Cefdinir

Abstract

Cefdinir (Omnicef®) is an oral third-generation cephalosporin with good in vitro activity against many pathogens commonly causative in community-acquired infections. The drug provides good coverage against Haemophilus influenzae, Moraxella catarrhalis and penicillin-susceptible Streptococcus pneumoniae, the most common respiratory tract pathogens. Cefdinir is stable to hydrolysis by commonly occurring plasmid-mediated β-lactamases and retains good activity against β-lactamase-producing strains of H. influenzae and M. catarrhalis. The drug distributes into various tissues (e.g. sinus and tonsil) and fluids (e.g. middle ear), and has a pharmacokinetic profile that allows for once-or twice-daily administration. Cefdinir, administered for 5 or 10 days, has shown good clinical and bacteriological efficacy in the treatment of a wide range of mild-to-moderate infections of the respiratory tract and skin in adults, adolescents and paediatric patients in randomised, controlled trials. In adults and adolescents, cefdinir is an effective treatment for both lower (acute bacterial exacerbations of chronic bronchitis [ABECB], communityacquired pneumonia) and upper (acute bacterial rhinosinusitis, streptococcal pharyngitis) respiratory tract infections, and uncomplicated skin infections. Its bacteriological and clinical efficacy in patients with lower respiratory tract infections was equivalent to that of comparator agents (cefprozil [bacteriological only], loracarbef, cefuroxime axetil and cefaclor). In one trial in patients with ABECB, cefdinir produced a higher rate of clinical cure than cefprozil (95% CIs indicated nonequivalence). Cefdinir also produced good clinical and bacteriological responses equivalent to responses with amoxicillin/clavulanic acid in patients with acute bacterial rhinosinusitis. In addition, it was at least as effective as penicillin V (phenoxymethylpenicillin) in streptococcal pharyngitis/tonsillitis and as effective as cefalexin in uncomplicated skin infections. In paediatric patients aged ≥6 months, cefdinir showed similar efficacy to that of amoxicillin/clavulanic acid or cefprozil in acute otitis media, and cefalexin in uncomplicated skin infections. Cefdinir given for 5 or 10 days was at least as effective as penicillin V for 10 days in patients with streptococcal pharyngitis/ tonsillitis. Cefdinir is usually well tolerated. Diarrhoea was the most common adverse event in trials in all age groups. Although the incidence of diarrhoea in cefdinir recipients was generally higher than in adults and adolescents treated with comparators, discontinuation rates due to adverse events were generally similar for cefdinir and comparator groups. In conclusion, cefdinir is a third-generation cephalosporin with a broad spectrum of antibacterial activity encompassing pathogens that are commonly causative in infections of the respiratory tract or skin and skin structure. Depending on the infection being treated, cefdinir can be administered as a convenient once-or twice-daily 5-or 10-day regimen. Clinical evidence indicates that cefdinir is an effective and generally well tolerated drug with superior taste over comparator antibacterial agents and is therefore a good option for the treatment of adults, adolescents and paediatric patients with specific mild-to-moderate respiratory tract or skin infections, particularly in areas where β-lactamase-mediated resistance among common community-acquired pathogens is a concern. Cefdinir has a broad spectrum of antibacterial activity encompassing a number of Gram-positive and -negative pathogens that are commonly causative in community-acquired respiratory and skin infections. Results of many studies published since 1995 show that cefdinir has good activity against penicillin-susceptible strains of Streptococcus pneumoniae, S. pyogenes and methicillin-susceptible Staphylococcus aureus, including β-lactamase-producers. However, in common with many other β-lactam antibacterials, cefdinir shows less activity against penicillin-intermediate and -resistant pneumococci and is inactive against methicillin-resistant S. aureus. Cefdinir is also active against the important respiratory tract Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis, including β-lactamase-producing strains of both micro-organisms. In addition, the drug shows good in vitro activity against H. parainfluenzae. Cefdinir is stable to hydrolysis by many plasmid-encoded β-lactamases, including TEM-1, TEM-2, TEM-6, TEM-7, TEM-9, TEM-10, HMS-1, CAZ-2, SHV-1, OXA-1, OXA-2, OXA-3 and P99 type 1a. However, it is susceptible to hydrolysis by TEM-3, TEM-4, TEM-5, PSE-2, P99 type 1c, SHV2, SHV-3, SHV-4, SHV-5, MEN-1, K-l, CARB-1, CARB-2, CARB-3 and OXA-4 β-lactamases. The bactericidal effect of cefdinir is achieved by its binding to penicillinbinding proteins. This leads to damage of the cell wall, cell lysis and death of susceptible bacteria. Cefdinir is rapidly bactericidal against a number of pathogens at minimum bactericidal concentrations of two to four times the minimum inhibitory concentration. Cefdinir has also shown efficacy in several animal models of infection, including pneumonia caused by H. influenzae or penicillinsusceptible strains of S. pneumoniae and subcutaneous abscesses induced by S. aureus. In adults, mean maximum plasma cefdinir concentrations (Cmax) were 1.6 and 2.87 mg/L after single doses of 300mg and 600mg at a mean time of ≈3 hours. In paediatric patients, mean cefdinir Cmax values were 2.3 and 3.86 mg/L approximately 2 hours after administration of 7 and 14 mg/kg doses of the suspension. Cefdinir has a linear pharmacokinetic profile over the 200–400mg dose range, but displays nonlinear pharmacokinetics at a higher dose (600mg). At therapeutic dosages, cefdinir does not...