cefdinir and Pneumococcal-Infections

Acute bacterial rhinosinusitis is a common infection resulting in substantial morbidity. Cefdinir, an oral cephalosporin, has extended-spectrum, bactericidal activity against common acute bacterial rhinosinusitis pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Cefdinir shows rapid oral absorption and good respiratory tissue penetration, and may be administered once daily. In randomised clinical trials, cefdinir showed efficacy similar to that of other recommended regimens in the treatment of acute bacterial rhinosinusitis, namely amoxicillin/clavulanate and levofloxacin. Cefdinir is well tolerated and has shown a low propensity to suppress the normal commensal flora. Cefdinir oral suspension is rated highly by children in terms of its taste and smell. As the only once-daily beta-lactam currently recommended by acute bacterial rhinosinusitis guidelines (for first-line use in patients with mild acute bacterial rhinosinusitis and no recent antibacterial use), cefdinir offers a convenient and attractive treatment option.

Topics: Acute Disease; Administration, Oral; Anti-Infective Agents; Cefdinir; Cephalosporins; Drug Administration Schedule; Haemophilus Infections; Haemophilus influenzae; Humans; Moraxella catarrhalis; Moraxellaceae Infections; Pneumococcal Infections; Randomized Controlled Trials as Topic; Sinusitis; Streptococcus pneumoniae

Of several oral cephalosporins, cefdinir is recommended as an alternative therapy for children with acute otitis media who have type 1 hypersensitivity to beta-lactams. Because the current cefdinir dosage of 14 mg/kg/d is approved for treatment of acute otitis media caused by penicillin-susceptible Streptococcus pneumoniae, we hypothesized that a 25-mg/kg dose given daily would be more effective for nonsusceptible S. pneumoniae.. We performed pharmacokinetic analyses on 37 infants and children who were given cefdinir in dosages of 14 or 25 mg/kg once daily for 10 days, for the treatment of respiratory and skin or skin structure infections. Cefdinir plasma concentrations were determined with validated liquid chromatology, and pharmacokinetics and pharmacodynamics were determined in relation to the minimum inhibitory concentration values of S. pneumoniae.. The maximal plasma concentrations and area-under-the-curve values were significantly higher after the 25-mg/kg in relation to the minimum inhibitory concentration values for S. pneumoniae strains. The pharmacodynamics measure of bacteriologic effectiveness was <40% of the dosing interval (ie, 24 hours), indicating that many of the penicillin-nonsusceptible S. pneumoniae causing acute otitis media would not be effectively treated. Diarrhea occurred in 20% of the 39 subjects that received the larger dosage of cefdinir.. A cefdinir dosage of 25 mg/kg daily would be ineffective for treatment of acute otitis media caused by penicillin-nonsusceptible S. pneumoniae strain.

Topics: Acute Disease; Anti-Infective Agents; Cefdinir; Cephalosporins; Child; Child, Preschool; Humans; Infant; Microbial Sensitivity Tests; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Respiratory Tract Infections; Soft Tissue Infections; Streptococcus pneumoniae; Treatment Outcome

Given the relatively high prevalence of recurrent and persistent acute otitis media (AOM) and the prominent etiologic role of Streptococcus pneumoniae, especially penicillin-nonsusceptible strains in children with these conditions, new alternative treatments are desirable.. Children 6 months-4 years of age with AOM considered to be at risk for recurrent or persistent infection received large dosage cefdinir 25 mg/kg oral suspension once daily for 10 days. Children were evaluated pretreatment (day 1), on therapy (days 4-6), end of therapy (days 12-14) and at follow-up (days 25-28). All children had tympanocentesis at enrollment. In culture-positive children, tympanocentesis was repeated after 3-5 days (days 4-6) unless evidence of absence of middle ear effusion was documented.. Of 447 children enrolled, 230 were clinically and bacteriologically evaluable (74% 2 years old or younger; 57% treated for AOM in previous 3 months). Bacteriologic eradication, based on repeat tympanocentesis on days 4-6, was achieved in 74% (170 of 230) of children; 76% (201 of 266) of AOM pathogens were eradicated. Eradication of penicillin-susceptible, -intermediate and -resistant S. pneumoniae was 91% (50 of 55), 67% (18 of 27) and 43% (10 of 23), respectively (P < 0.001); eradication of H. influenzae was 72% (90 of 125). Overall clinical response at days 12-14 was 83% (76 and 82% for children with S. pneumoniae and Haemophilus influenzae, respectively). Sustained clinical response at days 25-28 was 85%. Clinical response was 83% for culture-positive children versus 96% for culture-negative children at baseline tympanocentesis (P < 0.001).. In this study of AOM among children at risk for persistent or recurrent infection, large dose cefdinir resulted in an overall successful clinical response at end of treatment of 83%. This regimen was efficacious against penicillin-susceptible S. pneumoniae, but effectiveness was markedly decreased against nonsusceptible strains and was moderate for H. influenzae strains.

Topics: Acute Disease; Administration, Oral; Anti-Infective Agents; Cefdinir; Cephalosporins; Child, Preschool; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media with Effusion; Paracentesis; Penicillin Resistance; Pneumococcal Infections; Recurrence; Risk Factors; Streptococcus pneumoniae; Treatment Outcome

Of 393 isolates of Streptococcus pneumoniae from U.S. children collected in 2005-2006, nonvaccine serotypes accounted for 89.1%, with serotype 19A the most prevalent, representing 30.5% of all isolates. The MIC(90) of faropenem against serotype 19A isolates was 1 mug/ml, compared to > or =8 microg/ml against amoxicillin/clavulanate, cefdinir, cefuroxime axetil, and azithromycin.

Topics: Adolescent; Anti-Bacterial Agents; beta-Lactams; Child; Child, Preschool; Drug Resistance, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Phenotype; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; United States

LBM415 is a peptide deformylase inhibitor active against gram-positive bacterial species and some gram-negative species. In multiselection studies, LBM415 had low MICs against all Streptococcus pneumoniae strains tested, regardless of their genotype, and selected resistant clones after 14 to 50 days. MIC increases correlated with changes mostly in the 70GXGXAAXQ77 motif in peptide deformylase. The postantibiotic effect of LBM415 ranged from 0.3 to 1.4 h.

Topics: Amidohydrolases; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Peptides; Pneumococcal Infections; Species Specificity; Streptococcus pneumoniae; Time Factors