Ceftazidime (CAZ, SN 401) is a new parenteral aminothiazolyl cephalosporin with a broad spectrum spectrum of antibacterial activity. The antibacterial activity of CAZ against Gram-positive and Gram-negative organisms was compared with that of cefotaxime (CTX), cefmenoxime (CMX), cefoperazone (CPZ) and cefsulodin (CFS). The results are summarized as follows:
1. CAZ was more effective than CTZ, CMX, and CPZ against Gram-negative bacteria including K. oxytoca, S. marcesens, E. cloacae, P.vulgaris, P. aeruginosa and P. cepacia. Its activity against Gram-positive bacteria was slightly less than that of the control β-lactem antibiotics.
2. Bactericidal activity of CAZ against S. aureus, E. coli and P. aeruginosa was confirmed through counting viable cells and determining the minimum bactericidal concentration (MBC).
3. CAZ was resistant to hydrolysis by various bacterial β-lactamases. Moreover, it was quite stable to cefuroxime hydrolysing enzymes which hydrolysed cefuroxime-type β-lactam antibiotics.
4. CAZ showed high affinity to PBPs, with stronger affinity to PBP3.
5. CAZ was the most effective in systemic infections in mice due to S. marcescens and P. aeruginosa. Also this compound showed much higher antibacterial activity than cefoperazone but not than cefotaxime against systemic infections in mice due to E. coli and K. pneumoniae.

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To clarify the mechanism of the strong antibacterial activities of ceftazidime (CAZ, SN 401) against Pseudomonas aeruginosa and Serratia marcescens, the penetrability through the outer membrane and the affinity to the penicillin-binding proteins were investigated with those microbes.
The MICs of CAZ were not much different to the β-lactamase-free mutant and the penetrabilityincreased mutant from that to the wild strain of P. aeruginosa that produces the type lb β-lactamase chromosomally. Whereas, MICs of benzylpenicillin and cefoperazone were higher to the wild parent strain than those to the mutants. The obtained results suggest that CAZ possesses a good penetrability through the outer membrane and high stability to the β-lactamase. In fact, CAZ bound well to the PBPs of P. aeruginosa either with the whole cells or the membrane fraction, regardless of the presence of penetration barrier of the outer membrane.
Since affinities to the PBPs of S. marcescens were almost same level in either CAZ or cefotaxime, it was suggested that the stronger activity of CAZ is based upon better penetrability through the outer membrane than the latter drug.

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Ceftazidime (CAZ, SN 401) manifested the most powerful antipseudomonal and antiserratia activities among cephem antibiotics ever known. The drug exhibited strong activities also against S. pyogenes, S. pneumoniae, Klebsiella spp., E. coli, Enterobacter spp., Citrobacter spp., P. mirabilis, P.vulgaris and P. morganii as high as those of other 3rd generation cephems. CAZ was confirmed to be not only stable to various β-lactamases but also possess lower binding affinities to the enzymes, resulting in rare resistant clinical isolates of gram-negative bacteria. The drug possessed the binding affinities to the penicillin-binding proteins (PBPs) 3, 1a, 1b and 2 in order either in E. coli or P. aeruginosa, indicating that the drug may manifest a strong bactericidal effect. Moreover, CAZ demonstrated a marked synergy of bactericidal effect with the serum complement and cultured macrophages derived from ICR mice. The obtained results suggested that CAZ is expected a good in vivo effect.

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The antibacterial activity of ceftazidime (CAZ, SN 401) was compared with that of other cephem antibiotics, against a total of 1, 188 bacterial strains of Staphylococcus, Streptococcus, E. coli, Klebsilla, Serratia, Enterobacter, Citrobacter, Proteus, Pseudomonas, Acinetobacter, Achromobacter, Flavobacterium, Alcaligenes, Peptococcus, Clostridium, and Bacteroides, all isolated from various clinical materials in 1980 and 1981, and the following results were obtained:
1. CAZ had the characteristics of the ‘third generation’ cephem antibiotic showing comparatively low activity against Gram-positive cocci, and high activity against Gram-negative bacilli.
2. CAZ was highly active against E. coli, Klebsiella, Clostridium perfringens, Proteus mirabilis, Proteus vulgaris and Proteus inconstans and was also comparatively active against Pseudomonas putrefaciens, Serratia, Proteus rettgeri, Proteus morganii, Pseudomonas aeruginosa and Pseudomonas cepacia.
3. The antibacterial activity of CAZ against Pseudomonas aeruginosa and Pseudomonas cepacia was remarkably high compared with the conventional cephem antibiotics.

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The in vitro and in vivo antibacterial activity of a new cephalosporin, ceftazidime (CAZ, SN401) was compared with other cephalosporins against gram-positive and negative bacteria.
CAZ had a broad antibacterial spectrum; especially it was more active than or as active as cefmenoxime against indole-positive Proteus (P. vulgaris, P. morganii, P. rettgeri, P. incostans) and E. cloacae. CAZ was shown to have greater activity than other cephalosporins against Serratia, P. aeruginosa, P. cepacia, Acinetobacter calcoaceticus, Achromobacter xylosoxidans.
CAZ was as stable as latamoxef to inactivating enzymes (penicillinase and cephalosporinase) which were produced by facultative anaerobes. However, it was as unstable as cefmenoxime to inactivating enzymes produced by B. fragilis; its stability was not so good as that of cefmetazole and latamoxef.
In a protection test in mice, CAZ was as effective as cefmenoxime and latamoxef in the infections due to E. coli, Klebsiella, and it was more effective than cefmetazole and cefazolin. In Serratia infections, CAZ was not affected by inoculum size and its effectiveness was equivalent or superior to to cefmenoxime and latamoxef. The effects of CAZ in P. aeruginosa infections were superior to those of cefmenoxime, latamoxef, cefoperazone and cefsulodin.

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Ceftazidime (CAZ, SN 401) showed high antibacterial activity against most of anaerobic bacteria except for the strains of β-lactamase producing Bacteroides fragilis group and Fusobacterium varium, Fusobacterium mortiferum, Eubacterium lentum and Clostridum difficicile. The activity of CAZ against recent clinical isolates was as strong as that against the standard strains.
When the bacteria were serially subcultured in the drug-contained medium, resistance was increased step by step, but the increasing rate of the resistance to the drug was higher in non β-lactamase producing B. fragilis than in β-lactamase producing B. fragilis.
CAZ was less stable to β-lactamase produced by B. fragilis than cefbuperazone (T-1982) and cefotaxime (CTX) but more stable thar cefazolin (CEZ), cefoperazone (CPZ) and cefpiramide (CPM).
In the protection test against the experimental intraperitoneal infections with B. fragilis in mice, CAZ was inferior to cefmetazole (CMZ) and comparable to CPZ when the challenge organisms were β-lactamase producing ones. When the challenge organisms were non β-lactamase producing ones, however, CAZ showed high elimination effects, comparable to those of CMZ, even in the small dose groups. The bacterial elimination efficacy of CAZ in the kidney, in particular, was stronger than that of CMZ.
Increase of C. difficile by CAZ in cecum of mice was only minor.

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Bacteriological evaluation was attempted on ceftazidime (CAZ, SN 401), a new cephem antibiotic, with cefotiam (CTM), ceftizoxime (CZX). cefmetazole (CMZ), cefsulodin (CFS), cefoperazone (CPZ), and gentamicin (GM) as the control drugs. CAZ showed a broad antibacterial spectrum against gram-positive and gram-negative bacteria, but its antibacterial activity against gram-positive bacteria was inferior to that of CTM, CZX, and CMZ. Against gram-negative bacteria, however, the antibacterial activity of CAZ, although slightly inferior to that of CZX, was practically equivalent or superior to that of CTM and apparently superior to that of CMZ. Also CAZ was found to possess potent antibacterial activity against indole-positive Proteus spp., Serratia, and P. aeruginosa.
Studies were also conducted on the influence of various factors on antibacterial activity of CAZ, and it was recognized that the drug is hardly affected by pH of culture, addition of horse serum, or inoculum size. Studies on the mode of the antibacterial activity of CAZ revealed its marked bactericidal action against any one of the bacterial strains used. As a result of investigation on the affinity of CAZ to penicillin binding proteins (PBPs), it was observed that the affinity was in the order of PBP 3, lBs, and 1A in E. coli and PBP 1A, 1B, and 3 in P. aeruginosa, and these findings conformed well to the results of morphological changes under drug action.
As to the therapeutic effects in experimental intraperitoneal infections in mice, those of CAZ against S. aureus were inferior to those of CTM, CZX, and CMZ. On the other hand, CAZ was undoubtedly superior to CTM or CMZ and equivalent or slightly inferior to CZX against gram-nagative bacteria such as E. coli, Klebsiella, and Serratia. Against P. aeruginosa, CAZ was superior to GM, CFS, and CPZ and, furthermore, showed an excellent efficacy against GM-resistant strains as well.

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Effects of ceftazidime (CAZ, SN 401), a new cephem antibiotic, were compared with those of conventional antibiotics in the experimental local infections in mice, in an attempt to find out the most effective dose regimen.
In the investigation made on the effects of CAZ against models of experimental urinary tract infections produced with E.coli and Serratia in mice, CAZ was more effective than cefotiam, ceftizoxime, or cefmetazole. In the case of P.aeruginosa, CAZ was more effective than cefsulodin or cefoperazone and less effective than gentamicin. As to the influence of dosage frequency on the therapeutic efficacy, CAZ was more effective when it was repeatedly administered; thus, duration of the effective concentration of the drug was considered to be an important factor that decides the therapeutic efficacy of CAZ. Our studies using models of experimental respiratory infections produced with K.pneumoniae in mice revealed that CAZ was superior to cefotiam or cefmetazole and practically equivalent or slightly superior to ceftizoxime. In this infection also, higher therapeutic efficacy of CAZ was obtained by its repeated administration.

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Laboratory investigations were carried out on ceftazidime (CAZ, SN 401), a new semisynthetic cephalosporin.
CAZ showed a potent activity against clinically isolated gram-nagative bacilli. Especially, it showed excellent antibacterial activity against P.aeruginosa and S.marcescens. Moreover, it was active against indole-positive Proteus spp., E.cloacae, C.diversus and C.freundii.
The addition of subinhibitory concentration (1/2 MIC) of ethylenediaminetetraacetic acid (EDTA) caused little change in the MIC of CAZ for P. aeruginosa and no change in the MIC of CAZ for S.marcescens, whereas marked reduction in MICs of CEZ and benzylpenicillin for both strains was observed by the addition of subinhibitory concentration of EDTA.
The potent activity of CAZ against both strains is considered, at least in part, to be due to the higher permeability of the outer membrane of these organisms.

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Ceftazidime (CAZ, SN 401), a novel aminothiazolyl cephalosporin, has higher antibacterial activity than cefazolin (CEZ) against a wide variety of gram-negative organisms.
The effects of CAZ on cross-linked peptidoglycan synthesis was investigated and compared with those of CEZ, using ether-treated cells of Pseudomonas aeruginosa KM 338, Serratia marcescens IFO 12648 and Escherichia coli K 12.
The minimum inhibitory concentrations of CAZ against these organisms were 6.25. 0.2 and 0.1μg/ml, whereas those of CEZ were 51, 200, 6, 400 and 1.56μg/ml, respectively.
The cross-linking reaction of peptidoglycan synthesis in P.aeruginosa and S. marcescens was inhibited by CAZ at lower concentration than that of CEZ. The concentrations of CAZ and CEZ for 50% inhibition were 0.19 and 32μg/ml against P.aeruginosa, and 21 and 82μg/ml against S.marcescens, respectively. On the other hand, the concentratison of these antibiotics for 50% inhibition were both 3.7μg/ml against E.coli.

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Experimental studies on ceftazidime (CAZ, SN 401), a new injectable cephem antibiotic, was made in vitro and in vivo. The results obtained were as follows:
Minimum inhibitory concentrations (MICs) of ceftazidime against clinical isolates of various strains were compared with those of cefotaxime, ceftizoxime and cefoperazone. As far as staphylococci were concerned, ceftazidime was found to be not so active as the other 3 drugs. As to Gram-negative bacilli, ceftazidime was almost as active as cefotaxime and ceftizoxime against indole-positivie Proteus, although it was slightly less active against a number of strains of Enterobacteriaceae. Against S.marcescens, ceftazidime was marginally less active than ceftizoxime, but it was more active than cefotaxime. Ceftazidime was superior to cefoperazone in its activity against all the strains studied. Against P. aeruginosa, it was shown to be even superior to cefsulodin, no need to say of its superiority over the above 3 antibiotics. Ceftazidime inhibited growth of 10 out of the 15 strains studied at the concentration of 1.56μg/ml or lower. Following an intravenous dose of 100mg/kg of ceftazidime in 5 rabbits with S.aureus meningitis, the peak serum levels were achieved at 15 min. in all the animals, and the mean serum level was 107μg/ml. The mean peak level of ceftazidime in cerebrospinal fluid (CSF), was 10.4μg/ml, which was attained at 45 min. on the average after the administration. The CSF/serum ratio was 9.72%. The mean serum half-life of ceftazidime was 49.6 min. and its half-life in CSF was 138 min. Its CSF/serum ratio was 2.78 and the CSF/serum ratios of AUC (areas under the curve) were 11.7% in 15-60 min., 16.2% in 15-120 min. and 19.4% in 15-480 min.
The above results indicate that penetration of ceftazidime is one of the best of those exhibited by various β-lactam antibiotics. When MIC is also taken into consideration, these results strongly suggest high possibility of the excellent clinical effects of ceftazidime against meningitis caused by S. pneumoniae and gram-negative bacteria, and they are considered to have offered sufficient grounds for the clinical use of ceftazidime in patients with meningitis.

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The in vitro antibacterial activity of ceftazidime (CAZ) was assessed against recent clinical isolates of gram-negative bacteria.
The activity of CAZ was compared with the activity of cefazolin (CEZ), cefmetazole (CMZ), gentamicin (GM) and amikacin (AMK). Against C.freundii, CAZ was more active than other 4 drugs. CAZ against S.marcescens was more active than GM and AMK.
Against Pseudomonas group, the activity of CAZ was comparable to GM and AMK and superior to other cephalosporins; CEZ and CMZ.

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We studied in vitro and in vivo antibacterial activity of ceftazidime (CAZ, SN401) comparing with that of cefazolin, cefmetazole, cefotaxime, cefuroxime, cefoxitin, cefoperazone, latamoxef, cefsulodin and gentamicin, and obtained the following results.
1. CAZ showed broad spectrum and high antibacterial activity against Gram-positive and negative bacteria.
2. In particular, it showed high antibacterial activity against Gram-negative bacteria, which was almost equivalent to that of cefotaxime, cefoperazone and latamoxef, and higher than that of these drugs against S. marcescens.
3) Antibacterial activity against P.aeruginosa was comparable to that of aminoglycoside antibiotics, higher than that of cefsulodin and cefoperazone which are anti-pseudomonal cephems.
4. CAZ was highly stable to β-lactamses produced by various Gram-negative bacteria.
5. The antibacterial activity of CAZ was bactericidal and which was little affected by kinds or pH of media, inoculum size, etc.
6. In a protection test in mice, excellent effects were obtained, reflecting the high in vitro antibacterial activity of CAZ.

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Ceftazidime (CAZ, SN401), a new parenteral cephalosporin antibiotic, was administered to 14 healthy male volunteers to study its tolerance and pharmacokinetics, by intramuscular injection (0.5g), 1-hour intravenous drip infusion (1g and 2g, in a cross over method), 2-hours intravenous drip infusion (2g), intravenous bolus injection (0.5g and 1g, in a cross over method) and multiple intravenous bolus injection (1g, at 12 hour intervals, 9 times).
1. In the examinations on tolerance such as subjective and objective symptoms, physical examinations, haematology, serum biochemistry, urinalysis, etc., no abnormalities attributable to CAZ were noted.
2. CAZ achieved high plasma levels after intramusclar and intravenous injections, corresponding to the increase of the administered dose. The plasma half life of CAZ was 1.6-2.1 hours, which was comparatively long, and even at 8 hours after administration, 0.9-5.7μg/ml of CAZ was detected in plasma.
3. CAZ was not inactivated in the body and about 90% of the dose was excreted within 12 hours after administration regardless of dose levels or administration routes.
4. In multiple dose of CAZ (1g of i. v. bolus injection, 9 times, 12 hourly), there was no variation in the plasma level and urinary excretion level, nor tendency to accumulation.
From the above results, CAZ was considered to be a safe drug with favorable pharmacokinetics, and from its high antibacterial activity, CAZ was expected to be a clinically effective drug in various infections.

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Ceftazidime (CAZ, SN401) is a new semisynthetic cephalosporin, with marked resistance to β-lactamase, low MICs for gram-negative bacilli, and a broad spectrum of antibacterial activity against various species of pathogenic bacteria, including Haemophilus influenzae, Enterobacter cloacae Citrobacter freundii, Serratia marcescens, indole-positive Proteus, and Pseudomonas aeruginosa. The patients, 11 females and 6 males aged from 11 to 85 years, were treated with CAZ during the period from Aug.´81 to Feb.´82 in the Department of Surgery, Tenshi Hospital. The patients include 11 with acute peritonitis (10 due to acute appendicitis and 1 to cecal CROHN's disease), 5 with acute or subacute cholecystitis and cholangitis due to cholelithiasis, and 1 with fistula ani. 1 g of CAZ was given intravenously in 17 cases before operation. During the operation, blood, bile, ascites and tissue specimens were taken and these were sent to the Research Laboratories of Shin Nihon Jitsugyo Co., Ltd. for determination of CAZ concentration by microbioassay using Proteus mirabilis ATCC 21100 as the test organism.
The new knowledge obtained from this study on the CAZ concentrations in infected tissues is as follows:(i) Given at a dose of 1 g intravenously before opration, CAZ concentrations in common duct bile increased quickly in about 1 to 2 hours, reaching the maximum level of 24.5μg/ml, then declined slowly.(ii) CAZ penetrated into bile through gallbladder wall, in the cases of bile duct obstruction, and achieved comparatively high level quickly after injection.(iii) CAZ achieved high levels in gallbladder wall ranging from 17.5 to 42.2μg/g at 28 to 65 minutes after injection.(iv) In infected appendix wall, CAZ reached high levels quickly after injection.(v) Concentrations of CAZ in the gallbladder wall and appendixes, were directly proportional to the degree of the pathological changes of inflammation.(vi) The CAZ concentrations in purulent ascites, common duct bile, gal. lbladder bile, gallbladder wall, infected appendix, pus in the appendix and other infected tissues were higher than the MICs for Escherichia coli and Klebsiella pneumoniae after 1 g of CAZ intravenous administration.
Therefore, CAZ appears to be a very useful drug when used for chemotherapy of acute peritonitis, biliary tract infections and abdominal infectious diseases.

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1. Seven healthy male volunteers received either ceftazidime (CAZ, SN401) and cefotiam (CTM) or CAZ and cefoperazone (CPZ) in a cross over method for the comparative study on pharmacokinetics. All the drugs were administered intravenously.
1) Four of the volunteers received each 1g of CAZ and CTM by intravenous bolus. The beta half lives were 1.50 hrs for CAZ and 0.94 hr for CTM, and the urinary recovery rates up to 8 hrs were 91.5% and 72.9%, respectively. Semen concentrations of CAZ and CTM at 8 hrs were 1.46μg/ml and 1.16μg/ml respectively, and at 24 hrs the concentration of CAZ was 0.42μg/ml but CTM was not detected.
2) Five of the volunteers received each 1g of CAZ and CTM by drip infusion for 30 min. The peak serum concentrations of CAZ and CTM were 77.8μg/ml and 61.3μg/ml, the beta serum half lives, 1.60 and 0.96 hr, and the urinary recovery rates up to 12 hrs were 76.3 and 65.2%, respectively.
3) Five of the volunteers received CAZ in the doses of 0.5g and 1g, and CPZ at 1g, by drip infusion for 30 min. The peak serum concentrations were 42.6μg/ml, 92.1μg/ml and 102.4μg/ml, the beta serum half lives were 1.49, 1.66 and 1.74 hrs, and the urinary recovery rates up to 12 hrs were 91.8%, 83.1% and 27.2%, respectively.
Urine samples were collected every 2 hrs in the above studies 2) and 3), for the study on antibacterial activity of these antibiotics in the urine. As the test organisms, E.coli and K. pneumoniae, both with comparable sensitivity to CAZ and CTM, were used in the study 2), and E. coli and P. aeruginosa, which show comparable sensitivity to CAZ and CPZ, in the study 3). Comparison of the bacterial growth inhibitions in various dilutions of urine samples revealed that CAZ had the highest antibacterial activity in the urine. This is considered to be partly due to comparatively short half life of CTM and to the low urinary recovery rate of CPZ.
2. CAZ was administered intravenously to 2 male rabbits, one dehydrated and the other overhydrated, in the dose of 1g, and the drug concentrations in serum and organ tissues were determined. On the whole, CAZ concentrations were higher in the dehydrated rabbit, and particularly high in its testis and prostate gland.

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Ceftazidime (CAZ, SN401) was given to mice, rats and rabbits at a dose of 20mg/kg for the study on absorption, distribution, metabolism and excretion, and the following results were obtained.
1. Following s. c. injection in mice, and i. m. injection in rats, the plasma levels of CAZ quickly rose and the peak level was attained at 15-30 min. after the administration. Penetration of the drug into organs was very rapid and the highest concentration of the drug was observed in kidney. The CAZ concentrations in rats after i. v. administration were high in the order of those in kidney, plasma, lung, myocardium, spleen and liver.
2. When multiple doses of CAZ were given to rats by i. v. injection for 7 days, the drug concentrations in plasma and organs, and urinary excretion were not different from those after a single dose, and no tendency toward accumulation was observed.
3. In exudate taken from granuloma pauches in rats, the peak level of 5.8μg/ml was achieved at 1 hour after a single i. v. injection. This was higher than the peak level of 2.8μg/ml achieved by CEZ.
4. Plasma concentration of CAZ was compared with that of CEZ in rabbits in a cross over method. The peak plasma level of CAZ was lower than that of CEZ in both cases of i. m. and i. v. injections, but half life of CAZ was longer than that of CEZ, and the plasma level of CAZ was higher than that of CEZ at 1 hour after i. v. injection.
5. Urinary recovery rate (0-24 hrs.) was 58.5% after subcutaneous injection in mice, 72.5% after i. v. injection in rats, 66.8% after i. m. injection in rats, 77.8% after i. v. injection in rabbits and 76.7% after i. m. injection in rabbits; most of the drug was excreted within 0-3 hrs. The biliary recovery rate of CAZ up to 24 hrs. in rats was only 0.22%, and therefore, the mechanism of excretion of the drug was thought to be done mainly through kidney.
6. Investigation was made for active metabolite of the drug by bioautography. As a result, no metabolite was observed in plasma, urine or bile.
7. Serum protein binding of CAZ was low, ranging from 26.6%(rabbits) to 13.1%(dogs). It was 20.9% in humans.

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The antibacterial activity of ceftazidime (CAZ, SN401), a new cephem antibiotic, was examined against clinical isolates using the plate dilution method with inoculum size of 10⁶cells/ml. The MICs of the drug were≤0.4μg/ml for E. coli and K.pneumoniae, ≤0.02μg/ml for P.mirabilis and P.morganii, ≤0.8μg/ml for S.marcescens, and≤6.3μg/ml in 91.3% of P.aeruginosa. Pharmacokinetics of CAZ in 6 healthy adults were investigated. Serum levels following intravenous administration of thedrug at a dose of 1.0gwere 173*u;g/ml at 5 min., 90μg/ml at 30 min., 63μg/ml at l hour, 10μg/ml at 4 houms and 2.4μg/ml at 8 hours, respectively, by bioassay method. The β-phase biological half life of the drug was estimated to be 1.6 hours. Cumulative urinary excretion of the drug was 90.2% within 8 hours.
Twenty one patients with infections were treated with CAZ administered by intravenous drip infusion in two divided dose of 2.0g per day for 7-17 days. Excellent response was obtained in 120f these patients, good in 6, fair in 2 and poor in 1. The efficacy rate was 85.7%. No clinical side effect occurred and in only one patient elevated transaminase was observed. CAZ is considered to be an effective and well tolerated drug for infected patients.

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Ceftazidime (CAZ, SN401) was given by drip infusion to a total of 11 patients with intractable chronic respiratory infections, namely 6 patients who had not responded to other antibiotics and 5 patients with severe conditions, and the clinical efficacy and safety of the drug were evaluated.
1. The clinical efficacy was assessed as excellent in 3 cases, good in 4, fair in 3 and poor in 1, with the efficacy rate 63.6%.
2. In the cases of the intractable chronic respiratory infections caused by Pseudomonas aeruginosa, the treatment with a high dose of 2g twice daily, i. e. a total of 4 g per day, was found to be more effective than 2 g daily.
3. In the 5 cases of infections caused by P.aeruginosa, the causative organism became negative in 1 case, decreased in 2 cases and no change was observed in 2 cases. In the 3 cases of Klebsiella pneumoniae infections, the causative organism was eradicated in 2 cases, and no change was obtained in 1 case. The organism was decreased in the case of Enterobacter cloacae infection.
4. No adverse effect developed in any patient, and an abnormality in laboratory findings was observed in only 1 case as a slight increase in eosinophil.

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Ceftazidime (CAZ, SN401) was evaluated for its clinical efficacy in 28 patients, namely, 10 with pneumonia, 3 with acute cystitis, 5 with chronic cystitis, 6 with acute pyelonephritis, 2 with chronic pyelonephritis and 2 with acute cholecystitis.
The clinical response obtained was excellent in 9 patients, good in 15, fair in 1 and poor in 3. Out of 24 strains assumed to be causative organisms, 21 strains of organisms were eradicated and 1 decreased in number and the others were replaced.
The only side effect noted was exanthema in 1 patient. Laboratory abnormalities were mild erythropenia and slight elevation of GPT in 1 case each. From the above results, the drug was considered to be useful in respiratory tract infections and urinary tract infections.

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To evaluate the clinical efficacy of ceftazidime (CAZ, SN401), a newly developed cephalosporin, in the treatment of bacterial infections, CAZ was administered to 14 patients with chronic respiratory tract infections, mostly with some underlying diseases. In all of the patients, pathogenic organisms were isolated from their sputum: namely, P.aeruginosa (11 cases), H.infiuenzae (4), P.maltophilia (1) and E.cloacae (1). These patients were given 2 to 6 g of CAZ daily in 2 divided doses by drip infusion. Pathogenic organisms isolated from sputum were eradicated in 10 out of the 14 cases (Efficacy rate: 71%) after the treatment with CAZ. The overall assessment of clinical efficacy of CAZ was found to be excellent or good in 9 cases out of the 14 cases (Efficacy rate: 64%).
Ceftazidime is, therefore, expected to be a remarkable therapeutic antibiotic for the treatent of intractable respiratory infections especially caused by P. aeruginosa.

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In vitro antimicrobial activity of ceftazidime (CAZ, SN401), a new derivative of cephalosporin, was examined by a broth dilution method with Dynatech MIC 2000 system. Also, the therapeutic efficacy of CAZ was evaluated in patients with respiratory tract infections.
The minimum inhibitory concentrations (MICs) of CAZ were compared with those of cefazolin (CEZ), cefmetazole (CMZ), ceftizoxime (CZX), cefsulodin (CFS), piperacillin (PIPC) and sulbenicillin (SBPC), against the following 100 strains (each 20 strains) of clinical isolates of S.aureus, E.coli, K.pneumoniae, S.marcescens and P.aeruginosa. Against S.aureus, CAZ was shown to be less active than CEZ, CMZ and CZX. In contrast, CAZ was far more active than CEZ and CMZ, although slightly less active than CZX, against E.coli, K.pneumoniae and S.marcescens, and more active than CZX, CFS, PIPC and SBPC against P. aeruginosa.
Eight patients were treated with intravenous drip infusion of CAZ at the doses of 1-2g twice a day. Two patients were excluded from the evaluation of the therapeutic efficacy of CAZ because one died from rapid progress of lung cancer shortly after start of the CAZ treatment of secondary infection and the other, who was d suspected case of lung abscess, showed no evidence of secondary infection and was diagnosed as the case of lung cancer. In the remaining six patients, response to the treatment with CAZ was good in 2 and fair in 2 and poor in the other 2. Neither undesirable symptoms nor abnormal laboratory findings were observed during or after the administration of CAZ.

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Clinical investigations were performed on Ceftazidime (CAZ, SN401), a new broad spectrum cephalospor in.
Ceftazidime was administered to a total of 11 patients with respiratory tract infections (8 with pneumonia, 1 with lung abscess, 1 with panbronchiolitis and 1 with pyothorax). The drug was administered at a daily dose of 1g (5 cases) or 2g (6 cases) for 9 days (1 case) or 14 days (9 cases). Ceftazidime was discontinued after 4 days' therapy in 1 patient with pneumonia because of rash.
The following 3 potential pathogens were isolated from the sputum and pleural effusion of these patients at the start of the treatment with ceftazidime: 1 strain each of β-Streptococcus, S. aureus and B. fragilis. All of them were eradicated during the treatment with ceftazidime. The clinical response to the treatment with ceftazidime was excellent in 4 cases and good in 7 cases. A female patient with pyothorax by B.fragilis showed a pattern of fever like HERXHEIMER's reaction but she did not show any shock symptom. A slight elevation of serum transaminase was observed in 2 patients and rash in 1.
From the above results, it is concluded that ceftazidime is one of the most effective and useful antibiotics against severe RTIs.

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Clinical studies on ceftazidime (CAZ, SN401) were carried out and the following results were obtained.
Five patients with respiratory tract infections and 10 with urinary tract infections received ceftazidime, and the clinical response was excellent in 2 patients and good in 13.
There was no side effect considered to be attributable to this drug.
These results indicate that ceftazidime can be a new useful antibiotic with high clinical efficacy expected.

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In-vitro and clinical evaluations were carried out on ceftazidime (CAZ, SN401), a newly developed cephalosporin, and the following results were obtained:
The MICs of 142 strains of 10 species of clinical isolates were compared with those of the other cephalosporins (CPZ, CTX, CZX, CMX, LMOX, CMZ, CEZ) and gentamicin.
Antibacterial activity of ceftazidime against gram-negative bacilli was as high as those of the other antibiotics. Against P.aeruginosa and S. marcescens, in particular, ceftazidime exhibited the highest activity among the antibiotics studied.
In the clinical study, a daily dose of 1-2g of ceftazidime was given by drip infusion for 6-14 days to the patients with respiratory tract infections (4), urinary tract infections (2), cholecystitis (3), septicemia (1) and lymphadenitis purulenta of the neck (1). The clinical efficacy obtained was excellent or good in 8 out of the 11 cases (efficacy rate: 73%). Adverse effects were observed in 2 cases, i. e. transient elevation of S-GOT and S-GPT in 1 case and rash in the other 1 case, but the symptom disappeared in both the cases on withdrawal of the drug.

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Serum concentrations of ceftazidime (CAZ, SN401) were determined after intravenous injection of 1g of the drug in 4 aged patients.
The serum level at 5 minutes after injection reached over 100μg/ml. Serum half lives in 3 patients whose serum creatinine levels were below 1.5 mg/dl were 2.5, 3.5 and 5.1 hours, respectively. The patient with impaired renal functions (S-Cr: 2.5mg/dl, Ccr: 11.6) showed prolonged T_1/2 of 12.2 hours.
Ceftazidime was given to 14 patients (3 with pneumonia, 1 with bronchiolitis, 6 with pyelonephritis, 3 with biliary tract infections, and 1 with decubital infection). Thirteen responded satisfactorily.

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In vitro and clinical studies on ceftazidime (CAZ, SN401) were carried out and the following results were obtained:
The antibacterial activity of CAZ against E.coli (14 strains), Klebsiella (27) and Serratia (27) was compared with that of CMZ, and CAZ was found to be higher. Its activity was comparable to that of CFS against 24 strains of P.aeruginosa. The plasma concentration and the urinary recovery of CAZ were determined by 1-IPLC. The mean plasma concentration immediate after an i. v. dose of 1g was 138 μg/ml, and at 30 minites, it reached 62 μg/ml. The plasma halflife was 1.6-1.8 hours. The urinary recovery averaged 93% of the dose in the first 6 hours after injection.
As to the clinical response, CAZ was given to 9 patients with complicated urinary tract infections, and the results were assessed as good in 8 and fair in 1.
When CAZ was evaluated microbiologically, E.coli, Serratia, Proteus and Enterobacter were eradicated but no change was observed as to S. faecalis. From the above, CAZ was considered to have broad antibacterial spectrum against gram-negative bacilli including P.aeruginosa and to be highly useful in the clinical use.

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Ceftazidime (CAZ, SN401) was used in 11 patients with broncho-pulmonary infections and 2 with urinary tract infections. Deily doses of CAZ ranged from 1 to 2g.
Clinical effects in 5 cases of respiratory tract infections (bronchitis in 1 case and pneumonia in the other cases) accompanying lung cancer were assessed as fair in 4 cases and poor in 1. In 4 cases of pneumoniaccompanying bronchiectasis or chronic pulmonary emphysema, or that without underlying diseases, excellent response was observed in 1 case and good in 3. In the cases of lung abscess and diffuse pan-bronchiolitis (1 case each), clinical response was fair, but in the 2 cases of urinary tog infections, the clinical response was evaluated as excellent in 1 and good in the other.
Causative organisms were: P. aeruginosa (4 cases), K. pneumoniae (2), Serratia (1), E. coli (1) and unknown (5). After administration of CAZ, K. pneumoniae and E. coli were eradicated, Serratia was replaced, and P. aeruginosa eradicated in 1 case or decreased in 2, and replaced in 1. No evidence of side effect was noted.

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Clinical effectiveness of ceftazidime (CAZ, SN401), a new cephalosporin, was studied in 14 cases of infections.
CAZ was administered at a dose of 0.5-3g/day by intravenous infusion. The results were good in 3 (75%) out of 4 cases of respiratory tract infections, and excellent or good in 8 cases (80%) out of 10 urinary tract infections. Seven out of 8 cases of pseudomonal infections were cured. Adverse reaction to CAZ was observed in 1 case of slight elevation of GPT.

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Ceftazidime (CAZ, SN401) is a new parenteral aminothiazol cephalosporin, which possesses exceptionally high, broad-spectrum antibacterial activity, particulary against the strains of Pseudomonas aeruginosa, with high stability to a wide range of β-lactamases.
CAZ was used in the treatment of 6 cases of respiratory tract infectious diseases: 4 cases of pneumonia and 2 cases of diffuse panbronchiolitis (DPB). The ages of the patients ranged from 30 to 78 years (mean 54 years), and there were 4 males and 2 females.
CAZ was administered by intravenous drip infusion. The dose of the antibiotic varied from 1.0g 12-hourly to 2.0g 12-hourly and 2.0g 8-hourly depending on the severity of the infections. The duration of the treatment varied from 11 to 33 days (mean 18.5 days) and the total doses ranged from 22 to 184g (mean 56.7g).
Clinical responses were good in 3 cases of pneumonia, fair in each 1 case of pneumonia and DPB, poor in 1 case of DPB and unassessable in 2 cases (each 1 case of pneumonia and of DPB).
Bacteriological response was good in 2 cases of DPB but CAZ failed to eradicate P. aeruginosa (Mucoid strain) in 2 cases.
No adverse reactions to CAZ were observed during the study.
In conclusion, CAZ seemed to be an active and useful antibiotic in respiratory tract infections with no severe side effects.

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Ceftazidime (CAZ, SN401) was used in the treatment of 39 patients (male 23, female 16) with intractable respiratory tract infections who had been previously treated unsuccessfully with other antibiotics, and the clinical response and side effects of CAZ were evaluated. Most of the patients had infections caused by P. aeruginosa. The mean age of the patients was 60.7 years, and the mean body weight was 41.9kg; this background of the patients indicate that most of them were elderly, light in body weight. CAZ was administered by drip infusion in all the cases, 1g doses twice daily, in most cases. The mean duration of CAZ therapy was 24.7 days, and the mean total dose administered was 54.2g: both the dosage and the duration of CAZ treatment were large and long.
Efficacy rate was 57% in the 32 cases of airway infections and 43% in the 7 cases of serious pneumonia (6) and lung abscess (1).
When the efficacy of CAZ was assessed for each causative organism, CAZ was effective against P. aeruginosa in 12 cases out of the 20 (efficacy rate: 60%) with eradication rate 20%.
In the 4 cases of infections due to glucose non-fermentative Gram-negative bacilli, the efficacy rate was 75%, with eradication rate 25%. Besides, eradication occurred in the 1 case each of S. pneumoniae, H. influenzae, K. pneumoniae, S. marcescens and Bacteroides.
Adverse reactions such as transient skin rash and the elevations of GOT, GPT, Al-P and BUN were noted in 2.5-5%, but these were improved rapidly on with-drawal of CAZ.
In conclusion, CAZ is an effective antibiotic in the treatment of intractable respiratory tract infections mainly caused by P. aeruginosa.

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Laboratory and clinical studies were performed on a new cephem-antibiotic, ceftazidime (CAZ, S N401).
A sensitivity test using clinical isolates showed that the antibacterial activity of CAZ was higher than those of cefoperazone, cefmetazole and cefazolin against all of E. coli, Klebsiella, P. aeruginosa and a variety of Gram-negative rods.
Seven patients were treated with CAZ. The drug was given 0.5 to 1g b. i. d. for 2 to 10 days either by intravenous drip infusion or bolus injection.
Three cases were evaluated as good, two as fair, and two were unknown or unassessable. As one patient complained of nausea and vomiting, the treatment was stopped. An elevation of BUN and transient increase in eosinocytes were observed in one patient and a slight elevation of GOT in one patient.

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MICs of ceftazidime (CAZ, SN401) against 25 clinical isolates of S. aureus, E. coli, K. pneumoniae, P. mirabilis, E. cloacae, S. marcescens, H. influenzae and P. aeruginosa were compared with those of latamoxef (LMOX) and cefoperazone (CPZ), except H. influenzae and P. aeruginosa. For H.influenzae, LMOX and ampicillin (ABPC), for P. aeruginosa, CPZ, cefsulodin (CFS), cefpiramide (CPM) and gentamicin (GM) were used for comparison.
MICs of CAZ varied from 6.25-12.5μg/ml for S. aureus, which were about the same as those of LMOX, and for most strains of E. coli, K. pneumoniae and P. mirabilis, MICs of CAZ were ≤0.2μg/ml, which were also similar to those of LMOX and CPZ. For E. cloacae and S. marcescens, CAZ showed a wide range of MICs in the same order as those of LMOX and CPZ, but as for S. marcescens, the activity of CAZ was superior to that of the other 2 drugs. Against H. influenzae, MICs of CAZ were ≤0.2μg/ml, which were similar to those of LMOX and lower than those of ABPC. When compared with CPZ, CFS, CPM and GM, CAZ showed the MICs of ≤3.13μg/ml for 84% of P.aeruginosa, which indicated the highest activity among these drugs.
After 2g of CAZ was administered by 1 hour i. v. drip infusion to a patient with aseptic meningitis in the convalescent stage, the CAZ level in cerebrospinal fluid 7 hours after aministration was 1.80μg/ml, which demonstrated good penetration of CAZ into cerebrospinal fluid.
In the clinical evaluation, a total of 18 patients (7 with respiratory tract infections (RTI) comprising 6 with pneumonia and 1 with infected bronchiectasis, 2 with biliary tract infections (BTI), 6 with urinary tract infections (UTI), 2 with septicemia and 1 with meningitis) were treated with CAZ at a dose of 1.0g twice a day either one-shot intravenously or by drip infusion.
CAZ was effective in 5 out of the 6 cases of pneumonia and in 1 case of infected bronchiectasis due to E. coli. Also, clinical response of CAZ was evaluated as good in 1 case out of the 2 cases of BTI, and fair in the other, in which cholangioma was found as the underlying disease. In the 6 cases of UTI, clinical response was evaluated as excellent in 2 cases, moderate in 3, poor in 1 case. In 2 cases of septicemia and 1 case of meningitis, clinical response was good.
The strain of P. aeruginosa was isolated from 1 case of pneumonia and 3 of UTI, and the organisms were eradicated in 3 cases and replaced in 1 case by administration of CAZ.
Neither abnormality in laboratory findings nor clinical side effect was noted.

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Ceftazidime (CAZ, SN401), a new cephem antibiotic, was studied clinically. MICs of CAZ for clinical isolates of gram-negative bacilli were determined and compared with those of cefoperazone, ceftizoxime, latamoxef and cefotiam (or cefsulodin). CAZ inhibited the growth of all strains of E. coli, P. mirabilis and K. pneumoniae at ≤0.39μg/ml, ≤0.2μg/ml and ≤0.78μg/ml, respectively.
Ninety per cent and 96% of the strains of S. marcescens and indole positive Proteus were inhibited at ≤1.56 jig/nil of CAZ. MICs of CAZ for E. cloacae and C. freundii were 0.1-100≤μg/ml, and that for P. aeruginosa was 0.1-50μg/ml, showing the wide range of MICs. CAZ was most active against these 5 species.
The serum and urinary concentrations (Urinary recovery rate) of CAZ were determined in 4 healthy volunteers after 1g i. v. and were compared, in a cross-over manner, with those of cefoperazone. Influence of probenecid was also investigated. The serum concentration of CAZ 5 min. After an i.v. injection averaged 98.2μg/ml and the serum half-life (β phase) was 1.82 hrs. Urinary recovery rate up to 24 hrs. averaged 92.1%, 3 times higher than that of cefoperazone.
Total clearance of CAZ was 98.12ml/min., slightly higher than that of cefoperazone, but renal clearance of 90.33 ml/mm. was 4 times higher than that of cefoperazone. Almost no influence by probenecid was noted. CAZ was administered to a total of 7 patients; 4 with respiratory tract infections, each 1 with cholecystitis, peritonitis and urinary tract infections, at a daily dose of 1-4g for 6-14 days.
The clinical response was excellent in 1 case, good in 3, fair in 1 and poor in 2 cases.
No side effect was observed clinically, but a slight elevation of s-GOT and S-GPT was noted in each 1 case.

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Clinical efficacy of ceftazidime (CAZ, SN4O1), a new cephem antibiotic, was evaluated in patients with chronic bronchitis, by drip infusion of 1 g, b. i. d. In 8 cases of exacerbation of infections in chronic bronchitis, good response was obtained in 5 cases, poor in 3, with efficacy rate of 62.5%. Out of 3 cases evaluated as poor, 2 were prolonged intractable cases continually excreting P. aeruginosa. The other was also a prolonged intractable case accompanied with dyspnea.
Neither abnormality in laboratory findings nor clinical side effect was observed. From the above results, CAZ was expected to be highly useful in the treatment of infectious recurrence of chronic bronchitis.
In view of intractability of respiratory tract infections by P. aeruginosa, however, CAZ was considered worthwhile further studying in terms of dosage, administration method, etc., in order to find the best clinical application of the high in vitro activity of CAZ against P. aeruginosa.

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Ceftazidime (CAZ, SN401), a new parenteral aminothiazolyl cephalosporin, was evaluated clinically for 14 patients aged 46-80 years with respiratory tract infection (5 patients) and with urinary tract infection (9 patients). A daily dose of ceftazidime was 2-3g by intravenous injection twiice a day and dumtlon of ceftazidime therapy was for 5 to 14 days.
The results were as follows.
1. The clinical response to ceftazidime therpy of respiratory tract infection was good in 2 cases, poor in 3 cases and that of urinary tract infection was good in 6 cases, fair in 2 cases, and poor in 1 case. The efficacy rate was 57.1%.
2. Ceftazidime was clinically active autibiotic against Pseudomonas.
3. Erytherna, as a side effect, was transiently observed in one case. In the laboratory data, no significant side effect was observed after the administration of ceftazidme.

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Ceftazidime (CAZ, SN401) was studied in vitro and clinically and the following results were obtained.
1. In the in-vitro study, CAZ was most active among cephem antibiotics against clinical isolates of S. marcescens, P. aeruginosa, P. cepacia and Acinetobacter, and as active as CTX, CZX, and T-1982, against E. coli and K. pneumoniae.
2. CAZ was administered to a total of 11 patients; 6 with respiratory tract infections, 2 with urinary tract infections, 2 with septicaemia and 1 with cholecystitis.
The clinical efficacy was assessed in 10 of the 11 patients, and was rated as good in 6 patients, fair in 1, and poor in 3, with an efficacy rate of 60.0%.
3. Causative organisms were isolated from 4 patients. Their bacteriological response was ‘persisted’in 1 case and ‘unknown’ in 3.
4. During the CAZ treatment, skin rash and elevation of GOT and GPT were noted in two indirividual cases but both of them were mild.
5. CAZ will prove to be even more useful if it is used in selected cases.

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Ceftazidime (CAZ, SN401), a new cephem antibiotic, was investigated for antimicrobial activity, absorption and excretion, and clinical effects. The following results were obtained.
1) CAZ had high activity against strains of E. coli, K. pneumoniae, P. mirabilis and P. aeruginosa, isolated from patients, and the peaks of the MIC distribution for these strains were at 0.2μg/ml, 0.2μg/ml, 0.1μg/ml and 3.13μg/ml, respectively. CAZ was slightly less active against S. aureus and the MIC distribution peak was at 12.5μg/ml.
2) Absorption and excretion: When 1.0g of CAZ was administered to each of two patients with normal renal function by a 1-hour intravenous drip infusion, the serum levels reached 82.6μg/ml and 88.6μg/ml respectively, at the time when the infusion was over. The serum levels declined rapidly and were 2.8μg/ml and 3.6μg/ml, respectively, after 8 hours.
Urinary recovery rate in the first 8 hours was about 85% after d. i. v. administration of 1.0g of CAZ.
3) Clinical results: 3 cases of acute pyelonephritis were treated with CAZ in the dose of 2.0g per day for 14 days. These cases were assessed as ‘effective’ cases. No abnormal laboratory findings or adverse effects due to CAZ were observed.

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Ceftazidime (CAZ, SN401) is a new parenteral aminothiazolyl cephalosporin with high broad specrtum antibacterial activity. CAZ was administered for the treatment of 20 episodes in 17 patients with respiratory tract infections, 4 episodes of sepsis and 5 episodes in 4 patients with other bacterial or suspected infections. These patients received the antibiotic for the period ranging from 7 to 69 days at the daily doses of 0.5 to 6g. Twenty-three of the 29 episodes responded well to the therapy with CAZ.
The isolated causative organisms were 4 strains of H. influenzae, 2 strains of P. aeruginosa and K.pneumoniae, and each 1 strain of Serratia, A.hydrophila, P. morganii, E. aerogenes and S. aureus. In all strains except for E. aerogenes and 1 of the 2 strains of P. aeruginosa, causative organisms were eradicated by CAZ. MICs were determined for 7 of those strains, and the MICs for E. aerogenes ranged from 25 μg/ml (10⁶CFU/ml) to 100μg/ml (10⁸CFU/ml). The MICs for the other 6 strains were 1.56μg/ml or lower with inoculum of 10⁶CFU/ml.
The pharmacokinetic behaviour of CAZ was evaluated in 4 patients. In 2 patients with normal renal functions, the peak serum concentrations following 1g CAZ intravenous infusion (60 and 77 minutes) were about 60μg/ml, which was achieved at the completion of injection. The serum levels ranged from 2.3 to 3.5μg/ml at 8 hours after the administration. In 2 patients with serious renal disfunction (32 and 5 ml/min. of creatinine clearance), the peak serum concentrations were about 90μg/ml after an intravenous injection, followed by the serum levels above 20 and 40μg/ml which were sustained for 8 hours and 19 hours, respectively.

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Ceftaziclime, (CAZ, SN401), a new broad-spectrum injectable cephalosporin, was studied in 21 patients: 20 with respiratory tract infections and 1 with urinary tract infection, and the following results were obtained.
CAZ was used intravenously in all; at a dose of 1.0g or 2.0g twice a day, in principle, in patients with normal renal function, and at a dose of 1.0g once a day in the patients with renal insufficiency.
The clinieal response of CAZ Was excellent in 4 patients, good in 14, fair in 2 and poor in 1.
No clinical side effects were observed. Laboratory tests revealed an elevation of transaminases in 5 cases, a decrease in WBC counts in 2 casses and eosinophilia in 1 case, but all these were only mild and alleviated rapidly following termination of the CAZ therapy. No severe side effects caused by the drug were observed.

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Serum and urinary levels of ceftazidime (CAZ, SN401) after a single dose of 1g administered by 1 hour continual infusion at fixed speed were determined by bioassay and HPLC in 4 healthy volunteers. The serum levels determined by HPLC were higher than those by bioassay; the regression formula was y=0.798x+1.19, though the correlation coefficient was 0.992. As to the urinary levels, the results obtained by both the methods were in good agreement with each other: the regression formula was y=0.994x-0.0268 and the correlation coefficient was 0.984. The mean serum levels of CAZ reached the peak at the completion of the infusion and they were 61.2μg/ml by bioassay and 77.0μg/ml by HPLC. The levels 8 hours after were 1.15μg/ml by bioassay and 1.17μg/ml by HPLC. The serum half-life of the β-phase of CAZ obtained by pharmacokinetic analysis using the results by bioassay was 1.54 hours and that by HPLC was 1.42 hours. Urinary recoveries of CAZ up to 8 hours were 77.4% by bioassay and 80.5% by HPLC.
CAZ was administered to 9 patients with various infections and clinical efficacy was assessed in 8 patients, excluding 1 with tuberculous peritonitis. All the 5 patients with urinary tract infection and 1 patient with septicemia caused by acute pyelonephritis had underlying diseases (diabetes mellitus; 1, cerebral infarction; 4, both of them; 1). Clinical and bacteriological response to CAZ was: excellent in 1 case with septicemia out of the 3 cases of infections caused by E. coil and good in the other 2: The response obtained in 1 case of polymicrobial infections due to E. coli and Klebsiella was good, and that in 2 cases of infections caused by P. aeruginosa was fair. The efficacy was assessed as good in 1 patient with secondary infection of pulmonary emphysema caused by P. aeruginosa and in 1 with biliary tract infection who had gall stone. Drug fever occurred in 1 patient, but no abnormality was noted in laboratory data.

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The authors have carried out in-vitro and clinical evaluations of ceftazidime (CAZ, SN 401), a new semisynthetic cephalosporin antibiotic.
The antibacterial activity of CAZ was compared to that of cefotaxime (CTX), cefmenoxime (CMX), cefoperazone (CPZ) and gentamicin (GM), against a total of 156 clinically isolated strains of S. aureus, E. coil, K. pneumoniae, Enterobacter, S. marsescens, Proteus, and P. aeruginosa.
The antibacterial activity of CAZ against S. aureus, E. coil, K. pneumoniae, Enterobacter, S. marsescens and Proteus was comparable to those of CTX and CMX. Against P. aeruginosa, it was comparable to that of GM and more active than CTX, CMX and CPZ.
CAZ was administered to a total of 17 patients: 16 with respiratory tract infections (RTI) and 1 with urinary tract infection (UTI).
The clinical results obtained were excellent or good in 14 (87.5%) out of the 16 cases of RTI and good in the case of UTI.
No side effect of the drug was observed.

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Ceftazidime (CAZ, SN 401), a new cephalosporin derivative recently developed by Glaxo Group Research in the U. K., was examined for its antibacterial activity as well as for its clinical usefulness.
The results obtained were as follows:
1. In vitro antibacterial activity against standard strains and clinical isolates: MICs of the drug against S. aureus strains ranged from 3.12 to 25 μg/ml. MICs of the drug against E. coli, K. peuinoniae and Proteus strains were lower than those of CXM, CMZ and CEZ, and P. aeruginosa and Serratia were very sensitive.
2) Clinical results: CAZ (1-2g×2/day by drip infusion) was given to six patients with bacterial infections, including 3 cases of respiratory tract infections, each 1 case of biliary tract infections, perinephritis and typhoid fever.
Three of the cases, i. e. typhoid fever, pneumonia and perinephritis, well responded to the therapy.

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We assessed the in vitro antibacterial activity against clinical isolates, clinical efficacy and safety of ceftazidime (CAZ, SN401), a new cephem antibiotic developed by Glaxo in the UK, and obtained the following resutls.
1. Susceptibility of clinical isolates to CAZ: With the inoclum size of 10⁶ CFU/ml, the peak distribution of MICs of CAZ was found at 12.5 μg/nil for S. aureus, 0.2 μg/ml for E. coli, 0.2μg/ml for K. pneumoniae, 0.025μg/ml or below for P. mirabilis and P. vulgaris, and 1.56μg/ml for P. aeruginosa. The antibacterial activity of CAZ against Proteus sp. and P. aeruginosa was affected by inoculum size, and with 108 CFU/ml, the activity of CAZ was reduced. 2. CAZ was administered at a daily dose of 2 g to a total of 10 patients: 1 with septicemia, 2 with pneumonia, 1 with lung abscess, 3 with infected to lung cancer, 1 with chronic obstructive pulmonary disease with infection, 1 with diffuse panbronchiolitis and 1 with pulmonary tuberculosis. The clinical results of the 9 cases excluding 1 case of pulmonary tuberculosis were evaluated as excellent in 2 cases, good in 4, fair in 2, and 1 as unassessable case.
In all cases, no side effect was noted.

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Antimicrobial activity, human pharmacokinetic properties and clinical efficacy of ceftazidizne (CAZ, SN401), a newly developed injectable cephalosporin, were evaluated and the following results were obtained.
1) Antimicrobial activity of CAZ against various clinically isolated strains was compared with that of ceftiam and cefmetazole. Though antimicrobial activity of CAZ against S. aureus was inferior to cefotiam and cefmetazole, against E. coli, K. pneumoniae, H. influenzae, P. mirabilis, indol positive proteus and S. marcescens, CAZ was more active than cefotiam and cefmetazole, with the peak MICs ranging 0.05-0.18μg/ml. CAZ was more active than any other cephalosporins against glucose nonfermentative gram-negative bacteria such as P. aeruginosa, P. cepacia and Acientohacter.
2) The peak serum levels of CAZ after 1-hour intravenous drip infusion of 1.0g were 65 and 71μg/ml (mean: 68μg/ml), and the mean urinary recovery up to 8 hours from the start of infusion was 91.2%.
3) A daily dose of 1.0-4.0g of CAZ was administered to 32 cases and an efficacy evaluation was made in 28 cases. Four cases responded excellently to CAZ treatment, 16 cases effectively, 4 cases fairly and 4 cases poorly. Skin eruption was observed in 1 case but there was neither other clinical side effect nor abnormal chagne in laboratory findings.
As a result, CAZ is considered to be a useful drug for the treatment of infectious diseases.

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The in-vitro antimicrobial activity of ceftazidime (CAZ) was compared with that of cefazolin (CEZ), cefotaxime (CTX) and cefoperazone (CPZ) against gram-positive cocci and gram-negative bacilli. Against Pseudomonas app. cefsulodin (CFS) was also added in the comparison.
Against S. aureus and S. epidermidis CAZ was less active than the other cephems. Against Streptococci CAZ was as active as CEZ and CPZ, but was less active than CTX.
Against strains of the Enterobacteriaceae such as E. coli, Shigella, Salmonella, K. pneumoniae, Citrobacter and Enterobacter, CAZ showed the strong activity comparable to that of CTX and CPZ. Against Serratia, CAZ was the most active agent of all the antibiotics tested. Though the antimicrobial activity of CAZ against Proteus spp. was less than that of CTX, its MIC ranged from 0.05 to 0.78μg/ml. Against P. aeruginosa and P. cepacia, CAZ was more active than CFS.
CAZ was given to 8 patients, namely 5 with respiratory tract infections, two with urinary tract infections and 1 with subacute bacterial endocarditis. The clinical efficacy obtained was: excellent in 1 cases, good in 6 and poor in 1. The poor response was recorded in a case of lobar pneumonia caused by S. pneumoniae.
As for side effect, itching exanthema accompanied by elevation of transaminase was observed in 1 case.

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Ceftazidime (CAZ, SN 401), a new parenteral cepharosporin derivative, was given to 19 adult patients. Clinical efficacy of this drug was assessable in 16 patients with various infections, consisting of 14 cases of respiratory tract infections such as bronchopneumonia (10), chronic bronchitis (2), acute bronchitis (1) and pulmonary suppuration (1), and 2 cases of sepsis suspected. CAZ was given intravenously at a dose of 2-4 g/day. The cumulative clinical and bacteriological efficacy was obtained in 12 out of the 16 patients (75%): excellent in 4, good in 8 and poor in 4.
In the bacteriological study, P. aeruginosa isolated from sputum was decreased or eradicated in 4 out of 6 cases, and H. influenzae, K. pneumoniae, E. coli, and Citrobacter sp. were eradicated in all the cases by the administration of CAZ.
These results suggest that CAZ has clinical efficacy in GNR infections including those caused by P. aeruginosa.
Slight elevation of serum GPT level was observed in 2 patients, and skin rash and eosinophilia were noted in 1 case. No other side effects were observed.

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Laboratory and clinical studies were performed on ceftazidime (CAZ, SN401), a new aminothiazolyl cephalosporin.
The in vitro activity of CAZ against various clinical isolates was determined. Percentages of the strains susceptible to 12.5μg/ml or less were 85% of S. aureus, 15% of S. faecalis, 96% of E. coli, 93% of K. pneumoniae, 85% of Enterolacter sp. 82% of S. marcesens, 89% of Proteus sp. and 92% of P. aerreginosa. Especially, MICs for most of Enterobacteriacae were 1.56μg/ml or less.
Six patients comprising 2 with sepsis, each 1 with acute pharyngitis, chronic bronchitis, acute pyelonephritis, and acute cystitis were treated with CAZ at a daily dose of 2-4g for 5-22 days. Clinical response was excellent in 2, good in 2 and fair in 2 patients. Bacteriological effects were good in 5 cases and unknown in 1 case. No clinical side effect was observed. In laboratory findings, elevation of Al-P was observed in 1 case, but its association with CAZ was unknown.

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Clinical studies on ceftazidime (CAZ, SN401) were performed with the following results:
1) Ceftazidime was administered intravenously to 2 patients with pneumonia, 2 with diffuse panbronchitis and 1 with acute bronchitis. The daily dose ranged from 1.0 to 2.0g for 3 to 25 days. The clinical results were good in all 5 patients.
2) There were no side effects in these 5 patients. From these results, Ceftazidime is considered to be a useful injectable antibiotic, particularly in respiratory tract infections with P. aeruginosa.

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Laboratory and clinical studies were carried out on ceftazidime (CAZ, SN401), a new injectable cephalosporin.
As for the antibacterial activity against 324 strains of 10 species of clinical isolates, CAZ showed high activity against gram-negative bacilli, and it was far more active than cefmetazole (CMZ).
When compared with ceftizoxime (CZX), CAZ was shown to be slightly less active against E. coli, K. aerogenes and P. mirabilis, but almost comparable or more active against the other strains. In particular, against P. aeruginosa, its activity was 1-2 times higher than that of cefoperazone (CPZ) and comparable to that of gentamicin (GM) or cefsulodin (CFS). Against S. aureus, CAZ was obviously less active than CMZ or CZX and the peak of MIC of CAZ was 6.25μg/ml. The concentrations of CAZ in the serum and sputum were determined in 4 patients after intravenous drip infusion at the dose of 1g. The serum concentrations immediately after drip infusion ranged from 62.5-87μg/ml, and the mean half-life was 1.68 hours. Not less than 2μg/ml of CAZ was recovered in sputum in 3 of the cases and the peak concentration was 4.6μg/ml.
The clinical responses to CAZ in a total of 20 patients, 8 with pneumonia, 6 with acute exacerbation of bronchiectasis, 4 with acute exacerbation of chronic bronchitis and each 1 with infection following old pulmonary tuberculosis and organized pneumonia, were excellent in 4 cases, good in 11, fair in 2 and unassessable in 1, with the efficacy rate of 78.9%, which suggested the clinical usefulness of CAZ in respiratory tract infections.
As for the side effects, rash, increase in Al-P level and decrease in WBC counts were noted in 1 case each, but all of them wele onlymild.

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