A Comparison of Cefditoren Pivoxil 8-12 mg/kg/day and Cefditoren Pivoxil 16-20 mg/kg/day in Treatment of Children With Acute Presumed Bacterial Rhinosinusitis: A Prospective, Randomized, Investigator-Blinded, Parallel-Group Study

OBJECTIVES: Cefditoren pivoxil (CDT) has been used in the treatment of rhinosinusitis. However, little is known about the efficacy of this drug at low and high doses. This study was to compare the efficacy and safety of low dose (8-12 mg/kg/day) and high dose (16-20 mg/kg/day) CDT in the treatment of children with uncomplicated acute rhinosinusitis (ARS). METHODS: This investigation was a randomized, investigator-blinded, and parallel study, conducted in patients (aged 1-15 years) with a clinical diagnosis of uncomplicated ARS. Two groups of patients randomly received low dose or high dose CDT for 14 days. Patients' symptoms were assessed quantitatively using a quantitative symptom score (the S5 score). The changes in sinus symptoms and adverse events were provided by patients and their parents/caregivers. The response rate and adverse effects were evaluated at days 7 and 14. The relapse rate was recorded at days 21 and 28. The recurrences of sinus symptoms at day 60 were also assessed. RESULTS: One hundred forty patients were recruited and randomized; 72 received low dose CDT (group I) and 68 received high dose CDT (group II). There were no significant differences in demographic data including sex, age, presenting symptoms, medical history, and X-ray findings between two groups. The responses rate at day 14 in groups I and II were 95.5% and 95.4%, respectively (P>0.99). There were no significant differences between groups in relapse rate at day 28 and no recurrence at day 60 in either group. The most common treatment-related adverse events were diarrhea (4.2% in group I vs. 2.9% in group II) and vomiting (2.8% in group I vs. 10.3% in group II). There was no statistically significant difference in adverse events between groups. CONCLUSION: Both low and high doses regimens of CDT appeared a similar clinical outcome for treatment in uncomplicated ARS in pediatric patients.

UPLC method development and validation for cefditoren pivoxil in active pharmaceutical ingredient.

The objective of the study was to develop UPLC method for the determination of purity of Cefditoren Pivoxil in API and its validation. UPLC is a better technique than HPLC in terms of performance and speed, so it was selected. The method was developed using Acetonitrile and Ammonium Acetate buffer (pH 6.7) and Kromacil column C18 (50×2.1mm, 3.5μ) as a stationary phase at a flow rate of 0.25ml/min. Validation was done by linearity, precision, and robustness studies. The precision was found to be within the limits. The linearity studies indicated the drug obeys Beer’s law and revealed the specified range of linearity for drug was between 80μg/ml and 120μg/ml. The robustness was observed from the insignificant variation in the analysis by changes in flow rate, mobile phase ratio, wavelength, column oven temperature and pH. Forced Degradation study revealed the drug degraded initially by the influence of acid, alkali, and peroxide. Solution stability study showed the drug was not stable for more than 2 h at 25˚C but stable at 5˚C. It can be concluded that the proposed method was simple, precise, and robust and can be useful for determination of purity of Cefditoren Pivoxil in API by using UPLC.

In vitro antimicrobial activity of cefditoren against Streptococcus pneumoniae and Haemophilus influenzae clinical isolates / 대한내과학회지

BACKGROUND: The aim of this study was to determine the in vitro activity of cefditoren, an oral third-generation aminothiazolyl cephalosporin, against Streptococcus pneumoniae and Haemophilus influenzae clinical isolates in a tertiary hospital. METHODS: We have studied the in vitro activities of cefditoren and other oral antibiotics against 120 S. pneumoniae isolates, including 80 penicillin non-susceptible isolates and 80 H. influenzae isolates from clinical specimens of patients at the Asan Medical Center. Minimal inhibitory concentrations (MICs) were determined by the agar dilution method. RESULTS: All S. pneumoniae strains tested were inhibited by 1 g/mL of cefditoren (MIC50/MIC90 0.25/1 microgram/mL; range 0.015~1 microgram/mL). The MICs were lower for penicillin-susceptible S. pneumoniae (MIC90 0.015 g/mL) as compared to penicillin-intermediate resistant (MIC90 0.5 g/mL) or penicillin- resistant strains (MIC90 1 microgram/mL). Cefditoren was active against all tested H. influenzae strains (MIC50/MIC90 0.015/0.03 microgram/mL; range <0.008~0.03 g/mL) and its activity was comparable to levofloxacin and cefixime. CONCLUSIONS: Cefditoren had an excellent activity against S. pneumoniae and H. influenzae irrespective of penicillin or ampicillin resistance, respectively. The results of this study suggest that cefditoren is a good choice of an antibiotic to use for empirical oral treatment of community-acquired respiratory tract infections.

In vitro Activities of Oral Cephem and Telithromycin Against Clinical Isolates of Major Respiratory Pathogens in Japan

The in vitro antibacterial activities of oral cephem antibiotics and ketolide telithromycin against major respiratory pathogens possessing beta-lactam-resistant mutations (within the pbp gene) and/or macrolide-resistant genes (erm and mef) were examined in clinical isolates collected at 66 institutes in all over the Japan between 2002 and 2003. Telithromycin showed the strongest antibacterial activity against methicillinsusceptible Staphylococcus aureus strains with and without macrolide-resistant genes, such as ermA or ermC gene. All the cephem antibiotics showed potent antibacterial activity against Streptococcus pyogenes, with minimum inhibitory concentrations (MICs) of 0.015 mg/L or lower. Cefdinir had a much higher MIC90 against genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) than cefditoren and cefcapene (8 mg/L cefdinir vs. 1 mg/L cefditoren and cefcapene). The majority of gPRSP harbored either ermB or mefA, and the antibacterial activity of telithromycin against these strains was decreased however some susceptibility was still sustained. Cefditoren exerted the strongest antibacterial activity against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, with an MIC90 of 0.5 mg/L. These results underline the importance of checking the susceptibility and selecting an appropriate antibiotic against target pathogens.

In Vitro Activity of Cefditoren against Respiratory Pathogens / 감염과화학요법

BACKGROUND: Cefditoren is a third generation orally administered cephalosporin with excellent activity against respiratory pathogens. This study was performed to determine the comparative antibacterial activity of cefditoren against clinical isolates of respiratory tract infection. MATERIALS AND METHODS: According to the NCCLS guideline, in vitro activities of cefditoren and other antibiotics were tested against respiratory pathogens including 117 isolates of Streptococcus pneumoniae, 60 isolates of Haemophilus influenzae, and 31 isolates of Moraxella catarrhalis. RESULTS: The level of cefditoren activity against S. pneumoniae (MIC50/90, 0.5/1 microgram/mL) was superior to amoxicillin+/-clavulanate (MIC50/90, 4/16 microgram/mL), clarithromycin (MIC50/90, >32/>32 microgram/mL), and most of the marketed cephalosporins (MIC50/90, 8-64/16-128 microgram/mL). Although the MIC of cefditoren was relatively higher than those of new fluoroquinolone agents (MIC50/90, 0.03-1/0.06-1 microgram/mL), it was comparable to ceftriaxone (MIC50/90, 0.5/1 microgram/mL). In addition, cefditoren was active against two quinolone resistant pneumococci strains with MIC of 0.5 microgram/mL. In detail, cefditoren was active against pneumococci strains with MIC50 and MIC90 values of 0.015/0.12, 0.12/0.5, and 0.5/1 microgram/mL for penicillin-susceptible, -intermediate, and -resistant pneumococci, respectively. Cefditoren was also active against all respiratory isolates of H. influenzae (MIC50/90, 0.03/0.06 microgram/mL) and M. catarrhalis (MIC50/90, 0.03/0.05 microgram/mL) irrespective of beta-lactamase production or ampicillin resistance. CONCLUSION: Cefditoren is considered to be a good option for outpatient treatment of respiratory infections, particulary if there is concern about S. pneumoniae infection with decreased susceptibility to penicillin or beta-lactamase producing organisms.

In Vitro Activity of Cefditoren against Respiratory Pathogens / 감염과화학요법

BACKGROUND: Cefditoren is a third generation orally administered cephalosporin with excellent activity against respiratory pathogens. This study was performed to determine the comparative antibacterial activity of cefditoren against clinical isolates of respiratory tract infection. MATERIALS AND METHODS: According to the NCCLS guideline, in vitro activities of cefditoren and other antibiotics were tested against respiratory pathogens including 117 isolates of Streptococcus pneumoniae, 60 isolates of Haemophilus influenzae, and 31 isolates of Moraxella catarrhalis. RESULTS: The level of cefditoren activity against S. pneumoniae (MIC50/90, 0.5/1 microgram/mL) was superior to amoxicillin+/-clavulanate (MIC50/90, 4/16 microgram/mL), clarithromycin (MIC50/90, >32/>32 microgram/mL), and most of the marketed cephalosporins (MIC50/90, 8-64/16-128 microgram/mL). Although the MIC of cefditoren was relatively higher than those of new fluoroquinolone agents (MIC50/90, 0.03-1/0.06-1 microgram/mL), it was comparable to ceftriaxone (MIC50/90, 0.5/1 microgram/mL). In addition, cefditoren was active against two quinolone resistant pneumococci strains with MIC of 0.5 microgram/mL. In detail, cefditoren was active against pneumococci strains with MIC50 and MIC90 values of 0.015/0.12, 0.12/0.5, and 0.5/1 microgram/mL for penicillin-susceptible, -intermediate, and -resistant pneumococci, respectively. Cefditoren was also active against all respiratory isolates of H. influenzae (MIC50/90, 0.03/0.06 microgram/mL) and M. catarrhalis (MIC50/90, 0.03/0.05 microgram/mL) irrespective of beta-lactamase production or ampicillin resistance. CONCLUSION: Cefditoren is considered to be a good option for outpatient treatment of respiratory infections, particulary if there is concern about S. pneumoniae infection with decreased susceptibility to penicillin or beta-lactamase producing organisms.

In Vitro Antimicrobial Activity of Cefditoren pivoxil, an Oral Cephalosporin, against Major Clinical Isolates / 감염과화학요법

BACKGROUND: Cefditoren is an oral cephalosporin with excellent activity against Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, which are the predominant bacterial causes of community-acquired respiratory tract infections. The current study attempted to determine the antibacterial activity of cefditoren against the major clinical isolates. METHODS: According to the NCCLS recommendations, antibacterial activities of cefditoren were measured against total 504 major clinical isolates. MICs were determined by the agar dilution method, a series of doubling dilutions from 128 to 0.03 microgram/mL, on E. coli, K. pneumoniae, E. cloacae, C. freundii, S. marcescens, P. mirabilis, and Staphylococcus spp. In case of H. influenzae, S. pneumoniae, and M. catarrhalis, broth microdilution method, a series of doubling dilutions from 16 to 0.015 microgram/mL, was performed. RESULTS: Cefditoren had variable activity against Enterobacteriaceae. MIC cumulative curves showed that cefditoren had low MIC distributions against E. coli and P. mirabilis, and MIC90 were 8 and 0.5 microgram/mL, respectively. Against K. pneumoniae, E. cloacae, C. freundii, and S. marcescens, cefditoren's MIC90 values ranged from 32 to >128 microgram/mL. For clinical isolates of methicillin-susceptible S. aureus and methicillin-susceptible S. epidermidis, cefditoren had MIC90 values of 1 microgram/mL and 0.5 microgram/mL, respectively. Cefditoren had MIC90 values of 1 microgram/mL for penicillin-susceptible and penicillin-not-susceptible strains of S. pneumoniae. Cefditoren had MIC90 values of 0.03 microgram/mL and 0.5microgram/mL against H. influenzae and M. catarrhalis, respectively. CONCLUSION: Cefditoren had excellent activity against S. pneumoniae, H. influenzae, and M. catarrhalis. Cefditoren had variable activity against Enterobacteriaceae. The results of this study confirm the excellent activity of cefditoren against the major respiratory tract pathogens and suggest that cefditoren could be a good antibiotic for empiric oral treatment of community-acquired respiratory tract infections.

In Vitro Antimicrobial Activity of Cefditoren pivoxil, an Oral Cephalosporin, against Major Clinical Isolates / 감염과화학요법

BACKGROUND: Cefditoren is an oral cephalosporin with excellent activity against Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, which are the predominant bacterial causes of community-acquired respiratory tract infections. The current study attempted to determine the antibacterial activity of cefditoren against the major clinical isolates. METHODS: According to the NCCLS recommendations, antibacterial activities of cefditoren were measured against total 504 major clinical isolates. MICs were determined by the agar dilution method, a series of doubling dilutions from 128 to 0.03 microgram/mL, on E. coli, K. pneumoniae, E. cloacae, C. freundii, S. marcescens, P. mirabilis, and Staphylococcus spp. In case of H. influenzae, S. pneumoniae, and M. catarrhalis, broth microdilution method, a series of doubling dilutions from 16 to 0.015 microgram/mL, was performed. RESULTS: Cefditoren had variable activity against Enterobacteriaceae. MIC cumulative curves showed that cefditoren had low MIC distributions against E. coli and P. mirabilis, and MIC90 were 8 and 0.5 microgram/mL, respectively. Against K. pneumoniae, E. cloacae, C. freundii, and S. marcescens, cefditoren's MIC90 values ranged from 32 to >128 microgram/mL. For clinical isolates of methicillin-susceptible S. aureus and methicillin-susceptible S. epidermidis, cefditoren had MIC90 values of 1 microgram/mL and 0.5 microgram/mL, respectively. Cefditoren had MIC90 values of 1 microgram/mL for penicillin-susceptible and penicillin-not-susceptible strains of S. pneumoniae. Cefditoren had MIC90 values of 0.03 microgram/mL and 0.5microgram/mL against H. influenzae and M. catarrhalis, respectively. CONCLUSION: Cefditoren had excellent activity against S. pneumoniae, H. influenzae, and M. catarrhalis. Cefditoren had variable activity against Enterobacteriaceae. The results of this study confirm the excellent activity of cefditoren against the major respiratory tract pathogens and suggest that cefditoren could be a good antibiotic for empiric oral treatment of community-acquired respiratory tract infections.