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)

The in vitro activity of cefetamet, the microbiologically active metabolite of the orally administered prodrug cefetamet pivoxil, was compared with that of cephalexin, cefaclor, cefuroxime and amoxicillin. Cefetamet was highly active against Enterobacteriaceae, Neisseria spp., Vibrio spp., Haemophilus influenzae and streptococci other than enterococci. Cefetamet inhibited cefaclor-resistant species such as Proteus vulgaris, Providencia stuartii, Providencia rettgeri and Serratia marcescens. Staphylococci, Pseudomonas aeruginosa and cephalosporinase-overproducing strains of Enterobacter cloacae were resistant to cefetamet. The superior activity of cefetamet compared with older oral beta-lactam antibiotics against a large number of gram-negative pathogens correlated with enhanced stability towards beta-lactamases. In accordance with the in vitro findings, cefetamet pivoxil showed good activity in experimental infections in the mouse and rat, suggesting satisfactory bioavailability in these animals after oral administration.
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PMID:In vitro antibacterial properties of cefetamet and in vivo activity of its orally absorbable ester derivative, cefetamet pivoxil. 250 97

Bacterial resistance to the beta-lactam drugs is extremely widespread, as a result of extensive drug use. Loss of susceptibility is primarily attributable to hydrolysis by inactivating enzymes, namely the beta-lactamases. While the number of characterised beta-lactamases may exceed 100, only a few are a problem in the treatment of community-acquired infections (TEM-1, TEM-2, SHV-1, BRO-1). Chromosomally mediated and extended-spectrum beta-lactamases are usually dominant in nosocomial pathogens where oral antibiotic therapy is seldom used. Therefore, the threat posed by beta-lactamases must be considered in general practice. Several effective strategies have been implemented in order to overcome beta-lactamase-mediated resistance, e.g. use of non-beta-lactam drugs or beta-lactamase inhibitors. Another option has been the development of new beta-lactam compounds that possess a high intrinsic stability against the hydrolytic action of common beta-lactamases. Among these compounds, the oral third generation cephalosporins represent an important breakthrough. Cefetamet pivoxil, a new oral third generation cephalosporin, is characterised by excellent antimicrobial potency against Enterobacteriaceae, and Moraxella (Branhamella) catarrhalis and Haemophilus influenzae, irrespective of their ability to produce beta-lactamases. The Gram-positive respiratory pathogens, Streptococcus pyogenes and penicillin-susceptible S. pneumoniae, are also satisfactorily covered. The activity of cefetamet has recently been corroborated in a survey conducted in Italy involving 4191 isolates. However, cefetamet shows no activity against enterococci, staphylococci, Listeria, alpha-streptococci, Pseudomonas, Acinetobacter and anaerobes. Given this antibacterial profile, cefetamet pivoxil may provide a useful alternative to other oral antibacterial agents in the empirical therapy of acute community-acquired respiratory and urinary tract infections. From the results of the Italian survey, cefetamet emerged as the only agent among those considered (which included cefuroxime, cefaclor, cefalexin, cefadroxil, ampicillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, doxycycline, erythromycin and clindamycin) that might be selected as the drug of choice in the empirical therapy of outpatient infections.
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PMID:Stability in the presence of widespread beta-lactamases. A prerequisite for the antibacterial activity of beta-lactam drugs. 751 61

Cefetamet pivoxil is an oral third-generation cephalosporin which is hydrolysed to form the active agent, cefetamet. Cefetamet has excellent in vitro activity against the major respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and group A beta-haemolytic streptococci; it is active against beta-lactamase-producing strains of H. influenzae and M. catarrhalis, but has poor activity against penicillin-resistant S. pneumoniae. Cefetamet has marked activity against Neisseria gonorrhoeae and possesses a broad spectrum of activity against Enterobacteriaceae. Both staphylococci and Pseudomonas spp. are resistant to cefetamet. Cefetamet pivoxil has been investigated in the treatment of both upper and lower community-acquired respiratory tract infections and has demonstrated equivalent efficacy to a number of more established agents, namely cefaclor, amoxicillin and cefixime. In patients with group A beta-haemolytic streptococcal pharyngotonsillitis, a 7-day course of cefetamet pivoxil was as effective as a 10-day course of the standard agent, phenoxymethylpenicillin, in this indication. In complicated urinary tract infections, cefetamet pivoxil showed similar efficacy to cefadroxil, cefaclor and cefuroxime axetil. Cefetamet pivoxil was effective in the treatment of otitis media, pneumonia, pharyngotonsillitis and urinary tract infections in children. Preliminary data indicate that single dose cefetamet pivoxil can effectively eradicate N. gonorrhoeae from both men and women. Cefetamet pivoxil has a tolerability profile similar to that of other oral cephalosporins, with gastrointestinal effects being the most commonly reported adverse events. To date, no symptoms of carnitine deficiency have been reported with cefetamet pivoxil. Cefetamet pivoxil offers effective alternative oral therapy for outpatient treatment of community-acquired respiratory tract infections, with the advantage of improved activity against H. influenzae and increased beta-lactamase stability. However, its use in areas with a high incidence of penicillin-resistant S. pneumoniae is likely to be limited. Cefetamet pivoxil is also effective in the treatment of urinary tract infections, although further trials are required to define any comparative advantages over other oral agents.
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PMID:Cefetamet pivoxil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. 768 77

Cefetamet pivoxil is an orally absorbed prodrug ester of the microbiologically active cephalosporin, cefetamet. The prodrug ester is completely hydrolysed to the active compound cefetamet on its first pass through the gut wall, the liver or both. Cefetamet is classified as a third generation cephalosporin with excellent activity against streptococci, Enterobacteriaceae, Neisseria and Haemophilus species. It has enhanced stability against beta-lactamases compared with penicillins and first and second generation cephalosporins. The antibacterial spectrum is comparable with that of cefotaxime except for its poor activity against staphylococci. Following a 20-minute zero-order intravenous infusion, cefetamet had a rapid distribution phase followed by a monoexponential decline. The average pharmacokinetic parameters from 152 healthy volunteers were: total body clearance 136 ml/min (8.16 L/h); renal clearance 119 ml/min (7.14 L/h); nonrenal clearance 17 ml/min (1.02 L/h); volume of distribution at steady-state 0.29 L/kg; terminal elimination half-life 2.2 hours; 88% of the dose recovered in the urine. Cefetamet is not extensively bound to plasma proteins. Consequently, these data indicate that cefetamet is predominantly eliminated unchanged by the kidney via glomerular filtration with possibly a minor component of tubular secretion. Cefetamet has a relatively small apparent volume of distribution consistent with that of other beta-lactam antibiotics. Results following ascending intravenous doses of cefetamet in healthy young male volunteers demonstrated that the pharmacokinetics of intravenous cefetamet are independent of the dose. The absolute bioavailability of cefetamet tablets following oral cefetamet pivoxil administration is enhanced by the presence of food. Under fed conditions, 50 to 60% of the final oral dose is absorbed into the systemic circulation. This food effect is observed when cefetamet pivoxil is administered within 1 hour of a meal. Food also produces a slight delay in the time to reach peak plasma concentrations of this drug. Changes in fluid volume intake with cefetamet pivoxil administration have no effect on the bioavailability of this drug. Similar absorption characteristics have been observed for all of the tablet dosage formulations studied during clinical development. The absolute bioavailability of the final syrup dosage formulation was between 38 and 47%. Little improvement in the bioavailability of this preparation has been observed with food. The absorption and disposition of cefetamet in human subpopulations [i.e. children, elderly (< 75 years of age), renal impairment, liver disease and patients taking concomitant drugs] have been studied extensively. Only impaired renal function appears to significantly alter the elimination of this drug.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cefetamet pivoxil clinical pharmacokinetics. 822 59

Cefetamet pivoxil, the prodrug ester of cefetamet, is a new third-generation cephalosporin with a broad spectrum of activity. The in vitro activity of cefetamet was superior to that of cefaclor, ceftibuten, amoxicillin plus clavulanic acid, and amoxicillin alone when tested against 403 strains of freshly isolated upper and lower respiratory tract pathogens. Cefetamet killed 100% Haemophilus influenzae and H. parainfluenzae, including beta-lactamase-producing strains, at < or = 0.25 mg/l, Streptococcus pyogenes and S. pneumoniae at < or = 0.5 mg/l, S. agalactiae at < or = 0.1 mg/l, and streptococci at < or = 2.0 mg/l. Moreover, at < or = 4 mg/l (breaking point), cefetamet was also highly effective against Escherichia coli (94%), Klebsiella pneumoniae (92%), K. oxytoca (91%) and, at 1 mg/l, against Moraxella catarrhalis (90%), including beta-lactamase-producing strains. Furthermore, time-killing analyses at 4 x MIC demonstrated that cefetamet was bactericidal against beta-lactamase-producing H. influenzae, M. catarrhalis, and K. pneumoniae within 6 h and S. pneumoniae within 4 h. Hydrolysis studies confirmed cefetamet's stability to TEM1 and SHV1, the most common enterobacterial beta-lactamases.
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PMID:Cefetamet pivoxil: comparable evaluation with other orally available antibiotics against selected species of respiratory pathogens. 875 Dec 62

Cefetamet pivoxil is an oral, third-generation cephalosporin whose broad spectrum of antibacterial activity and favorable pharmacokinetic profile make it particularly suitable for the treatment of a wide range of infectious diseases. Cefetamet has high in vitro activity against both gram-positive and gram-negative bacteria that cause a number of respiratory tract and urinary tract infections. These include penicillin-sensitive Streptococcus pneumoniae, Streptococcus spp, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Proteus spp., Klebsiella spp. and Neisseria gonorrhoeae. It is not active against staphylococci, enterococci, Pseudomonas spp. or Bacteroides fragilis but does inhibit most bile-sensitive (oral) Bacteroides spp. Animal toxicology studies indicate that neither cefetamet pivoxil nor the active compound cefetamet have significant teratogenic, mutagenic, photogenic or allergenic potential. Cefetamet is eliminated unchanged in the urine with a half-life of 2.2 h. Volume of distribution approximates the extracellular fluid space (0.3 1/kg), protein binding is minima (22%) and oral bioavailability of cefetamet pivoxil is approximately 50% when taken with food. No significant drug interactions have been noted to date. The efficacy and tolerability of cefetamet pivoxil have been evaluated in the treatment of gram-positive and gram-negative infections in almost 5,000 patients. In comparative studies, cefetamet pivoxil was at least as effective, and in many cases clinically superior, to most currently recommended antibiotics for the treatment of urinary tract infections including gonorrhea and complicated infections in high risk patients. Efficacy has also been demonstrated in acute exacerbations of chronic bronchitis, pneumonia and infections of the ear, nose and throat. Clinical trials have shown that a 7 day treatment period with cefetamet pivoxil is as effective as a 10 day course of phenoxymethylpenicillin in the treatment of pharyngotonsillitis. Cefetamet pivoxil has been well-tolerated in clinical trials with only 1.2% of patients on standard doses discontinuing therapy prematurely. The most common adverse effects are gastrointestinal (diarrhea, nausea, vomiting) which occur in less than 10% of patients. Many current antibiotic treatment regimens involve the administration of three or more daily doses. However, standard doses of cefetamet pivoxil 500 mg twice daily provide unbound plasma concentrations of cefetamet which generally exceed the MIC(90) for susceptible organisms throughout the dosing interval and have been demonstrated to be clinically effective. This should result in good compliance with therapy in out-patients. Dosing regimens for cefetamet pivoxil should be adjusted in patients with impaired renal function while standard doses can be given to elderly patients and those with liver disease. Standard doses in children are 10 mg/kg or alternatively, children may receive a dose reduced in proportion to the ratio of their body surface area to that of an adult.
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PMID:Cefetamet pivoxil: a review of its microbiology, toxicology, pharmacokinetics and clinical efficacy. 1861 3