cefditoren and Bacterial-Infections

Cefditoren pivoxil, an oral third-generation cephalosporin, was approved by the Food and Drug Administration in September 2001. It has been used in Japan for several years. The greatest therapeutic potential of cefditoren appears to be its activity against gram-positive and gram-negative organisms causing respiratory tract infections and skin and skin-structure infections, such as Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Cefditoren is also effective against methicillin-susceptible strains of Staphylococcus aureus. Nevertheless, cefditoren has no activity against atypical pathogens, including Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella sp. Moreover, cefditoren does not inhibit Pseudomonas aeruginosa or Bacteroides fragilis. In virtually all studies, cefditoren has compared favorably against other orally administered antibiotics used against the most commonly isolated respiratory tract pathogens. Its side effect profile includes diarrhea, nausea, vomiting, headache, and dyspepsia. Cefditoren is indicated for treatment of mild-to-moderate acute exacerbations of chronic bronchitis, pharyngitis-tonsillitis, and uncomplicated skin and skin-structure infections caused by susceptible strains of organisms in adults and adolescents (> or = 12 yrs of age). Based on its reported antimicrobial activity, cefditoren has potential for empiric management of most commonly encountered respiratory tract infections. Additional studies will further define its role in clinical practice.

Topics: Acute Disease; Bacterial Infections; Bronchitis, Chronic; Cephalosporins; Clinical Trials as Topic; Community-Acquired Infections; Drug Interactions; Humans; Maxillary Sinusitis; Pharyngitis; Pneumonia, Bacterial; Skin Diseases, Bacterial

Cefditoren is an advanced-generation, broad-spectrum cephalosporin antibiotic approved for the treatment of acute bacterial exacerbation of chronic bronchitis (AECB), group A beta-hemolytic streptococcal pharyngotonsillitis, and uncomplicated skin/skin structure infections in adult and adolescent patients.. This article briefly reviews the chemistry, antimicrobial activity, pharmacokinetics, efficacy, and safety of cefditoren.. Literature was identified by a MEDLINE search (January 1985 to October 2001) of the medical literature, review of the English-language literature, reference lists within these articles, as well as data presented at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy.. Cefditoren has a broad spectrum of activity against many gram-negative and gram-positive aerobes, including Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Cefditoren is stable to hydrolysis by many common beta-lactamases. Cefditoren is rapidly absorbed (time to peak plasma concentration, approximately 2-3 hours) from the gastrointestinal tract and is almost completely eliminated via renal clearance of unchanged drug. The terminal disposition half-life of the compound is approximately 0.8 to 1.3 hours.. Cefditoren is effective in the management of AECB (in regimens of 400 mg twice daily for 10 days) and acute maxillary sinusitis, pharyngotonsillitis due to S pyogenes, and uncomplicated skin/skin structure infections (in regimens of 200 mg twice daily for 10 days). Cefditoren possesses broad activity against common pathogens of the respiratory tract and skin and is stable in the presence of numerous beta-lactamases. Its pharmacokinetic properties, in conjunction with in vitro susceptibility data, document the feasibility of twice-daily dosing.

Topics: Administration, Oral; Adolescent; Adult; Area Under Curve; Bacterial Infections; Cephalosporins; Chromatography, High Pressure Liquid; Half-Life; Humans; Intestinal Absorption; Microbial Sensitivity Tests; Randomized Controlled Trials as Topic

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Cephalosporins; China; Community-Acquired Infections; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections

To evaluate cefditoren in inducer-substrate combinations to screen for AmpC induction.. 100 clinical isolates (25 P. aeruginosa, 25 E. cloacae, 14 M. morganii, 13 S. marcescens, 12 C. freundii, 7 P. rettgeri, and 4 E. aerogenes) were tested by the Kirby-Bauer disc approximation method using cefditoren and ceftazidime discs as substrates, and cefditoren and imipenem discs as inducers.. None of the strains showed induction of AmpC with cefditoren-ceftazidime as inducer-substrate combination. Imipenem-cefditoren as inducer-substrate combination was not useful for evaluating strains of P. aeruginosa since no inhibition zones surrounding the cefditoren disc were found. Among evaluable enterobacteria (those showing substrate inhibition zone), inducible Amp C was detected in 48 out of 63 (76.2%) with cefditoren, and in 33 out of 68 (48.5%) isolates with ceftazidime as substrate. Significantly (p=0.013) higher number of AmpC producers were detected with cefditoren versus ceftazidime (76.2% vs. 48.5%), due to the differences found for E. cloacae (72.8% vs. 21.7%; p=0.0009) and S. marcescens (100% vs. 54.5%; p=0.03). Higher mean reductions of diameters around substrate discs were found for cefditoren (4.17 mm) vs. ceftazidime (3.79 mm), reaching statistical significance (p<0.05) for indol-positive proteae: M. morganii (5.32 mm vs. 3.92 mm) and P. rettgeri (3.47 mm vs. 2.64 mm).. Cefditoren showed no induction capability, and when used as substrate (with imipenem as inducer) it offered detection rates of AmpC inducible enterobacteria higher than the imipenem-ceftazidime combination, mainly for Enterobacter spp. and Serratia spp., with higher diameter reductions for indol-positive proteae.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Proteins; beta-Lactamases; Ceftazidime; Cephalosporins; Enterobacteriaceae; Humans; Imipenem; Microbial Sensitivity Tests; Species Specificity

As the post-marketing surveillance of cefpodoxime proxetil (Banan), MICs of cefpodoxime (CPDX, an active form of Banan) against 1090 clinical isolates of 22 species from 15 medical institutions all over Japan from June 2000 to March 2001 were measured using the broth microdilution method approved by the Japanese Society of Chemotherapy and compared with those of oral cephem antibacterials, cefaclor, cefdinir, cefditoren, and cefcapene. In this study, remarkable change in the activity of CPDX was observed in Streptococcus pneumoniae and Haemophilus influenzae compared with the susceptibility in the studies before Banan was launched. This cause is considered to be the increase in the incidence of the following resistant strains: penicillin-intermediate S. pneumoniae (47.3%), penicillin-resistant S. pneumoniae (PRSP, 15.1%), and beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae (24.0%), which were scarcely isolated in 1989 when Banan was launched. Other tested drugs also exhibited low activity against these resistant strains. However, CPDX showed comparatively good activity with MIC90 of 2 micrograms/mL against PRSP. Against methicillin-susceptible Staphylococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, and Moraxella catarrhalis, CPDX also showed comparatively good activity with MIC90 of < or = 4 micrograms/mL, which was almost equal to that in the studies before its marketing. Against quinolones-resistant Neisseria gonorrhoeae, CPDX showed excellent activity with MIC90 of 0.5 microgram/mL. Against members of the family Enterobacteriaceae except for Citrobacter freundii, Enterobacter spp., Proteus vulgaris, and Morganella morganii, CPDX showed good activity. However, in Escherichia coli, Klebsiella spp. Proteus spp., and Providencia spp., there are some high-resistant strains to all tested drugs including CPDX. Against Peptostreptococcus spp., MIC90 of CPDX was 8 micrograms/mL and its MIC range was widely distributed from 0.03 to 32 micrograms/mL, which were similar to those in the studies before its marketing. In this study, CPDX showed the decrease in the activity against several species as did other drugs tested, but against most of species tested, CPDX maintained good activity. Furthermore, it is necessary to pay much attention to the trend of resistant strains.

Topics: Adolescent; Adult; Bacteria; Bacterial Infections; Cefaclor; Cefdinir; Cefpodoxime; Cefpodoxime Proxetil; Ceftizoxime; Cephalosporins; Child; Drug Resistance, Bacterial; Humans; Japan; Product Surveillance, Postmarketing; Time Factors

Topics: Administration, Oral; Bacterial Infections; Bronchitis; Cephalosporins; Drug Approval; Drug Interactions; Humans; Pharyngitis; Prodrugs; Skin Diseases, Bacterial; United States; United States Food and Drug Administration

CS-834 is a novel oral carbapenem antibiotic. This compound is an ester-type prodrug of the active metabolite R-95867. The antibacterial activity of R-95867 was tested against 1,323 clinical isolates of 35 species and was compared with those of oral cephems, i.e., cefteram, cefpodoxime, cefdinir, and cefditoren, and that of a parenteral carbapenem, imipenem. R-95867 exhibited a broad spectrum of activity covering both gram-positive and -negative aerobes and anaerobes. Its activity was superior to those of the other compounds tested against most of the bacterial species tested. R-95867 showed potent antibacterial activity against clinically significant pathogens: methicillin-susceptible Staphylococcus aureus including ofloxacin-resistant strains, Streptococcus pneumoniae including penicillin-resistant strains, Clostridium perfringens, Neisseria spp., Moraxella catarrhalis, most members of the family Enterobacteriaceae, and Haemophilus influenzae (MIC at which 90% of strains are inhibited, < or =0.006 to 0.78 microg/ml). R-95867 was quite stable to hydrolysis by most of the beta-lactamases tested except the metallo-beta-lactamases from Stenotrophomonas maltophilia and Bacteroides fragilis. R-95867 showed potent bactericidal activity against S. aureus and Escherichia coli. Penicillin-binding proteins 1 and 4 of S. aureus and 1Bs, 2, 3, and 4 of E. coli had high affinities for R-95867. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Among the drugs tested, CS-834 showed the highest efficacy against experimental pneumonia in mice caused by penicillin-resistant S. pneumoniae.

Topics: Administration, Oral; Animals; Bacterial Infections; Bacterial Proteins; beta-Lactamases; Carbapenems; Carrier Proteins; Cefmenoxime; Cefpodoxime; Ceftizoxime; Cephalosporins; Drug Stability; Hexosyltransferases; Imipenem; Mice; Microbial Sensitivity Tests; Muramoylpentapeptide Carboxypeptidase; Penicillin-Binding Proteins; Peptidyl Transferases; Pneumonia, Staphylococcal; Prodrugs; Thienamycins