Multiple-dose pharmacokinetics of ceftriaxone were investigated in 7 patients with bronchopneumonia using an intramuscular regimen of 1 g given every 24 h for 7 days. Serum, sputum, and urine samples were collected serially following the first dose (day 1) and last dose (day 7). Mean peak serum concentrations of ceftriaxone occurred at 2 h on both days and were 67.8 and 75.1 μg/ml, respectively, on day 1 and day 7. Ceftriaxone had a half-life of 6.9 h on day 1 and 7.4 h on day 7. The half-life of ceftriaxone in sputum was 5.9 and 6.6 h, respectively, on days 1 and 7. Approximately 50% of the dose of ceftriaxone was recovered in the urine within 24 h on day 1, 60% on day 7. Tissue distribution of ceftriaxone was determined in 103 patients following intramuscular administration of a single 1-gram dose at different times up to 24 h prior to surgery. High concentrations of ceftriaxone were found in lung, tonsil, middle ear mucosa, and nasal mucosa, and therapeutic levels of ceftriaxone persisted for 24 h after administration.

The efficacy of ceftriaxone, 1 g given intramuscularly once daily, was evaluated in 38 patients with pneumonia (n = 11), pulmonary empyema (n = 2), bronchitis (n = 4), tonsillitis (n = 9), sinusitis (n = 7), and otitis (n = 5). Causative organisms were Streptococcus pneumoniae (n = 11), viridans type streptococcus (n = 1), Haemophilus influenzae (n = 6), group A streptococcus (n = 10), Staphylococcus aureus (n = 3), Klebsiella pneumoniae (n = 2), Pseudomonas aeruginosa (n = 1), Escherichia coli (n = 2), Proteus mirabilis (n = 1), and Proteus vulgaris (n =1). Sterilization of infected foci was obtained in 89.4% of those treated, with clinical recovery in 86.8%. The ceftriaxone regimen was well tolerated.

In vivo and in vitro studies were carried out to assess tha levels in bronchial mucus of ampicillin, amoxycillin, bacampicillin, cefotaxime and erythromycin, and to compare their minimum bactericidal concentrations and killing rate against hospital strains of Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae. Both the percentage ratios of serum/mucus concentration peaks and of serum/mucus area under the concentration time curve values were higher for erythromycin than for the other antibiotics. Determination of the minimum bactericidal concentrations showed that the bacterial strains were sensitive to small quantities of erythromycin, and the time necessary to sterilize inocula varied from 4 to 16 hours.

Alveolar macrophages, lymphocyte and granulocyte percentages, together with OKT3 + , OKT4+, OKT8+ lymphocyte subsets and OKT4+/OKT8+ ratio, were evaluated in bronchoalveolar lavage (BAL) fluid and in peripheral venous blood (PVB) of neoplastic and nonneoplastic subjects, in order to assess these aspects of immunity in neoplastic disease and to find out if the modifications in the bronchoalveolar environment are correlated to the ones in the circulation blood. BAL was performed in 30 patients undergoing fiberoptic bronchoscopy to ascertain the presence of lung cancer. Twelve of them had positive findings for epidermoid bronchogenic carcinoma, while in the remaining subjects the diagnosis was not confirmed. The 30 examined subjects were then grouped according to their smoking habit. In PVB, no significant difference was seen between neoplastic and nonneoplastic subjects, whereas in BAL the neoplastic patients showed a significant increase of lymphocytes OKT3 + and OKT8 + . This tends to confirm that PVB is not a good indicator of organ immunity and may justify the reduced activity of alveolar macrophages in subjects affected by bronchogenic neoplasia. Between smokers and nonsmokers, lymphocyte subsets showed more significant differences than between neoplastic and nonneoplastic subjects (decrease of T4+ lymphocytes, increase of T8+ lymphocytes and, therefore, reduction of T4/T8 ratio); there were also scalar variations in the three groups (smokers with cancer, smokers without cancer and nonsmokers without cancer). Thus, the possible autonomous role of cigarette smoke and the presence of neoplasia in the immunity alterations of the alveolar environment with final joint effects were confirmed. These data may indicate a possible correlation between cigarette smoking, immunological alterations in BAL and the onset of bronchogenic carcinoma