amoxicillin-potassium-clavulanate-combination and cefditoren

A high number of individuals in the population are exposed to antibiotics for the treatment of respiratory tract infections. It is important to review the adverse events profile related to antibiotic exposure during the clinical development of drugs that are or have been recently included in the therapeutic armamentarium.. Safety data from all 13 clinical trials of cefditoren on community acquired respiratory infections were reviewed. Safety population was defined as all randomized patients with at least one dose intake. Adverse events considered by investigators as related during antibiotic exposure were considered.. The overall safety population consisted in 4,592 patients for cefditoren and 2,784 for comparators. Overall reported diarrhoea related to cefditoren administration was significantly higher (p < or = 0.001) than comparators (9.9% vs 6.9%) due to the significant difference in the pooled pharyngotonsillitis studies (8.3% vs 3.2%), while no significant differences in others pathologies were found, with 9.4% (with cefditoren) vs 10.3% (with comparators) in the case of community-acquired pneumonia (CAP). Dyspepsia and abdominal pain were reported as adverse events in < 2.7% patients regardless the treated disease. In females population lower related vaginosis rate was found in cefditoren vs comparators, mainly due to differences among patients treated for sinusitis (4.5% vs 8.1%) and CAP (2.3% vs 5.5%) although differences were not significant (p = 0.017 and p = 0.008, respectively).. This study analysing reported adverse events from clinical trials showed an adverse events profile of cefditoren similar to those of standard antibiotics used in the treatment of respiratory tract infections.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cephalosporins; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Male; Penicillins; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Superinfection; Vaginitis

beta-Lactam antibiotics share a common structure and mechanism of action, although they differ in their spectrum of antimicrobial activity and utility in treating different infections. The current classes include the penicillins, the penicillinase-resistant penicillins, the extended- spectrum penicillins, the cephalosporins, the carbapenems, and the monobactams. This article discusses some of the newest beta-lactams available for use in the United States: ertapenem, cefditoren, and cefepime. A new formulation of amoxicillin-clavulanate, which contains higher doses of amoxicillin, is also discussed.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactams; Cefepime; Cephalosporins; Ertapenem; Humans; Lactams; United States

Topics: Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Biofilms; Cephalosporins; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecalis; Female; Humans; Length of Stay; Male; Middle Aged; Treatment Outcome

This study explores the effects of cefditoren (CDN) versus amoxicillin-clavulanic acid (AMC) on the evolution (within a single strain) of total and recombined populations derived from intrastrain ftsI gene diffusion in β-lactamase-positive (BL⁺) and β-lactamase-negative (BL⁻) Haemophilus influenzae. DNA from β-lactamase-negative, ampicillin-resistant (BLNAR) isolates (DNA(BLNAR)) and from β-lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) (DNA(BLPACR)) isolates was extracted and added to a 10⁷-CFU/ml suspension of one BL⁺ strain (CDN MIC, 0.007 μg/ml; AMC MIC, 1 μg/ml) or one BL⁻ strain (CDN MIC, 0.015 μg/ml; AMC MIC, 0.5 μg/ml) in Haemophilus Test Medium (HTM). The mixture was incubated for 3 h and was then inoculated into a two-compartment computerized device simulating free concentrations of CDN (400 mg twice a day [b.i.d.]) or AMC (875 and 125 mg three times a day [t.i.d.]) in serum over 24 h. Controls were antibiotic-free simulations. Colony counts were performed; the total population and the recombined population were differentiated; and postsimulation MICs were determined. At time zero, the recombined population was 0.00095% of the total population. In controls, the BL⁻ and BL⁺ total populations and the BL⁻ recombined population increased (from ≈3 log₁₀ to 4.5 to 5 log₁₀), while the BL⁺ recombined population was maintained in simulations with DNA(BLPACR) and was decreased by ≈2 log₁₀ with DNA(BLNAR). CDN was bactericidal (percentage of the dosing interval for which experimental antibiotic concentrations exceeded the MIC [ft>MIC], >88%), and no recombined populations were detected from 4 h on. AMC was bactericidal against BL⁻ strains (ft>MIC, 74.0%) in DNA(BLNAR) and DNA(BLPACR) simulations, with a small final recombined population (MIC, 4 μg/ml; ft>MIC, 30.7%) in DNA(BLPACR) simulations. When AMC was used against the BL⁺ strain (in DNA(BLNAR) or DNA(BLPACR) simulations), the bacterial load was reduced ≈2 log₁₀ (ft>MIC, 44.3%), but 6.3% and 32% of the total population corresponded to a recombined population (MIC, 16 μg/ml; ft>MIC, 0%) in DNA(BLNAR) and DNA(BLPACR) simulations, respectively. AMC, but not CDN, unmasked BL⁺ recombined populations obtained by transformation. ft>MIC values higher than those classically considered for bacteriological response are needed to counter intrastrain ftsI gene diffusion by covering recombined populations.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Diffusion; Drug Resistance, Bacterial; Genes, Bacterial; Haemophilus influenzae; Humans; Microbial Sensitivity Tests

The aim was to study the pharmacodynamics of cefditoren, amoxicillin/clavulanic acid and cefuroxime against mixed Haemophilus influenzae strains.. Isolates [MICs (mg/L) of cefditoren, cefuroxime and amoxicillin/clavulanic acid] used were: one beta-lactamase-negative (beta(-); 0.015, 1 and 1), one beta-lactamase-positive (beta(+); 0.03, 4 and 8) and two strains exhibiting ftsI gene mutations [one beta(-) ampicillin-resistant (BLNAR; 0.015, 8 and 4) and one beta(+) amoxicillin/clavulanic acid-resistant (BLPACR; 0.03, 8 and 4)]. A computerized pharmacodynamic model simulating free antibiotic concentrations (calculated considering reported percentages of protein binding) of 400 mg twice-daily cefditoren, 500 mg twice-daily cefuroxime and 875/125 mg three times daily amoxicillin/clavulanic acid was used to explore antibacterial activity against initial mixed inocula with 25% of each strain. Areas under bacterial curves (AUBCs) from 0 to 24 h (log cfu.h/mL) were calculated and differences between values in antibiotic-free (AUBC(K)) and in antibiotic simulations determined (ABBC(0-24) = AUBC(K0-24)-AUBC(0-24)).. In antibiotic-free medium, total population increased by 1.7 log(10) cfu/mL from 0 to 24 h: final composition approximately 90% beta(-), approximately 6.5% beta(+), approximately 2.5% BLNAR and approximately 1% BLPACR. At the end of antibiotic simulations, the predominant population was BLPACR followed by beta(+) after amoxicillin/clavulanic acid or BLNAR after cefuroxime exposures. ABBC(0-24) was higher (P < 0.01) for cefditoren compared with cefuroxime or amoxicillin/clavulanic acid whether considering total population (70.4 versus approximately 33), beta(+) (77.8 versus approximately 52), BLNAR (66.1 versus 18.6-30.4) or BLPACR (40.8 versus approximately 0).. Cefditoren offered higher antibacterial effect than cefuroxime and amoxicillin/clavulanic acid against a mixed population of H. influenzae strains due to its higher activity against beta-lactamase-producing strains and those carrying ftsI gene mutations.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactams; Cefuroxime; Cephalosporins; Coculture Techniques; Colony Count, Microbial; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Selection, Genetic

To investigate the bactericidal activity, against Haemophilus influenzae strains exhibiting different resistance phenotypes, of simulated serum concentrations obtained in humans after administration of 400 mg of cefditoren twice daily, 500 mg of cefuroxime twice daily, 875/125 mg of co-amoxiclav twice daily or 875/125 mg of co-amoxiclav three times daily.. An in vitro computerized pharmacodynamic simulation was carried out and colony counts determined over 24 h. Four H. influenzae strains were used, one ampicillin-susceptible strain (Strain 1) and three ampicillin-resistant strains following CLSI and BSAC breakpoints: one beta-lactamase-positive strain with an MIC of co-amoxiclav of 0.5 mg/L (Strain 2), one beta-lactamase-negative ampicillin-resistant strain (BLNAR; ampicillin MIC = 16 mg/L) (Strain 3) and one beta-lactamase-positive strain with an MIC of co-amoxiclav of 4 mg/L (Strain 4). All strains were susceptible to cefuroxime and co-amoxiclav according to current CLSI breakpoints, but Strains 3 and 4 were resistant according to BSAC breakpoints. All strains exhibited cefditoren MIC or= 6 log(10) reduced with all antibiotics tested at 12 and 24 h. Against Strains 3 and 4, log(10) reductions at 12 and 24 h were significantly higher for cefditoren versus cefuroxime (P < 0.01) (although both exhibited bactericidal activity, i.e. >or= 3 log(10) reduction) and versus the two co-amoxiclav regimens (P < 0.001) (that exhibited negligible initial inocula reductions).. Cefditoren exhibited the highest bactericidal activity maintained over time against ampicillin-resistant H. influenzae, regardless of beta-lactamase production and/or BLNAR phenotype. From the pharmacodynamic perspective, BSAC breakpoints seem more adequate to define or detect BLNAR strains.

Topics: Amoxicillin-Potassium Clavulanate Combination; Ampicillin Resistance; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cefuroxime; Cephalosporins; Computer Simulation; Drug Resistance, Bacterial; Haemophilus influenzae; Half-Life; Kinetics; Microbial Sensitivity Tests; Phenotype

The aim of this study was to explore bactericidal activity of total and free serum simulated concentrations after the oral administration of cefditoren (400 mg, twice daily [bid]) versus the oral administration of amoxicillin-clavulanic acid extended release formulation (2,000/125 mg bid) against Haemophilus influenzae. A computerized pharmacodynamic simulation was performed, and colony counts and beta-lactamase activity were determined over 48 h. Three strains were used: ampicillin-susceptible, beta-lactamase-negative ampicillin-resistant (BLNAR) (also resistant to amoxicillin-clavulanic acid) and beta-lactamase-positive amoxicillin-clavulanic acid-resistant (BLPACR) strains, with cefditoren MICs of < or =0.12 microg/ml and amoxicillin-clavulanic acid MICs of 2, 8, and 8 microg/ml, respectively. Against the ampicillin-susceptible and BLNAR strains, bactericidal activity (> or =3 log(10) reduction) was obtained from 6 h on with either total and free cefditoren or amoxicillin-clavulanic acid. Against the BLPACR strain, free cefditoren showed bactericidal activity from 8 h on. In amoxicillin-clavulanic acid simulations the increase in colony counts from 4 h on occurred in parallel with the increase in beta-lactamase activity for the BLPACR strain. Since both BLNAR and BLPACR strains exhibited the same MIC, this was due to the significantly lower (P < or = 0.012) amoxicillin concentrations from 4 h on in simulations with beta-lactamase positive versus negative strains, thus decreasing the time above MIC (T>MIC). From a pharmacodynamic point of view, the theoretical amoxicillin T>MIC against strains with elevated ampicillin/amoxicillin-clavulanic acid MICs should be considered with caution since the presence of beta-lactamase inactivates the antibiotic, thus rendering inaccurate theoretical calculations. The experimental bactericidal activity of cefditoren is maintained over the dosing interval regardless of the presence of a mutation in the ftsI gene or beta-lactamase production.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Colony Count, Microbial; Genes, Bacterial; Haemophilus influenzae; Kinetics; Microbial Sensitivity Tests; Peptidoglycan Glycosyltransferase; Protein Binding; Spectrophotometry, Ultraviolet