Cefixime (CFIX), a new oral cephalosporin, showed a broad spectrum of antibacterial activity against grampositive and gram-negative bacteria including P. cepacia, S. marcescens and P. aeruginosa. The in vitro activity of CFIX was in general much stronger than that of CCL. Clinical isolates of R plasmid carrying strains were inhibited by relatively low concentrations of CFIX. CFIX was also active against β-lactamase producing strains, except for a strain of P. maltophilia. Enzymatic studies using spectrophotometric assay were carried out to examine the resistance of CFIX to β-lactamases (PCase, CSase and CXase) obtained from various bacteria. The results indicate that CFIX has strong resistance to all types of PCase and CSase tested, because it was not hydrolyzed by any of those enzymes. However, CFIX was hydrolyzed by the enzyme of P. maltophilia and Flavobacterium spp. On the other hand, the 50 percent effective dose (ED₅₀) of CFIX in mice infection was 1.90mg/kg against E. coli ML4707 and 1.78mg/kg against K. pneumoniae GN6445.

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MIC₈₀ of cefixime (CFIX) to 23-54 clinical isolates of S. aureus, S. epidermidis, β-Streptococci, S. pneumoniae, E. coli carrying R-plasmids, K. pneumoniae, P. mirabilis, P. vulgaris, M. morganii, P. rettgeri, C. freundii, E. cloacae, S. marcescens, P. aeruginosa, A. calcoaceticus, H. influenzae resistant to ABPC, and B. fragilis were 50, 100, 0.39, 0.2, 0.39, 0.1, ≤0.013, ≤0.013, 6.25, 0.1, 3.13, 100, 0.78, 100, 12.5, 0.05, and 50μg/ml, respectively.
CFIX was manifested strong binding affinity to PBP 3, la, and lb of E. coli in the order. Although CFIX showed high binding affinity to PBP lb, lc, and 3 fractions of S. marcescens, that to PBP 3 and 2 fractions of A. calcoaceticus and to essential PBP 2 and 3 fractions of S. aureus were moderate.
When 0.75 units/ml of the complement which did not influence on the growth of E. coli and ID₅₀ of CFIX were simultaneously added to the culture, synergy of the bactericidal activities was confirmed. The synergy, however, was weaker than that of the complement and ceftizoxime (CZX). The cells of E. coli NIHJ-JC2 were well engulfed and digested intracellularly by mouse cultured macrophages in the presence of 1/2 MIC of CFIX. Whereas the bacterial cells multiplied in the macrophages and destroyed them in the absence of the antibiotic.

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Cefixime (CFIX), a new oral cephalosporin developed in Japan, has a broad antibacterial spectrum and strong antibacterial activities which are equivalent to the third generation cephem antibiotics.
Antibacterial activity of CFIX was examined and compared with other oral cephalosporins and other antimicrobial agents against 819 strains of bacteria, including S. aureus, S. epidermidis, β-haemolitic Streptococci (group A and B), S. faecium, S. pneumoniae, N gonorrhoeae, H. influenzae, C. diversus, E. cloacae, S. marcescens, P. vulgaris, M. morganii, Flavobacterium (F. meningosepticum, F. odoratum and F. indologenes), A. anitratus and anaerobic bacteria (Peptococcus, Peptostreptococcus, Veillonella and Lactobacillus), which were isolated from clinical materials from 1983 to 1984.
The results can be summarized as follows.
1. CFIX showed the strongest antibacterial activity against N gonorrhoeae, H. influenzae and P. vulgaris. Its antibacterial activity was equivalent to that of ceftizoxime and superior to that of cephalexin and cefaclor. CFIX also showed strong activities against C. diversus, S. marcescens and M. morganii.
2. As the antibacterial activity of CFIX to group A and B Streptococci and S. pnemoniae, was equivalent to that of cefaclor, and stronger than cephalexin.
3. CFIX showed weak antibacterial activities to S. faecium, Staphylococcus, E. cloacae, A. anitratus and Flavobacterium.
4. In the anaerobic gram-positive organisms and Veillonella, MIC values of CFIX distributed over a wide range, which was a similar situation to control drugs.

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1. Cefixime (CFIX) exhibited a marked in vitro antibacterial activity against clinical isolates of gram-negative bacteria including indole-positive Proteus spp., E. cloacae, E. aerogenes, C. freundii and S. marcescens which are not susceptible to cefaclor or cephalexin.
2. CFIX was highly stable to various types of β-lactamases produced by organisms other than B. fragilis.
3. The therapeutic effect of CFIX orally given in normal and immunosuppressed mice infected with S. pyogenes, S. pneumoniae, E. coli, K. pneumoniae, P. vulgaris or P. mirabilis was by far superior to that of cefaclor and cephalexin.
4. The therapeutic effect of CFIX in mice infected with K. pneumoniae by inhalation was about 20 times higher than that of cefaclor. The remaining bacterial counts in the lung and blood after dosing with 5mg/kg of CFIX was lower than that after dosing with 80mg/kg of cefaclor. The inhibition of bacterial growth in the lung and blood of the infected mice was stronger in repeated doses than in a single dose. CFIX at 20mg/kg maintained 3 and 60 times the MIC level respectively in the lung and serum 6 hrs after dosing.
In contrast, cefaclor at 80mg/kg maintained only 2 times the MIC level in the lung1 hr after dosing 3 times the MIC level in the serum 4 hrs after dosing. The most effective dosage schedule of CFIX in this model infection was started from 4 hrs after infection. Synergism of neutrophils and both drugs was obtained in the in vitro phagocytic killing of K. pneumoniae. The killing activity of CFIX at 0.02μg/ml was almost thesame as that of cefaclor at 0.2μg/ml in the presence of neutrophils.

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We examined minimal inhibitory concentrations (MICs) of cefixime (CFIX) against 169 strains of Shigella, 122 strains of Salmonella, 54 strains of Escherichia coli, and 98 strains of Campylobacter jejuni isolated from patients with diarrhea. MICs of CFIX were higher against Campylobacter jejuni, but remarkably lower against Shigella, Salmonella, and Escherichia coli than those of ampicillin, nalidixic acid, kanamycin, and pipemidic acid. Only one strain of Shigella sonnei was resistant to CFIX (MIC=25μg/ml). MIC of ampicillinagainst this strain was more than 100μg/ml.

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The MICs of cefixime (CFIX), an oral cephalosporin, for fresh clinical isolates detected from August 1983 to July 1984 were measured and compared with those of the other antibiotics.
CFIX provided extremely potent antibacterial activity against S. pyogenes, S. pneumoniae, H. influenzae, N. gonorrhoeae, E. coli, K. pneumoniae, C. diversus and P. mirabilis, but weaker antibacterial activity against S. saprophyticus. The MIC₅₀ of CFIX for C. freundii, E. cloacae, E. aerogenes and S. marcescens ranged from 3.13 to 6.25μg/ml. This fact suggested that CFIX is relatively stable to beta-lactamase controlled by chromosome, but the wide distribution of MIC implied the decline of activity caused by the multiply resistant factor.

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The in vitro and in vivo antibacterial activities of cefixime (CFIX), a new 3rd generation oral cephalosporin, against anaerobic bacteria were evaluated and compared with those of cephalexin (CEX), cefaclor (CCL), amoxicillin (AMPC), ofloxacin (OFLX) and clindamycin (CLDM). The results were as follows:
1. The antibacterial spectrum of CFIX against standard strains of anaerobic bacteria was somewhat broader than that of CEX and CCL and was almost equal or narrower than that of AMPC and OFLX. CFIX provided potent antibacterial activity against almost all of the strains tested except certain strains of the B.fragilis group, F. mortiferum, C. difficile, C. innocuum and E plauti, and the MICs at the highest were 3.13μg/ml at inoculum size of 10⁸cells/ml.
2. The susceptibility distribution of CFIX against clinical isolates reflected the results with standard strains of anaerobic organisms; CFIX provided a satisfactory antibacterial activity against these organisms.
3. CFIX was more stable than CET, CEZ, PCG and ABPC to β-lactamase by B.fragilis.
4. The effect of CFIX on viability suggested that the drug had a bactericidal activity against B. fragilis.
5. In experimental model with mice, CFIX provided a therapeutic effect against polymicrobial infection with E. coli and β-lactamase producing B. fragilis in the peritoneal cavity and abscess caused by F. necrophorum.
6. CFIX, unlike ABPC, caused no abnormal growth of C. difficile in mouse cecum.

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The in vitro and in vivo antibacterial activities of cefixime (CFIX), a new orally active cephalosporin, were compared with those of cephalexin (CEX), cefaclor (CCL) and amoxicillin (AMPC). The following results were obtained.
CFIX had a broad antibacterial spectrum against gram-positive and gram-negative standard organisms. The antibacterial activity of CFIX was less potent than that of CEX, CCL and AMPC against Staphylococcus aureus, and more potent than that of CEX and CCL against Streptococcus pyogenes and Streptococcus pneumoniae. The antibacterial activity of CFIX was more potent than that of CEX, CCL and AMPC against gram-negative bacteria including Enterobacteriaceae such as Citrobacter spp. Enterobacter spp. and Serratia spp. and glucose non-fermentative rods. The antibacterial activity of CFIX was slightly affected by the pH of the medium, the addition of horse serum, and inoculum size. Time-kill curve confirmed the bactericidal activity of CFIX.
Against the intraperitoneal infection with S. aureus in mice, the therapeutic efficacy of CFIX was inferior to that of CEX and CCL. Against S. pyogenes, the efficacy of CFIX was superior to that of CEX and inferior to that of CCL. Against S. pneumoniae, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis and Serratia marcescens, the efficacy of CFIX was superior to that of CEX and CCL.

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The therapeutic efficacies of cefixime (CFIX) were evaluated in models of local infections in mice and compared with those of cephalexin (CEX) and cefaclor (CCL), and following results were obtained.
In experimental pulmonary infection with Klebsiella pneumoniae DT-S in mice, CFIX demonstrated superior efficacy to CEX and CCL and also showed strong bactericidal action and inhibitory activity of regrowth. In experimental urinary tract and uterus infections with Escherichia coli 444, K. pneumoniae KC-1, and Serratia marcescens T-55 in mice, the efficacy of CFIX was superior to that of CEX and CCL. CFIX showed high peak and prolonged serum levels in normal mice following oral administration. The peak serum concentration of CFIX was lower than that of CEX, but comparable to that of CCL. CFIX had longer half life than that of CEX and CCL.

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The antibacterial mechanisms of a new orally active cephalosporin, cefixime (CFIX), were investigated using E. coli K12, S. marcescens IFO12648 and P. aeruginosa KM338 as test organisms.
The minimal inhibitory concentrations of CFIX for the above organisms were 0.39, 0.39 and 400μg/ml, respectively, showing that CFIX is very active against E. coli K12 and S. marcescens IFO12648 and less active against P. aeruginosa KM338.
CFIX well penetrated the outer membranes of these organisms and was extremely stable to β-lactamases produced by the organisms.
A low concentration of CFIX inhibited cross-linking of peptidoglycan synthesis in ether-treated strain cells of the above 3 organisms.
From above results, we concluded that the excellent antibacterial activity of CFIX against E. coli K12 and S. marcescens IFO12648 can be explained by the high permeability of the outer membrane of these bacteria, good stability to β-lactamases produced by these bacteria and its high sensitivity for target enzymes concerning with the peptidoglycan synthesis. However, the mechanism of resistance in P. aeruginosa KM338 to CFIX was not clarified in this study.

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The in vitro antibacterial activity of cefixime (CFIX), a distinctive new oral cephalosporin, was compared with that of cefaclor, cephalexin and amoxicillin.
1. CFIX was more active than the reference drugs against stock strains of a wide variety of gram-negative bacteria including opportunistic pathogens. CFIX was far more active than the reference drugs against clinical isolates of E. coli, K. pneumoniae, indole-positive and-negative Proteus species, H. influenzae and N. gonorrhoeae. CFIX was less active than the reference drugs against
Staphylococcus, but was similar to cefaclor in activity against Streptococcus.
2. CFIX was active against clinical isolates of E. coli, K. pneumoniae and P. mirabilis that were resistant to cefaclor and cephalexin, and against those of E. coli, P. mirabilis, N. gonorrhoeae and H. influenzae that were resistant to amoxicillin (ampicillin) except a few strains of E. coli.
3. The antibacterial activity of CFIX was affected by the inoculum size against gram-negative bacilli but not by the test media, pH of the media or the media supplemented with serum against gram-positive and-negative bacteria.
4. The bactericidal activity of CFIX against gram-negative bacteria including Proteus species, C. freundii, E. aerogenes, S. marcescens was stronger than that of the reference drugs. The viable cell counts of E. coli in MH broth rapidly decreased for 20 h at twice the MIC of CFIX. In addition, in the in vitro kinetic model simulating human serum and urinary concentrations in man after oral dosing, CFIX had the most potent bactericidal activity. CFIX showed synergistic effect on phagocytosis and killing of PMN against E. coli at 1/16 the MIC, whereas cephalexin showed the same effect at 1/4 the MIC.
5. Patterns of development of E. coli resistance to CFIX were similar to those to cefaclor and cephalexin.

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The mechanism of action of cefixime (CFIX), a new oral cephalosporin, was compared with that of cefaclor and cephalexin to elucidate its excellent antibacterial activity against gram-negative bacteria.
1. CFIX was extremely stable to both plasmid-mediated penicillinase and chromosomal β-lactamase except the B. fragilis enzyme, and its stability was superior to that of cephalexin and cefaclor.β-lactamase inducing activity of CFIX against bacteria possessing inducible cephalosporinase was far inferior to that of cefmetazole and cefoxitin.
2. The antibacterial activity of CFIX was the most potent of the reference drugs against E. coli whose resistance is mediated by ampicillin-resistance plasmid or chromosomal genes and was not affected by introduction of the ampicillin-resistance plasmids into the host strain.
3. The ability of CFIX to penetrate the outer membrane of both E. coli and E. cloacae was less than a quarter that of cephalexin and cefaclor.
4. CFIX had very high affinity for PBPs 3, la and lbs of E. coli whereas cephalexin had fair affinity for PBPs la, 4 and 3.
5. The effect of CFIX on the morphology of E. coli was compared with that of the reference drugs by optical microscopy and scanning electronmicroscopy. Filamentous and spheroplast-like cells were observed at lower concentrations of CFIX than at those of cefaclor and more shortly after exposure to CFIX than after exposure to cefaclor.

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The therapeutic effect of cefixime (CFIX), a new oral cephem antibiotic, was compared with that of cefaclor, cephalexin, and amoxicillin against systemic and local infections in mice, rats and rabbits. CFIX was far more potent than cefaclor, cephalexin and amoxicillin in protective activity against systemic infection induced by all the test gram-negative bacteria in mice.The protective activity of CFIX was more potent than that of cefaclor and cephalexin against Streptococcus pyogenes and was almost the same as or slightly inferior to that of cefaclor against S. pneumoniae. Against Staphylococcus aureus CFIX was less active than the control drugs but more active than cephalexin.
The therapeutic effect of CFIX was superior to or almost the same as that of the control drugs in experimental respiratory infection induced by S. pneumoniae and K. pneumoniae in mice.The therapeutic effect of CFIX was superior to that of the control drugs against experimental pyelonephritis inducedby Escherichia coli and Proteus mirabilis in mice.These findings suggest that the total AUC values over the MICs of CFIX in the serum, lungs, and kidneys of mice for the above test organisms were the largest of alI the testdrugs.The therapeutic effect of CFIX was superior to that of the other drugs in rats and rabbits with ascending urinary tract infection induced by gram-negative bacteria and endocarditis induced by S. pyogenes.

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The microbiological assay methods for measuring concentrations, bioautography method and stability of cefixime (CFIX) in biological specimens are described.
The concentrations of CFIX in the serum, urine and bile were assayed by the cup and disc-plate diffusion methods, using E. coli ATCC 39188 as the test organism and Nutrient agar (Difco) as the test medium. P. rettgeri ATCC 35565 and B. subtilis ATCC 6633 were also used, the former for assaying lower concentrations and the latter for higher concentrations of CFIX.
The minimal detectable concentrations of CFIX by the disc-plate method were 0.06-0.13μg/ml for E. coli ATCC 39188, 0.016-0.03μg/ml for P. rettgeri ATCC 35565 and 2-4μg/ml for B. subtilis ATCC 6633. The sensitivity for CFIX by the cup-plate method was approximately twice that by the disc-plate method. For determination of CFIX concentrations in human serum, serum standard solutions were made with fresh pooled human serum. Lyophilized serum products prepared from human blood were also used, but it was necessary to confirm that the standard curve prepared with the serum agreed with that prepared with the fresh serum. The standard solutions were prepared with M/15 phosphate buffer (pH 7.0) for assay of urine and bile samples, and the samples were diluted 5-fold or more with the same buffer. Serum and urinary levels of CFIX after oral administration to human were also determined by high performance liquid chromatography. CFIX concentrations obtained by HPLC were in good agreement with these obtained by microbiological assay.
Bioautography method of silica gel thin layer chromatography was examined for detecting CFIX and its active metabolites in human urine. The results showed that the active substance in urine was CFIX itself.
CFIX was stable in human serum and urine during 40 days storage at -20°C.

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The pharmacokinetics of cefixime (CFIX), a new oral cephalosporin, were investigated in rats and dogs and compared with those of cefaclor, cephalexin and amoxicillin. Upon oral administration to either rats or dogs, CFIX produced higher and more sustained serum levels than the reference drugs. The biological half-life of CFIX was 2.29h in rats and 6.93h in dogs. Although the concentrations of CFIX in rat kidney, liver and spleen were lower than those of cephalexin and amoxicillin, they were sustained similarly to the serum levels. The 24-hour urinary and biliary recovery rates of CFIX in rats after oral dosing with 100mg/kg were 34.1 and 21.9%, respectively. The urinary excretion of CFIX was significantly lower than that of the reference drugs, however the biliary excretion was higher. In dogs, 23.4 and 0.2% of the given dose of 40mg/kg of CFIX was excreted in the 24-hour urine and bile, respectively.
Bioavailability of CFIX after oral dosing was 38% in rats and 47% in dogs, as calculated from intravenous data. CFIX, as well as cephalexin, was mainly absorbed from the upper and middle parts of the small intestine in rats, but the absorption rate of CFIX was slower than that of cephalexin. The unabsorbed CFIX was inactivated partially in the cecum and large intestine, and 27.3% of the oral dose was excreted in the 24-hour feces.
Entero-hepatic circulation of CFIX was observed in rats after both oral and intravenous dosing, however, the circulation process contributed little to the serum levels. The serum, urine and bile samples were examined by bioautography and high performance liquid chromatography. CFIX was found to be metabolically stable. Binding of CFIX to serum protein in all species was the highest of the test drugs: 63% for human, 93% for dog, 61% for rat serum.

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We investigated the effect of cefixime (CFIX) on bacterial flora in the intestinal tracts of 5 healthy male volunteers given the drug in oral doses of 200mg twice a day for 14 consecutive days.β-Lactamase activity against the drug in the feces differed by volunteer. In volunteers with low β-lactamase activity, the drug was detected in high concentrations in the feces and changes in the bacterial flora were marked. Various kinds of anaerobic bacteria decreased and Enterococcus faecalis and Enterococcus faecium increased, however these changes returned to normal soon after the end of the dosing period. In volunteers with high β-lactamase activity, no CFIX was detected in the feces and the effect of the drug on the bacterial flora was slight. No diarrhea occurred in any of the 5 volunteers given the drug orally. However, comparatively small numbers of Clostridium difficile and its toxin were detected in 2 volunteers during and at the end of the dosing period. Antibody against Clostridium difficile toxin was detected in the sera of these volunteers and non-toxin-producing-Clostridium difficile was already present in the fece of another volunteer. There were no changes in susceptibility of main bacterial species such as Bacteroides and E.coli isolated from the feces of 5 volunteers before and at the end of the dosing period.

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Clinical Studies were performed on cefixime (CFIX), a new oral cephalosporin. The following results were obtained.
1) CFIX was administered to 11 cases with various respiratory tract infection.
The efficacy was excellent in 2 cases, good in 6 cases and fair in 3 cases out of 11 cases.
The efficacy rate was 73%.
2) Mild elevation of serum level of GOT·GPT was noted in one case with chronic hepatitis. Otherwise there was no adverse reaction.
3) It was considered that CFIX was effective for respiratory tract infection.

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New cephalosporin, cefixime (CFIX) was evaluated in the treatment of 13 cases with respiratory tract infection.
CFIX was administered at a daily dose of 200 milligrams for 7 to 14 days by orally.
As a result, it was evaluated that 9 cases out of 13 (69.2%) were effective cases. Excellent result was noted in 1 case, good results were noted in 8 cases, and fair results were noted in 4 cases.
Diarrhea in only one case was obserbed as side effect of CFIX during this trial.
It could be concluded from this study that CFIX was highly useful and it may be used for the treatment of respiratory tract infection with chronic respiratory disorder.

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Pharmacokinetic profile of cefixime (CFIX), a new oral cephalosporin, was investigated in the following three studies using 9 healthy male volunteers and results were as follows.
1) Comparative study of CFIX and cefaclor in fasting state: Calculated peak serum concentration (C_max), time to reach peak serum concentrations (T_max), serum half-lives in elimination phase (T_1/2), and area under the curve (AUC) after dosing with CFIX 100mg were 1.6μg/ml, 3.67 hrs, 2.50 hrs and 12.1μg·hr/ml. Those after dosing with cefaclor 250mg were 10.5μ/ml, 0.06 hrs, 0.50 hrs and 8.187mu;g·hr/ml, respectively.
2) Comparative study on the influence of food between light and heavy meals: C_max, T_max, T_1/2, AUC after a single dosing with CFIX 100mg in the volunteers having light or heavy meal were 1.47μg/ml, 5.0 hrs, 3.76 hrs and 12.8μg·hr/ml for light meal, and 1.19μg/ml, 6.0 hrs, 3.34 hrs and 9.88·g·hr/ml for heavy meal, respectively.
3) Effect of probenecid: The effect of probenecid on the serum concentration of CFIX was rarely observed, but its effect on urinary excrection was found significantly.
From the above results, the pharmacokinetic profile of CFIX is characterized by a long T_max and T_1/2 and a relatively low urinary excretion rate. The absorption of CFIX is somewhat restricted by the food, especially by the heavy meal. There were the effect of probenecid on the urinary excretion of CFIX in human body.
In addition, no abnormal findings on laboratory tests or subjective symptoms were observed in volunteers throughout the studies.

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Susceptibility of cefixime (CFIX), a new orally active cephem antibiotic, was tested against 172 clinical isolates of 7 species, using plate dilution method with inoculum size of 10⁶ cells/ml. The MICs range of CFIX were obtained at 3.13-6.25μg/ml and over 50μ/ml, biphasic, for S. aureus, under 0.78μg/ml for E. coli, Klebsiella spp. and P. morganii, 0.78-1.56μg/ml for P. mirabilis, 0.39>100μg/ml for S. marcescens and over 12.57mu;g/ml for P. aeruginosa. The above mentioned activity was superior to that of reference drugs which were CEX, CFT and CCL except the activity against S. aureus.
Twenty six patients with infections were treated with CFIX at a daily oraI dose of 100-200mg b.i.d. and t. i. d. in 3-10 days. The clinical effects to the treatment was excellent in 11 cases, good in 13 cases, and fair in 2 cases. The effective rate was 92.3%. No adverse reaction and no abnormal laboratory findings were observed.

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Cefixime (CFIX) is cephalosporin derivative for oral administration and exerts a good antibacterial activity to gram negative bacteria. Though the peak concentration of CFIX in human blood serum is lower than that of oral cephalosporins used until now, it is remarkable that its half-life is longer.
11 patients were treated with CFIX; 4 with acute bacterial bronchitis, 5 with acute pneumonia, and 2 with diffuse panbronchiolitis.
The antipyretic periods were 3 days in 1 case, 4 days in 2 cases, 5 days in 3 cases and in the rest a slight fever lasted while CFIX was given for 2 weeks.
The clinical effects of CFIX were excellent in 2 cases, good in 4 cases, fair in 3 cases and poor in 2 cases. The efficacy rate obtained in 11 cases of respiratory tract infection was 54.5%.
K. pneumoniae which had brought about infection in 2 cases and H. influenzae which had caused infection in 1 case disappeared.
No side effects were observed. No abnormal laboratory findings were observed, either.

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To evaluate the clinical efficacy of cefixime (CFIX), the treatment was made with the drug in 11 patients including 1 with acute tonsillitis, 2 with acute bronchitis, 5 with pneumonia, 1 with bronchiectasis, 1 with acute cystitis and 1 with acute pyelonephritis. Responses were excellent in 2 patients, good in 8 and fair in 1.
Side effects were not observed. The laboratory test recognized an elevation of GOT and GPT in one patient.

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The clinical efficacy of cefixime (CFIX), a new cephalosporin antibiotic, was investigated in 21 patients suffered from respiratory tract infections. CFIX was given in a daily dose of 200mg and/or 400mg in 2 divided doses for oral administration. CFIX was given for 10 to 14 days and the total doses given to each patient ranged from 2000mg to 5600mg (mean±SD: 4260±1420mg).
Among the 21 patients treated with CFIX, the clinical response was excellent in 2, good in 12, fair in 6 and poor in 1. Slight elevations of GOT-GPT or BUN were observed in 3 patients and an eosinophilia reached the ratio to 11% was observed in one patient during the treatment. No side effects were recognized in any of the patients.

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In the present study, cefixime (CFIX) was given orally to 15 patients with upper respiratory tract and pulmonary infections. The subjects were 6 male and 9 female patients aged from 21 to 75 years, with an average of 46 years. The breakdown of the patients was acute pneumonia in 11 patients, acute bronchitis in 2, bronchiectasis associated with pulmonary infection in 1 and acute tonsillitis in 1. The underlying disease was encountered in 5 of the 15 patients; pulmonary emphysema in 2, bronchiectasis in 2 (one of whom was afflicted with diabetes, Hepatopathy and Stenocardia) and complication of both diseases in 1. The severity of the diseases was “moderate” in 10 and “mild” in 5.
CFIX was given orally to all the patients except 1 with acute tonsillitis in a daily dose of 200mg in 2 divided portions. To only one patient with acute tonsillitis, CFIX was given 50mg three times a day. The duration of treatment ranged from 4 days to 15 days, the average being 9 days. Judgement of efficacy was made on each patient on the basis of objective assessment of clinical symptoms, chest X-ray findings, WBC, blood sedimentation values and CRP, and was classified in 4 grades of “excellent”, “good”, “fair” and “poor” judging from the overall views at the discretion of the doctor in charge. The overall effect of CFIX was “excellent” in 2, “good” in 9, “fair” in 1 and “poor” in 3, with an effectiveness rate of 73%(11 of the 15 patients) inclusive of “good” and better response. In the 11 patients with acute pneumonia, the efficacy rate was as high as 73%(“excellent” in 1, “good” in 7 and “poor” in 3.). CFIX was effective in all the three patients with acute bronchitis or acute tonsillitis, and fair in one patient with pulmonary infection with bronchiectasis.
BacterioIogical examinations revealed that K. oxvtoca, S. pneumoniae and H. influenzae were eradicated, E. coli was substituted for S. pneumoniae, and S. aureus, S. pneumoniae and S. pyogenes were not assessable. No side effects were encountered in any of the patients, and there were no abnormal findings attributable to CFIX on laboratory tests.
The present study confirms that CFIX is a drug which can be safely used at the Outpatient Department for the patients with mild or moderate upper respiratory tract and pulmonary infections.

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On a new oral cephem, cefixime (CFIX), antibacterial activities against β-lactamase-positive and -negative isolates of H. influenzae were investigated. Its clinical efficacy and safety were also evaluated in patients with respiratory tract infections.
1. Against 73 strains of H. influenzae including 11β-lactamase-positive strains, 72 strains were inhibited at 0.39μg/ml or less of CFIX, and its antimicrobial activity was superior to those of CCL, ABPC and BRL 25, 000.
2. The subjects consisted of 5 male and 5 female patients aged from 43 to 89 years old. The breakdown of the diseases was infectious exacerbation of bronchiectasis in 4 patients, chronic bronchitis in 3, acute bronchitis in 1, infectious exacerbation of chronic pulmonary emphysema and pneumonia in one case. Classified by causative organism, the organism was H. influenzae in 4 cases, E. cloacae in 2, B. catarrhalis in 2, S. pneumoniae and E. coli in one each. As for the administration method, CFIX was given to 4 patients in a dose of 100mg and to 6 patients in a dose of 200mg two times a day. The overall effect of CFIX on 10 patients with respiratory tract infections was “excellent” in 1, “good” in 5, “fair” in 1 and “poor” in 3. The dosage regimen of 200mg/day showed “good” in 1, “fair” in 1 and “poor” in 2. Whereas, the dosage regimen of 400mg/day showed “excellent” in 1, “good” in 4 and “poor” in 1.
Classified by causative organism, two of the 4 strains of H. influenzae were eradicated with a good clinical response, another one decreased with no clinical response. The other one persisted from the view of bacteriological effect, but the clinical effect was “fair” Two strains of B. catarrhalis were eradicated, and the overall effect on 2 patients infected with the organism was “excellent” in one and “good” in one. One strain of E.cloacae was eradicated, with an effectiveness of “good”, but in the other strain, microbial substitution to S. aureus was observed. One strain of S. pneumoniae was eradicated and the case caused by the organism responded as “ good” to the drug. The other strain of E. coli persisted with “;poor” clinical response.
No side effects ascribable to CFIX were encountered. Laboratory examinations disclosed that a slight rise of GOT and GPT was noted, but the values turned to normal within a short period after dosing.

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Cefixime (CFIX), a new orally active cephalosporin, was shown that it possessed a broad antimicrobial spectrum covering gram-positive cocci and gram-negative bacilli.
Minimal inhibitory concentrations of the agent against each 20 clinical isolates of S. aureus, E. coli, K.pneumoniae, S. marcescens, Enterobacter spp. and P. aeruginosa were determined by use of MIC 2000 system. Although CFIX was less active than cefaclor (CCL) and amoxicillin (AMPC) against S. aureus, this drug was much more active than CCL and AMPC against E. coli, K. pneumoniae, S. marcescens and Enterobacter spp. Against P. aeruginosa CFIX was substantially inactive.
Thirteen patients suffering from respiratory tract infections received orally 100 or 200mg of CFIX twice a day. One patient showed an excellent and eight good clinical response, while two other patients responded only fairly and other two poorly. No undesirable symptoms and signs due to administration of the drug were observed. In one case elevation of blood urea nitrogen was observed.

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I. Serum and sputum concentrations of cef i x ime (CFIX)
Serum and sputum concentrations of CFIX were measured in seven patients with chronic respiratory tract infection (RTI). CFIX was orally given by a single dose of 200mg to three patients and by 100mg b. i. d. to four patients. Microbioassay was performed by the plate diffusion method using E. coli ATCC 39188 for the serum and P. rettgeri No.69 for the sputum.
Peak serum concentration of CFIX was 2.01μg/ml at six hours after a single administration of 200mg. Peak sputum concentration was 0.03μg/ml at seven hours after and that level was maintained till 11 hours after.
Peak serum concentration with 100mg b. i. d. were 1.04μg/ml at six hours after and 0.9μg/ml at 12 hours after. The sputum concentration was maintained 0.02 to 0.05μg/ml for a long period of time.
II. Clinical results
Clinical evaluation of CFIX was performed in 31 patients with RTI. They were consisted of 13 males and 18 females aged from 25 to 74 years old of whom 28 suffered from acute exacerbation of chronic RTI. CFIX was given orally to 20 patients in daily doses of 200mg and to 11 patients in daily doses of 400mg in two divided portions. The duration of administration were seven days in 20 patients, 14 days in six and eight days, 11 days, 21 days and 24 days in one each. CFIX was withdrawn in one patient on day six.
A total of 18 strains comprising H. influenzae nine strains, S. pneumoniae six strains and P.aeruginosa three strains were identified from the sputum before administration.
Fourteen strains were eradicated; one strain was partially eradicated; three strains were unchanged and three strains changed to the other strains.
The clinical efficacy rate was 93.5%(29/31): excellent in six cases, good in 23 cases and poor in two cases.
Side effects were observed in four cases, but not serious. They were stomach discomfort and heartburn in two and stomach discomfort and bitterness in one each.
There were no abnormal findings in laboratory test values in any of the patients.
From the above results, it is concluded that CFIX is effective, safe and useful antimicrobial agent.

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Basic and clinical studies were performed on cefixime (CFIX), a new third generation oral cephalosporin, and results were as follows.
The MICs of CFIX against clinical isolated, indole positive Proteus, ABPC-resistant Klebsiella, ABPC-resistant E. coli were determined and compared with those of ABPC, CEX, CXD and CCL against the same organisms.
CFIX was found to more active against strain of indole positive Proteus, ABPC-resistant Klebsiella, ABPCresistant E. coli than ABPC, CEX, CXD and CCL.
In the clinical studies, daily doses of 100-400_mg of CFIX were administered orally for 3-21 days to 31 patients, including 19 cases with respiratory tract infections, 8 cases with urinary tract infections, 3 cases with bacillary dysentery, 3 cases with colitis and 1 case with acute lymphadenitis.
Efficacy rate was counted 73.7% in respiratory tract infections and 100% in urinary tract infections. The overall efficacy rate was 79.4%.
Bacteriologically, the elimination of each strain of H. influenzae, Enterobacter, E. coli, S. sonnei was observed.
The strain of S. flexneri was not eliminated.
As to side effect, dizziness in one case, anorexia in one case and epigastric pain in one case were observed.
Abnormal laboratory findings were noted 5 cases, leukopenia in one case, elevation of s-amylase in one case, slight increase of GOT in one case and that of GOT and GPT in 2 cases.
From these results, CFIX as oral antibacterial agent is evaluated to be useful except for the treatment of serious infections.

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The clinical study of cefixime (CFIX), a newly developed oral cephalosporin antibiotic, was made in the field of Internal Medicine. The subjects were total 8 patients (4 inpatients & 4 outpatients) of whom 7 were urinary tract infection (5 with acute cystitis & 2 with chronic cystitis) and 1 with acute submaxillitis. The causative organisms were E.coli, P. mirabilis and E. aerogenes in UTI and unknown in acute submaxillitis. CFIX was administered 100_mg b. i. d. for 4-7 days.
The clinical effect of CFIX was “;markedly effective”; in 1, “;moderately effective”; in 4 and “;poor”; in 2 with UTI, and “;moderately effective”; in with acute submaxillitis.
Side-effect and abnormal laboratory finding were encountered in none of the treated cases.

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Fundamental and clinical studies on cefixime (CFIX), a new orally cephalosporin antibiotic, were performed and the following results were obtained.
CFIX and long active cephalexin (L-CEX) were orally administered to healthy adult male volunteers at a dose of 100mg and 500mg respectively. On CFIX the maximum serum concentration of 1.17μg/ml was reached at 4 hours after administration. The serum half life (T_1/2) of CFIX was 3.76 hours. The 24-hr urinary recovery was 25.6%. On the other hand the maximum serum concentration of L-CEX reached 4.91μg/ml at 4 hours. T_1/2 of L-CEX was 1.86 hours. The 24-hr urinary recovery was 85.4%.
CFIX was administered to 10 patients with various infections in the field of internal medicine in daily dose of 100-400mg for 4-14 days.
The clinical result was “excellent” in 1, “good” in 5, “poor” in 2 and “inevaluable” in 2 patients. All six bacterial strains detected were eradicated.
Anorexia and soft stool were noted in one case each and no abnormal laboratory findings were noted.
From these results, it is concluded that CFIX is an useful cephalosporin antibiotic for the treatment of infections in the field of internal medicine.

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The clinical effect of cefixime (CFIX), a new oral 3rd generation cephalosporin antibiotic, was investigated in 11 patients with respiratory tract infections. The breakdown of disease was acute bronchitis in 6 patients, pneumonia in 2, pulmonary fibrosis in 2 and acute tonsillitis in 1. CFIX was given in doses of 50mg or 100mg 2 times a day (morning and evening).
The overall effect of the drug was “excellent” in one case, “good” in 8 cases, “fair” and “not assessable” was in each one case. The effectiveness rate inclusive of “good” and better response, was 90%(9 of the 10 patients evaluated).
Bacteriologically, H.influenzae (2 strains) and Klebsiella (2 strains) were identified. Only one strain of H.influenzae persisted and the other causative organisms were eradicated.
The only side effect was diarrhea in one patient. Laboratory examinations disclosed abnormalities in liver function such as GOT and/or GPT in 2 patients and a rise of S-Cr in one. However, all these changes were slight and not considered to pose problems in clinical practice.

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One hundred miligram of cefixime (CFIX) was administrated orally to 6 aged volunteers (70-81 years old) for pharmacokinetic analysis and following results were obtained, C_max: 1.34μg/ml, T_max: 3: 31 hr, T_1/2: 3.99 hr, AUC: 12.17μg·hr/ml.
These data indicate that the aged show a little bit higher serum concentration and delayed excretion of CFIX, in comparing with the younger volunteers.
Clinical evaluation was performed on 7 patients with respiratory tract infections and 7 patients with urinary tract infections. Satisfactory response was obtained in 5 patients with RTI and 5 patients with UTI. Anorexia was noted in one patient during CFIX treatment, but it was mild. No other adverse reaction was observed.

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A clinical study of cefixime (CFIX), a new oral cephalosporin antibiotic, was carried out with following results.
Twelve cases of respiratory and urinary tract infection (including 5 cases of pneumonia, 2 cases of chronic bronchitis, each one case of pulmonary emphysema, pulmonary abscess, pleurisy, bronchiectasis and acute pyelitis) were treated by oral administration with 100-200mg per dose of CFIX given in 2-4 times per day for 7-29 days.
The clinical efficacy was excellent in 6 cases, good in 5 cases and fair in 1 case, with an clinical effectiveness of 91.7%.
Bacteriological effect was as follows: Out of three isolates of H.influenzae, two were eradicated but one was replaced to S.aureus. One strain of H.parainfluenzae, 2 of Haemophilus sp., 2 of S.pneumoniae and 1 of Staphylococcus sp. were eradicated.
No clinical side effect was observed. In the laboratory findings, elevation of transaminase in 4 cases and eosinophilia in 1 case were observed.
The serum and sputum concentration of this antibiotic was studied in three cases with chronic bronchial infection. Peak levels of the sputum concentration were 0.04 to 0.12μg/ml after an oral administration of CFIX 200mg. The ratio of sputum concentration to serum concentration is 1.8 to 10%.

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Cefixime (CFIX) is a new oral cephalosporin antibiotic developed by Fujisawa Pharmaceutical Co. Ltd. Fundamental and clinical studies of CFIX were carried out, with the following results.
1. The MIC of CFIX against 25 strains each of S.pyogenes and S.pneumoniae was superior to that of CCL and NFLX, but inferior to that of AMPC. The MIC of CFIX against 25 strains each of E.coli and K.pneumoniae was superior to that of CCL and AMPC, but somewhat inferior to that of NFLX. The MIC of CFIX against 25 strains of H.influenzae was superior to that of CCL and AMPC. That is, CFIX provide potent antibacterial activity against the organism, like NFLX. The MIC of NFLX against 25 strains of S.marcescens was the most excellent. There were most of the organisms resistant to CCL and AMPC. However, only two strains of the organism were strongly resistant to CFIX, but the other strains were inhibited by the drug. The MIC of CFIX against S.marcescens was broad and flat, and superior to that of CCL and AMPC.
2. The serum and sputum concentrations of CFIX were measured in 3 patients with chronic respiratory tract infection given 200mg or 100mg of the drug. Peak sputum level of CFIX after oral dosing with CFIX 200mg was 0.22μg/ml at 12 hours in one patient, and 0.07μg/ml at 8 hours in another patient. Peak sputum level after oral dosing with CFIX 100mg was 0.11μg/mI at 4 hours. In the 3 patients, the penetration rate of CFIX into the sputum from serum was about 1/10.
3. CFIX was given to 26 patients with respiratory tract infections. The breakdown of the diseases was tonsillitis in 7 patients, pharyngitis in 1, bronchitis in 12, bronchiectasis in 1 and pneumonia in 5. The daily doses of CFIX were 200mg and 400mg at 2 divided portions. Duration of administration ranged from 3 to 15 days.
Clinical and bacteriological effects were found excellent or good in 2 patients with tonsillitis caused by S.pyogenes and H.parainfluenzae, 1 with pharyngitis caused by H.parahaemolyticus, 1 each with pneumonia and bronchiectasis caused by H.influenzae, 2 with bronchitis caused by S.pneumoniae and K.oxytoca and 1 with bronchitis caused by K.oxytoca.
The overall effect of CFIX on infections was “good” or better response in 23 of 26 patients, with an effectiveness rate of 88%. That is, CFIX possessed extremely satisfactory effect on the infections.
Nausea and vomiting were encountered in one patient as side effects. A slight increase in Al-P and GOT was also observed in one each. The side effects were alleviated after withdrawal of the drug, and no marked changes in laboratory tests were noted. Accordingly, CFIX was well tolerated.
It is concluded from the results that CFIX is a useful drug as the 3rd generation oral cephem.

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A new synthetic antibiotics, cefixime (CFIX), was orally administrated to 11 cases associated with acute tonsillitis (one case), acute bronchitis (two cases), or infectious exacerbation of chronic bronchitis or bronchiectasis (8 cases) in a daily dose of 200mg (in the two divided dose) for a duration of 5-15 days. The two patients of them were insusceptible to previous antibacterial therapy. Following results were obtained;
1. The clinical efficacy of cases of acute tonsillitis or acute bronchitis were good in the all cases, and cases of infectious recurrence of chronic bronchitis or bronchiectasis were good in 6 cases, fair in one case and poor in one case. The total efficacy of these all cases were good in 9 cases, and the clinical efficacy rate was 82%.
2. Bacteriologically, causative organisms in sputum or pharyngeal swab were detected in three cases, and one strain of α-Streptcoccus and one of P.aeruginosa were eradicated, but another strain of P.aeruginosa was remained after the administration of CFIX. Thus the rate of eradication was 67%.
3. As for side effect after the administration, neither clinical symptom nor sign, but one case of mild leukopenia and one of mild anemia in laboratory data were observed.
These results suggest the usefulness of the administration of CFIX against acute or chronic recrudescent respiratory tract infections.

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Cefixime (CFIX), a new oral cephalosporin antibiotic, was administered to patients with RTI and UTI, and examined for its clinical effect. The subjects consisted of 22 patients (8 males and 14 females). Their ages ranged from 18 to 76 years with an average of 49.0 years. The breakdown of the infections was acute pharyngitis in 6 patients, acute tonsillitis in 3, acute bronchitis in 7, pneumonia in 2, acute pyelonephritis in 1, acute cystitis in 1 and chronic cystitis in 2.
In clinical effect, the improvement rates of “moderately improved” or better response and of “slightly improved” or better response were 72.2%(16 patients) and 81.8%(18 patients) of the 22 patients. The causative organisms identified were 9 cases and the breakdown of the organisms was S.pneumoniae in 4 cases, E.coli in 3, S.aureus in 1 and P.aeruginosa in 1. P.aeruginosa in 1 persisted, but the remaining organisms were eradicated in the other 8 after dosing with CFIX.
As for side effects attributed to the drug, eruption occurred in the labia oris of one patient. However, the eruption disappeared rapidly after withdrawal of the drug. Laboratory examinations disclosed an increase of SGOT, S-GPT and AL-P values in one patient. However, the values returned to normal after the discontinuation of the drug.

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Bacteriological and clinical studies on cefixime (CFIX), a new oral cephalosporin antibiotic agent, were performed and following results were obtained.
1) CFIX showed strong antibacterial activities against S.pyogenes, E.coli, K.pneumoniae, P.mirabilis, S.marcescens, E.cloacae, H.infuenzae isolated from clinical materials. The MIC₈₀ values of CFIX against these bacteria were 0.2, 0.39, 0.78, 0.05, 12.5, 50, 0.1μg/ml with inoculum size of 10⁶cells/ml, respectively.
2) Serum and sputum levels of CFIX after single oral dose of 100 mg were measured in one patient with chronic bronchitis. The serum concentration was long-lasting with the peak of 0.48μg/ml at 6 hours after administration and still remained 0.17μg/ml at 12 hours. Sputum concentration was under detection limit of 0.03μg/ml at 4, 6 and 8 hours after administration.
3) Clinical evaluation of CFIX was performed on 16 patients including 2 cases of bacterial pneumonia, one case of acute bronchitis, 3 cases of chronic bronchitis, 6 cases of acute cystitis and 4 cases of acute pyelonephritis. The dosage level was 100 to 200mg, once or twice a day. The clinical response was excellent or good in all cases without remarkable side effects.

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Cefixime (CFIX), a new cephalosporin antibiotic, was orally administrated to 12 patients with urinary tract infection and one patient with pneumonia. The patients received the drug for 4 to 14 days in dose of 150-300 mg/day.
Clinical effects were excellent in one case, good in 8 cases and fair in 4 cases, showing an efficacy rate of 69.2%.
Neither side effects nor abnormal laboratory findings possibly related to this drug were observed in any of these cases.

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Clinical efficacy and safety of cefixime (CFIX), a new oral antibiotics of cephalosporin, were evaluated in 12 patients.
CFIX was administered to 12 cases consisting of 1 case with acute enterocolitis, 1 case with cholecystitis, 4 cases with acute pyelonephritis, 4 cases with chronic pyelonephritis and 2 cases with chronic bronchitis, at daily dosis of 100mg-400mg for 3 days-15 days by oral route. Clinical efficacy was evaluated to be excellent in 1 case, good in 8 cases, fair in 1 case and poor in 2 cases. Thus CFIX was effective in 9 out of 12 cases in total with a rate of effectiveness of 75%
No apparent subjective symptoms due to side effect were observed. Slight degree of elevation of Al-P was observed in one case after the medication.

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Cefixime (CFIX) was administered to a total of 35 patients: 34 with respiratory tract infections, 1 with urinary tract infection. It was given orally twice a day at a dose of 200mg to the patients with respiratory tract infections, and 100mg to those with urinary tract infection.
Clinical response was excellent in 3 cases, good in 26, fair in 2, poor in 2, and undetermined in 2.
Laboratory tests revealed eosinophilia in 3 cases and leukopenia in 1, although these findings were alleviated rapidly following cessation of the therapy. No severe side effects caused by the drug were observed.

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The antibacterial activity and clinical effect of cefixime (CFIX) were studied with the following results.
1) Antibacterial activity
We measured the MICs of CFIX against 188 strains of clinically isolated organisms such as S. aureus, E. coli, K. pneumoniae, P. mirabilis, P. vulgaris, M. morganii, S. marcescens and P. aeruginosa and compared with those of CCL, CEX and AMPC. CFIX is inferior to CCL, CEX and AMPC in antibacterial activity against S. aureus, but superior to the three drugs against E. coli, K. pneumoniae and P. mirabilis. CFIX was also provided with antibacterial activity against P. vulgaris, M. morganii, and S. marcescens which are resistant to CCL, CEX and AMPC, but was ineffective against P. aeruginosa.
2) Clinical results
CFIX was administered to a total of 22 patients with various infections; 4 patients with pneumonia, 6 with acute bronchitis, 2 with acute tonsillitis, 3 with acute aggravation of chronic bronchitis, 6 with acute aggravation of diffuse panbronchiolitis (one identical case) and 1 with acute pyelonephritis. All the subjects except one patient in whom the drug was discontinued the drug because of side effects were evaluated for clinical response. The effect of CFIX was ‘markedly improved’ in 3, ‘moderately improved’ in 12, ‘slightly improved’ in 4 and ‘poor’ in 2, with an overall effectiveness rate of 71.4%.
Bacteriologically S. pneumoniae and P. putida isolated from two different patients with pneumonia and E. coli from a patient with acute pyelonephritis were eradicated, and S. marcescens, P. aeruginosa and E. coli isolated from the three different patients with acute aggravation of chronic respiratory infection persisted, and H. influenzae was replaced with K. pneumonia in a patient. Side effects attributed to the drug were diarrhea in one patient and epigastric pain in one other patient. There were no abnormal findings on laboratory tests.

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Cefixime (CFIX), an oral cephem newly developed by Fujisawa Pharmaceutical Co., was examined for antibacterial activity in vitro and clinical usefulness. The results were as follows:
1) Antibacterial activity in vitro: The MICs of CFIX for clinically isolated E. coli, Klebsiella, Proteus group, Enterobacter, and Serratia, were lower than those of such popular oral β-lactam antibiotics as cephalexin (CEX), cefaclor (CCL) and amoxicillin (AMPC).
2) Clinical trials: Thirteen patients with infections comprising 1 with cholecystitis and 12 with RTI i. e. 7 with acute bronchitis, 3 with chronic bronchitis, 1 with pneumonia, and 1 with infected bulla, were treated with CFIX 100mg×2/day for 4-11 days. Six of seven patients with acute bronchitis responded well to the therapy. The remaining one patient had non-bacterial infection. One of the three patients with chronic bronchitis was a fair responder but the other two were poor responders. One of the latter yielded S. aureus and P. aeruginosa on sputum culture. The patients with pneumonia, infected bulla, and cholecystitis were each good responders. The efficacy rate was 69.2%.
Neither untoward reactions nor abnormal laboratory findings attributable to the drug were detected except in one patient who complained of nausea and vomiting on the third day of administration.
These results strongly suggest the clinical usefulness of CFIX as a new oral antibiotic.

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This study was carried out to evaluate the therapeutic efficacy and safety of cefixime (CFIX) in the field of internal medicine.
CFIX was given orally to 13 patients in a dose of 100mg twice daily for 4-22 days (average: 11.7 days). The subjects consisted of 12 patients with respiratory tract infection and 1 with urinary tract infection; 3 with pharyngolaryngitis, 1 with tonsillitis, 2 with acute bronchitis, 2 with acute exacerbation of chronic bronchitis, 3 with pneumonia, 1 with infected lung cancer and 1 with acute cystitis.
The overall effect of CFIX was “excellent” in 2, “good” in 8 and “fair” in 3, with an effectiveness rate of 76.9%. The causative organisms were identified as E. coli in 2 patients, which were eradicated after treatment with CFIX. No side effects or abnormal laboratory data were observed in any of the 13 patients.
Considering its broad spectrum, prolonged serum level and clinical results, it was concluded that CFIX is an oral antibiotic of first choice which is highly useful for the treatment of infections in the field of internal medicine.

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Fundamental and clinical studies on cefixime (CFIX), a new oral cephalosporin, were performed and the following results were obtained.
All of clinically isolated strains of E. coli (35 strains), K. pneumoniae (23), P. mirabilis (28) and P. vulgaris (12) were inhibited by concentrations of 12.5 μg/ml of CFIX, showing a peak distribution in 0.39/μg/ml, 0.1μg/ml, ≤0.025μg/ml and ≤0.025μg/ml, respectively. S. aureus (39 strains) were somewhat less sensitive to CFIX, showing a peak distribution in 12.5μg/ml. All of 40 strains of P. aeruginosa were resistant to ≥100μg/ml of CFIX.
CFIX was given to 14 patients with RTIs 100-300mg (400mg for only one) twice a day for 4-16 days.
The subjects consisted of 1 with acute bronchitis, 3 with chronic bronchitis, 4 with infected bronchiectasis, 1 with infected bronchial asthma, 1 with infected pulmonary fibrosis, 2 with pneumonia, 1 with lung abscess, 1 with infected lung cancer.
The overall effect of CFIX was ‘good’ in 9 patients, ‘poor’ in 4 and ‘excluded’ in 1. Bacteriological effects of CFIX were not favorable in patients infected with S. aureus or P. aeruginosa.
There were no adverse reactions in any of patients, but an increase of S-GOT and eosinophilia was seen in one patient each.
The sputum concentrations of CFIX were measured in one patient each of infected bronchial asthma and lung abscess, given 200mg twice a day. The concentrations were 0.16μg/ml in one patient and 0.06μg/ml in the other.

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Bacteriological and clinical studies on cefixime (CFIX), a new oral cephem, were performed and the following results were obtained.
1) Antimicrobial activity of CFIX against clinically isolated S. aureus was inferior to those of CEX and AMPC, the peak MIC value was 12.5μg/ml. But CFIX showed far more superior activity to those of CEX and AMPC against E. coli, K. pneumoniae, S. marcescens and Proteus spp., the peak MIC value was 0.18, 0.05, 0.18 and s 0.025μg/ml. But CFIX was less active against P. aeruginosa, P. cepacia and Acinetobacter spp., the peak MIC value was 200 ≤ 3.13 and 6.25μg/ml.
2) CFIX was administered to 24 patients and the clinical efficacy evaluated in 22 respiratory infections and one urinary tract infection. Clinical effect was ‘excellent’ in one, ‘good’ in 14, ‘fair’ in 5, ‘poor’ in 3 and the efficacy rate was 65.2%. As the side effect, anorexia and abdominal fullness was observed in one case. In two cases, slight and transient eosinophilia was observed after treatment.

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Laboratory and clinical studies were performed on cefixime (CFIX), a new orally active cephalosporin antibiotic, and results were as follows.
1) Antimicrobial activity
MICs of CFIX against various clinical isolates were determined. CFIX was significantly more active than cefaclor, cefroxadine and amoxicillin against E. coli, Klebsiella spp., Enterobacter spp., S. marcescens, Proteus spp., Citrobacter spp. and H. influenzae. And against S. pyogenes and S. pneumoniae, CFIX was more active than cefaclor and cefroxadine but less active than amoxicillin. It was less active than the three reference drugs against S. aureus, and it had no activity against S. faecalis and P. aeruginosa with few exceptional strains.
2) Serum concentration and urinary excretion
Serum concentrations of CFIX were measured in three healthy adults, given orally 200mg of CFIX after meal. The peak of mean serum concentrations was 1.94μg/ml after 4 hours. Even after 8 hours, it was measured as 1.23 μg/ml. The mean 8-hr urinary recovery rate was only 17%.
3) Clinical efficacy
Nine patients with bronchitis, 1 with pharyngitis, 1 with pyelonephritis, 5 with cystitis were treated with CFIX daily dose of 200-600mg for 2-38 days. Clinical responses were excellent in 3, good in 8, fair in 1, poor in 3 and unknown in 1 patient. A mild iching was observed in a patient and a slight and transient elevation of s-GPT was seen in the other patient.

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In vitro antimicrobial activities against clinical isolates and clinical efficacy of cefixime (CFIX), a newly developed oral cephem antibiotic, were evaluated.
All of H.influenzae (23 strains), E. coli (27 strains) and K. pneumoniae (27 strains), 80% of M. morganii (10 strains), 43.5% of S. marcescens (23 strains) and 24% of E. cloacae (25 strains) were considered as susceptible, when MIC of less than 1.56μg/ml were regarded as susceptible strain against CFIX.
No susceptible strain among S.aureus (27 strains), P. aeruginosa (27 strains) and A. calcoaceticus (21 strains) was detected.
Above results indicated that sensitivity distribution of CFIX against major clinical isolates was slightly inferior to those of CZX, but superior to CEX.
Two patients with acute bronchitis, 2 with acute exacerbation of chronic bronchitis, 3 with pneumonia and 4 with urinary tract infection were treated with CFIX at daily doses of 100 to 400mg, for 4 to 14 days. Isolated organisms were H.influenzae in 3 and B.catarrhalis in 1 case from sputa, and E.cloacae, E.aerogenes and S. marcescens in 1 each from urine. Overall clinical results were excellent in 3, good in 6 and poor in 2 cases. All of isolates were eradicated after the treatment, except for one colonization by S. faecalis. Overall clinical efficacy was 81.8%.
Loose stool with the isolation of 10³cells/g of C.difficile was seen in one case without pseudomembranous colitis. The mild elevation of serum amylase and also mild elevations of hepatic enzymes were seen in one case each.

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Fundamental and clinical studies on cefixime (CFIX), a novel oral cephem antibiotic, were carried out with following results.
1) Antibacterial activity: The in vitro antibacterial activity of CFIX was tested by the serial microbroth dilution method using MIC 2000 system (Dynatek Co.). The minimum inhibitory concentrations (MICs) of CFIX against total 1, 130 strains consisting of 28 standard strains and 1, 102 clinical isolates were compared with those of cefroxadine (CXD), cefaclor (CCL), amoxicillin (AMPC), cefazolin (CEZ), cefotiam (CTM), ceftizoxime (CZX), latamoxef (LMOX) and piperacillin (PIPC).
CFIX provided very potent antimicrobial activity against gram-negative rods such as E. coli, Klebsiella spp., Proteus spp., H. influenzae and S. marcescens. The drug was also active against most of the cocci such as S. pyogenes, S. pneumoniae and B. catarrhalis except Staphylococcus species.
2) Serum and sputum levels of CFIX: The pharmacokinetic study was made in two patients with chronic bronchitis. Serum and sputum levels of CFIX were measured by the bioassay method in the patients given orally 200mg of CFIX. The peak serum concentrations were 1.21μg/ml in one patient and 1.88μg/ml in the other at 4 to 6 hours after administration. The peak sputum concentrations were under the detectable limit of measurement.
3) Clinical evaluation and adverse reaction: Twenty-one patients with respiratory infections (1 with acute bronchitis, 5 with pneumonia, 10 with chronic bronchitis, 3 with bronchiectasis and 2 with diffuse panbronchiolitis) were treated with 200 or 400mg of oral CFIX daily for 5 to 14 days. The effectiveness rate was 78.9%(excellent in 3, good in 12, fair in 1, poor in 3, and not assessable in 2).
Hematochemical tests, and renal function tests were performed before and after treatment with CFIX. No adverse reaction of subjective and objective symptoms or abnormal test values were encountered.

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Fundamental and clinical studies of cefixime (CFIX) a new oral cephalosporin derivative developed by Fujisawa Pharmaceutical Co., Ltd. were carried out in patients with respiratory tract infection.
The peak minimal inhibitory concentrations (MICs) of CFIX were 0.05μg/ml against respiratory pathogenic H. influenzae, 0.1μg/ml against respiratory pathogenic K. pneumoniae, 0.39μg/ml against respiratory pathogenic E. coli, 0.78μg/ml against respiratory pathogenic Enterobacter and 0.2μg/ml against respiratory pathogenic S. pneumoniae.
CFIX was superior to other cephalosporins in antibacterial activity.
The serum concentrations peaked at 0.21μg/ml and 0.42μg/ml 4 hours and 6 hours after a single dose of 100mg in respective patients case 10 and case 19. The sputum concentration in patient case 19 was under the minimum measurable limit, but that in patient case 10 was measurable two times during the dosing period and peaked at 0.031μg/ml. The sputum concentrations were measurable many times and peaked at 0.16μg/ml in this course of patient (case 14) with bronchiectasis.
CFIX was administered orally in daily doses of 100mg-400mg.
Nineteen respiratory tract infections were subjected to clinical evaluation of CFIX. And, the rates of clinical therapeutic efficacy was 68.4%. None of them showed adverse effects. The safety of CFIX was good.
From the above results, it was concluded that CFIX is one of the most effective and useful oral antibiotics for the treatment for the respiratory bacterial infection, particularly for those due to H. influenzae and β-lactamase positive Branhamella catarrhalis.

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Cefixime (CFIX) is a new oral semisynthesized antibiotic of the third generation cephalosporin group, having resistance to β-lactamase and broad spectrum.
CFIX was administered orally to 2 cases in a single dose of 500mg and to 6 in 200mg before the operation. Tissue specimens and bile samples were taken during the operation. CFIX concentrations were determined by bioassay using. E. coli ATCC 39188 as the assay organism.
CFIX concentrations in the common duct bile ranged from 55.3 to 238.0μg/ml 183 to 223 minutes after oral administration of 500mg. The concentrations were 77.1 to 207.0μg/ml in the gallbladder bile and 2.0 to 21.3μg/g in the gallbladder wall. CFIX concentrations in the common duct bile ranged from 0.3 to 98.8μg/ml (mean 33.4± 31.9μg/ml) 80 to 263 minutes after oral administration of 200mg. In bile and wall of the gallbladder, the concentrations were 0.1 to 69.7, μg/ml and < 0.15 to 8.9μg/g, respectively. These values were higher than the MICs of CFIX against the organisms isolated from subjects in clinical study.
For clinical efficacy, CFIX was administered orally to 12 cases with biliary tract infections accompanied by cholelithiasis in a dose of 100 to 200mg 2 or 3 times a day for 6 to 27 days. The subjects were consisted of 7 cases with cholecystitis, 4 with cholecystitis & cholangitis and 1 with cholangitis after choledochoduodenostomy. The clinical response was excellent in 4 cases, good in 7, fair in 1 and poor in none. No adverse effects were observed. The isolated organisms before CFIX treatment were 8 strains from 6 cases; 5 strains of E. coli, 2 of K. pneumoniae and 1 of S. epidermidis. Except 1 strain each of E. coli and K. pneumoniae, the organisms were eradicated after CFIX treatment.
Therefore, CFIX appears to be a very useful drug when used for chemotherapy on biliary tract infection.

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