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The diffusion of clarithromycin and roxithromycin into respiratory tract tissues was studied in 174 adult patients undergoing surgery. Patients received clarithromycin 250 mg orally (500 mg in the case of lung tissue), or roxithromycin 150 mg orally, both given every 12 h, for three days with the last dose administered at different times before surgery. Clarithromycin reached peak tissue levels 4 h after administration and achieved mean peak concentrations of 8.32 mg/kg +/- 2.57 in nasal mucosa, 6.47 mg/kg +/- 2.8 in tonsil, and 17.47 mg/kg +/- 3.29 in lung tissue. Roxithromycin reached peak tissue levels between 4 and 6 h after administration, achieving mean peak concentrations of 1.78 mg/kg +/- 0.73 in nasal mucosa, 2.2 mg/kg +/- 1.21 in tonsil, and 2.14 mg/kg +/- 0.87 in lung tissue. Clarithromycin and roxithromycin demonstrated contrasting pharmacokinetic behaviour. Roxithromycin was characterized by high concentrations in serum and low concentrations in tissues. Clarithromycin on the other hand, is characterized by therapeutic serum concentrations and high tissue concentrations.

In the early eighties, the advantages of outpatient parenteral antibiotic therapy (OPAT) (reduced costs, no hospitalization trauma in children, no immobilization syndrome in elderly, reduction in nosocomial infections by multiresistant organisms) were identified in the United States, and suitable therapeutic programs were established. Currently, more than 250,000 patients per year are treated according to an OPAT program. In order to understand the different ways of managing OPAT and its results, a National OPAT Registry was set up in 2003 in Italy. Analysis of data concerning osteomyelitis, septic arthritis, prosthetic joint infection and spondylodiskitis, allowed information to be acquired about 239 cases of bone and joint infections, with particular concern to demographics, therapeutic management, clinical response, and possible side effects. Combination therapy was the first-line choice in 66.9% of cases and frequently intravenous antibiotics were combined with oral ones. Teicoplanin (38%) and ceftriaxone (14.7%), whose pharmacokinetic/pharmacodynamic properties permit once-a-day administration, were the two top antibiotics chosen; fluoroquinolones (ciprofloxacin and levofloxacin) were the most frequently utilized oral drugs. Clinical success, as well as patients' and doctors' satisfaction with the OPAT regimen was high. Side-effects were mild and occurred in 11% of cases. These data confirm that the management of bone and joint infections in an outpatient setting is suitable, effective and safe.

Augmentin (875 amoxicillin and 125 mg potassium clavulanate) was administered orally to patients with chronic bronchitis. Concentrations of amoxicillin and clavulanic acid were measured in serum, sputum and urine. Peak serum levels for amoxicillin of 11.23 +/- 2.61 micrograms/ml were observed at 2 hours and for clavulanic acid of 2.55 +/- 0.54 micrograms/ml at 1 hour. After 9 hours, 50% of the amoxicillin and 39% of the clavulanic acid had been renally excreted. The peak sputum concentration of amoxicillin was 1.31 +/- 0.42 micrograms/ml at 4 hours and of clavulanate was 0.79 +/- 0.23 micrograms/ml at 2 hours. Patients awaiting surgery received an oral dose of augmentin as above. Samples of lung, tonsil, middle ear mucosa and prostate were obtained and tissue concentrations of both compounds measured. Peak levels of amoxicillin ranged from 0.87 micrograms/g (tonsil) to 2.56 micrograms/g (lung) and of clavulanic acid from 0.20 micrograms/g (prostate) to 0.56 micrograms/g (lung) between 3 and 4 hours after dosing.

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