We compared the antibacterial activity of cefixime with amoxicillin and cefaclor against Streptococcus pneuinoniae and Streptococcus pyogenes in the presence of β-lactamase-producing-Moraxella (Branhamella) catarrhalis. The antibacterial activity of amoxicillin against S. pneumomiae and S. pyogenes was about 10 times stronger than that of cefixime or cefaclor. The inhibition zones of amoxicillin and cefaclor disks against S. pneurnoniae and S. pyogenes on the basal layer of M.(B.) catarrhalis were markedly reduced by agar double-layer method. In contrast, the inhibition zones of cefixime disks were hardly affected. The bactericidal activity of amoxicillin and cefaclor against S. pncumoniae was markedly reduced in the presence of M.(B.) catarrhalis, (10⁷ cfu/ml) but that of cefixime hardly at all. The bactericidal activity of amoxicillin and cefaclor against S. pneunioniae and S. pyogenes was clearly reduced by inactivating both drugs by β-lactamase-producing M.(B.) catarrhalis. Since cefixime is extremely stable to β-lactamase of M.(B.) catarrhalis and has potent antibacterial activity against the same organisms, cefixime seems to be a useful drug against S. pncumoniac and S. pyogenes in the presence of M.(B.) catarrhalis.

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We assessed the pathogenicity of Enterococcss faecalis and Proteus mirabilis and the in vivo activity of antimicrobial agents against these organisms by ascending urinary tract infection models in mice. The organisms assessed were E. faecalis-16148 and P. mirabilis-P 3003 clinically isolated from inpatients with complicated urinary tract infections. The results were as follows.
(1) The number of viable bacteria in the kidney of polymicrobial infection models using these two organisms was smaller for E. faecalis and larger for P. mirabilis than in monomicrobial infections. This suggests that in combined E. faecalis and P. mirabilis infections, P. mirabilis is more prominent than E. faecalis.
(2) The efficacy of antimicrobial agents (enoxacin, ofloxacin, lomefloxacin, pipemidic acid, ampicillin) was assessed by checking the number of viable bacteria in the kidney in combined E. faecalis and P. mirabilis infections. To eradicate P. mirabilis in polymicrobial infection models required twice the dose of each drug necessary in monomicrobial infection. The results suggest that P. mirabilis is more resistant in poymicrobial than in monomicrobial infection.
(3) In combined infections, E. faecalis was more effectively eradicated by the drugs tested than was P. mirabilis, reflecting the characteristics of E. faecalis as a cause of opportunistic infections.
(4) In combined infections, histopathological investigation showed nonspecific inflammation in parallel to the number of viable cells in kidneys, as in monomicrobial infection.

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We studied the clinical efficacy of combined single local antibiotic injection (mainly lincomycin, LCM) and systemic clindamycin (CLDM) treatment in 10 patients with anaerobic lung abscess. The mean abscess diameter on the chest X-rays was 5.8cm (range 2.0-13.0 cm). Cavities were seen on the chest X-ray in six cases, and only a small bubble was seen on CT in one case. Neither cavities nor bubbles were seen in the other three cases. Pus was obtained from the small lesions without cavities and in all cases causative anaerobes were isolated. An antibiotic was locally injected into the lesion immediately after percutaneous lung puncture to aspirate pus. The drug locally injected was LCM (600 mg) in 9 cases and CLDM (1, 200 mg) in 1 case. Systemic clindamycin treatment was started intravenously in 5 cases (1, 200 mg per day) and orally in the other 5 cases (900 mg per day). Nine cases were cured without recurrence. The duration of systemic clindamycin treatment was 12-30 days (mean 19.5 day) in 9 cases. The tenth case was successfully treated by combining imipenem/cilastatin sodium with CLDM in mid-course. Even in the most severe case, with a huge lung abscess, clinical findings such as fetid sputum and fever disappeared rapidly, and the chest X-ray findings improved quickly. We consider this treatment useful for speeding recovery from anaerobic lung abscess.

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We studied the transfer of aztreonam (AZT) to the bronchoalveolar system, using bronchoalveolar lavage (BAL) and compared the findings with our previous results for cefmenoxime (CMX), astromicin (ASTM) and ofloxacin (OFLX). The subjects were 24 patients with various respiratory diseases: 9 with chronic bronchitis, 8 with lung cancer, 3 each with pulmonary tuberculosis and interstitial pneumonia and one with diffuse panbronchiolitis. BAL was performed 60 min after a single intravenous injection of 1 g (group I) or 2 g (group II) of AZT. The concentration of AZT, total protein and albumin were measured in serum and in bronchoalveolar lavage fluid (BALF), and the following results obtained.
1) In group I, the concentration of AZT was 37.5-101.1μg/ml in serum, and 0-0.5μg/ml in BALF, the mean value±standard deviation being 62.01±21.32μg/ml and 0.26±0.19μg/ml, respectively.
2) In group II, the concentration of AZT was 71.7-158.6μg/ml in serum, and 0-1.5μg/ml in BALF, the mean value±standard deviation being 106.47±27.20 μg/ml and 0.58±0.52μg/ml, respectively.
3) The concentration of AZT in BALF and serum was in proportion to the intravenous dose of AZT.
4) No significant statistical difference among diseases was noted in the concentration of AZT.
5) The transfer of AZT to BALF was similar to that of CMX, ASTM and OFLX in our previous study.

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We described in the last paper how erythromycin given orally enhanced the production of interleukin-1 and tumor necrosis factor by both peripheral blood mononuclear cells and alveolar macrophages. Thus we investigated the kinetics of the immunological action of erythromycin and other macrolides in vitro. When peripheral blood adherent cells from normal volunteers were incubated with erythromycin, clarithromycin or josamycin, the production of interleukin-1α, interleukin-1β and tumor necrosis factor was enhanced dose-dependently. This stimulatory effect depended on the number of cells cultured, and peaked around 8 to 12 h after incubation. These macrolides also had a priming effect, producing interleukin-1α. The production of interleukin-1 was partially blocked by ouabain, H-7 and W-7. We therefore hypothesize that Na⁺, K⁺, -ATPase, protein kinase C and/or calmodulin play a role in the stimulatory effect of macrolides.

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