Indole-positive strains of Klebsiella are classified into Klebsiella oxytoca and K. planticola in Bergey's Manual (1984 ed.). We studied the sensitivities of clinical isolates of these two Klebsiella species to ampicillin (ABPC), piperacillin (PIPC), cephaloridine (CER), cefoperasone (CPZ), latemoxef (LMOX), and aztreonam (AZT). The results were as follows.
1. Forty-eight strains of 246 indole-positive Klebsiella isolated in eleven general hospitals were identified as K. planticola.
2. The sensitivity distribution of K. planticola to β-lactam antibiotics was similar to that of K. pneumoniae rather than to K. oxytoca.
3. The β-lactamase of K. planticola was identified as penieillinase from its substrate specificity.
4. AZT, a monobactam antibiotic, showed a high degree of antibacterial activity to K. oxytoca as well as to K. pneumoniae and to K. planticola.
5. AZT was not hydrolyzed by either the β-lactamase of K. planticola or that of K. oxytoca.
6. The β-lactamase of K. oxytoca was identified as a cephalosporinase from its substrate specificity.
The present results indicate that K. planticola should be carefully differentiated front K. oxytoca in clinical laboratories.

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The changes in the intestinal bacterial flora in humans after administration of cephalexin (CEX) or amoxicillin (AMPC) have not been described in any detail. In this study, CEX or AMPC were given orally to 3 healthy volunteers each in a daily dose of 250mg, 3 times a day for 3 days, and changes in the bacterial flora in the feces, the fecal contents or C. difficile D-1 toxin, of the drug and of β-lactamase activity were examined.
On the whole, anaerobes were more susceptible than aerobes. Bifidobacterium, Eubacterium and Peptococcaceae decreased in one subject treated with CEX, and markedly so in another. However, the cell counts returned to normal after the drug was discontinued. C. difficile D-1 toxin was present in the feces of two of the three volunteers during and after administration of CEX. On the other hand, all fecal bacteria in one of the volunteers treated with AMPC greatly increased, while Bifidobacterium, Eubacterium, Peptococcaceae and lecithinase (-) Clostridium decreased markedly in the other two. C. difficile D-1 toxin was detected in the feces of the latter two volunteers, and excreted for about 20 days.β-lactarnase activity was found in all fecal specimens.

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After a single intravenous injection, the exudate concentrations of ASPC, ABPC, PIPC and SBPC in the inflammatory pouches of rats infected with S. aureus or E. coli were compared with those in uninfected controls. When the drugs were administered 5 days after infection with S. aureus, the penetration of these penicillins into exudate was significantly retarded: the drugs reached slowly the lower peak concentrations and were eliminated gradually from the exudate compared to the control group, giving larger T_max. and T_1/2. values and smaller C_max. values. The same treatments 7 days post-infection resulted in further retardations in the penetration. Similar retardations were also observed in the pouches infected with E. coli, however, the differences between each parameter of the infected and uninfected pouches were less than those found in S. aureus infection.
To compare the antibacterial effect of ASPC and other penicillins in these experimental models, the viable counts in the exudates after a single intravenous injection were determined and it was found that the effects of these penicillins were well correlated to their AUC values. Of these penicillins, ASPC giving the highest exudate concentration and the largest AUC value gave the strongest antibacterial effect on the both infections.

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The transport of fosfomycin into three kinds of exudates (suction blister fluid, burn blister fluid, and exudates from excoriated skin wounds) from blood was studied after intravenous bolus injection of fosfomycin (50mg/kg). Concentrations of fosfomycin in serum and in the above fluids or exudates were determined by bioassay using Proteus sp.(MB-837) as a test organism. Concentrations of fosfomycin in serum reached 246±54.6μg/ml (mean±SD) 15 minutes after injection, and decreased to 13.3±10.0 μg/ml after 8 hr. Peak concentrations of the antibiotic in suction blister fluid, burn blister fluid, andexudates from excoriated wounds occurred after approximately 1 hour. According to calculations made by a modified deconvolution method, T_max (time of maximum concentration), C_max (maximum concentration), AUC^0-8h (area under the curve), apparent transport rate constant K₁ (serum to exudate), K₂ (exudate to serum) and K₁/K₂ were, respectively, 1.5 hr, 79.87mu;g/ml, 391.8μg·hr/ml, 0.631 hr^-1, 0.839 hr^-1 and 0.752 for suction blister fluid, 1.3 hr, 80.97mu;g/ml, 358.7μg·hr/ml, 0.612 hr^-1, 1.10 hr^-1, and 0.556 for burn blister fluid, and 0.7 hr, 73.4μg/ml, 229.2μg·hr/ml, 0.986 hr^-1, 2.27 hr^-1, and 0.434 for exudates from excoriated skin wounds.

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We studied whether the routine method of administration of streptomycin (SM) so far done in Otawara Red-Cross Hospital based on age, body weight and renal function is appropriate or not. Serum concentrations of SM after intravenous drip-infusion were measured on the first and 30th day of administration of SM combined with measurements of creatinine clearance, urinary excretion of β₂-microglobulin (β₂-MG) and N-acetyl-β-D-glucosamioidase (NAG) and vestibulo-cochlear functions. Daily dosage of SM was 1g in 5 of 10 patients, 0.75g in 4 patients and one patient received 0.75g every other day. Serum concentrations of SM on the 30 th day did not change significantly compared with those on the first day, serum half lives and volumes of distribution did not either. However serum half life prolonged by more than 20% in 4 of 10 patients. Mild vestibular dysfunction developed in 3 patients, who were consisted with the patients with prolonged serum half life, high trough level and increased urinary excretion of β₂-MG and NAG.
We conclude that the dosage of SM should further be reduced in patients with mild renal dysfunction and measurement of β₂-MG and NAG may be useful to detect such patients.

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There have been numerous reports that penicillin compounds in large doses inhibit platelet aggregation. It has been suggested that antibiotics with a carboxyl group, such as carbenicillin (CBPC), ticarcillin (TIPC) and latamoxef (LMOX), inhibit platelet aggregation by coating the platelet membrane. The platelet surface carries a negative charge, and the platelets there by repel each other. We studied the effects of antibiotics on platelet aggregation, electrophoretic mobility (E. P. M.), and platelet adhesiveness, both in vitro and in vivo.
1) in vitro study
he effects of the antibiotics, LMOX (200-1, 000μg/ml) and tobramycin (TOB) (5-50μg/ml) and their combination on platelet function was studied. LMOX suppressed ADP-induced human platelet aggregation, especially primary aggregation, at 1, 000μrg/ml, but not at lower doses. However, TOB (50μg/ml) did not suppress platelet aggregation. Even at high doses, both these antibiotics did not suppress collagen-induced platelet aggregation. LMOX (1, 000μg/ml) raised E. P. M. compared with the control, while ADP-induced primary aggregation had a negative correlation with E. P. M.
These antibiotics were found to have no effect on platelet adherence to the subendothelium of rabbit aorta when examined by BAUMGARTNER's method. Thrombus formation was also slightly reduced by the combination of LMOX+TOB (1, 000+50μg/ml).
2) in vivo study
LMOX or TIPC (intravenously, 400mg/kg/day for 7 days) significantly suppressed ADP-induced platelet aggregation, and slightly suppressed collagen-induced platelet aggregation. These antibiotics raised E. P. M. compared with the controls.
The platelet aggregation system and the coagulation system may possibly influence each other. Since vitamin K-dependent clotting factors (II, VII, IX, X) activate the platelet surface, β-lactams which inhibit ADP-induced platelet aggregation by nonspecific coating of platelet membranes may affect the vitamin K-dependent clotting system.

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Recently there have been many reports of bleeding tendencies in patients receiving antibiotics. These are considered to be caused by the influence of antibiotics on platelets, blood vessels and vitamin K-dependent clotting factors. Hypoprothrombinemia was observed in patients treated with antibiotics, especially with N-methyltetrazolethiol (NMTT) drugs such as latamoxef (LMOX), cefinenoxime (CMX) and cefoperazone (CPZ). We studied the effect of antibiotics on platelet function and blood coagulation in clinical cases.
1) Platelet aggregation was studied in 15 patients treated with cephems (2-4g/day). In 7 patients in whom platelet aggregation was suppressed before antibiotic administration, it recovered after successful treatment.
2) Blood coagulation was studied in 58 patients treated with antibiotics. Prothrombin time (PT), activated partial thromboplastin test (APTT), hepaplastin test (HPT), thrombotest (TT), and protein induced by vitamin K absence (PIVKA-II) were measured before and after treatment with antibiotics.
The patients were divided into two groups. Antibiotics without NMTT were administered to 30 patients, and antibiotics with NMTT were administered to 28 patients. No PIVKA-II positive patients were found in the group given drugs not containing NMTT, but six in the group given NMTT drugs. Three patients were given LMOX, and three CMX. Two patients showed bleeding tendencies. In one patient treated with LMOX, vitamin K epoxide appeared after administration of vitamin K. Antibiotics containing NMTT induce vitamin K absence because they inhibit epoxide reductaee. So in the case of antibiotic treatment for patients with poor oral intake, vitamin K should be administered prophylactically.

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