This study was to investigate the transfer of cefmenoxime (CMX) to the retroperitoneal fluid after extensive panhysterectomy.
Twenty-two cases were examined and they were divided into 2 groups, 10 with 1.0g and 12 with 2.0g bolus intravenous administration of CMX.
1. In 1.0g group, CMX concentration in the retroperitoneal fluid was observed 42.0±9.59μg/ml (Mean±S. D.) at 1 hour and thereafter decreased gradually, but it still remained 7.91±5.18μg/ml at 6 hours after the administration.
2. In 2.0g group, its concentration was 33.4±34.5μg/ml at 30 minutes and reached to the peak level of 45.1±24.6μg/ml at 1 hour and then declined slowly, but it remained 13.3±8.28μg/ml at 6 hours after the injection.
The results demonstrated sufficient transfer of CMX to the retroperitoneal fluid.

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A study was carried out with the aminoglycoside antibiotic micronomicin (MCR) to determine its clinical efficacy in respiratory infections on the one hand and its serum levels on the other.
MCR was administered in single dose of 60mg twice daily by intravenous drip infusion over 1 hour to 5 patients with infections aggravation of chronic bronchitis and 3 with pneumonia. Of the total of 8 patients treated, 3 had remarkable and 4 had good responses with a response rate of 87.5%, while 1 has no benefit.
Adverse effects on the clinical picture or on laboratory test results were not observed.
The peak serum concentration of MCR after a 1.5 hours drip infusion of 90mg was 7.74μg/ml. In view of the risk of adverse effects, the serum concentration lay on appropriate levels.
It is expected therefore that the intravenous drip infusion of MCR will be of particular interest in the treatment of relapse of chronic bronchitis and pneumonia.

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As indexes for administration of cefoperazone (CPZ) in the treatment of gyneco-obstetrical infections, sensitivities to CPZ of important pathogenic organisms and CPZ concentrations in the exudate of the pelvic dead space were determined, and a pharmacokinetic analysis was made on the results.
Sensitivities to CPZ were determined for freshly isolated organisms from gynecological material consisting of 227 strains of 7 aerobic bacteria and 70 strains of 1 anaerobic bacterium, in a total of 297 strains. MIC₈₀, values of CPZ againstE. coli, K. pneumoniae, P. aeruginosa, E. cloacae, C. freundii, S. aureus, S. epidermidis and B. fragilis were 0.39, 0.78, 6.25, 25, 50, 12.5, 12.5μg/ml and 6.25μg/ml, respectively. On the whole, these activities are relatively superior to those of other antibiotics.
CPZ concentrations in the exudate of the pelvic dead space and their changes with time after 2g single dose by drip infusion were C_max 93.89μg/ml, T_max 1.53 hours, T 1/2 4.33 hours and AUC 759.4 hr·μg/ml. After 1g single dose, they were C_max 37.7μg/ml, T_max 3.2 hours, T 1/2 2.78 hours and AUC 339.2 hr·μg/ml. Similarly, after 2g single dose intravenously, they were C_max 111.02μg/ml, T_max 0.761 hours, T 1/2 6.22 hours and AUC 1,083.9 hr·μg/ml, and after 1g single dose, they were C_max 29.1μg/ml, T_max 2.65 hours, T 1/2 4.82 hours and AUC 296.9 hr·μg/ml. Similarly, after 2g single dose intramuscularly, they were 39.4μg/ml, T_max 2.70 hours, T 1/2 8.19 hours and AUC 584.7 hr·μg/ml, and after 1g single dose, they were C_max 26.4μg/ml, T_max 5.79 hours, T 1/2 5.53 hours and AUC 435.7 hr·μg/ml. As indicated, there were noted dose-dependent responses and the kinetics of CPZ exudate concentrations varied with the administration routes. Whatever the dose level and the administration route were, CPZ exudate concentrations covered MIC₈₀ values against important clinical isolates for 10 to 12 hours. This suggests that we can well expect of the antibacterial activity of this drug by any of these administration routes and dosages on the intrapelvic lesions.

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Forty-three children and 4 adults with Campylobacter enteritis were studied in the treatment of fosfomycin (FOM). FOM was administered per orally in doses ranging from 50 to 100mg/kg/day for children and 3g/day for adults for 5 days. Main symptomes such as diarrhea and fever were disappeared within 2 days on the average.
Campylobacter jejuni in stool specimen disappeared within a week in 95% of these patients. The duration of main symptomes and the period of positive stool culture were evidently shortened in FOM-treated group compared with non-treated group. All of the isolated strains were sensitive to FOM by mono-concentration disk method. MIC₅₀ of these strains remained between 1.56 and 3.13μg/ml. None of these MIC was beyond 12.5μg/ml.

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This study was undertaken to determine the source, serological characteristics and susceptibility to the chemotherapeutic agents on recently isolated strains ofSerratia marcescens. Of the 351 isolates, the most frequent source was the respiratory tract and the second urinary tract. The most common serotype was type 14 and the second 4. Among the types ofS. marcescens, type 14 and 4 were most frequently associated with respiratory infections. The strains from infected urine had common types 14, 4 and 14·12. By the disk sensitivity testing, the strains from urine had a tendency of multiple resistance and the strains type 14·12 also had the same tendency.In vitro tests for susceptibility to 16 chemotherapeutic agents were performed. Norfloxacin and ofloxacin were most active drugs and inhibited about 70% of the strains at a concentration of 0.39 μg and 0.78 μg or less per ml, respectively. The new cephalosporins (cefmenoxime, ceftizoxime and latamoxef) and aztreonam inhibited from 76 to 86% of the strains at 6.25 μg or less per ml. This was comparable to the percentage inhibited by some aminoglycosides (gentamicin, tobramycin, amikacin and sisomicin) ranging from 60 to 80%. Minocycline and nalidixic acid were moderate in activity. Chloramphenicol was less active.

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We treated infections accompanied with induction chemotherapy in 9 patients with acute leukemia by the combination of amikacin (AMK) and cephapirin (CEPR). The result was that 1 case was markedly effective, 2 cases were effective, 3 cases were marginally effective, 2 cases showed no effect and 1 case who underwent prophylactic medication had no infection. We recognized no adverse effects by AMK or CEPR.
We concluded that the combination of AMK and CEPR was useful as first choice to the treatment of infections during induction chemotherapy of acute leukemia.

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The transfer of intravenously-administered latamoxef (moxalactam; LMOX) into the cerebrospinal fluid (CSF) is excellent and the usefulness of LMOX in the treatment of meningitis caused by Gramnegative bacilli has already been well established1-13). Because LMOX has weak activity against Gram-positive bacteria, however, some other complementary antibiotic must be employed concomitantly when LMOX is used before the causative bacterium has been identified. Accordingly, in a clinical study conducted by MCCRACKEN et al.13) in which they compared a group administered LMOX with a group concomitantly administered amikacin and ampicillin (ABPC) with respect to the clinical efficacy in the treatment of neonatal meningitis caused by Gram-negative bacilli, ABPC was also used concomitantly with LMOX until the causative bacteria were identified.
However, there are reports that the transfer of an antibiotic into the CSF is altered when other non-antibiotic drugs are administered concomitantly with the antibiotic14, 15). Therefore, it is thought to be necessary to investigate the effect of concomitant use of antibiotics on the transfer of individual antibiotics into the CSF in meningitis since it is difficult to obtain an effective concentration of an antibiotic in the CSF due to the limitation of its ability to cross the blood-CSF barrier, making it difficult to cure this disease.
On this basis, we administered LMOX and ABPC singly or as a mixture to rabbits with experimental meningitis caused byStaphylococcus aureus and we compared their concentrations in the serum and the CSF in the case of single and mixed administrations.

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In order to demonstrate the distribution of an antibiotic to normal breast tissues and its penetration into the axillary wound exudate, 1g of a new cephem antibiotic, cefotiam (CTM), was infused intravenously over 1 hour in 14 patients with breast cancer before and after mastectomy.
CTM concentrations were assayed by the cylinder-plate method, usingProteus mirabilis ATCC 21100 as the test organism.
1. Overall CTM levels in the normal breast tissues ranged from 3.6 to 27.7 μg/g, and 5.2 μg/g of CTM still remained 170 minutes after administration. No significant differences were found in CTM levels of 3 parts of the breast tissue from the same patient.
2. Serum CTM levels rapidly declined after the end of infusion of CTM.
3. Concentrations of CTM in axillary wound exudate after mastectomy ranged from 5.2 to 13.6 μg/ml at 3 hours after administration and were almost undetectable at 24 hours.
It is concluded that CTM levels in breast tissues were almost the same as those in other tissues.

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Reliability of cefsulodin (CFS) disc sensitivity test for estimating approximate values of MICs and its utilization for evaluation of proper administrative dose were studied against 106 strains of Pseudomonas aeruginosa and Staphylococcus aureus isolated from clinical materials using 2 different kind of discs. The disc results were compared with MICs determined using agar dilution method at inoculum level of 10⁶ CFU/ml. The results of CFS disc susceptibility test with 8 mm diameter disc (Showa) and 6 mm diameter disc (Wako), both of them contained 30μ g, were well correlated with MICs. It is capable to use disc results for estima-tion of approximate value of MICs.
For interpretation of CFS disc tests, three category system has been used in USA and Europe, but four category system in Japan. MIC break points proposed for classifying bacteria into three categories of sus-ceptibility: resistant (R) MIC < 32μg/ml, moderately susceptible (MS) MIC 16^-32μg/ml, and susceptible (S) MIC ≤ 8μg/ml. Those in four category system were as follows: (+++) MIC ≤ 3μg/ml,(++) 3μg/ml < MIC ≤ 15μg/ml,(+) 15μg/ml MIC ≤ 60μg/ml,(-) MIC > 60μg/ml. Based on CFS pharmacokinetic data and the recommended dosage schedule (less than 2 g a day), MIC break points < 3μg/ml and < 15μg/ml, appear to be more useful than that of ≤ 8μg/ml and <32μg/ml for evaluating a proper administrative dose level.
In this study, approximately 73 and 94% of strains of P. aeruginosa and S. aureus isolated from clinical materials, respectively, were inhibited at a concentration of 12.5μg/ml CFS. This susceptibility result well indicate usefulness of this drug.

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Susceptibilities of 101 strains of 25 bacterial species or subspecies to amoxicillin (AMPC) were determined by the 2-fold agar dilution method in parallel with the diameter of inhibition zone by the single-disc method, under the experimental conditions established by KANAZAWA.
The experiments demonstrated significant correlation between the MIC by the dilution method and the diameter of inhibition zone in each of conventional assay of the over-night (about 16 hours) incubation, delayed assay (about 24 hours incubation), and rapid assay (after 3-4 or 5-6 hours incubation), thus confirming applicability of the single-disc assay for AMPC.
Analysis of the data obtained by using AMPC disc containing 30μg revealed the primary regression equa-tion to be: D (diameter, mm)=27.1-9.9log MIC (μg/ml) in conventional assay, D=32.2-12.8 log MIC (μg/ml) in delayed assay, D=19.8-6.2 log MIC (μg/ml) in 3-4 hours rapid assay, and D=24.0-7.8 log MIC (μg/ml) in 5-6 hours rapid assay, and particularly for /β-lactamase producing Staphylococci, D=23.7-8.1 log MIC (μg/ml) in conventional assay, D=16.7-9.0 log MIC (μg/ml) in 3-4 hours rapid assay, and D=20.7-9.2 log MIC (μg/ml) in 5-6 hours rapid assay, respectively.
The range of variations in MICs estimated from the diameter of inhibition zone by the disc test was then calculated in comparison with that in MIC determined by the 2-fold agar dilution assays, as reference for the experimental errors which may be involved in the estimation of MIC of AMPC by the single-disc assay.

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Patients with chronic complicated urinary tract polymicrobial infections due to Pseudomonas aeruginosa and other bacteria were treated with cefsulodin using cefotiam or cefmenoxime as a concomitant drug. Each drug was given to the patients in daily dose of 1 or 2 g by drip infusion twice a day for 5 to 16 days. The results were as follows.
1. Overall clinical efficacy was excellent in 7 cases (44%), moderate in 6 cases (38%) and poor in 3 cases (19%), the effectiveness rate being 81.3%.
2. Bacteriologically, 38 strains (88.4%) were eradicated, 1 strain decreased and 4 strains unchanged out of the 43 clinical isolates from the patients.
3. No side effects and no abnormalities of laboratory findings were observed.

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Cefoxitin (CFX) was administered to 12 patients with respiratory tract infections, including mainly patients with pulmonary suppuration or pyothorax. The results were as follows:
1. CFX was effective in 75% of the total patients, and in 83% of the 6 patients with pulmonary suppuration or pyothorax.
2. Microorganisms which were considered to be causative were isolated in 8 of 12 patients. Bacterio-logical responses were “eradicated” in 4 patients, “replaced” in 3 patients, “unchanged” in 1 patient.
3. A slight elevation of S-GPT was observed in one patient and elevation of A1-P in another following CFX administration; however, these values returned to normal shortly after completion of drug administration. No adverse effects, allergic symptoms or laboratory abnormalities were observed.

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The clinical effects of cefoxitin (CFX) were studied in 31 cases of respiratory tract infections.
The results were as follows:
1. As for the clinical effects, CFX was excellent in 5 cases, good in 13, fair in 8 and poor in 5 out of 31 patients; the efficacy rate was 58.1%.
2. The efficacy rate was 57.1% in bronchopneumonia, 61.1% in pneumonia and 50.0% in acute exacerbation of chronic respiratory tract infections.
3. The efficacy rate was 70.6% in the group of 4g/day or less and 42.9% in the group of 6g/day or more.
4. The efficacy rate was 50.0% in 6 cases that had not been responded to other antibiotics previously.
5. As for side effects, skin eruption was observed in only 1 patient.
6. No abnormality was observed in laboratory tests due to CFX.
7. In conclusion, CFX is a useful drug in the treatment of respiratory tract infections.

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Sixteen patients who underwent transurethral resection of prostate preoperatively received intravenous injection of cefmetazole in a dosis of 2 gram. Pharmacokinetic study revealed that concentration of cefmetazole in prostatic tissue well correlated to serum concentration with nearly the same half-life times.

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Patients received 2 gram of cefmetazole, twice on the day of transurethral prostatectomy and the next day, once for the succeeding 2 days. Thirteen out of 34 cases showed significant preoperative bacteriuria. Only 3 of them persisted on the 5th day. Postoperative courses were uneventful in all cases with neither acute epididymitis nor significant fever.

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The MICs and MBCs of cefotaxime (CTX), desacetylcefotaxime (Des-CTX) and ceftriaxone (CTRX) were determined in relation to 4 of the principal bacterial species which cause meningitis, i.e., S. pneumoniae, S. agalactiae, H. influenzae and E. coli. These tests were performed using final inocula of 10⁸cells/ml and 10⁸cells/ml. Comparison was made with the MIC and MBC values of benzylpenicillin (PCG) and ampicillin (ABPC).
1. Against 25 strains of S. pneumoniae, the MIC₉₀ values with inocula levels of 10⁸ and 10⁶cells/ml were as follows: CTX, 0.05 and 0.024μg/ml; Des-CTX, 0.39 and 0.20μg/ml; CTRX, 0.10 and 0.05μg/ml, respectively; and PCG, <0.012μg/ml at both size. Similarly, the MBC₉₀ values were: CTX, 0.01 and 0.05μg/ml; Des-CTX, 0.78 and 0.39μg/ml; CTRX, 0.20 and 0.10μg/ml; and PCG, 0.024 and 0.012μg/ml, respectively. It is thus apparent that PCG showed the lowest values for both the MIC and MBC, followed by CTX, CTRX and then Des-CTX. Against 25 strains of S. agalactiae, the MICH values with inocula of 10⁸ and 10⁶cells/ml were as follows: CTX, 0.05 and 0.05μg/ml; Des-CTX, 0.39 and 0.20μg/ml; CTRX, 0.10 and 0.05μg/ml; and PCG, 0.39 and 0.20μg/ml, respectively. Similarly, the MBC₉₀ values of Des-CTX were 0.78 and 0.39μg/ml, while the other 3 antibiotics showed the same values with both the 10⁸ and 10⁸cells/ml inocula: 0.10μg/ml for CTX, 0.20μg/ml for CTRX and 0.39μg/ml for PCG. Accordingly, CTX showed the lowest values, followed by CTRX and then PCG being about the same as Des-CTX.
Against 25 strains of H. influenzae, the MIC₉₀ values with inocula levels of 10⁸ and 10⁶cells/ml were as follows: CTX, 0.10 and 0.05μg/ml; Des-CTX, 0.39 and 0.39μg/ml; CTRX, 0.10 and 0.05μg/ml; and ABPC, 50 and 6.25μg/ml, respectively. Similarly, the MBC₉₀ values were: CTX, 0.20 and 0.10μg/ml; Des-CTX, 1.56 and 1.56μg/ml; CTRX, 0.39 and 0.20μg/ml; and ABPC, >100 and 50μg/ml, respectively. Accordingly, in terms of the MIC₉₀, CTX and CTRX showed the same values, but in terms of the MBC₉₀ CTX was superior. In both cases, Des-CTX and ABPC were third and fourth, respectively. Four (16%) of these strains were found to be,β-lactamase producing and to be resistant to ABPC, but they showed the same susceptibility to CTX, Des-CTX and CTRX as the ABPC-sensitive strains.
Against 25 strains of E. coli, the MIC₉₀ values of CTRX with inocula of 10⁸ and 10⁶cells/ml were 0.10 and 0.05μg/ml, respectively, while the other 3 antibiotics showed no differences as a function of the inoculum size: CTX, 0.05μg/ml; Des-CTX, 0.78μg/ml; and ABPC, > 100μg/ml. Similarly, the MBC₉₀ values were the same for each drug at both the 10⁸ and 10⁸ inoculum size: CTX, 0.20μg/ml; Des-CTX, 3.13μg/ml; CTRX, 0.39μg/ml; and ABPC, >100μg/ml. The order of potency, in descending order was thus CTX, CTRX, Des-CTX, ABPC. Five (20%) of these strains were found to be resistant to ABPC, but they showed the same susceptibility to CTX, Des-CTX and CTRX as the ABPC-sensitive strains.
2. CTX showed the same or superior antibacterial activity, compared to CTRX against each of the 4 tested bacterial species. There was not even 1 strain which was found to be more sensitive to CTRX than to CTX. In addition, comparing CTX and PCG, PCG was superior against all strains of S. pneumoniae, and CTX was superior against all strains of S. agalactiae.
3. Comparison of the MICs and the MBCs for each of the strains reveals that the MBCs of each of the antibiotics were usually twice as large as the MICs in the cases of S. pneumoniae and S. agalactiae, 2-4 times as large in the case of H. influenzae, and 4 times as large in the case of E. coli.

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Clinical studies on a new cephalosporin antibiotic, cefotaxime (CTX) were carried out in 79 patients with various types of infections in internal medicine.
The efficacy rates were 65.8% in 39 cases of respiratory tract infections, 94.1% in 17 cases of biliary tract infections, 75.0% in 12 cases of urinary tract infections, 80.0% in 11 cases of other infections, and 75.3% in all cases.
After CTX therapy, body temperature was improved in 76.7% of all 79 patients, particularly being excellent in all cases of biliary tract infections. Furthermore, symptoms such as cough, dyspnea, chest pain, moist rale and anorexia were improved to a great degree after CTX therapy.
Adverse reactions and abnormal laboratory findings consisted of mild liver injury in 1 out of 79 cases.
CTX was assessed to be an effective antibiotic for various types of infections in internal medicine.

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1. Cefotaxime (CTX) was microbiologically and clinically studied in surgery.
CTX shows excellent antibacterial activity in vitro against Gram-negative bacilli including E. coli, Klebsiella spp., and Proteus spp. in comparison with cefmetazole (CMZ) and cefazolin (CEZ).
2. Antibacterial activity of CTX is found to be superior to that of CEZ and equal to that of CMZ against Gram-positive bacteria (S. aureus and S. epidermidis).
3. The antibacterial activity of CTX against anaerobic bacteria exceeds that of CEZ and almost equal to that of CMZ. It also showed minimum inhibitory concentration values which, clinically speaking, offer great expectation.
4. CTX is also superior to CMZ and CEZ in its antibacterial activity against P. aeruginosa.
5. Clinical studies were carried out in the group A for which CTX was administered a drug of first choice for postoperative infections in surgery, and in the group B for which CTX was administered as a drug of second choice since the antibiotic of first choice had been ineffective for these cases.
As a result, high effective rates were obtained in both groups (80.3% for the group A, and 77.1% for the group B). With reference to the group B, an effectiveness rate of 100%, was obtained for the cases in which CEZ had been ineffective and 55.6% was obtained for 10 cases in which mainly combination of CMZ had been ineffective.
6. Side effects appeared in 3 cases (1 case each of tinnitus and malaise, vomiting and nausea, and fever) with an incidence rate of 1.46%.
Abnomal clinical laboratory findings appeared in 4 cases (1 case each of leukopenia and increase in GOT and GPT; eosinophilia; increases in platelet and monocyte; and increases in GOT, GPT and Al-P) with an incidence rate of 1.95%.

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[in Japanese]

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[in Japanese]

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