Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cefaclor”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed1990

Oral cephalosporins in perspective.

Oral cephalosporins, after 25 years of use, continue to present the clinician with a therapeutic challenge. The older agents have been extensively prescribed for ambulatory adult and pediatric patients with a wide variety of infections caused by gram-positive and some gram-negative organisms. The newer agents, cefaclor, cefuroxime axetil, and cefixime, have increased in vitro activity against beta-lactamase-secreting strains of Haemophilus influenzae and Branhamella catarrhalis which has made them more popular for the treatment of otitis media and respiratory tract infections in children. The new agents are also more active against most gram-negative organisms. However, clinical trials have failed to show a clear-cut superiority over older, proven therapy when used to treat infections of the respiratory tract, middle ear, skin and soft tissue, urinary tract, and bone and joints when caused by sensitive organisms. Published reports of clinical trials continue to support the recommendation that oral cephalosporins, especially the newer and more expensive agents, be reserved for second- or third-line therapy when amoxicillin, penicillin V, or trimethoprim/sulfamethoxazole have either failed or produced patient intolerance. Erythromycin/sulfisoxazole and amoxicillin/clavulanate potassium are equally efficacious and also less expensive than cefaclor, cefuroxime axetil, and cefixime and could be considered second-line therapy prior to the use of the newer cephalosporins for infections in the ambulatory patient.

Cephalosporins↗
PubMed2000

Differential costs and outcomes among pediatric oral antibiotic formulations identified from a large prescription database.

Differential performance of oral antibiotics continues to be a difficult characteristic to measure. As payers make efforts to identify selected antibiotics to place on their formularies or to reimburse, the challenge to these decision-makers is to determine which agent will work best in their population. Given the differences from one clinical trial to another, identifying performance characteristics that might impact effectiveness in clinical practice is quite challenging. This study's aim was to determine which beta-lactam and macrolide antibiotic provided the best clinical and economic outcome when used in difficult pediatric infections that previously experienced amoxicillin or cotrimoxazole failure. The findings demonstrated that cefaclor, azithromycin, and amoxicillin/clavulanate were associated with a decreased need for subsequent antibiotic therapy. Total drug treatment costs for beta-lactams and macrolides were lowest for cefaclor and azithromycin, respectively. These results are consistent with previous published literature and seem plausible given potential compliance advantages of these products as reported in studies of product tolerability and taste.

Administration, Oral↗
PubMed1992

Cefetamet pivoxil in community-acquired pneumonia: an overview.

A total of 305 patients with community-acquired pneumonia have participated in comparative or non-comparative studies involving cefetamet pivoxil. Of these, 211 (55 adults and 156 children) were involved in a series of open, prospective, comparator-controlled, multi-centre studies. Adults were randomized to receive either cefetamet pivoxil 1000 mg twice daily or amoxycillin 750 mg 3-times daily for 10 days. Children received either cefetamet pivoxil 10 mg/kg twice daily, cefetamet pivoxil 20 mg/kg twice daily or cefaclor 10 mg/kg 3-times daily for 7 to 8 days. The remaining 94 patients were treated openly with cefetamet pivoxil, with most patients receiving cefetamet pivoxil 500 mg twice daily for an average of 10 days; an elderly sub-group of these patients aged 70 to 103 years received therapy for an average of 11 days. The main causative organisms isolated were Streptococcus pneumoniae and Haemophilus influenzae. In adult patients, a successful clinical outcome was achieved in 100% of assessable patients receiving cefetamet pivoxil 1000 mg twice daily, and about 90% in those receiving 500 mg twice daily. The success rate in children was 98% for both dose levels of cefetamet pivoxil and 90% for those receiving cefaclor. In elderly patients, the percentage was 78% for the 500 mg twice daily patients. Thus, the standard dose of cefetamet pivoxil (500 mg twice daily in adults, 10 mg/kg twice daily in children) was well tolerated and proved to be at least as effective as the comparator drugs which were given 3-times a day.

Adolescent↗
PubMed1989

Synthesis and biological evaluation of 3-chloro-1-carbacephem compounds.

The 3-chloro-1-carbacephem nucleus was prepared for the first time from a 3H-1-carbacephem compound through a sequence of reactions involving addition of thiophenol, oxidation of sulfide to sulfoxide, and alpha-chlorination of the sulfoxide, followed by elimination of phenylsulfinic acid. The 2-beta-methyl analog was similarly prepared, but the 2 alpha-methyl analog was not obtained. Optical resolution of the 3-chloro-1-carbacephem compound was achieved by the employment of penicillin acylase. That is, the 7-phenylacetamido derivative was enantioselectively hydrolyzed to afford the optically active 7-amino-3-chloro-1-carbacephem compound. Carbacefaclor, the carbacephem analog of cefaclor, was directly and efficiently prepared by enzymatic phenylglycylation of the racemic 7-amino-3-chloro-1-carbacephem compound by using immobilized penicillin acylase. Carbacefaclor thus prepared exhibited comparable antibacterial activity against most gram positive bacteria tested and higher activity against typical gram negative bacteria as compared with cefaclor. Moreover, carbacefaclor possessed remarkably high chemical stability.

Cephalosporins↗
PubMed2001

High rates of multiple antibiotic resistance in Streptococcus pneumoniae from healthy children living in isolated rural communities: association with cephalosporin use and intrafamilial transmission.

OBJECTIVE: Streptococcus pneumoniae is one of the most clinically significant pathogens with emerging antibiotic resistance. We performed a surveillance study in isolated rural populations of healthy children to estimate the prevalence of pneumococcal resistance and to contrast factors that predict pneumococcal carriage with those that specifically predict resistant pneumococcal carriage. METHODS: The study was conducted in 1998 in 2 rural communities in Utah. Families were recruited directly for participation through community canvassing. Surveillance nasopharyngeal cultures were obtained from children who were younger than 8 years. Antibiotic usage and information on other potential risk factors were obtained from questionnaires and local pharmacy records. Resistance was determined by testing isolates for susceptibility to penicillin, cefaclor, trimethoprim-sulfamethoxazole, erythromycin, ceftriaxone, and trovafloxacin. Selected resistant isolates were characterized further by serotyping, pulsed field gel electrophoresis, and Southern blot with DNA probes specific for the pneumococcal lytA gene and for antibiotic resistance genes. RESULTS: In April 1998, surveillance nasopharyngeal cultures were obtained from 368 children aged </=8 years in community A and 369 children in community B. The number of antibiotic courses per child within 1 year before culture was higher in community B than A (mean: 2.2 vs 1.7). Conversely, oral cephalosporins were more frequently used in community A than B (community A: 22% received cephalosporins within 4 months; community B: 12%). Colonization with S pneumoniae was detected in 24% of children in community A and 14% in community B; 36% of isolates from community A and 28% of isolates from community B were resistant or intermediately susceptible to at least 1 antibiotic tested. Reduced susceptibility was most common to trimethoprim-sulfamethoxazole and cefaclor (28% and 26%, respectively). Pneumococcal carriage (susceptible or resistant) was independently associated with age <5 years (odds ratio [OR]: 2.2), child care exposure (OR: 2.4), presence of a sibling with a positive culture (OR: 3.3), and residence in community A (OR: 1.7). Among carriers, age <2 years (OR: 2.6), use of cephalosporins within the preceding 4 months (OR: 2.7), and having a sibling colonized with resistant S pneumoniae (OR: 5.5) were independent predictors of reduced susceptibility or resistance. Each pair of resistant isolates from siblings was indistinguishable by pulsed field gel electrophoresis and other molecular typing techniques. Several pneumococcal isolates from these isolated rural areas had the molecular characteristics of international clones of multiple-drug-resistant pneumococci that have been associated with worldwide spread. CONCLUSIONS: Young age and intrafamilial transmission were important risk factors for carriage of both susceptible and resistant S pneumoniae. In contrast, previous cephalosporin use was linked specifically to resistant pneumococcal carriage, which suggests that modifications in antibiotic usage patterns may have salutary effects on antimicrobial resistance. These results extend previous observations in large cities regarding the penetration of multiple-drug-resistant clones of pneumococci into community populations.

Anti-Bacterial Agents↗
PubMed1999

In vitro activity and pharmacodynamics of oral beta-lactam antibiotics against Streptococcus pneumoniae from southeast Missouri.

STUDY OBJECTIVES: To determine the frequency of reduced susceptibility to penicillin, and to compare the in vitro activity and pharmacodynamics of oral beta-lactam antibiotics against clinical isolates of Streptococcus pneumoniae from southeast Missouri. SETTING: Cape Girardeau, Missouri (population 35,500). Interventions. Minimum inhibitory concentrations (MICs) were determined for penicillin, amoxicillin, amoxicillin-clavulanic acid, cefprozil, cefuroxime, cefpodoxime, cefaclor, and loracarbef by E test for 108 isolates of S. pneumoniae. The MIC50, MIC90, and percentage susceptibility were calculated for each agent. Pharmacokinetic variables were obtained from the literature, and serum concentration-time profiles were simulated for a 25-kg child taking pediatric dosages commonly administered to treat otitis media. The average time above MIC (T > MIC) was calculated as percentage of the dosing interval using free concentrations and the MIC for each individual isolate. Analysis of variance (Scheffe post hoc test) was used to determine differences among agents for in vitro activity and T > MIC (level of significance, p<0.05). MEASUREMENTS AND MAIN RESULTS: The frequency of penicillin-nonsusceptible S. pneumoniae was 28.7% (31/108). For 25 penicillin-intermediate isolates, amoxicillin and amoxicillin-clavulanic acid were significantly more active than cefprozil, cefaclor, and loracarbef. The T > MIC for amoxicillin and amoxicillin-clavulanic acid, simulated at 13.3 mg/kg every 8 hours, was significantly longer than that for all other beta-lactams. CONCLUSION: Amoxicillin and amoxicillin-clavulanic acid have superior in vitro activity and longer T > MIC for penicillin-intermediate isolates than the other oral beta-lactams.

Administration, Oral↗
PubMed1989

Sultamicillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. Sulbactam is a semisynthetic beta-lactamase inhibitor which, in combination with ampicillin, extends the antibacterial activity of the latter to include some beta-lactamase-producing strains of bacteria that would otherwise be resistant. The combination of sulbactam plus ampicillin for parenteral use has previously been shown to be clinically and bacteriologically effective in a variety of infections. The chemical linkage of sulbactam and ampicillin has now produced an orally effective compound, sultamicillin, with antibacterial activity and clinical efficacy which are similar to those of the parenteral formulation. Sultamicillin has been shown to be clinically effective in non-comparative trials in patients with infections of the respiratory tract, ears, nose and throat, urinary tract, skin and soft tissues, as well as in obstetric and gynaecological infections, and in the treatment of gonorrhoea. In a small number of controlled trials, sultamicillin has shown comparable clinical efficacy to phenoxymethyl penicillin (penicillin V) and to amoxycillin (alone and in combination with clavulanic acid) in the treatment of paediatric streptococcal pharyngitis and acute otitis media, respectively; to cefaclor in the treatment of acute otitis media in adults; and to bacampicillin, cloxacillin and flucloxacillin plus ampicillin in skin and soft tissue infections in adults, children and adult diabetic patients, respectively. Sultamicillin was superior in efficacy to bacampicillin in the treatment of chronic respiratory infections, to cefaclor in the treatment of acute otitis media in adults, and to cefadroxil in the treatment of patients with complicated urinary tract infections. However, in single-dose treatment of uncomplicated gonorrhoea, sultamicillin (1500mg plus probenecid 1g) was inferior to a 2g intramuscular dose of spectinomycin. While in several studies the incidence of diarrhoea associated with sultamicillin was greater than that with comparative antibacterials, sultamicillin-associated diarrhoea was generally mild and transitory, although occasionally severe enough to necessitate discontinuation of treatment. Further studies in larger groups of patients are needed to clarify the therapeutic efficacy and safety of sultamicillin in comparison with other antibacterial regimens, and to determine the optimum single dosage for the treatment of gonorrhoea. Nonetheless, sultamicillin appears to provide a similar pharmacodynamic and pharmacokinetic profile to that of parenteral sulbactam plus ampicillin and, as such, will extend the therapeutic efficacy of ampicillin, with the further advantage of allowing treatment of patients with an oral formulation, thus avoiding the potentially adverse clinical and financial effects of prolonged parenteral therapy.

Ampicillin↗
PubMed1991

Microbiological evaluation of cefpodoxime proxetil.

Cefpodoxime, the active de-esterified molecule of the orally absorbable cephalosporin cefpodoxime proxetil, inhibits streptococci, Neisseria spp., and most Enterobacteriaceae, with MIC50 and/or MIC90 values of less than or equal to 2 mg/L; with regard to the latter family of bacteria, the MIC50 and/or MIC90 values of cefpodoxime are consistently greater than or equal to 4 mg/L for only Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Morganella morganii. The MIC50 of cedpodoxime for coagulase-negative staphylococci is greater than 2 mg/L, while the MIC for Staphylococcus aureus strains is 4 mg/L. In comparison with other orally absorbable cephalosporins, cefpodoxime is slightly less active than cefixime, cefetamet, and cefotiam against Gram-negative bacteria, but more active than cefuroxime, cefaclor, and cefalexin. Against staphylococci, the activity of cefpodoxime is comparable to that of cefotiam and cefuroxime, and superior to that of cefaclor, while cefixime and cefetamet have insufficient activity against these species. In common with other cephalosporins, cefpodoxime has no activity against enterococci. In vitro models simulating human serum cefpodoxime concentrations demonstrate that a dosage regimen of 200mg is probably sufficient to treat most infections. However, further study is needed to clarify whether infections due to bacteria such as S. aureus, with higher cefpodoxime MICs, can be treated with this dose regimen.

Ceftizoxime↗
PubMed1993

Cefetamet pivoxil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

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.

Bacteria↗
PubMed1995

Cefixime. A review of its therapeutic efficacy in lower respiratory tract infections.

Cefixime is an orally active third generation cephalosporin with in vitro antibacterial activity against most important lower respiratory pathogens. The drug is active against Haemophilus influenzae, Moraxella catarrhalis and penicillin-susceptible Streptococcus pneumoniae but not Staphylococcus aureus. Cefixime has a long elimination half-life (3 hours compared with 0.5 hours for cefaclor and 1.5 hours for cefalexin), which allows once daily administration. Several trials have established the clinical efficacy of the drug in patients with lower respiratory tract infection (LRTI). In comparative studies cefixime had similar efficacy to amoxicillin +/- clavulanic acid, cefaclor, cefalexin, cefuroxime axetil and clarithromycin. Trials evaluating the efficacy of cefixime as the oral component of intravenous to oral switch therapy have produced promising preliminary results although further carefully designed trials are needed in this area. As with certain other drugs of its class, gastrointestinal disturbances are the most frequently reported adverse events in patients taking cefixime and cases of pseudomembranous colitis have been reported. Thus, cefixime is an effective treatment for mild to moderate LRTI and may have a role as the oral component of intravenous to oral switch therapy although further well designed studies are needed to confirm initial favourable results in this important emerging area of antibacterial therapy.

Anti-Bacterial Agents↗
PubMed2001

Cefpodoxime proxetil: a review of its use in the management of bacterial infections in paediatric patients.

UNLABELLED: Cefpodoxime proxetil is an oral third generation cephalosporin with a broad spectrum of antibacterial activity. The drug has in vitro activity against many common Gram-positive and Gram-negative pathogens associated with common paediatric infections, making the drug a useful option for empirical therapy. In randomised controlled trials conducted in children with acute otitis media, oral cefpodoxime proxetil 8 to 10 mg/kg/day (usually administered in 2 divided doses) for 5 to 10 days was at least as effective as standard regimens of amoxicillin/ clavulanic acid, cefixime, cefuroxime axetil or cefaclor as assessed by either clinical or bacteriological criteria. Cefpodoxime 8 to 10 mg/kg/day (administered in 2 divided doses) for 5 to 10 days was at least as effective as standard 10-day regimens of penicillin V in the treatment of children with pharyngitis and/or tonsillitis. Significant differences in favour of cefpodoxime proxetil were demonstrated in terms of clinical (1 study) and bacteriological (2 studies) criteria. The clinical efficacy of 5 days of treatment with cefpodoxime proxetil is similar to that of 10 days of treatment with penicillin V. In children with lower respiratory tract infections (primarily pneumonia), clinical and bacteriological efficacy rates achieved with cefpodoxime proxetil treatment were similar to those produced by cefuroxime axetil or amoxicillin/clavulanic acid in randomised controlled trials. Cefpodoxime proxetil also demonstrated clinical efficacy in paediatric patients with skin and soft tissue infections. In randomised studies that included both adults and children with a variety of infections (e.g. abscess, atheroma, furuncle and carbuncle, infected wounds, cellulitis), cefpodoxime proxetil showed efficacy similar to that of cefuroxime axetil or cefaclor. Cefpodoxime proxetil is well tolerated by paediatric patients, with adverse events (primarily gastrointestinal tract disturbances and skin rashes) that are consistent with those reported for other oral cephalosporins. CONCLUSION: Cefpodoxime proxetil is a third generation cephalosporin with a broad spectrum of antibacterial activity and a favourable pharmacokinetic profile which allows twice-daily administration. It is generally well tolerated and demonstrates good bacteriological and clinical efficacy in paediatric patients with various infectious diseases, including acute otitis media, tonsillitis and/or pharyngitis. Based on these characteristics, cefpodoxime proxetil is a suitable option for the treatment of paediatric patients with various common bacterial infections.

Acute Disease↗
PubMed1999

Rapidly emerging antimicrobial resistances in Streptococcus pneumoniae in Australia. Pneumococcal Study Group.

OBJECTIVE: To examine the prevalence of resistance in Streptococcus pneumoniae to key antimicrobials in Australia during 1997. DESIGN: Prospective, Australia-wide, laboratory-based survey. SETTING: 11 microbiology laboratories from seven Australian States and Territories (five private laboratories and six public hospital laboratories) between March and November 1997. STRAINS: Up to 100 consecutive, clinically significant strains of S. pneumoniae isolated by each laboratory. MAIN OUTCOME MEASURES: Susceptibility to penicillin, amoxycillin-clavulanate, cefaclor, ceftriaxone, erythromycin, tetracycline, and sulfamethoxazole-trimethoprim (cotrimoxazole), measured by a gradient diffusion, minimum inhibitory concentration technique. RESULTS: Of 1020 strains, 16.8% had intermediate susceptibility to penicillin and 8.6% were resistant. Rates of resistance to other drugs were: amoxycillin-clavulanate, 3.1%; cefaclor, 21.4%; ceftriaxone, 3.1%; erythromycin, 15.6%; tetracycline, 15.7%; and cotrimoxazole, 33.4%. Non-invasive isolates harboured more resistances than invasive isolates, and resistance was more prevalent in isolates from children under two years. Multiple resistance was also common, with 21.2% of strains resistant to two or more classes of drug, and 9.3% of non-invasive and 1.7% of invasive isolates resistant to four classes. There were no obvious differences in resistance rates between private and public hospital laboratories. CONCLUSIONS: Rates of antimicrobial resistance are rising rapidly in S. pneumoniae in Australia. Recommendations for empiric treatment of invasive and respiratory infection need to take account of these changes.

Australia↗
PubMed1984

Binding of 125I-labeled beta-lactam antibiotics to the penicillin binding proteins of Escherichia coli.

125I-Labeled derivatives of the beta-lactam antibiotics cephalexin, cephradine, cefaclor and 6-alpha-aminopenicillanic acid have been obtained by reacting these compounds with (125I)-Bolton-Hunter reagent. The following target proteins were found in Escherichia coli: (1) The derivatives of cephalexin, cefaclor and cephradine preferentially interact with the high molecular weight penicillin binding proteins ( PBP1a and PBP1b ); (2) The 125I- derivative of 6-alpha-aminopenicillanic acid is preferentially bound by the low molecular weight penicillin binding proteins 4 and 5/6. The iodinated derivatives showed a very high affinity of binding to their target proteins with apparent half-saturating concentrations in the nano -molar range.

Ampicillin↗
PubMed1987

Synthesis and structure-activity relationships of a new oral cephalosporin, BMY-28100 and related compounds.

The synthesis and structure-activity relationships of 7-[D-alpha-amino-alpha-(4-hydroxyphenyl)-acetamido]-3-[(Z)-1-propenyl]- 3-cephem-4-carboxylic acid (BMY-28100) and its analogs in the 3- and 7-side chains are described. The 3-(substituted-propenyl) groups were introduced by the Wittig reaction of the 3-phosphoniomethyl cephems which were derived from the 3-chloromethyl derivatives. The reaction gave predominantly the cis isomer regarding the 3-side chain. The cis and trans isomers showed characteristic UV and 1H NMR spectra. Most of cephems of this series were well-absorbed orally and more active both in vitro and in vivo than cephalexin and cefaclor against Gram-positive organisms. Their Gram-negative activity varied depending on the 3- and 7-substituents. Compounds with a cis-propenyl group showed the best Gram-negative activity among the 3-alkenyl analogs prepared, whereas the D-4-hydroxyphenylglycyl and D-4-hydroxy-3-methoxyphenylglycyl substitutions in the 7-side chain were found suitable to improve the Gram-negative activity of 3-cis-propenyl series of cephalosporins to the level favorably compared with that of cefaclor. The 3,4-dihydroxyphenyl analog was found to be metabolized in vivo to the 4-hydroxy-3-methoxyphenyl derivative and, therefore, showed nearly the same in vivo activity as that of the latter. BMY-28100 was selected for further evaluation and the results will be reported in the subsequent paper.

Animals↗
PubMed1988

Pharmacokinetics of FK482, a new orally active cephalosporin, in animals.

The pharmacokinetic profile of FK482 was studied in mice, rats, rabbits and dogs after oral dosing and compared with that of cefixime, cefaclor and cephalexin. Considerable differences in oral absorption of FK482 were observed among the animal species. Absolute bioavailabilities of FK482 were 12.6% in mice, 15.3% in rats, 32.3% in rabbits and 72.3% in dogs. In mice and rats, the absorption of FK482 was poor, and was the lowest of the reference antibiotics. FK482 was moderately well absorbed, with higher plasma levels than cefixime in rabbits and, like cefixime, gave higher plasma levels and a longer half-life than cefaclor or cephalexin in dogs. The increase in the area under the serum concentration time curve (AUC) of FK482 was strictly proportional to the increase in dose in the range of 2.5 to 40 mg/kg in rats and dogs, and 2.5 to 20 mg/kg in rabbits and the urinary recovery rates were almost constant. All tissue concentrations of FK482 in rats and rabbits were lower than those of the reference antibiotics and reflected its lower plasma concentrations in these animals. The urinary recovery rates of FK482 were 9.8% for mice, 15.5% for rats, 45.8% for rabbits and 47.1% for dogs. The biliary recovery rate of FK482 was low; 1.4% in rats and less than 0.1% in rabbits and dogs. No active metabolites were detected in the plasma, urine or bile samples from rats, rabbits or dogs. FK482 was mainly absorbed in the jejunum, and was inactivated in the large intestine. The serum-protein binding of FK482 was almost the same as that of cefixime: 60-77% for mouse, rabbit and human serum, and 90-93% for rat and dog serum.

Administration, Oral↗
PubMed1992

RU 29 246, the active compound of the cephalosporin-prodrug-ester HR 916. I. Antibacterial activity in vitro.

The aminothiazolyl-cephalosporin RU 29 246 is the active metabolite of the prodrug-pivaloyl-oxyethyl-ester HR 916. RU 29 246 in vitro activity includes a wide range of clinically relevant bacterial pathogens. Against methicillin-sensitive Staphylococci RU 29 246 (MIC90 of 0.25 approximately 2 micrograms/ml) was clearly more active than cefaclor, cefuroxime, cefpodoxime, cefixime and ceftibuten, but slightly less active than cefdinir. RU 29 246 inhibited hemolytic Streptococci of the serogroups A, B, C and G as well as penicillin-sensitive Streptococcus pneumoniae at concentrations similar to cefdinir, cefpodoxime and cefuroxime (MIC90 less than or equal to 0.13 micrograms/ml), but less than the other oral cephalosporins investigated (cefixime, cefaclor and ceftibuten). MIC90s of RU 29 246 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella spp., Shigella spp., Proteus mirabilis and Haemophilus influenzae were less than or equal to 0.5 micrograms/ml. Only RU 29 246 and cefdinir demonstrated moderate activity against Acinetobacter baumannii (MIC90 greater than or equal to 4 micrograms/ml). Most strains of Pseudomonas spp., Serratia marcescens, Enterobacter spp., Hafnia alvei and Bacteroides spp. were resistant to RU 29 246. RU 29 246 killed Escherichia coli and Staphylococcus aureus at a rate of 99% to 99.9% at concentrations of two times MIC. The pH value of the medium (range 5.5 to 8.5) and the inoculum size (range 10(5) to 10(7) cfu/ml) had no or only low influence on the antibacterial activity of RU 29 246. RU 29 246 is a broad spectrum cephalosporin including in its activity both Gram-positive and Gram-negative pathogens and therefore--depending on the bioavailability of its prodrug--looks promising as to its therapeutic perspective.

Anti-Bacterial Agents↗
PubMed1992

RU 29 246, the active compound of the cephalosporin prodrug-ester HR 916. III. Pharmacokinetic properties and antibacterial activity in vivo.

The pharmacokinetics of the broad spectrum cephem RU 29 246 and its prodrug-ester HR 916 B were investigated in mice, rats and dogs and compared to those of cefpodoxime proxetil, cefuroxime axetil and cefixime. HR 916 B is well absorbed following oral administration and efficiently converted to the antibacterially active form. In mice, mean peak blood levels of 31.1 micrograms/ml of the parent compound were recorded within 20 minutes after oral administration of a single dose equivalent to 40 mg/kg RU 29 246. The bioavailability calculated on the basis of the areas under the concentration-time curves (AUC) and the urinary recoveries was about 90%. In rats, peak blood levels of 14.5 micrograms/ml were obtained 1 hour after an oral 20 mg/kg dose. The bioavailability was calculated as 70%. In dogs, 40% of an oral 10 mg/kg dose was recovered in the urine within 24 hours. Cmax was 15.9 micrograms/ml at 4.6 hours. Mean elimination half-lives of RU 29 246 were 0.35, 0.5 and 2.1 hours in mice, rats and dogs, respectively. After an oral HR 916 B dose equivalent to 50 mg/kg of RU 29 246, tissue concentrations at 0.5 hour ranged between 0.8 micrograms/g in brain and 95.7 micrograms/g in murine kidneys. These values of HR 916 B are similar to, or distinctly higher than, those of the reference compounds. Of the oral cephalosporins tested, HR 916 B had the most balanced antibacterial spectrum. With ED50s of between 0.9 and 11.5 mg/kg against staphylococci, its activity was similar to that of the additional reference compound cefaclor and higher than that of cefuroxime. Cefixime and cefpodoxime proxetil displayed low antistaphylococcal activity or were inactive. In septicemias with Enterobacteriaceae, cefixime and cefpodoxime proxetil were more potent than HR 916 B and cefaclor. Cefuroxime axetil was inactive against most of these infections. HR 916 B was also highly effective against murine lung infections caused by Klebsiella pneumoniae DT-S or Streptococcus pneumoniae 1147.

Animals↗
PubMed1999

Determination of the antimicrobial susceptibilities of Canadian isolates of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Canadian Antimicrobial Study Group.

The susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several antimicrobial agents were tested by two different methods. Beta-lactamase was produced by 68/211 (32.2%) of H. influenzae isolates and 64/75 (85.3%) of M. catarrhalis isolates. For S. pneumoniae, 19/156 (12.2%) isolates were resistant to penicillin (MIC > or = 0.12 mg/L) and two isolates had MICs of 1.5 mg/L. For some combinations of agents and organisms, different methods gave different values for the proportion of isolates susceptible. Regardless of methodology, for H. influenzae, the most active antimicrobials based on proportion of strains susceptible were ciprofloxacin (100%) and cefpodoxime (98.5-100%). For M. catarrhalis, the most active agents were azithromycin, cefaclor, cefixime, cefpodoxime, cefuroxime, ciprofloxacin, clarithromycin and loracarbef (100% each); the least active was ampicillin. Against penicillin-sensitive and -resistant pneumococci, the activity was not significantly different for azithromycin and clarithromycin (93.4-100%) and ciprofloxacin (MIC90 2.0 and 1.5 mg/L, respectively) but was different for cefuroxime (99.3% and 31.6%, respectively), cefaclor (MIC90 0.75 and > or = 256 mg/L, respectively), cefpodoxime (MIC90 0.047 and 1.5 mg/L, respectively) and loracarbef (MIC90 0.75 and > or = 256 mg/L, respectively). This study indicates the increasing incidence, in Canada, of beta-lactamase resistance in H. influenzae and M. catarrhalis and penicillin resistance in S. pneumoniae.

Anti-Bacterial Agents↗