Piperacillin proved to be very useful for the treatment of pneumonia in children.
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PMID:Clinical and bacteriological evaluation of the efficacy of piperacillin in children with pneumonia. 1772 85


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