Aims The aim of this study was to determine the potential influence of variables such as the cell content in the fluid, and serum levels, on the concentrations of ceftibuten, cefixime and azithromycin in the middle ear fluid of patients suffering from acute otitis media. Methods This randomized, open study compared the penetration of ceftibuten (9 mg kg−1, 18 patients), cefixime (8 mg kg−1, 16 patients) and azithromycin (10 mg kg−1, 16 patients) into the intracellular and extracellular compartments of middle ear fluid of 50 paediatric patients (aged 8–14 years) with acute otitis media. Middle ear fluid was extracted by tympanocentesis 4, 12 and 24 h after dosing and divided into two fractions: with cells (as collected) (C+) and cell‐free (C−). Antibiotics were assayed in C+ and C− samples by h.p.l.c. Results Ceftibuten achieved greater penetration into middle ear fluid than cefixime and azithromycin. Higher concentrations of ceftibuten (CTB) and cefixime (CFX) were found in the C− fraction (CTB: 4 h 13.3±1.86; 12 h 4.7±1.18; 24 h 0.5±0.2. CFX: 4 h 3.2±1.4; 12 h 1.5±0.5; 24 h>0.1 mg l−1 ) than in the C+ fraction (CTB:4 h 8.4±4.3; 12 h 2.88±1.19; 24 h 0.3±0.27. CFX: 4 h 1.2±0.6; 12 h 0.8±0.2; 24 h>0.1 mg l−1 ) at the each time point, while the opposite was true for azithromycin (C−: 4 h 0.11±0.04; 12 h 0.12±0.08; 24 h 0.23±0.12. C+: 4 h 0.38±0.24; 12 h 0.9±0.03; 24 h 1.05±0.3 mg l−1 ). Conclusions This study demonstrates that the penetration of antibiotics into the middle ear fluid is influenced by its serum concentrations as well as by the cell content in the fluid. Ceftibuten achieved higher middle ear fluid concentrations than cefixime in C+ and C− fractions at all time points. Both ceftibuten and cefixime concentrations are negatively influenced by the cell content in the fluid. In contrast the concentration of azithromycin to the middle ear fluid is positively influenced by the cell content in the fluid.

SummaryThis report summarises the results of 5 studies carried out to determine the penetration of clarithromycin and its 14-hydroxy metabolite into oral and respiratory tissues. 128 patients 'of both sexes undergoing dental surgery, rhinoplasty, lung resection or tonsil resection, or presenting with an acute exacerbation of chronic bronchitis, were administered clarithromycin (generally 250mg twice daily; 500mg twice daily for lung resections) for 3 days prior to sample collection. Serum, tissue and secretion samples were assayed for clarithromycin and 14-hydroxy clarithromycin using an agar diffusion bioassay or high performance liquid chromatography. Concentrations were assayed in triplicate and standard curves created using computerised linear regression analysis. Following oral administration, the pharmacodynamics of clarithromycin in oral and respiratory tissues and serum include therapeutic levels that exceed the minimum inhibitory concentrations for common respiratory pathogens for up to 12 hours following administration.The clinical efficacy of an antibiotic is contingent not only on good activity, but also on the ability to achieve and maintain therapeutic drug concentrations in serum and infected tissues. In respiratory tract infections, macrolide antibiotics have traditionally attained therapeutic drug concentrations in both serum and respiratory tissues. Clarithromycin is a new macrolide that is effective in the treatment of respiratory tract infections, and thus drug levels in serum and respiratory tissues need to be examined throughout the dosing period. MethodsPatients 128 adult patients with acute exacerbation of chronic bronchitis, lung cancer or bronchiectasis, or undergoing oral surgery, tonsil resection or rhinoplasty, were enrolled in a total of 5 studies. Patients were excluded from study participation if they had a known or suspected hypersensitivity to macrolides, received antibiotics or antimicrobial treatment within 72 hours of study initiation, were neutropenic, had serious renal insufficiency (creatinine clearance ~ 50 mlfmin) or hepatic failure, or, if female, were pregnant or lactating. All patients gave informed consent prior to any study-specific procedures. Study DesignPatients were hospitalised and consumed standardised meals during the entire study. Clarithromycin tablets were administered by study personnel 1 hour before or 2 hours after meals at a dosage

Streptococcal pharyngitis is a common infection in children and adolescents. The great majority of these infections are caused by group A beta-haemolytic streptococci. Although the use of penicillins for group A beta-haemolytic streptococcal pharyngitis has reduced the incidence of rheumatic fever, in the past decade several studies of pharyngitis treatment have reported penicillin failure. It has also been suggested that in comparison with the penicillins the cephalosporins are associated with a lower rate of clinical failure. Cephalosporins have drawbacks in cost, administration frequency or adverse effect profile. Moreover, there is the theoretical risk of cross-antigenicity to cephalosporins in penicillin-allergic patients. Erythromycin is a traditional alternative to penicillins, especially in penicillin-allergic patients, for the treatment of tonsillopharyngitis. However, increased resistance as well as failure rates as high as 24.7% have been reported for erythromycin in the treatment of pharyngitis. Therefore oral penicillins, and alternatively oral cephalosporins, should be considered first-line agents for the treatment of culture-confirmed group A beta-haemolytic streptococcal tonsillopharyngitis. Cephalosporins are useful especially for the treatment of recurrent streptococcal tonsillopharyngitis.

Concentrations of cefaclor (CFC) or amoxicillin-clavulanic acid (AMX/CA) in middle-ear fluid collected preserving the stability and clearing the cell contents has been compared to those obtained using the traditional method. Sixty-seven children with effusive otitis media were treated orally with CFC (20 mg/kg of body weight) or AMX/CA (20 mg/kg) (4:1 ratio). The concentrations in cell-free fluid (C؊) appear higher than those in the total fluid (C؉) (as assayed traditionally).

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