cefdinir and cefditoren

Acute kidney injury (AKI) was a common organ damage that often occurred after cisplatin. This study was aimed at investigating the pharmacokinetic changes of cefdinir and cefditoren in AKI rats, and elucidating the possible molecular mechanisms.. The renal injury model was established by intraperitoneal injection of cisplatin (12 mg/kg). Plasma creatinine, blood urea nitrogen, the mRNA expression of Kim-1, hematoxylin and eosin staining and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay were used to measure the degree of renal damage. On this basis, the pharmacokinetic changes of cefdinir and cefditoren were investigated in normal and AKI rats. RT-PCR and Western blot were performed to clarify the molecular mechanisms for the changes in the related transporters expression.. The cumulative urinary excretion of cefdinir was significantly decreased and the plasma concentration was remarkably increased in AKI rats. The expression of organic anion transporter 1 (Oat1) and Oat3 in kidney was decreased. However, pharmacokinetics of cefditoren was not influenced. The expression of organic anion-transporting polypeptide 1a1 (Oatp1a1), Oatp1a4, Oatp1b2 and multidrug resistance-associated protein 2 (Mrp2) in liver was unchanged in AKI rats.. The molecular mechanism of decreased expression of Oat1 and Oat3 was achieved through activating p53, and then increasing the expression of Bax and Caspase-3 and down regulating Bcl-2 in AKI rats. On this basis, the cumulative urinary excretion of cefdinir was significantly decreased and the plasma concentration of cefdinir was remarkably increased in AKI rats. However, the pharmacokinetic changes of cefditoren were not observed. Accordingly, cephalosporin antibiotics such as cefditoren should be firstly selected for the treatment in patients with AKI in clinic.

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Cefdinir; Cephalosporins; Cisplatin; Disease Models, Animal; Gene Expression Regulation; Kidney; Male; Organic Anion Transport Protein 1; Organic Anion Transporters, Sodium-Independent; Rats, Wistar; Renal Elimination

The antibacterial susceptibility to frequently prescribed antibiotics of Streptococcus pneumoniae isolated from the pediatric patients with acute respiratory infectious diseases was investigated in a study of three medical institutions in Korea. Total 143 clinical isolates of S. pneumoniae were available for susceptibility tests between May 2003 and July 2007. Antimicrobial susceptibility data for S. pneumoniae were analyzed by using agents of amoxicillin, cefaclor, cefuroxime, cefdinir, and cefditoren as the test antibiotics. The prevalence of each resistance class, penicillin-resistant S. pneumoniae (PRSP) were high with the proportion of MIC range (susceptible = 8.4%, intermediate resistance = 18.2%, resistance = 73.4%). MIC90 and susceptible (S) rate of antimicrobial agents to the strains tested were amoxicillin (MIC90 = 4 microg/ml, S = 76.2%), cefaclor (MIC90 = 128 microg/ml, S=8.4%), cefuroxime (MIC90 = 16 microg/ml, S = 24.5%), cefdinir (MIC90 = 16 microg/ml, S = 21.8%), and cefditoren (MIC90 = 0.5 microg/ml, S=90.2%) respectively. Against clinical isolates including PRSP, cefditoren demonstrated the strongest antibacterial activity intrinsically among the antibiotics tested. Conclusively, the antimicrobial activity of cefditoren to S. pneumoniae strains isolated from pediatric patients with acute respiratory infection is very high. In South Korea, where the antibiotic resistance ofS. pneumoniae is issued, cefditoren is expected to be used as a primary or secondary antibiotic. Moreover, cefditoren may serve as a useful option for secondary antibiotics after failure of amoxicillin treatment, which is most primarily used for acute respiratory S. pneumoniae infection in children.

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Cefaclor; Cefdinir; Cefuroxime; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Korea; Respiratory Tract Infections; Streptococcus pneumoniae

Horizontal transfer of the mutated ftsI gene from beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae to a susceptible strain was examined in vitro under selection with nine oral beta-lactams (ampicillin, amoxicillin, cefprozil, cefuroxime, cefpodoxime, cefdinir, cefcapene, cefditoren, and tebipenem). Compared to the penicillins and the carbapenem, the cephalosporins showed a wide selection window for the genetic transfer.

Topics: Ampicillin; Bacterial Proteins; beta-Lactams; Carbapenems; Cefdinir; Cefprozil; Cephalosporins; Gene Transfer, Horizontal; Haemophilus influenzae; Mutation; Penicillin-Binding Proteins

A total of 2865 strains of the causative organisms isolated from the patients with acute pharyngitis and tonsillitis at the primary medical institutions were used in this study. The MICs of levofloxacin (LVFX) and other oral antimicrobial drugs were determined and evaluated by the NCCLS guideline. LVFX, cefditoren (CDTR) and cefcapene (CFPN) were potently active against 773 isolates of Hemophilus influenzae, the MIC50S of LVFX being < or = 0.06 microgram/mL and also the same as the MIC90S of LVFX. LVFX was the most active against 496 isolates of Enterobacteriaceae. The MIC50S of LVFX were < or = 0.06 microgram/mL and were lower than those of CDTR, cefdinir (CFDN) and cefpodoxime (CPDX) (MIC50S: 0.5 microgram/mL). The MIC90S of these cephems were markedly higher than the respective MIC50S, whereas MIC50 of LVFX was 0.12 microgram/mL, only twice the MIC50. Against the majority of Streptococcus pyogenes (555 isolates) and Streptococcus spp. (495 isolates), CDTR, CFDN, CPDX and CFPN were highly active (MICs: < or = 0.06 microgram/mL), and clarithromycin (CAM) and azithromycin (AZM) were also active against these organisms (MICs: 0.12 to 0.25 microgram/mL). Against S. pneumoniae (92 isolates), CDTR and CFDN were active (MIC50S: 0.12 and 0.25 microgram/mL, respectively). However, the MIC90S of these drugs were 4-8 times the MIC50S. Against Moraxella (Branhamella) catarrhalis (454 isolates), LVFX was potently active, the MIC90 of LVFX being < or = 0.06 microgram/mL and MIC90S of the other cephems being 0.5 microgram/mL or more. When the susceptibility of these strains to LVFX was evaluated by the NCCLS guideline, about 3% of other Streptococcus spp. were resistant to the drug but no test strains resistant to LVFX were detected in H. influenzae, S. pyogenes or Enterobacteriaceae. On the other hand, the percentages of strains susceptible to the cephems tested were 60-90%, which were quite different according to kinds of drugs and species used. Furthermore, the strains of S. pneumoniae resistant to CFDN and CPDX, and those to CAM and AZM were 21-25% and 50% or more, respectively, whereas no LVFX-resistant strains were detected. The major pathogens isolated from patients with pharyngitis and tonsillitis in the primary institutions were highly susceptible to LVFX. These results suggest that LVFX is a useful drug which is potently active against the strains resistant to oral cephem and macrolide antibiotics.

Topics: Acute Disease; Ampicillin; Anti-Infective Agents; Azithromycin; Cefdinir; Cefpodoxime; Ceftizoxime; Cephalosporins; Clarithromycin; Enterobacteriaceae; Haemophilus influenzae; Humans; Levofloxacin; Ofloxacin; Penicillin G; Pharyngitis; Streptococcus pneumoniae; Streptococcus pyogenes; Tonsillitis

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

Each 20 strains of beta-lactamase producing methicillin susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Bacteroides fragilis group were used as the test strains. Drug susceptibility of these strains to faropenem (FRPM), cefdinir, cefditoren, cefcapene, cefteram, cefaclor, and ampicillin was determined by an agar dilution method according to the NCCLS guideline M100-S9. beta-Lactamase activity of the test strains was determined by a spectrophotometric method. In the present study, FRPM was highly active against beta-lactamase-producing strains, and no close correlation was found between the MICs of FRPM for the test strains and their beta-lactamase activities. These results suggest that FRPM has potential in successful application for the treatment of infectious diseases with various types of bacterial pathogens including beta-lactamase producing strains.

Topics: Anti-Bacterial Agents; Bacteria; beta-Lactamases; beta-Lactams; Cefdinir; Cephalosporins; Drug Resistance, Microbial; Humans; Lactams; Microbial Sensitivity Tests

One hundred and thirteen strains of Streptococcus pneumoniae (S. pneumoniae) were isolated from the clinical specimens of patients with respiratory tract infections between January and December 1998 in three hospitals in Hokusetsu area of Osaka. We investigated susceptibility of 113 strains of S. pneumoniae to benzylpenicillin (PCG) and other antimicrobial agents and their serotypes. 1) Of the 113 strains of S. pneumoniae isolated, 25.7% were susceptible (PSSP), 51.3% were intermediate (PISP) and 23% were resistant to benzylpenicillin (PRSP). 2) The MICs of cefaclor, cefditoren, cefpodoxime, cefdinir, erythromycin, clindamycin and minocycline were elevated, but the MIC values of cefditoren ranged from < or = 0.03 to 1.0 microgram/ml. The susceptibility of 113 strains to cefditoren was comparatively high. 3) The MIC values of imipenem, meropenem and vancomycin for 81 strains of PISP and PRSP ranged from < or = 0.015 to 1.0 microgram/ml, from < or = 0.015 to 2.0 micrograms/ml and from 0.13 to 0.5 microgram/ml, respectively. The susceptibility of these strains to three antimicrobial agents was superior to that to the other antimicrobial agents examined. 4) Of the 60 strains examined, 19, 6, and 23 serotypes were 30, 25 and 18.3%, respectively. The three serotypes were observed in PISP and PRSP with a high frequency. 5) Isolates of S. pneumoniae were 37.2% for children under 2 years of age and 30.9% for children from 2 to 6 years of age. Most of the strains isolated from these children were resistant.

Topics: Anti-Bacterial Agents; Cefdinir; Cefpodoxime; Ceftizoxime; Cephalosporins; Child; Child, Preschool; Clindamycin; Erythromycin; Humans; Minocycline; Penicillin G; Penicillins; Respiratory Tract Infections; Serotyping; Streptococcus pneumoniae

The frequency and the antibacterial sensitivity of Streptococcus pneumoniae strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology clinic in Gifu Prefecture from February to March, 1999, were investigated with several antibiotics. A total of 128 strains of Streptococcus pneumoniae were isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S. pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S. pneumoniae (PISP), and 30 strains (23.4%) of penicillin-resistant S. pneumoniae (PRSP); the resistant bacteria being relatively prominent. In these hospitals, PSSP was isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology clinic with almost no discernible difference. PISP was isolated by 63.3%, higher in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals conversely. The MIC90s in PISP and PRSP were determined with the antibiotics. In result, only cefditoren (CDTR) showed favorable antibacterial activities with the MIC90 of 0.78 microgram/ml among penicillins or oral cephems. The MIC90s of carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial activities. Among new quinolones such as tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest antibacterial activities with the MIC90 of 0.39 microgram/ml. Other agents showed very low antibacterial activities as the MIC90s were 25 micrograms/ml in minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and clindamycin (CLDM).

Topics: Amoxicillin; Anti-Bacterial Agents; Cefaclor; Cefdinir; Cefixime; Cefmenoxime; Cefpodoxime; Ceftizoxime; Cephalosporins; Ciprofloxacin; Clarithromycin; Clindamycin; Drug Resistance, Microbial; Fluoroquinolones; Humans; Imipenem; Japan; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Minocycline; Naphthyridines; Ofloxacin; Penicillin G; Penicillins; Streptococcus pneumoniae; Thienamycins

Against enterohemorrhagic Escherichia coli (EHEC) O157 clinically isolated, the effects of faropenem (FRPM), a novel oral penem antibiotic, on the MICs, bactericidal activity, verotoxin (VT)-release, and lipopolysaccharide (LPS)-release were investigated in vitro and compared with those of other types of antibacterial agents. The MICs of FRPM in aerobic and anaerobic culture condition, were 0.78 and 0.39 microgram/ml, respectively. In aerobic condition, FRPM was more active than ampicillin, amoxicillin (AMPC), fosfomycin (FOM), kanamycin (KM), minocycline (MINO), and clarithromycin (CAM), but was slightly less active than cefdinir (CFDN), cefditoren (CDTR), and norfloxacin (NFLX) against O157 clinical isolates. In anaerobic condition, however, FRPM showed as strong activity as CFDN, CDTR, and NFLX. FOM, NFLX, and KM as well as the beta-lactams including FRPM indicated the powerful bactericidal activity against one strain of O157 clinical isolates. The effects of MINO and CAM were bacteriostatic. FOM and the beta-lactams including FRPM promoted verotoxin type 1 (VT1)-release, but rather suppressed verotoxin type 2 (VT2)-release from the same isolate. NFLX, however, promoted VT1-release and vast amount of VT2-release. In the case of KM, MINO, and CAM, the release suppression of both VT1 and VT2 was observed. FRPM, AMPC, and FOM had very weak activity on LPS-release, while CFDN, CDTR, and NFLX released a large amount of LPS from the strain. KM, MINO, and CAM had relatively weak activity. In these in vitro experiments, FRPM demonstrated the effective profile to the treatment for EHEC infection, except for the effect on VT1-release. These results suggest the possibility that FRPM shows good clinical efficacy for EHEC infection.

Topics: Amoxicillin; Ampicillin; Anti-Bacterial Agents; Bacterial Toxins; beta-Lactams; Cefdinir; Cephalosporins; Clarithromycin; Escherichia coli O157; Fosfomycin; Kanamycin; Lactams; Microbial Sensitivity Tests; Minocycline; Norfloxacin; Shiga Toxin 1