The present study investigated the in vitro and in vivo antibacterial activity and β-lactamase stability of the cefotaxime (HR 756, CTX) provided by Hoechst Japan Limited and Nippon Roussel K. K. using various strains from stock cultures of the Laboratory of Microbial Resistance, Gunma University.
The results are summarized as follows.
(1) Cefotaxime was highly active against gram-positive and gram-negative bacteria. This compound showed potent antibacterial activity against bacteria resistant to β-lactam antibiotics.
(2) Cefotaxime was active against ampicillin resistant E. coli, S. marcescens and gentamicin resistant P. aeruginosa. This compound expressed no cross-resistance between ampicillin and gentamicin
(3) Cefotaxime displayed a much higher degree of bactericidal activity than did cefazolin and cefoxitin.
(4) The antibacterial and bactericidal activities were influenced by the inoculum size. The concentration of cefotaxime became lower as the inoculum decreased.
(5) Cefotaxime, like cefuroxime was stable to PCase and CSase. To CSase produced by P. vulgaris, this compound was most resistant of all the tested antibiotics.
(6) Cefotaxime was more effective than cefazolin and cefotiam against infections with E. coli and K. pneumoniae in mice.

View full abstract

The authors examined the antibacterial activity of cefotaxime (HR 756, CTX) incomparison with cefazolin (CEZ), cefoxitin (CFX), cefuroxime (CXM), cefamandole (CMD) andcefmetazole (CMZ), using a total of 1, 205 strains of Streptococcus, Haemophilus, Escherichia, Klebsiella, Enterobacter, Citrobacter, Serratia, Proteus, Pseudomonas, Flavobacterium, Achromobacter, Alcaligenes, Comamonas, Bacteroides and Fusobacterium, isolated from various kinds of clinical materialsduring 1978 and the first half of 1979.
Cefotaxime showed a more potent antibacterial activity than CEZ against all strains. It was also more active than CFX, CXM, CMD and CMZ against the majority of strains.
In particular, cefotaxime was highly antibacterially active against S.pneumoiae, S. pyogenes, S. agalactiae, Streptococcus group G, and Haemophilus influenzae. Cefotaxime was also considerably more active than other cephalosporins against E. coli, Klebsiella, C. diversus, P. mirabilis and P. rettgeri.

View full abstract

The in vitro and in vivo antibacterial activities of a new cephalosporin antibiotic, cefotaxime (HR 756, CTX) were compared with those of cefazolin, cefamandole, cefuroxime and cefmetazole. The following results were obtained.
Cefotaxime is a broad-spectrum antibiotic active against gram-positive and gram-negative organisms. It was particularly active against some gram-negative bacilli, e. g. indole-positive Proteus, Serratia and E. cloacae. Cefotaxime was more active against P. aeruginosa, P. cepacia, P. maltophilia and A. calcoaceticus than currently available cephalosporin preparations.
Cefotaxime was as stable as cefuroxime to β-lactamases (penicillinase and cephalosporinase).
Cefotaxime excelled cafazolin in its therapeutic efficacy in mice infected with cefazolin-resistant E. coli, P. mirabilis and C. freundii.

View full abstract

The in vitro and in vivo activity of cefotaxime.(HR 756, CTX) was investigated. B. fragilis group was insensitive to cefotaxime. But Fusodacterium and anaerobic cocci were sensitive to cefotaxime.
The β-lactamase from each of the fifteen B. fragilis organisms was predominantly a cephalosporinase, with little or no penicillinase activity.
Cephalothin (CET) and cefazolin (CEZ) were the most rapidly hydrolyzed, and cefotaxime was hydrolyzed slightly less rapidly than CET and CEZ.
Cefotaxime was more effective than CEZ against experimental subcutaneous abscess due to F. necrophorum in mice.

View full abstract

The in vitro and in vivo antibacterial activity of cefotaxime was compared with that of cefazolin and cefmetazole. The following results were obtained,
1) Cefotaxime showed broad antibacterial spectrum against gram-positive and gram-negative bacteria.
2) hi the sensitivity distribution to clinical isolates cefotaxime exhibited stronger antibacteria activity than cefazolin and cefmetazole against not only Streptococcus pyogenes, Streptococcus pneumimiae, Noisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis but also most strains of cephalo Sporin-resistant Escheriehia coli, Klebsiella pneumoniae, indole-positive Proteus sp., Serratia marcescens and Pseudoinonas aeruginosa, while slightly inferior to those of cefazolin and cefmetazole against Staphylococcus aureus.
3) Cefotaxime was bacteoicidal against Escherichia coli, Klebsiella pneumoniae, Serra Serratia marcescens and Pseudoinonas aeruginosa at concentrations generally equal to or only two fold higher than the minimum inhibitory concentration.
4) Cefotaxime was more effective than cefazolin and cefmetazole in experimental mice infections caused by giam-negative bacteria, including Proteus vulgaris, Proteus morganii, Serratia marcescens and Pseudomonas aeruginosa.

View full abstract

Pharmacokinetics (i.e., blood levels, biological half lives, distribution, urinary excretion and binding to protein) of the new cephalospolin antibiotic cefotaxime (HR 756, CTX) were investigated. Cefoiaxime was i.v. or i.m. injected to rabbits and rats in a dose of 20mg/kg.
1) Biological half lives of cefotaxime in blood were 30.39 min (i.m.) and 9.19 min (i.v.) in rabbits and 41.50min (i.m.) and 9.25min (i.v.) in rats. Its half life at the site of i.m. injection was calculated to be 24.40min in rats.
2) The maximum blood level in rats treated with i.m. cefotaxime was attained 15 min after injection. The organ where cefotaxime concentration was highest at that time was the site of injection (muscle), followed by serum, kidney, lung, duodenum, liver, other muscles, brain and spleen, in this order.
3) Maximum urinary concentrations of cefotaxime were observed in first 30min urine in rabbits and were 1.09mg/ml (i.m.) and 1.667mg/ml (i.v.). Excretion rates in 6hr urine in rabbits were 33.96%(i.m.) and 33.86%(i.v.) of the total injection dose and those in 24hr urine in rats wewe 59.92%(i.m.) and 59.41%(i.v.).
4) The binding rates of cefotaxime to human plasma and sera of the cow, dog, rabbits, rat and mouse were measured by two methods: centrifuging ultrafiltration and equilibrium dialysis.
The binding rate to human plasma was 70.13%(by the former method) or 61.31%(by the latter method). A large proportion of cefotaxime bound to protein was found to be reversible. The binding constant to albumin was 0.9049.

View full abstract

Minimal inhibitory concentrations (MIC) of cefotaxime, a new cephalosporin, to the clinical isolates and its passage into the CSF in staphylocococcal meningitis in rabbits were studied, and the following results were obtained.
1) MIC of cefotaxime against S. aureus was 2 to 4 times higher than that of cefazolin but an antibacterial activity against gram-negative rods was far superior to cefazolin. MICs to the inoculum size of 10⁸/ml against 10 strains of P. aeruginosa were 6.3-50 μ g/ml.
2) MIC of cefotaxime against cefazolin-resistant E. coli was lower than 0.8 μ g/ml. Studies with K. oxytoca suggested that cefotaxime was stable to β-lactamase and that its antibacterial activity was potent.
3) CSF concentrations and CSF/serum ratios of cefotaxime after its single intravenous injection of 100mg/kg in 8 rabbits with staphylococcal meningitis showed the following values after indicated periods of time, respectively; 10. 86 ± 1.79 μ g/ml and 8.3%(30min. after an one-shot intravenous injection), 8.11 ± 1.43 μ g/ml and 12.6%(1hr), 5.83 ± 0.18 μ g/ml and 15.7%(11/2hr) and 4.49 ± 1.16 μ g/ml and 34.0%(2hrs).
4) Cefotaxime of the same dose was injected to another 6 rabbits with staphylococcal meningitis, and the blood and CSF specimens were obtained at 15-min. interval for 8 times and thereafter twice at 30-min. interval, a total being 10 times. Half-life (T1/2) and area under the curve (AUC) in bloodand CSF were calculated and the following values were obtained ; an AUC in CSF concentration of 404min·μ g/ml up to 150min., a CSF/serum ratio of AUC of 12.4%, T1/2 of CSF concentration of 47.6min., which was 1.63 times as that of the blood. Based on these results it was considered that passage of cefotaxime into the CSF was superior to those of penicillin G and carbenicillin and almost equal to that of ampicillin.
5) The above results were interpreted to suggest that cefotaxime may be a potent antibiotic in the treatment of bacterial meningitis in human subjects and to form the sound basis of further clinical trial.

View full abstract

Cefotaxime (HR 756, CTX) for parenteral use, a new antibiotic of cephalosporin series with marked resistance to beta-lactamase, was used in 44 patients hospitalized due to acute or subacute infection of the abdominal organs; 26 patients with appendicitis, 10 with cholelithiasis, 2 with mastitis and others.
Cefotaxime in a dose of 1g was given intravenously during the operation. Tissue specimens were taken from various sites of the removed organs. Tissue specimens, bile and plasma samples were subsequently taken at intervals. Cefotaxime concentration was determined according to the bioassay method with ATCC 9341 strain of Micrococcus luteus.
Cefotaxime concentration in purulent ascites and A-biie increased gradually for 1 hour, followed by a slow decline. Cefotaxime was detected in the B-bile, obtained through the gallbladder wall at 10-20 minutes after intravenous administration.Cefotaxime concetration in
infectious gallbladder wall and inflammatory soft tissues reached the peak at 5-10 minutes after the intravenous administration, followed by a slow decline.
Cefotaxime concentration in the injected gallbladder wall and appendix was directly proportional to the degree of the pathological changes of inflammation. Cefotaxime was distributed quickly in the seriously infected organ or tissue, and stayed for a relatively long time. For the comparison to cefamandole and cefmetazole, cefotaxime reached quickly peak of tissue concentration than the other cephalosporins, but relatively early decline too.

View full abstract

Investigations were made into (1) factors influencing in vitro antibacterial activity of cefotaxime (HR 756, CTX)(2) its stability in broth media, human serum, urine and bile, and rabbit liver homogenate, and (3) the rate of its binding to serum protein.
Cefotaxime showed a high degree of antibacterial activity against 18 standard strains tested; it was much more active than cefazolin (CEZ) against gram-negative bacteria and nearly as effective as CEZ against gram-positive bacteria except S. aureus.
Minimum inhibitory concentrations of cefotaxime were affected by a change in inoculum size but not by changes in kind and pH of media and added horse serum.
Cefotaxime was stable for 7 days in broth media at 4 ° C, and in human serum, urine and bile rabbit liver homogenate kept frozen.
The order of the binding rate of cefotaxime to serum protein was the rabbit > rat > man > dog. In humans, the rate was low, 60%, as compared with 92.5% obtained with CEZ.

View full abstract

Cefotaxime (HR 756, CTX), a new cephalosporin, was examined for its acute toxicity in the mouse, rat and rabbit, and for its 1-month subacute intravenous toxicity in the rat.
In the acute toxicity test with mice and rats aged 6 weeks, intravenous LD₅₀, values were the lowest, and subsequently intraperitoneal, subcutaneous and oral ones followed in that order named. When examined in juvenile (1 week old) mice and rats by the subcutaneous injection, the drug toxicity was slightly greater than that in 6-week-old animals. The acute intravenous toxicity for rabbits was higher than that for mice and rats. By any dosage route, there was no sex difference in the drug acute toxicity for any species of the mouse, rat and rabbit, and toxic signs produced were only such behavioral changes as are known to be induced in common by cephalosporins.
In the subacute toxicity test, the drug given at a daily dose of 1, 000 mg/kg, a feasible highest dose for consecutive intravenous injections, caused dilatation of the cecum of slight to moderate degrees in most of rats and histopathological examinations on them showed hemorrhage or inflammatory cell infiltration in the organ. In some animals dosed at 500 or 125 mg/kg/day, similar changes, though of a slight degree, were observed macroscopically and histopathologically. Except these changes, the findings were inflammatory changes noted at the injection site, and some hematological and histopathological changes of slight degrees considered to have subsequently resulted from those inflammatory changes.

View full abstract

1. Cefotaxime (HR 756, CTX) was evaluated for its local tolerability when given intracutaneously to rabbits and applied to their eyes, and administered intramuscularly to rabbits and rats.
2. Intracutaneous administration of cefotaxime at 3-25% to rabbits caused concentiation-related inflammatory changes at the injection sites, which vanished rapidly.
3. Application of cefotaxime at 10-40% to the rabbit eyes induced no irritation.
4. Cefotaxime, when intramuscularly given at 25 and 40% singly to rabbits and rats and at 25% repeatedly to rats once daily for 7 days, produced acute myositis and degenerative and necrotic muscle-fibers at the injection sites, which were in degree the same as or lower than those induced by cefazolin (CEZ) and clearly slighter than those produced by cephaloridine (CER) and cephalothin (CET). The recovery of the muscle tissue injected with cefotaxime was rapid as with CEZ in comparison with that given CER and CET.
5. Inflammatory changes and degeneration and necrosis of the muscle fibers were also induced by single treatment with cefotaxime dissolved in 0.5% lidocaine solution and its repeated administration for 7 days (once a day). The lesions were of almost the same degree but tended to disappear slowly as compared with those produced by cefotaxime alone.

View full abstract

The kinetics of cefotaxime (HR 756, CTX) after intravenous administration (20 mg/kg) was studied in rabbits by high pressure liquid chromatography and bioassay.
The half-life for clearance of cefotaxime from plasma was 57.4 min. In plasma, its desacetyl metabolite (RU 628) was also detected, but the level was far lower than that of cefotaxime. When given to rabbits in an identical dose, this metabolite was cleared from plasma more rapidly than its parent compound, having a half-life of about 11 min.
Cefotaxime was distributed rapidly into organs. It was detected at the highest level in the kidney and subsequently high levels were seen in the lung and heart. Its brain level was quite low.
The compound was found to be eliminated from the body mainly through the urinary organs. About 75% of the given dose was recovered from urine in unchanged and desacetyl forms of cefotaxime during a 6-hr period postdosing. The ratio of cefotaxime to RU 628 in amount was approximately 13.3. The total recovery rate for cefotaxime and RU 628 from the bile during the same period was merely 0.24% of the dose and the two appeared in almost equal amounts.

View full abstract

Cefotaxime (HR 756, CTX), when given with FREUND's complete adjuvant, was evaluated for its antigenicity by examining active systemic anaphylaxis and PCA reaction in guinea pigs and Arthus reaction in rabbits. The results indicate that the compound was not antigenic.
The antigenicity of cefotaxime was further investigated using its protein conjugate in comparison with that of cefazolin (CEZ) and benzylpenicillin (PCG). The precipitating and skin sensitizing antibodies were produced against cefotaxime like CEZ and PCG.
Results of PCA reaction, quantitative precipitation reaction and quantitative hapten inhibition of precipitation reaction showed that cross-reactivity of cefotaxime with CEZ and PCG was very low. The hapten inhibition analysis suggests a very low degree of cross-reactivity of cefotaxime with cephaloridine (CER) and cephalothin (CET).
In direct Coombs test, cefotaxime showed positive reaction to the same extent as CEZ and to a lower extent than PCG and CER.

View full abstract

In vitro bactericidal activity of cefotaxime (HR 756, CTX) was compared with that of cefazolin (CEZ) against E. coli Ec-14 and K. pneumoniae Kp-26 by making the time-course of levels of each antibiotig in medium approximate that in human serum during and after 2-hr drip infusion of 2g.
Cefotaxime and CEZ were singly dropped into antibiotic medium 3 and Consera. In the former medium, the two antibiotics completely inhibited the growth of E. coli Ec-14. They were, however, less active against K. pneumoniae Kp-26, the strain regrowing as a result of inactivation of cefotaxime and and CEZ by addition of 8-lactamase, respectively, after 9-and 12-hr incubation. In Consera, cefotaxime had more potent bactericidal effect than CEZ against both the test strains; while the effect of CEZ was abolished between 5-and 9-hr incubation, that of cefotaxime lasted until it was inactivated by addition of β-lactamase after 9-hr incubation.
Cefotaxime was twice dropped into Consera at the interval of 9 hr. The two treatments completely inhibited the growth of E. coli Ec-14 and K. pneumoniae Kp-26; namely, no regrowth of the strains was caused by inactivation of cefotaxime by β-lactamase.

View full abstract

Cefotaxime (HR 756, CTX) was administered to rats via the tail vein at doses of 20, 40 and 80mg/kg/day near to clinical doses for 7 consecutive days, and its effects on fecal bacterial flora were investigated by examining the feces for Enterobacteriaceae, Staphylococci, Streptococci, Clostridia, Bacteroidaceae and Lactobacilli.
In all the dosage groups, Enterobacteriaceae decreased on the next day of treatment, thereafter remained at almost the same level, and began to increase immediately after end of administration. There was lithe influence, however, on other strains tested at any dose levels. On the other hand, cefazolin, a reference drug, decreased Enterobacteriaceae and Staphylococci.

View full abstract

Croton oil-induced rat subcutaneous granuloma pouch was inoculated with Escherichia coli Ec-14 or Staphylococcus aureus FDA 209 P. Cefotaxime (HR 756, CTX) and cefazolin (CEZ) were intravenously administered to the infected rats at two divided doses of 20 and 40 mg/kg at an interval of 6 hours, and their inhibitory effects on the bacterial growth were compared. Against E. coli cefotaxime was more effective than CEZ ; the former, even at the lower dose, showed the effect both after the first and second treatments but the latter only after the first treatment at the two dose levels.
The results of the treatments against S. aureus revealed that cefotaxime exhibited a lower degree of activity at 20 mg/kg but nearly the same extent at 40 mg/kg as compared with CEZ.

View full abstract

The following results were obtained in microbiological and clinical studies of cefotaxime (HR 756, CTX), a new wide spectrum antibiotics, resistant to β-lactamases.
1. Susceptibility tests of 200 clinically isolated strains of P. aeruginosa were performed by the standard method of the Japanese Society of Chemotherapy. With an inoculum size of 10⁶cells/ml, the growth of 83% of the strains was inhibited at concentration of ≤25 μg/ml.
2. In 9 patients without marked renal or hepatic disturbances, absorption and excretion of the drug were investigated for various modes of administration and doses. In patients given an i. m. injection of 500 mg, blood levels were slightly above 10 μg/ml at 1 hour. The half-life was 0.7-1.2 hours. In patients given a 2-hour 1 g drip infusion, blood levels were 36-42 μg/ml at the completion of administration. The half-life was 1.2-2 hours. Thirty min. after a single 1 g intravenous injection, blood levels measured 50 μg/ml. The half-life was 1.3-2 hours. Urinary excretion accounted for about 30-40% of the administered dose, lower than that of other reports.
3. The clinical efficacy of cefotaxime in 6 cases of RTI, 16 cases of UTI and 4 cases of other infections was excellent to good in 16 cases, fair in 5 cases, poor in 2 cases, and unclear in 3 cases. Almost all patients were aged and had underlying diseases. Adverse reactions and laboratory data abnormalities consisted of fever in 1 patient. A mild elevation of GOT and slight decrease in RBC were obserbed in another patients but this was attributed to the underlying disease.

View full abstract

Nine patients with severe lung infections, including four cases of lung cancer, two of bronchiectasis (one of which was complicated with CO₂, narcosis), and one each of severe pneumoconiosis, severe lung fibrosis, and pyothorax were treated with cefotaxime, (HR 756, CTX), 15.2-58.0mg per kg of body weight per time, by drip infusion and intravenous injection for a period of 7-20 days. The total dose given was 16-80g. Cefotaxime was bacteriologically effective in the following cases: K. pneumoniae eradicated in four patients, decreased in one, and H. influenzae, E. coli and P. mirabilis eradicated in one patient each. The overall clinical effectiveness was 85.7%.
Abnormal laboratory findings and side effects were not observed in any patient. In fact, abnormal liver function values seen before using cefotaxime became normal during treatment in one patient.

View full abstract

The clinical efficacy of cefotaxime (HR 756, CTX), a new cephalosporin antibiotic, was investigated in 14 patients with secondary infections associated with hematologic diseases.
The underlying disease was acute leukemia in 5 patients, chronic myelocytic leukemia in 2 patients, chronic lymphatic leukemia in 1 patient, malignant lymphoma in 4 patients, macroglobulinemia in 1 patient, and colonic cancer in 1 patient. The secondary infections were pneumonia in 5 patients, septicemia in 2 patients, colitis or peritonitis in 2 patients, abdominal abscess in 1 patient, perianal abscess in 1 patient, pharyngitis in 2 patients, and cystitis in 1 patient.
Cefotaxime was given in a daily dose of 1.5-8.0g in 2-4 divided doses. Each dose was administered over 60-90 min by intravenous drip infusion. The duration of treatment ranged from 3-29 days, with the total dose being 6.0-105g.
Among 6 patients treated with cefotaxime alone, the clinical response was excellent in 2, good in 2, fair in 1 and poor in 1. Out of 8 patients concomitantly receiving other antibiotics such as sulbencillin (SBPC), carbenicillin (CBPC), tobramicin (TOB) and gentamicin (GM), the response to treatment was excellent in 1, good in 4, poor in 1 and impossible to assess in 2. With regard to the causative organism, cefotaxime was effective against E. coli and K. pneumoniae. In 3 patients with P. aeruginosa infections, cefotaxime was evaluated to be good in 1 patient with bronchopneumonia, poor in combina tion with CBPC and GM in 1 patient with, septicemia, and good in combination with SBPC and TOB in 1 patient with pneumonia. Mild elevations of transaminase and Al-Pase was noted in a few patients.

View full abstract

The minimal inhibitory concentrations (MIC) of cefotaxime (HR756, CTX) was measured against S. aureus, E. coli, K. pneumoniae, Proteus spp., S. marcescens and P. aeruginosa isolated from clinical materials. Cefotaxime was administered intravenously at daily dose of 2 to 6 g for 7 to 24 days to 16 cases of respiratory tract infections and 8 cases of urinary tract infections. The results were obtained as follows:
1) The MIC values of cefotaxime against 50% of S. aureus were in the range of 0.78-1.56μg/ml. Most of E. coli and 80% of Proteus were inhibited at 0.78μg/ml or less. K. pneumoniae was 90% inhibited at 1.56μg/ml or less. S. marcescens was 65% inhibited at 12.5μg/ml or less. P. aeruginosa was 30% inhibited at <50μg/ml.
2) Excellent clinical responses were obtained in 4 cases of pneumonia and 1 case of cystitis. Good responses were obtained in 10 cases of pneumonia, in 1 case of lung abscess and in 4 cases of urinary tract infections. Poor responses were obtained in 2 cases out of 5 urinary tract infections with dwelling urethral catheter.
3) As side effect, transient GOT slight elevation was seen in 1 case and GOT, GPT and Al-P slight elevation was seen in another one.

View full abstract

Laboratory and clinical investigations of cefotaxime (HR 756, CTX) were performed and the results obtained were as follows:
1) Susceptibility of clinically isolated strains to cefotaxime was tested by agar plate dilution method and compared to susceptibility to cefazolin, cefotiam, cefmetazole, piperacillin, ampicillin, sulbenicillin and gentamicin. The minimum inhibitory concentrations of cefotaxime for H. influenzae, Klebsiella, E. coli, Serratia, P. aeruginosa and Enterobacter were 0.055 (0.05-0.2) μg/ml, 0.0678 (0.05-0.39) μg/ml, 2.747 (0.05-100) μg/ml, 0.179 (0.2-100) μg/ml, 27.344 (0.39-800) μg/ml and 10.64 (0.05-200) μg/ml respectively.
Cefotaxime was the most potent antibiotic tested thus for against H. influenzae, Klebsiella and Serratia.
2) Among 18 patients treated with cefotaxime for respiratory tract (12 cases) and other infections, clinical results were effective in 15 cases. No side effects clearly due to this drug were observed except one case of increased GOT and GPT during the administration.

View full abstract

In vitro antimicrobial activities of cefotaxime (HR 756, CTX), a new cephalosporin derivative, against clinically isolated gram-negative bacilli were examined and its clinical efficacy on respiratory tract infections was evaluated.
The peak of distribution of the minimum inhibitory concentrations of cefotaxime against patient strains of Staphylococcus aureus was found at 1.56 μg/ml, and this value was five fold lower than that of sulbenicillin (SBPC) and two fold higher than that of cefazolin (CEZ).
Against patient strains of Escherichia coli the peak of distribution of MICs of the drug was at 0.05 μg/ml and it was revealed that the drug had more potent antimicrobial activities than CEZ, dibekacin (DKB) or amikacin (AMK).
The peak of distribution of MICs against Klebsiella pneumoniae was at 0.025μg/ml or less, and the growth of 27 of 29 strains tested was inhibited by the drug at the concentrations of 0.39μg/ml or less.
Against clinical isolates of Pseudomonas aeruginosa the peak of distribution of MICs of the drug was at 25μg/ml and this value was 3 fold higher and 4 fold lower than those of AMK and SBPC respectively.
The pattern of distribution of MICs of the drug against Acinetobacter calcoaceticus was quite similar to that against Pseudomonas aeruginosa.
To make an evaluation of clinical efficacy, one or two grams of the drug was given to 11 patients by intravenous drip infusion. Three patients, i.e. each one of fever of unknown origin, of pulmonary tuberculosis and of lung cancer alone, were omitted and evaluation was made on the remaining 8 patients with respiratory tract infections. In a patient response was excellent. A good response was obtained in 6 patients but in a patient response was poor.
In 2 patients among 11 patients treated with the drug, transient elevation of serum GOT and GPT was observed, and in one of them decrease in the number of WBC and platelets was also seen. All these abnormal values returned to normal levels soon after cessation of the administration of the drug.

View full abstract

The clinical efficacy of cefotaxime was investigated in 20 patients with various types of infections (13 cases of UTI, 2 cases of pulmonary infection, 1 case of biliary tract infection, 1 case of cellulitis, and 3 cases of meningitis). Cefotaxime was administered by i.v. drip infusion in a daily dose ranging from 1 to 6g, for a term of 7 to 33 days. The total dose patients received ranged from 14 to 112g. Treatment with cefotaxime was effective in 15 out of 20 cases (75%), somewhat effective in 2 out of 20 cases (10%), ineffective in no case at all, and was undetermined in 3 out of 20 cases (15%). According to disease, treatment was effective in all cases for UTI due to E. coil, Enterobacter, S. faecalis and P. mirabilis. In the 2 cases of pulmonary infection, treatment was effective in 1 case and somewhat effective in 1 case. In the sole case of cellulitis, treatment was effective. Assessment of the 3 cases of meningitis was withheld.
Cutaneous reactions were negative in all cases. Elevated GOT and GPT were noted in 1 case of pneumonia, and in 2 cases of meningitis an elevation of GPT was observed during concurrent administration of another antibiotic. No abnormalities were observed in either hematopoeisis or renal function for any patient in the present study.

View full abstract

Phase one study was performed under our supervision on a new cephalosporin antibiotic, cefotaxime (HR 756, CTX), in which a total of 32 healthy male volunteers received cefotaxime in various combination of dose and route. Its safety was confirmed in all dosages.
Cefotaxime showed excellent antibacterial activity against a wide range of gram-negative pathogens except for P. aeruginosa.
Serum levels and urinary excretion were measured following intramuscular and intravenous bolus injection, as well as drip infusion, using bioassay and high-performance liquid chromatography. In general the values obtained from both methods coincided well.
It was possible to identify the metabolite in urine separately by the latter method. Thin-layer chromatography followed by bioautography did not detect the existence of metabolite due to its relatively low sensitivity.
Two patients were treated clinically with cefotaxime. One with pneumonia and pleurisy showed no response, but another with pyelonephritis responded well. No adverse reactions were observed.

View full abstract

The antibacterial activity, absorption and excretion and clinical responses to cefotaxime (HR756, CTX). were studied. The following results were obtained.
1. Antibacterial activity of cefotaxime against clinical isolates of E. coli, indole-positive Proteus, P. mirabilis, K. pneumoniae and E. cloaca. was 2-16 times as potent as that of cefotiam and 16-256. times as potent as that of cephalothin, cephaloridine and cefazolin.
Cefotaxime also showed comparatively high antibacterial activity against S. marcescens.
On the other hand, the antibacterial activity of cefotaxime was 1/4 as potent as gentamicin and cefsulodin, and 2 times as potent as carbenicillin against P. aeruginosa.
2. Absorption and excretion After i. v. administration of 500mg of cefotaxime to healthy adults, the serum level reached 46.2μg/ml in 5 minutes, declined thereafter with a half-life (β-phase) of 51.50 minutes, and was 0.055μg/ml at 6 hours. After i.v. administration of 1, 000mg, the serum level reached 69.3μg/ml in 5 minutes, declined thereafter with a half-life of 48.07 minutes, and was 0.126μg/ml at 6 hours.
Urinary recovery rate in 6 hours was 63.49% after i. v. administration of 500mg of cefotaxime and 67.44% after administration of 1, 000mg of cefotaxime.
3. Clinical results
Cefotaxime was administered at a daily dose of 1 to 4g for 1 to 21 days to 13 patients, i.e., one each with sepsis, subphrenic abscess and cholecystitis, 2 with bacterial pneumonia and 8 with urinary tract infections.
Cefotaxime was clinically effective in 6 of 13 cases and bacteriologically effective in 8 of 10 cases with identified pathogens.
As adverse reactions, skin rash and visual disturbances were observed in 1 patient. Pain at the site of injection and nausea at the time of i.v. injection were observed in another patient. These adverse symptoms disappeared. rapidly after discontinuation of cefotaxime treatment.
Abnormal laboratory findings were not observed.

View full abstract

Basic and clinical studies on cefotaxime were carried out and the following results were obtained
1) In vitro antibacterial activities
Antibacterial activities of cefotaxime were superior to cefazolin against E. colt, Klebsiella, Enterobactor and Serratia, and especially with 106cells/ml inoculum, its activities were prominent. Against P. aeruginosa, its resulting MIC was somewhat inferior to those of the abote strains, but superior to that of cefazolin.
2) Absorption and excretion
Serum and urine concentrations of cefotaxime were determined in 3 healthy volunteers after 1g intravenous dose. The average serum concentrations were 28μg/ml within 30min., 14.4μg/ml winthin 1hr., 4.8μg/ml within 2hrs., 1.2μg/ml within 4hrs. and 0.17μg/ml within 6hrs. Urinary recovery after a 1g intravenous dose was about 70% up to 6hrs. After administration of both cefotaxime and probenecid, urivary recovery was lower than with cefotaxime alone.
3) Clinical responses
We treated six patients with chronic cystitis, one patient with pneumonia and one patient with subacute bacterial endocarditis using 2g (6 cases) and 4g (2 cases) of cefotaxime per day intravenously and the results were good in all cases. No side effect were observed except one case of granulocytopenia.

View full abstract

Cefotaxime (HR 756), a new cephalosporin antibiotic, was studied experimentally and clinically. The following results were obtained:
1. Antibacterial activityCefotaxime was more active than cefazolin, cefotiam and cefmetazole against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens. Its antibacterial activity against Pseudomonas aeruginosa was almost equal to that of ticarcillin and sulbenicillin.
Combined effects of oefotaxime and dibecacin were superior to that of ticarcillin and dibekacin against Pseudomonas aeruginosa.
2. Clinical results
Cefotaxime was effective in 4 out of 5 cases of urinary tract infections, and in 1 out of 2 cases of FUO.

View full abstract

MIC of cefotaxime (HR 756, CTX), a new cephalosporin preparation, for various clinically isolated gram-negative rod was examined.
The concentrations in blood and in sputum after the administration of cefotaxime were determined with two patients. Cefotaxime was also administered to 16 patients with various infections. The results are described hereunder:
1. MIC of cefotaxime (to be referred to as CTX) for gram-negative rod was compared with those of cefazolin (CEZ), cefmetazole (CMZ), cefuroxime (CXM), and piperacillin (PIPC). It was observed that cefotaxime showed a sensitivity by far superior to other antibiotics for E. coli, K. pneumoniae, E. cloacae and S. marcescens. It showed an outstanding MIC in comparison with ampicillin (ABPC), CXM and CMD for H. influenzae. However, for P. aeruginosa, it was found inferior in sensitivity to PIPC, T-1551, cefsulodin (CFS) and gentamicin (GM) and slightly better than carbenicillin (CBPC).
2. The concentrations in blood and in sputum after intravenous administration and instillation of-2 g each of CTX in two patients were determined: blood concentrations in the cases of 2g i. v. were 78μg/ml in 30 minutes and 0.36μg/ml in 8 hours, and in the cases of 2 g instillation, 90.0μg/ml in 2 hours after instillation was finished and 4.0 μg/ml in 6 hours. The peak of the concentrations in sputum was ≤0.1μg/ml in both cases.
3. 16 cases of clinical trials included 10 cases of respiratory tract infection (to be referred to as RTI), 3 cases of urinary tract infection (to be referred to as UTI), and 3 cases of biliary tract infiction (to be referred to as BTI). Among 5 cases of pneumonia, it proved effective in 1 case, poor in 4 cases. In 4 cases of poor, 3 cases were old men of 67 years or more, and not good in general conditions, having S. faecalis believably as caused organisms or possibly with viral infection.
Among 4 cases of chronic RTI, it proved effective in 1 case, fair in 1 case and poor in 2 cases: 1 of the poor cases was bronchiectasis due to P. aeruginosa and the other was allergic bronchitis. CTX% vas. excellent for 1 serious case of acute bronchitis and it was effective for each 3 case of UTI and BTI.
As for side effects, no abnormalities were observed both clinically and in various inspections before and after administration.
Although the rate to effectiveness of CTX for RTI was low, this preparation is a new useful cephalosporin derivative.

View full abstract

Cefotaxime was administered to patients with acute cholecystitis as an i. v. drip infusion of lg or 2g, given every 12 hrs until a total of 18 doses had been reached. Changes in serum levels of the drug occurring after the initial and final doses were then compared. Cefotaxime's biological half-life increased from 1.09 hrs following the initial dose to 1. 33 hrs following the final dose. Serum levels following the final dose were high overall. No deterioration in either hepatic or renal function was observed throughout the term of administration.
Clinical trials were performed with a total of 7 patients, among whom there were 2 cases of pneumonia, 2 cases of pyelitis, 1 case of hepatic abscess, and 2 cases of cholangitis. The daily dose of cefotaxime administered varied from 2 to 6 g; the term of administration varied from 9 to 20 days. All patients received 2g divided doses of cefotaxime dissolved in 250 ml of 5 % glucose solution, which were infused over a 1-hour period. Clinical efficacy was good in 5 cases and poor in 2 cases. Bacteriological efficacy was good in 3 cases, poor in 2 cases, and undetermined in 2 cases. Adverse reactions to cefotaxime consisted of 1 case of rash and 1 case of slightly elevated GOT and GPT.

View full abstract

Cefotaxime (HR 756, CTX) was administered to 10 patients with respiratory tract infections. Pathogens were identified in 6 of the 10 patients with respiratory tract infections: H. influenzae in 3 patients, P. aeruginosa in 2 patients and A. aylosoxidans in 1 patient.
(1) Clinical and bacteriological effects: Evaluations were made in 8 of the 10 patients. The cefotaxime treatment success rate was 75%(6/8) in this study. Cefotaxime, 1 g twice daily, was considered to be especially effective against H. influenzae because clinical and bacteriological findings were markedly improved in 2 patients and moderately improved in the remaining 1 patient.
(2) Side effects: Fever and rash occurred in 1 patient each. These symptoms disappeared after the discontinuation of cefotaxime therapy. Increased alkaline phosphatase and eosinophilia were observed in 1 patient each. These abnormal laboratory findings disappeared after the termination of cefotaxime therapy.

View full abstract

The activity of cefotaxime (HR756, CTX) Sodium 7-(2-(2-amino-4-thiazolyl)-2-methoximinoactetamido) cephalosporinate was investigated against 28 Bacteroides ss. fragilis, 12 Bacteroides fragillis ss. thetaiotaomicron 5 Bacteroides fragilis ss. vulgatus.
Inoculum size did have an effect on MICs for strains tested. There were two to eight fold differences between the cefotaxime MIC at 10⁸ and 10⁶ CFU. MIC₅₀ of B. fragilis ss. fragilis was 3.1μg/ml at 10⁶, and 25μg/ml at 10⁸CFU.
MIC₅₀ of B. fragilis ss. thetaiotaomicron was 25μg/ml and 50μg/ml, respectively. MIC of B. fragilis ss. vulgatus ranged from 0.8-100μg/ml. Three patients with respiratory infections, one patient with urinary infection and another patient with Serratia septicemia were evaluated for cefotaxime. All but the patient with Serratia septicemia responded satisfactorily. Fair response was observed in the patient with Serratia septicemia.

View full abstract

A clinical study of cefotaxime (HR 756, CTX), a new cephalosporin antibiotic, was carried out with the following results. Four cases of various respiratory infections (including 3 cases of pneumonia and one case of chronic bronchitis) were treated by intramuscular, intravenous injection or drip infusion with 2, 000-4, 000 mg per day of cefotaxime given in 2-4 divided doses for 9-11 days.
The clinical response of the patients was excellent in one (acute pneumonia), good in one (acute pneumonia), fair in one (chronic pneumonia) and poor in one (chronic bronchitis with diffuse bronchiectasis).
In all cases the causative organisms, including Streptococcus pneumoniae, Klebsiella pneumoniae and Haemophilus influenzae, disapeared from the sputum after treatment.
In the case with chronic bronchitis who did not respond to cefotaxime, the pharmacokinetics of this antibiotic were studied. After drip infusion of 4g of cefotaxime: in 30 minutes, the blood level was 48.0μg/ml after 15 minutes, 38.1μg/ml after 30 minutes and 0.68μg/ml after 6 hours, indicating a half-life of 1.12 hours. The peak concentration of the drug in sputum was 1.7μg/ml, reached one hour after the end of infusion. Compared to other antibiotics such as ampicillin, cephacetrile and sulbeniAillin, the penetration of cefotaxime into the airway tissue and sputum seemed to be good. Therefore, the cause of the unsatisfactory response to the drug in this case might be due to extensive irreversible destruction of the airways.
No remarkable side effects were noted.

View full abstract

Cefotaxime (HR 756, CTX) was administered clinically to the patients with various infections, and favorable results were obtained as follows:
1) Cefotaxime showed a stronger antibacterial activity than CEZ against clinical isolates ofE. eoliandK. pneumoniae.
2) Cefotaxime was employed clinically in a total of 13 cases, which consisted of 6 cases of respiratory tract infection, 3 cases of urinary tract infection, 2 cases of fever of unknown origin, 1 case of subacute bacterial endocarditis, and 1 case of biliary tract infection. The therapeutic effect was excellent in 1 case and good in 5 cases. The efficacy rate was 46.2%.
3) No side effects were observed in this series except that a slight elevation of transaminase occurred in one case.
From these results, cefotaxime may be expected to be a valuable drug in the treatment of infections in internal medicine.

View full abstract

Clinical effectiveness of a new antibiotic, cefotaxime (HR 756, CTX) was examined in 12 cases of UTI, RTI and biliary tract infection.
Good response was observed in 9 cases, fair in 2 cases, ineffective in a case. An efficacy rate of 75% was obtained. Cefotaxime therapy was effective in 4 out of 5 cases of acute pyelonephritis, in 2 out of 4 cases of pneumonia, and in all 3 cases of cholecystitis. The side effects, a case of skin rash and another of numbness in the extremities, that were found during the course of therapy were promptly improved following interruption of therapy.
A case which was slightly impaired in hepatic function by administration of cefotaxime was improved soon after cessation of administration.

View full abstract

Cefotaxime (HR 756, CTX) was studied in respect of its nephrotoxicity in rabbits and clinical efficacy in man.
1. Cefotaxime was administrated intravenously to 3 rabbits in a daily dose of 500 mg/kg for 10 days. Proteinuria, hematuria and azotemia was not found in any rabbit, but degeneration of proximal tubular cells was seen in one rabbit.
2. When a daily dose of 50 mg/kg of sisomicin was concomitantly given with 500 mg/kg of cefotaxime for 10 days, the combination was significantly more nephrotoxic than that of either drug alone.
3. Clinical application of cefotaxime was attempted in 20 patients with various infectious diseases. Good responses were demonstrated in 17 patients, and no signs or symptoms of side effects or toxicity were observed, except for one patient who showed a transient elevation of transaminase and another patient with eosinophilia.

View full abstract

1) Clinical pharmacological studies of cefotaxime (HR 756, CTX) were conducted in patients with various renal function. The results are shown in Tables 1, 2 and 3, and Fig. 1, 2, 3, 4, 5 and 6. Higher serum levels and a moderately prolonged serum half-life of cefotaxime as well as a longer period of higher serum levels of desacetylcefotaxime were observed in patients with more severely impaired renal function. Urine excretion of cefotaxime was prolonged and diminished in relation to the degree of renal failure. The total amount of desacetylcefotaxime excreted into urine within 24 hours increased in relation to the degree of renal dysfunction more than creatinine clearance (Ccr) 20 ml/min per 1.48 m², but decreased in relation to the degree of renal dysfunction less than Ccr 20.
2) Cefotaxime was used in 13 cases. The results are shown in Table 4 and 5. Three cases (case 5, 9 and 11) were proven not to be suitable for treatment with cefotaxime and excluded from the evaluation of efficacy. Clinical efficacy was excellent in 4 cases, good in 5 cases, and poor in 1 case. No distinct serious side effects were observed.

View full abstract

Cefotaxime (HR 756, CTX) was used in 11 cases (cholecystitis 2 cases, pneumonia 1 case, pulmonary abscess 1 case, asymptomatic bacteriuria 2 cases, acute pyelonephritis 5 cases). Efficacy was evaluated to be excellent in 1 case, good in 8 cases, fair in 1 case and poor in 1 case. Cefotaxime was effective in 9 out of 11 cases in total for a rate of effectiveness of 82%.
Pain at the site of intramuscular injection was not so severe. No distinct side effects were observed.

View full abstract

Cefotaxime was administered to 10 patients, among whom there were 4 cases of UTI, 2 cases of septicemia, 3 cases of RTI and 1 case of biliary tract infection. Cefoeaxime was highly effective in 6 cases, effective in 3 cases and temporarily effective in 1 case. Clinical sign considered to be adverse reactions due to cefotaxime administration were not observed, and abnormal laboratory findings considered clearly due to cefotaxime also were not observed.

View full abstract

The authors report on the results of their laboratory and clinical investigations of cefotaxime, a new semisynthetic cephalosporin antibiotic.
The antibacterial activity of cefotaxime was compared to that of cefazolin, cephalothin and cephaloridine in a total of 179 clinically isolated strains ofS. aureus, S. faecalis, E. coli, Citrobacter, Klebsiella, Enterobacter, Serratia, ProteusandP. aeruginosa. Cefotaximeexhibited far greater antibacterial activity againstE. coli, Klebsiella, Enterobacter, Serratia, Proteus, Citrobacter, andPseudomonasthan did cefazolin, cephalothin or cephaloridine.
Cefotaxime was then administered to a total of 21 patients, among whom there were 15 cases of RTI, I case of biliary tract infection and 5 cases of UTI. The results obtained were excellent or good in 11 out of 15 (73.3%) of the RTI cases, while in both the sole case of biliary tract infection and 5 UTI cases excellent or good results were obtained for all patients. Adverse reactions and/or abnormal laboratory test results were observed in 3 out of 21 patients; 1 case each of rash, of eosinophilia, and of eosinophilia plus elevated GOT, GPT, and Al-p levels were noted. However, it was not necessary to discontinue the administration of cefotaxime due to these adverse reactions, and all 3 patients' conditions returned to normal following the completion of administration.

View full abstract

Cefotaxime (HR 756, CTX) was given to 8 patients with moderate or severe respiratory tract infections (5 cases), FUO (2 cases) and a biliary tract infection (1 case).
The clinical response was excellent in 1 patient, good in 4, poor in 1 and impossible to assess in 2.
As an adverse effect, drug fever was observed in 1 patient. Abnormal laboratory findings consisted of eosinophilia in 2 patients.

View full abstract

Cefotaxime (HR 756, CTX) was applied to 20 patients with various infections. 18 of 20 cases could be evaluated on the effect of cefotaxime in the present trial.
Excellent or good results were obtained in 5 of 6 cases with pulmonary infections, 2 of 3 cases with septicemia, 1 case with abscess, and 2 of 3 cases with fever of unknown origin.
No side effect was observed except 1 case with GOT, GPT elevation. It is expected that cefotaxime may constitute an advance in the antibiotic treatment of gram-positive and gram-negative infections.

View full abstract

Cefotaxime (HR 756, CTX), a new cephalosporin derivative recently developed by Hoechst AG. and Roussel-Uclaf SA, was examined with regard to itsin vitroantibacterial activity and clinical usefulness. The results obtained were as follows:
1) In vitroantibacterial activity against bacteria isolated from human infection foci: As toStaphylococcus aureusstrains, cefotaxime was found to be superior to carbenicillin, but inferior to cefamandole, cefazolin, and cephalothin. Almost allEscherichia colistrains were found to be very sensitive to cefotaxime (MIC 0.2μg/ml). MIC of the drug againstKlebsiella pneumoniaeandProteus mirabilisstrains (0.1-0.4μg/ml, 0.05-0.2μg/ml respectively) were lowest among those of antibiotics examined, except a few cross-resistant strains. Hundred-fold dilution of the bacterial inoculum yielded a significant decrease in the MIC of cefotaxime. The greater part ofPseudomonasstrains showed medium susceptivity to cefotaxime, although their MIC were distributed widely (0.4-100μg/ml).Serratiastrains were more sensitive to the drug than those ofPseudomonas.
2) Clinical trials: Thirteen cases various infections (R. T. I. 5; U. T. I. 7; biliary tract infection 1) were administered cefotaxime (1.0-4.0g/day, mostly by i. v. drip infusion). Ten of the patients had some underlying diseases. Eight out of ten assesable cases responded to the therapy; at least fairly. Neither clinical side effects nor changes in laboratory data attributable to the drug were observed in these patients, except for one who reacted with diarrhea.
These results obtained should support the usefulness of cefotaxime as a new antibiotics.

View full abstract

Fundamental and clinical studies on cefotaxime (HR 756, CTX) were carried out and the results. obtained were as follows;
1. In vitro antibacterial activity
Peaks of MIC distribution of CTX were 15.6μg/ml against S. aureus, less than 0.1μg/ml against E. coli, Klebsiella, P. mirabilis and P. vulgaris, and 12.5μg/ml against P. aeruginosa at a lower inoculum size.
CTX was less potent than cefazolin (CEZ) against S. aureus. However, CTX was considerably more potent than CEZ against gram-negative bacteria.
2. Serum levels and urinary recovery
CTX was administered at a dose of 2 g by intravenous drip infusion for 2 hours. Serum levels of CTX were 100μg/ml at the end point of infusion, 18μg/ml at 1 hour, 6.2μg/ml at 2 hours, 0.7μg/ml at 4 hours and trace at 6 hours after infusion. CTX was very rapidly excreted in urine. Urinaryrecovery of CTX was 51.9% at the end of infusion and 78.7% at 6 hours.
3. Clinical results
CTX was administered to 2 cases with septicemia, 1 case with lung abscess and 2 cases with pyelonephritis, totally 5 cases, at a daily dose of 4-6g. The clinical effects obtained were good in 1 casewith E. coli-caused pyelonephritis and fair in 1 case with E. coli-caused septicemia. CTX was discontinued in the latter case due to side effects (erythropenia and granulopenia). Signs and symptoms relapsed after that. CTX was evaluated to be poor in 3 other cases. No other adverse reactions than disturbed hematopoiesis in 1 case were observed.

View full abstract

A clinical study of cefotaxime (HR 756, CTX), a new broad antibacterial spectrum cephalosporin, was carried out. The following results were obtained.
Eight patients with respiratory tract infections (7 cases of pneumonia and 1 case of pyothorax) and one patient with a liver abscess were treated.
Cefotaxime was administered in a dose of 1 to 2 g twice daily by drip infusion with 500 ml of physiological saline solution for 7 to 35 days.
The clinical responses of the patients with respiratory tract infections were excellent in 2 cases, good in 3 cases, poor in 3 cases and unchanged in 1 case. The result in the patient with the liver abscess due to K. pneumoniae, E. coli and P. vulgaris infection was poor.
Side effects were not observed.

View full abstract

The results of previous studies have demonstrated that cefotaxime possesses a greater antibacterial activity against gram-negative pathogens than earlier cephalosporins, and that it has MIC values which allow for successful management of P. aeruginosa. It has been anticipated that in the future cefotaxime therapy will be effective, since the safety of the drug is excellent due to its low hepatic and renal toxicity, which permits high dose administraion.
In the present study, cefotaxime was employed against severe infections in 14 patients suffering from malignant neoplasms of the hematopoitic organs, and proved to be highly effective in 2 cases, effective in 5 cases, ineffective in 4 cases, and unevaluable in 3 cases. Its response rate was 63.6%. There were no adverse reactions observed.

View full abstract

Fundamental and clinical studies of cefotaxime (HR 756, CTX), a new injectable cephalosporin, were carried out. The peak MIC's against gram-negative rods isolated from patients were 0.1 μg/ml for E. coil, K. pneumoniae and P. mirabilis and 1.56 μg/ml for S. marcescens. Cefotaxime was far more. antibacterially active than cefazolin (CEZ) and T-1551. However, concentrations of 200 μg/ml only inhibited the growth of 38% of the strains of P. aeruginosa.
In mice with experimentally induced K. pneumoniae pneumonia, 120 mg/kg/day of cefotaxime was far more therapeutically effective than 300 mg/kg/day of CEZ.
Peak blood levels after 2-hour intravenous drip infusion of 1.0 g of cefotaxime ranged from 22.0-25.5 μg/ml (mean 23.2μg/ml). The urinary excretion rate up to 6 hours after administration was 38-62%.
Sputum concentrations were determined in 5 patients. Concentrations of 0.16-0.40 μg/ml were obtained in one patient, but less than 0.16 μg/ml in all other patients.
Pleural fluid concentrations, determined in two patients were 4.5 and 5.5 μg/ml, respectively.
Cefotaxime was administered to a total of 15 patients: 14 with respiratory tract infections and 1 with a subphrenic abscess. A dose of 1 g b. i. d. was given by intravenous drip infusion for 2-19 days to investigate clinical efficacy.
Among 14 patients able to be assessed, drug efficacy was good in 7 patients, fair in 4 patients, and poor in 3 patients.
Adverse reactions and laboratory data abnormalities were not seen in any patient. Cefotaxime was assessed to be a highly effective drug.

View full abstract

The antibacterial activity of cefotaxime in vitro against gram-positive microorganisms was less than that of cefazolin and cefuroxime, and was comparable to that of cefmetazole. On the other hand, the activity of cefotaxime against Haemophilus, Proteus, Klebsiella, Shigella, and Salmonella was very strong, and against Enterobacter, Citrobacter, and Serratia cefotaxime showed lower MICs than those of the other cephalosporins.
In clinical trials, cefotaxime's efficacy was good in 3 out of 4 patients with RTI. The antibiotic showed good results in 1 case and excellent results in 3 cases out of 8 cases of UTI The 4 UTI cases that did not respond to treatment were complicated by prostatic hypertrophy. Excellent results were obtained in 1 case each of pneumococcal meningitis, α-streptococcal subacute bacterial endocarditis, and a healthy typhoid carrier; good results were obtained in 1 case of fever of unknown origin.
An adverse reaction was observed in a patient with chronic panbronchiolitis, who suffered from dyspnea during drip infusion of cefotaxime.

View full abstract

A clinical study was performed on cefotaxime, a newly developed cephalosporin antibiotic, and the following results were obtained:
1) In 9 patients given a total of 12 doses of cefotaxime the drug's efficacy was excellent in 1 case of subcutaneous abscess, excellent in 3 cases and poor in 3 cases out of 6 cases of UTI, and good in 2 cases and poor in 3 cases out of 5 cases of RTI. Thus the results of treatment were good in 6 out of 12 cases. The majority of patients had some underlying disease.
2) An elevation of serum levels of GOT and GPT was noted as an adverse reaction in the patient with subcutaneous abscess; this patient happened to have Hodgkin's disease. The GOT levels fell to within the normal range during the term of cefotaxime administration, and GPT levels also fell to within the normal range upon discontinuation of administration. Other than this patient adverse reactions were not observed within the range of laboratory tests.
3) Based on the above findings cefotaxime may be said to be an effective antibiotic, particularly for infections due to E. coli and H. infiuenzae.

View full abstract

Fundamental and clinical studies of cefotaxime (HR 756, CTX) were carried out and the following results were obtained.
1. The MIC of cefotaxime were measured against clinically isolated pathogens at 10⁸ cells/ml and 10⁶ cells/ml inoculum size. These pathogens against which MIC of cefotaxime was less than 12.5 μg/ml were S. aureus 94%, S. epidermides 100%, S. faecalis 38% E. coli 91%, K. pneumonia 55%, Proteus sp. 33%, Citrobacter sp. 50%, Enterobacter sp., S. marcescens and P. aeruginosa 0% at 10⁸ cells/ml. gram-negative rods were almost less than 1.56 μg/ml at 10⁶ cells/ml, especially E. coli and K. pneumoniae were less than 0.20 μg/ml.
2. The peaks of serum levels after intramuscular injection and intravenous drip infusion of 1 g of cefotaxime were 44.4, 61.5 μg/ml at 30 minutes after im injection and just after the end of drip infusion, and T 1/2 were 63 and 51 minutes, respectively.
3. Cefotaxime was given to 2 patients with acute bronchitis, 1 patient with cystitis and 4 patients with septicemia at a dosage of 1-6 g/day for 3-15 days. Clinical responses to cefotaxime were good in 3 cases, fair in 1 case and poor in 3 cases. No side effect was observed.

View full abstract

Laboratory and clinical studies were made on cefotaxime (HR 756, CTX), a new cephalosporin antibiotic with the following results.
Cefotaxime was compared with cefazolin (CEZ), cefamandole (CMD), cefotiam (CTM), cefmetazole (CMZ), ampicillin (ABPC), ticarcillin (TIPC), chloramphenicol (CP) and sulbenicillin (SBPC) in antibacterial activity against 22 standard strains and 950 routine clinical isolates.
The minimum inhibitory concentration (MIC) of cefotaxime against gram-positive cocci was higher than those of CEZ, CMD, CTM and CMZ. Cefotaxime showed lower MICs against gram-negative bacilli than these drugs tested excluding P. maltophilia and Flavobacterium spp.
Cefotaxime was administered to three patients at a dose of 1, 000 mg and two patients at a dose of 2, 000 mg by intravenous drip infusion for one to two hours, and peak serum levels of 52-67 μg/ml and 92-127 μg/ml were obtained at the end of infusion, respectively.
Urinary recovery rate after injection of 1, 000 mg was 57.3%.
The peak sputum concentration was 0.07 μg/ml in the sputum of a patient with chronic bronchitis due to H. influenzae 2-3 hours after infusion of 1, 000 mg, and H. influenzae began to decrease in number from 10⁸-10⁹/ml and was eliminated from the sputum around 5-6 hours after injection. P. maltophilia was not eliminated from the sputum of another chronic bronchitis patient as though cefotaxime penetrated into her sputum at the peak level of 0.04 μg/ml after injection of 1, 000 mg. The peak sputum concentration of 0.2 μg/ml was assayed 1-2 hours after the end of infusion of 2, 000 mg.
Cefotaxime was given to a total of 29 patients-17 with pneumonia, 7 with chronic bronchitis, 1 with lung abscess, 1 with P. T. B. and 3 with pyelonephritis-by intravenous drip infusion for 6-18 days. Eighteen out of 22 patients evaluable responded effectively to cefotaxime treatment for an efficacy rate of 81.8%.
Total 10 cases showed the following adverse reaction of the drug: transient chills, and high fever at an early stage after starting i. v. treatment in 6 cases, eruption with or without itching in 3 and a slight elevation of S-GOT and S-GPT in 1.

View full abstract