Antibiotic concentrations in the infected focus are important in the chemotherapy of infectious diseases, and reports on this problem in pulmonary infection are rare. Although antibiotic levels in sputa have been determined, it is doubtful whether such antibiotic levels are really effective in infected lesions.
In the present study, solitary pulmonary abscess due to Staphylococcus aureus were efficiently produced in rabbits by a very simple technique. Rabbits were sensitized once a week for 4 weeks with a mixture of sterilized Staphylococcus aureus and FREUND's incomplete adjuvant. Then, mixtures of living cells of Staphylococcus aureus and the adjuvant were inoculated intrabronchially through a vinyl tube. Solitary pulmonary obscess was observed autonomically 2 or 4 weeks after inoculation of Staphylococci. Pulmonary abscess in rabbit is histologically similar to that in man.
To determine antibiotic levels in pulmonary abscess, penicillin G, streptomycin, erythromycin or ¹⁴C-labelled cefazolin was injected intramuscularly to the thigh of rabbits with pulmonary abscess 4 weeks after inoculation of Staphylococci. Blood, abscess pus, abscess wall, surrounding tissue and contralateral intact lung were taken for bioassay and radioassay. The levels of antibiotics in the serum and lungs of rabbits with pulmonary abscess were compared with those of healthy rabbits.
Results are as follows :
1) At different times, serum levels of antibiotics differed between rabbits with and without pulmonary abscess.
2) Similar tendencies were seen in penicillin G, streptomycin and cefazolin. When serum levels were high, the antibiotic levels in pulmonary abscess were relatively lower than those in the normal lungs, whereas after declination of the serum levels antibiotic levels in pulmonary abscess were relatively higher than those in the normal lungs. Erythromycin was well distributed to the lungs, but poorly distributed to pulmonary abscess.
3) The relationship between the dose and distribution of penicillin G to the tissues was studied. No differences in distribution to the tissues were noted between low and high dosing groups.
4) Bioassayed levels (bioactive antibiotic levels) and radioassayed levels (total antibiotic levels) of ¹⁴C-labelled cefazolin in the serum and tissues were compared : Ratios of bioassayed to radioassayed levels differed between rabbits with and without pulmonary abscess when the serum levels were high, and declined after injection of antibiotics. The ratio declined more slowly in abscess pus than in the tissues. To determine the total antibiotic concentration in tissues, bioassayed levels are corrected by the recovery rate of antibiotics in the tissues. The present study indicates that the correction by the recovery rate is not always suitable for the exact determination of the levels.

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1. Each drug was administered orally at the dosis of 250 mg × 4/day or 500 mg × 3/day to the patients with acute skin infection such as furuncle, furunculosis, carbuncle, folliculitis, cellulitis and secondary skin infection.
2. The maximum duration of therapy was 7 days.
3. No significant difference of effectiveness between two drugs was observed clinically.
4. Subjective side effects such as heart burn, nausea, vomiting, loss of appetite etc. occurred more frequently in the group administered erythromycin estolate.
5. Cases in which SGOT or SGPT was elevated to more than 30 were 5 in triacetyloleamdomycin group and 1 in erythromycin estolate group. (The number of cases in which SGOT or SGPT was checked before and after the administration was 14 in triacetyloleandomycin group and 18 in erythromycin estolate group.)

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Although antimicrobial activities of chemotherapeutic agents are commonly expressed in terms of the minimal inhibitory concentrations determined by 18 to 20 hours exposure of the organisms to the agents, these agents usually persist only for a shorter time in the human body after a single dose administration.
To study the effect of the exposure time on the number of viable organisms, 30 strains of E. coli at their logarithmic phase were exposed in vitro to various concentrations of cephalothin, cephaloridine and cefazolin for 1, 2 and 24 hours. The colony counts were determined during and after the exposure and the following results were obtained.
1) During the exposure to the antibiotics, the number of cells decreased. The higher the antibiotic concentration, the more pronounced was the decrease.
2) The higher the antibiotic concentration, the longer was the period of suppression of bacterial re-multiplication.
3) For a given multiple of the MIC, cephalothin showed a greater decrease in bacterial count and a longer period of suppression than either cephaloridine or cefazolin with 1 hour exposure. With 3 or 24 hours exposure, however, the difference between the effects of 3 antibiotics was less pronounced.

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Oral administration of ABPC or ACPC to mice resulted in a decrease of the number of cultured fecal bacteria with an increase of cecal weights. These effects were more pronounced in ABPC than in ACPC. Furthermore, in histological examinations of the cecum, Gram-negative tapered rods-fusiform bacteria could hardly be detected in ABPC treated mice, but a small number of these bacteria was observed in ACPC treated mice. Therefore, the difference in the effect on the cecum between both antibiotics is considered to be due to the difference in the number of fusiform bacteria after these treatment.

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We compared the antibacterial activity of DKB (3', 4'-dideoxykanamycin B) and that of gentamicin on 355 strains of Pseudomonas aeruginosa, and the mechanism of resistancl to DKB was studied.
1) The newly introduced semisynthetic aminoglycoside antibiotics, i. e., 3', 4'-dideoxykanamycin B (DKB), 6'-N-methyl DKB (6'-Me-DKB) and amikacin have been found to be effective against Pseudomonas aeruginosa which are resistant to the known aminoglycoside antibiotics.
2) DKB resistant Pseudomonas aeruginosa strains were isolated from clinical specimens before DKB was used.
3) The strain resistant to DKB and 6'-Me-DKB disclosed that the enzyme catalyzing inactivation of both DKB and 6'-Me-DKB was mediated by an R factor.
4) Enzymatic studies of inactivation reaction and chemical studies of the inactivated products indicated that DKB and 6'-Me-DKB were inactivated by acetylation of the 6' amino group of the drugs.

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The synergic actions of SBPC, CBPC and GM, DKB were observed on either strain of Ps. Aeruginosa No. 12, Nc-5, IFO-3445 by chequer board titration method, and the marked effect was observed especially with No. 12 strain.
In either case of the combination of SBPC with GM, CBPC with GM, and CBPC with DKB, the simultaneous administration showed the highest bactericidal effect, followed by the case of addition of GM, DKB after adding SBPC, and the reverse case showed the similar effect to that of each drug alone.
The electron microscopic observation revealed that the bacterial cell prolonged with SBPC, CBPC, showing the filament-like form, and GM resulted in the crack of the cell-wall followed by the cytoplasmic membrane with the flowing out of the cellular contents.
In combination, the bacterial cell was prolonged but its degree was less than that by SBPC, CBPC alone, moreover, the damage at the surface layer of the cell was observed, while the degree of cellular damage was much severer than that by each drug alone.
The therapeutic experiment of infection demonstrated that the combination of SBPC with GM and CBPC with DKB showed superior effects than those of each drug alone.
While, in combination of SBPC with GM, more favorable effect was obtained by the simultaneous administration in 2 hours after infection.

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