Plasma levels and distribution in pulmonary and bronchial tissues of CTM following injection into the jugular vein were investigated in rabbits with experimental pleuritis or pneumonitis as well as in normal rabbits. The experiments also included the assessment of the effect of concomitant administration of serratiopeptidase (TSP).
1. The pneumonitis+TSP group, pleuritis group and pleuritis +TSP group showed a tendency to delayed dissipation of CTM from the plasma, as compared with controls.
2. The CTM concentrations in tissues from the apical region of upper lobe (L1), lateral region of middle lobe (L2) and diaphragmatic region of lower lobe (L3) 30 minutes after injection did not differ significantly between the control and the TSP group, pleuritis group or pleuritis-FTSP group. In the pneumonitis group, the tissue CTM concentrations at all 3 sites (L1, L2, L3) were lower than those in the control group. They were increased by the concomitant administration of TSP, with statistical significance of increase in regions L2 and L8.
3. Thirty minutes after the injection of CTM, the pneumonitis group and pneumonitis +TSP group displayed essentially comparable CTM levels in pleural fluid, whereas the CTM concentrations in the pleural fluid were prone to be increased in the pleuritis+TSP group as comparing with the pleuritis group.
4. CTM levels in the tissues of trachea (B0), right and left main bronchi (B1) and lobar bronchi (B2) 30 minutes after the injection did not show any significant difference between control and TSP-treated normal groups. CTM concentrations tended to be increased, yet not significantly, in all these regions in the rabbits with pleuritis administered TSP, compared to those without TSP. A similar increasing tendency of CTM concentrations in these regions by concomitant administration of TSP was observed in rabbits with pneumonitis, and such an increase was significant in B1.
5. TSP-administered normal rabbits showed increasing tendency of CTM concentrations in bronchoalveolar lavage fluid 30 minutes after the injection of CTM comparing with controls. However, there was no significant change of CTM concentration with concomitant administration of TSP in the rabbits with pleuritis or pneumonitis.

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In 11 patients undergoing open-heart operation, 1 g of cefotiam (CTM) was administered intravenously by bolus technique at the start of operation. Samples of serum were obtained at 30, 60 and 90 minutes following administration. Samples of right atrial appendage tissue and serum were obtained simultaneously at the time of heart cannulation. Antibiotic concentrations of all samples were determined by agar well method using P. mirabilis ATCC21100 as the test organism.
The results were as follows:
1. Serum levels of CTM after 30, 60 and 90 minutes were 53.1 ± 17.6 μg/ml (Mean±S.D., n=10), 26.1±10.4 tμ/ml (n=11) and 13.5±5.5 μg/ml (n=7) respectively.
2. Myocardial tissue levels of CTM after 60 and 90 minutes were 9.4±4.7 μg/g (n=4) and 4.8±2.7 μg/g (n=7) respectively.
3. The concentration ratios of the myocardial tissue to serum were 0.36±0.10 (n=4) after 60 minutes and 0.35±0.09 (n=7) after 90 minutes.
CTM can transmigrate from blood to myocardial tissue easily as compared with other cephalosporins. Therefore, CTM, a new broad spectrum cephalosporin, can be considered as one of the highly useful antibiotics for the prevention and treatment of infections following cardiac operation.

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Clinical efficacy and safety of cefotiam were studied. Twelve patients with chronic sinusitis and 14 patients with chronic otitis media were intravenously given cefotiam in daily doses of 2g for 7 to 10 days. In chronic sinusitis, clinical responses were excellent in 6 patients, good in 3 and fair in 3, the rate of satisfactory clinical responses (excellent and good) being 75%. In chronic otitis media, the responses were excellent in 5, good in 4 and fair in 5, the rate of satisfactory clinical responses being 65%.
As for side effects, eruption and abdominal pain were observed in 1 patient.

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Cefotiam (CTM) was intravenously or intramuscularly given to 14 patients with infections in the field of otorhinolaryngology including 5 cases with chronic suppurative otitis media.Daily doses of CTM were 1 to 3g and its administration period was 3 to 10 days.Clinical responses were excellent in 1 patient, good in 8, fair in 2 and poor in 3, the rate of satisfactory clinical responses (excellent and good) being 64.3% (9/14). Staphylococci were most frequently isolated from the clinical materials.As for side effects, elevation of GOT and GPT was observed in 1 patient.

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Cefotiam (CTM) was intravenously given to 12 patients with infectious diseases in the field of otorhinolaryngology including 10 cases with chronic suppurative otitis media. Daily doses of CTM were 1 to 4g.Clinical responses were excellent in 3 patients, good in 5, fair in 1 and poor in 3.The rate of overall clinical effectiveness was 67%.Staphylococcus species were most frequently isolated from the patients and all of them were eradicated by the CTM treatment.No side effects and no abnormal laboratory findings relating to the drug administration were observed.

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CTM was administered at dose levels of 1 to 3g a day to 77 cases of otorhinolaryngological infections, and the following results were obtained:
1. The effect of the drug was determined in 75 cases. The responders were 3 out of 5 (60.0%) in acute suppurative otitis media, 4 out of 11 (36.4%) in chronic suppurative otitis media, 39 out of 43 (90.7%) in tonsillitis and peritonsillar abscess and 12 out of 16 (75.0%) in other diseases, a total of 58 out of 75 cases (77.3%).
2. The bacteriological effect of CTM was evaluated in 53 cases, and bacterial eradication wasd emonstrated in 41 cases (77.4%). Also, its antibacterial potency was 2 to 4 times superior in comparison to that of CEZ against isolated bacteria in which MICs were measurable.
3. Side effects which were neither severe nor specific were recognized in 3 out of 77 cases (3.9%). In the cases with abnormal laboratory values, none was determinable to be attributed to CTM.

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Clinical investigation with cefotiam (CTM) was performed, the following results were obtained.
CTM was administered to 18 cases of infectious diseases in the otorhinolaryngologic field.
Clinical results were excellent in 7 cases, good in 5 cases, fair in 4 cases and poor in 2 cases. Clinical efficacy was 66.7%. No side reactions were noted in any cases.

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Cefotiam (CTM) was intravenously given to 20 patients with infections in the field of otorhinolaryngology.
Daily doses of CTM were 2 to 4g divided into 2. Clinical responses were excellent in 11 patients, good in 8 anidnf a1ir, the rate of satisfactory clinical responses being 95% (19/20). Ninety-one % (10/11) of Gram-positive cocci isolated from the patients were eradicated by the CTM treatment, while 60% (6/10) of Gram-negativeb acilli were persisted.
As for the side effects, eruption and elevation of GOT and GPT were observed in 1 patient.

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Clinical studies of cefotiam (CTM), a new cephalosporin derivative, in otorhinolaryngological field were performed, and the results were summarized as follows.
1. CTM was intravenously injected to 31cases of otorhinolaryngological infections in daily dose of 1-4g.
2. Clinical efficacy was 33.3% in acute otitis media and chronic otitis media (acute exacerbation)(6 cases), 90% in acute tonsillitis (including peritonsillitis, peritonsillar abscess)(20 cases), 50% in acute pharyngitis (2cases), 100%in acute sinusitis (2cases) and 100% in epiglottis abscess (1case), respectively.
3. Bacteriological efficacy was 80% for β-Streptococcus, 100% for K.pneumoniae, 50%for P. aeruginosa, and 85.7% for Peptococcus and Peptostreptococcus, respectively.
4. No difference was observed in various daily doses for clinical efficacy.
5. As for side effects and laboratory findings, eruption in 1case, elevation of GOT in1 case and elevation of GOT, GPT in 2 cases were observed. But, all of the cases were normalized after stoppage of administration or postadministration.

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Clinical study was made on cefotiam (CTM) and the following results were obtained.
1. Tissue concentrations of CTM were determined 1 hour after intravenous injection (CTM1g) in chronic sinusitis and maxillary cyst.
Concentrations of CTM were 16.53μg/g, 13.26μg/g in mucosa of the maxillary sinus, maxillary cyst, respectively.
2. Antibacterial activity of CTM was measured on Escherichia coli, Staphylococcus epidermidis, Aerococcus, Acidaminococcus fermentans, Peptostreptococcus anaerobius;that were isolated from pus of maxillary sinus. The highest MIC on them was 3.13μg/ml.

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The clinical effectiveness and safety of cefotiam (CTM) in infectious diseases in the field of otorhinolaryngology was evaluated from 30 patients (otitis media 18, pharyngeal infection 4, chronic paranasal sinusitis 1, esophagitis 1, acute bronchitis 1, others 4).
Side effect (fever, nausea) was found in a 14 years old male patient. Skin test revealed positive in 1 patient. These cases were excepted from evaluating clinical effectiveness of CTM.
In 28 patients, the overall ratio of clinical effectiveness was 60.7%. In patients of otitis media, the clinical effectiveness ratio was 41.2%, whereas the ratio was 75.0-100% in patients of other diseases. In particular, the clinical effect was fair or poor in patients to whom the drug was given only once a day.
These results suggest that this chemotherapeutic drug should be administered at least twice a day, particullary to the patients of otitis media.
The bacteriological response to CTM was evaluated from 53 strains, isolated from 28 patients before treatment. Eradication rate of bacteria was 60.4%.
No abnormal laboratory findings, relating to the drug, were observed after treatment.

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Basic and clinical studies on cefotiam (CTM) for the infectious diseases in otorhinolaryngological field were performed and the following results were obtained.
1. The peak value in the serum level of CTM was 18.05μg/ml by 0.5g administration and 35.2μg/ml by 1g at 30 minutes after a single intravenous injection. CTM was rapidly excreted from the blood after injection and was detected a little amount in serum at 6 hours after the administration.
2. Tissue concentrations of the drug into palatine tonsil and the mucous membrane of the nasal cavity or maxillary sinus were seen in relatively rapid and good manner.
3. Chemotherapeutic results excepting Pseudomonas aeruginosa infections (3 cases) were excellent in 2 cases, good in 7 cases and poor in 3 cases of 12 patients with the infectious diseases in otorhinolaryngological field.
4. No adverse effects and abnormal values in the laboratory findings were revealed in every patients.

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Numbers of the strains of each bacterial species isolated from urinary tract infections were summed and their incidences were calculated for each a half year from the second half of 1980 to the first half of 1982. The incidences of Escherichia coli strains were found to be greatly reduced and those of Streptococcus faecalis strains were greatly increased. Those of Staphylococcus epidermidis strains were also increased. This trend was thought to be caused by the extensive and exclusive use of cephalosporin derivatives.
Minimal inhibitory concentrations of gentamicin (GM), amikacin (AMK), ampicillin (ABPC), cefazolin (CEZ), ceftizoxime (CZX), latamoxef (LMOX) and minocycline (MINO) against these isolated strains were estimated. The most sensitive drugs for E. coil were found to be CZX, LMOX, GM and AMK, CZX and MINO for Klebsiella, CZX and LMOX for Proteus, and GM for Pseudomonas aeruginosa. All Gram-positive cocci were found generally to be most susceptible to MINO, but S. faecalis and other Pseudomonas were also sensitive to ABPC.
Exclusive use of cephalosporins for the treatment may induce selective increases of the resistant species in normal flora. Since these flora could be the causative agents for various infections, these selections caused by the exclusive use of the monotype drugs are not preferable, and various different drugs should be used for the suitable cases.

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Using 3 kinds of medium, MUELLER-HINTON (M-H) agar, M-H agar added with defibrinated hores blood and lysed horse blood, susceptibilities of Campylobacter were tested quantitatively to 12 antibacterial agents. The result showed no remarkable difference between them.
MIC was examined with the cell concentration of MCFARLAND unit 0.5 and 100-times dilution, and there was no significant difference between them except for 2 strains, on which erythromycin showed MIC of 6.25μg/ml at MCFARLAND unit 0.5 and 0.39μg/ml at 100-times dilution.
Eighty-two clinical isolates of C. jejuni and 6 of C. coli were tested for their susceptibility to 12 antibacterial agents. These strains were most susceptible to gentamicin and amikacin and less susceptible to benzylpenicillin, carbenicillin and cephaloridine with the MIC of 25μg/ml. There were 2 peaks of susceptibility distribution to minocycline (0.2 and 50μg/ml).
In tests for β-lactamase of C. jejuni and C. coil, 3 strains obtained from 1 patient were positive.

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Nuclear magnetic resonance (NMR) spectrometry were applied for the measurement of inhibitory activity of some drugs towards β-lactamase in living cells. From the integrated values of the signals based on 5-H and 6-H of β-lactam ring or methyl proton of C-2 position of ABPC as substrate, the inhibition dose of 50% (ID50 value) to β-lactamase activity under the condition containing 10mg of ABPC was calculated. The ID50 values (mg) of clavulanic acid (CVA), N-formimidoylthienamycin (MK 0787) and dicloxacillin (MDIPC) known as β-lactamase inhibitor were less than 0.0001, 0.4 and 0.6, respectively, when each inhibitor was preincubated for 10 minutes. The ID50 values of cefoxitin (CFX), cefmetazole (CMZ), latamoxef (LMOX) and cefotaxime (CTX) known as β-lactamase resistant drugs were 1.4, 1.3, 0.4 and more than 20.0, respectively, under same condition. From these results, it was clearly shown that CVA is excellent inhibitor to the β-lactamase of RICHMOND'S class III in living cells. And the inhibitory effect of CFX, CMZ and LMOX was also clearly shown.

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Cefamandole sodium (CMD), a new cephalosporin-derivative, was synthesized in the Laboratory of Eli-Lilly Co.Ltd.U.S.A.in 1972.
CMD, which is several times more active than cefmetazole (CMZ, a cephamycin antibiotic) against Grampositive cocci, is only as active as the latter antibiotic against Gram-negative bacilli.Against Haemophilus influenzae, CMD exhibits an antimicrobial activity which is as strong as that of ampicillin sodium.
Our previous comparative tests on efficacy and safety of CMD versus cefazolin (CEZ) demonstrated that CMD was as effective and safe as CEZ in the treatment of respiratory tract infections.
In the present clinical trial, the efficacy and safety of CMD are evaluated by a comparative double blind method using CMZ, a more recently synthesized cephamycin antibiotic, as a reference drug.
For this purpose, a comparative double blind study was carried out in 50 institutions and clinics in Tohoku and Hokkaido districts in Japan.
A total of 272 inpatients, who was aged over 16 years and was diagnosed as having pneumonia, lung abscess or acute infectious exacerbation of chronic obstructive pulmonary diseases, was included in this trial.
They received 2g of CMD or CMZ twice a day by intravenous drip infusions, as a rule, for 14 days.
Of these patients, 264 (133 received CMD and 131 CMZ) were available for the evaluation of safety and usefulness.Two hundred and thirty-eight patients (122 received CMD and 116 CMZ) were adopted for the evaluation of efficacy.
Prior to the treatment, there was no significant difference with respect to age, sex, severity of infection and underlying diseases between subjects in 2 treatment groups.
An excellent or good clinical response was obtained in 82% of the patients treated with CMD, and in 81% of those treated with CMZ.Thus, there was no significant difference in cure rate between 2 treatment groups.
However, an excellent clinical response was found in 12.3% of the patients treated with CMD, whereas only in 4.3% of those treated with CMZ.This difference in percentage of excellent clinical response between 2 treatment groups was statistically significant (P <0.05).Of the 87 patients with moderate to severe infection who were treated with CMD, 13 showed an excellent response.Only 4 of 90 patients treated with CMZ showed an excellent response.Statistically the difference in the rate of excellent response between these 2 groups was significant (P<0.05).
In a group of patients who had respiratory infections associated with underlying pulmonary diseases, 7 of 50 patients showed a favorable response to CMD, while only 1 of 55 to CMZ. Thus it was found that the clinical efficacy of CMD exceeded that of CMZ in the treatment of respiratory infections which were moderate to severe, or were associated with underlying pulmonary diseases.
Bacteriological efficacy was evaluated based on the rate of elimination of causative organisms from the sputum.Elimination by CMD treatment was achieved in 82.5%, while that by CMZ treatment in 66.2% of the patients.This difference in elimination rate was statistically significant (P<0.05).In patients whose infections were due to multiple organisms, the organisms were eliminated in all (8/8) of the patientstreated with CMD, whereas in 7 of 12 treated with CMZ.This difference in rate of elimination of multiple organisms between 2 treatment groups was not significant (P<0.1).
Next, the incidence of adverse reactions was compared between 2 treatment groups.Mild undesirable signs and symptoms such as nausea, diarrhea, headache or eruption were seen in 3% of the patients treated with CMD and in 2.3% of those treated with CMZ (statistically not significant).

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On the 53 patients with ENT (ears, nose, and throat) diseases, ototoxicity after intravenous drip infusion of amikacin (Biklin®AMK) was studied.
Each dose of AMK was 400mg/day in adults and 4-8 mg/kg/day in children. From audiometric analysis, there were no patients with any hearing disturbances and subjective complaints concerning labyrinth injury.
Also abnormal laboratory findings were not found in them. An intravenous drip infusion of AMK in adequate dosage would be beneficial to use against some infectious diseases of otorhinolaryngologic field.

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Twelve patients with uterocervical cancer had panhysterectomy and were administered piperacillin (PIPC) at a dose of 2g by one shot injection 2 times a day for a period of 5-6days.
PIPC concentrations in serum and pelvic dead space exudate were investigated before and after administration for 3days (5times). Serum concentration was observed ca. 49μg/ml at 1hour after the first, third andfif th administration. Concentrations in pelvic dead space exudate at 1hour after the first, third and fifth administration were observed 26.7±5.8, 10.8±4.0 and 8.7±3.5μg/ml, respectively. The highest concentration was 63.0μg/ml at 1hour after, the first administration in case 4. It was thought that these concentrations were sufficient for the therapy of parametritis.
No side effects caused by the drug were observed.

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We employed latamoxef (LMOX) as antibiotic therapy subsequent to the performance of appendectomies in children. Fifteen patients, consisting of 8 cases of catarrhal appendicitis and 7 cases of gangrenous appendicitis, were administered LMOX at 50mg/kg/day, while 13 patients with peritonitis due to a perforated appendix were treated with a dosage of 90mg/kg/day. Both of these dosages were administered in 3 equally-divided doses, as one shot intravenous injections.
All of the cases of catarrhal and gangrenous appendicitis showed good, steady recovery after the surgery, and there were no instances of complications.
With regard to the 13 cases of perforating appendicitis, a clinical efficacy of at least good was obtained in 12 patients, for an efficacy rate of 92.3%. In addition, bacteriologically, 35 out of 36 strains that were isolated initially could no longer be detected after the LMOX therapy, indicating an eradication rate of 97.2%. Complications consisted of 1 case of dehiscence of the wound, and 1 case of adhesive ileus.
Comparison of the values of the laboratory tests before and after the LMOX therapy revealed no development of abnormalities. Moreover, with regard to side effects, with the exception of 1 case of transient diarrhea, there were no side effects which presented clinical problems.
It was found that the causative microbes involved in these cases of appendicitis-especially in the perforative appendicitis cases-were Gram-negative bacilli such as E. coli, and an anaerobic bacterium, B. fragilis. In many cases these bacteria existed as mixed infections, but LMOX shows good antimicrobial potency against both these types of microbes and was thus able to provide sufficient therapeutic efficacy even though it was administered alone.
We were quite satisfied and impressed with these results and judged them to be worth reporting.

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The combined actions of sisomicin (SISO), dibekacin (DKB) and cefotetan (CTT), cefotaxime (CTX), latamoxef (LMOX), cefsulodin (CFS) against E coil KC-14, S. marcescens T-55 and P. aeruginosa E-2 were studied. The following results, were obtained.
1. The combination of SISO-CTT, SISO-CTX, SISO-LMOX, SISO-CFS, DKB-CTT, DKB-CTX, DKBLMOX and DKB-CFS using the checker board dilution method on E. coli KC-14, S. marcescens T-55, P. aeruginosa E-2 were found to have a synergistic effect and the minimum FIC index values were 0.26-0.50 for SISO and 0.28, w 0.75 for DKB, respectively.
2. With the killing kinetic method, all combinations tested showed a synergistic effect.

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To investigate the clinical and bacteriological usefulness of orally administered fosfomycin calcium (FOM), the susceptibility of 558 strains to FOM was determined. These strains were isolated at our Center, between Feb. 1982 and Feb. 1983 from otorhinolaryngological infections. Several other drugs were also tested on the same strains for comparison.
The results were as follows.
1. The MICK, of FOM was 6.25μg/ml against each of aerobic Gram-positive cocci such as S. aureus, S. pyogenes, S. pneumoniae, anaerobic Gram-positive cocci such as Peptococcus spp., and H. influenzae. P. mirabilis, indole-positive Proteus spp., P. aeruginosa and K. pneumoniae were inhibited, respectively, at 3.13, 12.5, 12.5 and 50μg/ml. Most of the MICs were between 3.13 and 12.5μg/ml, and the difference between the MIC50 and the MIC90 was only 1 to 2 tubes since there were few resistant strains.
2. With the comparative drugs, there was a reduction seen in the sensitivities of pipemidic acid (PPA), ampicillia (ABPC), and cephalexin (CEX) against, respectively, P. aeruginosa, beta-lactamase-producing H. influenzae and S. aureus. FOM showed good and constant sensitivity for the weakly PPA-sensitive P. aeruginosa, weakly ABPC-sensitive beta-lactamase-producing H. influenzae and weakly CEX-sensitive S. aureus.
3. The MICs of FOM against the main problematic isolates from otorhinolaryngological infections were mostly between 3.13 and 12.5μg/ml, including the above weakly PPA-, ABPC-and CEX-sensitive strains. Based on these values, FOM may be said to have moderate antibacterial efficacy when administered orally in the usual dose. But concerning FOM's other unique characteristic of having strong activity against bacteria resistant to one or more other antibiotics, FOM was concluded to be a useful drug for the treatment of otorhinolaryngological infections when this unique characteristic is fully utilized.

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Out of 1,219 pediatric patients who were brought to our hospital with chief complaint of diarrhea and abdominal pain and in whom stool cultures were obtained for bacteriological studies in the 17 month period from May 1 in 1981 to September 30 in 1982, Campylobacter jejuni was isolated in 203 patients (16.7%).
In this study we assessed the efficacy of fosfomycin (FOM) for C. jejuni enteritis. Results of antibiotic susceptibility tests revealed that C. jejuni is highly sensitive to FOM. The efficacy of FOM was confirmed both clinically and bacteriologically. Moreover, improvement in diarrheal symptoms and the duration required for cultural conversion under FOM treatment were assessed. From the results obtained, it was considered that FOM is an antibiotic with high efficacy for the treatment of C. jejuni enteritis.

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The fundamental trials on intravenous administration of tobramycin (TOB) were studied in a total number of 29 neonates and premature babies who was divided into 3groups by their ages; 0-3, 4-7 and 8 or more days after birth. Moreover, the results obtained in them were compared with those in a small number of infants and the school children reported previously to investigate the possibility of administration of the drug to neonates and premature babies.
1. Analysis of the pharmacokinetics of TOB in neonates and premature babies demonstrated that its halflife (T1/2) became shorter with age; it was 5.37, 4.28 and 3.03 hours at the age of 0-3, 4-7 and 8 or more days, respectively when 1.5mg of the drug per kg body weight is instilled into the vein for 30 minutes. A similar trend was observed at a dose of 3.0mg per kg body weight.
2. Although the number of subject was small, T1/2 averaged 2.07hours at the dose of 1.5 mg/kg in 2 infants and 1.40hours at 3.0mg/kg in 3 infants.
These results indicate that administration of TOB based on the same conception as that in infants and school children should be avoided in neonates and premature babies.
Especially in0-3, 4-7day-old neonates and premature babies the behavior of the drug in the body suggests that once or twice administration a day may be safer and better to avoid its accumulation.
The peak serum concentrations in neonates and premature babies were slightly higher with decrease in number of days after birth, but it was not specially high as compared with those in infants and school children. It is, therefore considered that 1.5mg/kg is an adequate single dose to moderate cases.
On the basis of the above-mentioned results of the pharmacokinetic study we are confirming the clinical safety and utility of TOB in cases in which its administration is essential.

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The combined actions of cefoxitin (CFX) with amikacin (AMK), gentamicin (GM) and dibekacin (DKB) were studied against Gram-positive and Gram-negative bacteria. The following results were obtained.
1. The synergistic actions of CFX with AMK, GM and DKB were observed on S. aureus, S. epidermidis, E. coli, S. marcescens, K. pneumoniae, Proteus spp. and Acinetobacter by checker board titration method. The combination of CFX with AMK was most effective.
2. In case of the combination of CFX with AMK, the simultaneous administration showed the highest bactericidal effect, followed by the case of addition of AMK after adding CFX.
3. The phase-contrast microscopic observation on S. marcescens revealed that the bacterial cell prolonged with CFX showed a filament-like form and with AMK almost a normal form. In the combination, lysed cells were observed.
4. The therapeutic experiment of S. marcescens infection in mice demonstrated that the combination of CFX with AMK showed superior effect than that of each drug alone.

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Ten inpatients at the Second Department of Internal Medicine, Mie University Hospital, developed infections in the course of treatment for hematopoietic disorders and were administered cefoxitin (CFX). Patients suffered from the following infections: pharyngitis, 2; bronchitis, 2; pneumonia, 2; sepsis, 2; bacteremia, 1; suspected cases of bacteremia, 2; and fever of unknown origin, 1. The number of infections totaled 12 as 1 patient with pharyngitis also developed sepsis and 1 patient with pneumonia developed bacteremia.
Duration for the administration of CFX ranged between 5 and 18 days with a total dosage of between 30 and 108g. Of the 10 patients treated with CFX, 9 were treated concomitantly with micronomicin (MCR), doxycycline (DOXY), or sulbenicillin (SBPC), some were treated concomitantly with only 1 of the drugs and some were treated concomitantly with 2 of the drugs.
The following clinical results were obtained:
1. Following treatment, 4 patients were considered excellent, 5, good, and 3, poor. Clinical efficacy rate was 75%.
2. Four strains of Gram-positive cocci (1 strain of S. aureus, 2 strains of S. epidermidis and 1 strain of Streptococcus sp.) and 3 strains of Gram-negative rods (2 strains of P. aeruginosa and 1 strain of E. cloacae) were found in the clinical specimens of the 10 patients. These results differed somewhat from reported data that Gram-negative rods such as E. coli, Kkbsiella sp., Pseudomonas sp., Serratia sp., are dominant.
3. No serious side effects requiring cessation of treatment were observed. Elevations in the levels of S-GOT, S-GPT, serum alkaline phosphatase, blood urea nitrogen, etc. were observed. However, these elevated levels were not thought to be caused by CFX alone since CFX was administered concomitantly with MCR, DOXY or SBPC. Abnormalities noted in laboratory tests might have been due to anticancer drugs and/or blood transfusions.
4. Clinical results indicate that CFX is a very effective antibiotic for the treatment of infections complicated by hematopoietic disorders since CFX has a broad spectrum of antibacterial activity against Grampositive and Gram-negative pathogens.

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Antimicrobial susceptibility of 703 nonselected strains of 14 different bacterial species to cefazolin, cefmetazole, cefotiam, cefoperazone latamoxef, and cefotaxime (CTX) was examined. CTX was the most active against E. coil, Klebsiella, Serratia, P. mirabilis, H. influenzae, β-Streptococcus group A, β-Streptococcus group B and S. pneumoniae. On the other hand, CTX-resistant (MIC>50μg/ml) strains were isolated at the following frequencies: Citrobacter, 21.7%; Enterobacter, 7.7 %; Serratia, 4.6%; P. aeruginosa, 40.4% and B. fragilis, 28.6%.
Of the 411 strains classified as very sensitive (+++) or moderately sensitive (++) by disk method, 405 strains (98.5%) were inhibited by <12.5μg/ml of CTX. Only 1 strain (0.2%) was falsely classified as moderately sensitive and no strains were falsely categorized as resistant.

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Seventy-five patients with severe infection accompanying hematologic disorder, including leukemia and malignant lymphoma, were treated with cefotaxime (CTX).
CTX was administered by intravenous drip infusion at a daily dose ranging from 4 to 16 g for terms of 3 to 21 days. The total doses were ranged from 12 to 226g.
The results obtained were as follows:
1. Clinical effects: Excellent in 20 cases, good in 21 cases, fair in 7 cases and poor in 27 cases. The efficacy rate was 54.7% (41/75).
2. Clinical effectiveness on isolated organisms (27 cases): In single infection (21 cases), the efficacy rates were 80% for Gram-positive cocci, including S. aureus and 63.6% for Gram-negative bacilli other than P. aeruginosa. In mixed infection (6 cases), the rate was 50.0%.
3. There were no significant differences in the efficacy rates for those patients who were grouped by the initial number of neutrophil (less than 100, 101-500 and over 501/mm³).
3. There were no significant difference in the efficacy rates for those patients who were grouped by the initial number of lymphocyte (less than 500 and over 501 /mm³).
5. Side effects and abnormal laboratory findings: One case of skin rash and 2 cases of elevated GOT and GPT were observed.
CTX was therefore considered as a clinically useful antibiotic for the severe infections even in neutropenic state in patients suffering from malignant hematological diseases.

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Fifty-eight patients were treated with cefotaxime (CTX, Claforan®) intravenously. Almost all patients (54patients) had underlying diseases that were 16 cases of diabetes mellitus, 10 cases of respiratory diseases, 8 cases of cerebral vascular disturbance, 6 cases of renal diseases and blood diseases, 5 cases of carcinoma and hypertension, 4 cases of cholelithiasis, 3 cases of heart diseases and 7 cases of other diseases.
The clinical efficacy of CTX in 34 cases of RTI, 11 cases of UTI, 8 cases of BTI and 5 cases of other in-fection was excellent in 11 cases, good in 27 cases, fair in 12 cases, poor in 4 cases and unclear in 4 cases.
The over all clinical effectiveness was 70.4%. No adverse reaction was observed except for 2 cases (general fatigue in 1 case and eruption and itching in another).
These results obtained should support the usefulness of CTX.

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Susceptibilities of 228 strains of 32 bacterial species to rnicronomicin (MCR) were determined by the 2-fold agar dilution method in parallel with the diameter of inhibition zone by the single-lise method, under the experimental conditions established by KANAZAWA.
The experiments demonstrated significant correlation between MIC by the dilution method and 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 (after5-6or 3hours incubation), thus comfirming applicability of the single-disc assay for MCR.
Analysis of the data obtained by using MCR disc containing 30μg revealed the primary regression equation to be: D (diameter, mm) =25.7-9.5logMIC (μg/ml) in conventional assay, D=30.3-11.6logMIC (μg/ml) in delayed assay, D=21.0-7.0logMIC (tig/ml) in5-6hours rapid assay, D=16.8-4.8logMIC (μg/ml) in 3-4 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 dilution assays, as reference for the experimental errors which may be involved in the estimation of MIC of MCR by the single-disc assay.

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Micronomicin sulfate (MCR) is a new aminoglycoside antibiotic, and its antibacterial spectrum is similar to that of gentamicin (GM).According to the animal test, MCR has less ototoxicity than other aminoglycoside antibiotics such as GM.To check its clinical ototoxicity, MCR was given intramuscularly to20patients at dose o120-240mg/day, respectively for 8 days, and audiometry was carried out before and after administration of MCR.No evident change was detected between the preadministration hearing levels and the postadministration hearing levels.These data suggest that MCR is sufficiently safe in ototoxicity within dose of 120mg/day for 4days.

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