cefditoren and Streptococcal-Infections

The clinical significance of protein binding remains to be fully elucidated. The aim of this study was to evaluate the effect in the in vitro bactericidal activity of cefditoren through killing curves at Cmax concentrations against three Streptococcus pneumoniae strains (cefditoren MICs of 0.12, 0.25 and 0.5 mg/l) with or without human albumin (4 g/dl) and ibuprofen at Cmax concentrations (32.3 mg/l) and 10 times the Cmax (323 mg/l). Cefditoren was rapidly bactericidal (3 log(10) CFU/ml reduction) against the three strains at 4.2 mg/l concentration in Mueller-Hinton broth plus 5% lysed horse blood. In presence of human albumin, this effect was maintained against the most susceptible strain (MIC = 0.12 mg/l). Regrowths were observed with higher MIC values. The presence of ibuprofen (32.3 mg/l) slightly delayed regrowth while the increase of ibuprofen concentration up to 10 x Cmax recovered the bactericidal activity against all strains. The activity of an antimicrobial with high protein binding should not be linked exclusively with the theoretical unbound fraction extrapolated from the plasma concentration. The role of protein binding antagonists merits analysis due to their frequent use associated with cephalosporins in respiratory tract infections.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Binding, Competitive; Blood Proteins; Cephalosporins; Drug Interactions; Drug Resistance; Humans; Ibuprofen; Microbial Sensitivity Tests; Protein Binding; Serum Albumin; Streptococcal Infections; Streptococcus pneumoniae

This study investigates the susceptibility to cefditoren of penicillin-susceptible strains of invasive Streptococcus pneumoniae (n = 312) and of penicillin-intermediate strains of S. pneumoniae (n = 30) isolated mainly from patients with respiratory tract infections. The MIC(90)s of penicillin-susceptible and -intermediate isolates were as follows: cefditoren, < or =0.06 and 1 mg/L; penicillin G, < or =0.06 and 0.5 mg/L. Cefditoren showed the highest activity against the penicillin-intermediate strains investigated compared with the other beta-lactam antibiotics and is therefore considered to be a promising agent for the treatment of infections caused by pneumococci with reduced penicillin susceptibility.

Topics: Cephalosporins; Germany; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Penicillins; Respiratory Tract Infections; Streptococcal Infections; Streptococcus pneumoniae

Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important beta-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 beta-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 strains). Streptococcus pneumoniae and viridans group streptococci had penicillin nonsusceptible rates of 37.8 and 35.8%, respectively. Cefditoren (MIC(90) in microg/ml/% susceptible) activity against all tested H. influenzae (0.03/100) and M. catarrhalis (0.06-0.5/100) was comparable to cefixime and significantly greater than cefaclor. Cefditoren (MIC(90), 0.5 microg/ml) was 4- to 128-fold more active than comparison beta-lactams against the pneumoococci and was the most potent beta-lactam (including penicillin) versus beta-haemolytic streptococci. Cefditoren pharmacokinetics demonstrate a T(1/2) of 1.5-2 h and C(max) values of 2.8 and 4.6 microg/ml, respectively with 200 or 400 mg doses of cefditoren pivoxil; plasma concentrations exceed 1 microg/ml for 4 to 6 hours (33-50% of dosing interval). Consequently, a susceptible MIC of /= 18 and >/= 15 mm (5-microg disk) for all cited fastidious species tested. Categorical agreement between MIC and disk tests was 94.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. influenzae intermethod comparison results using the same interpretive criteria were in complete agreement, but exhibited a low r = 0.39. Cefditoren clearly possesses the most potent activity among currently studied oral cephalosporins or penicillin against commonly isolated bacterial pathogens causing bronchitis, pneumonia, sinusitis, or pharyngitis and was active against nearly all penicillin-resistant streptococci at

Topics: Cefaclor; Cefixime; Cephalosporins; Gram-Negative Bacterial Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Penicillins; Streptococcal Infections; Streptococcus

We isolated 73 streptococcus strains (41 from infections, and 32 from colonization) from various skin diseases between March, 1994, and June, 1998. In 29 out of 41 cases of infective origin, Staphylococcus aureus strains were simultaneously isolated. Twenty-four out of 28 patients with impetigo were suffering from atopic dermatitis. We confirmed that impetigo lesions where Streptococcus pyogenes was dominant in number always showed thick-walled pustules on an erythematous base; these skin lesions were considered to be an early manifestation of streptococcal impetigo. We further confirmed that thick-crusted lesions in streptococcal impetigo, where S. aureus exceeded S. pyogenes in number, were a late manifestation. Antimicrobial agents such as minocycline, fusidic acid, ofloxacin and tosufloxacin, were more effective against S. aureus strains than against beta-hemolytic streptococcal strains. In contrast, ampicillin, cefdinir, imipenem, erythromycin and vancomycin were more effective against beta-hemolytic streptococcal strains.

Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Cephalosporins; Erythromycin; Fluoroquinolones; Fusidic Acid; Humans; Imipenem; Microbial Sensitivity Tests; Minocycline; Naphthyridines; Ofloxacin; Penicillins; Skin Diseases, Bacterial; Species Specificity; Streptococcal Infections; Streptococcus; Vancomycin