3-羟基-6-O-甲基红霉素-9-肟基衍生物的合成及体外抗菌活性

目的　寻找并合成抗耐药菌活性的 3位羟基红霉素衍生物。方法　以红霉素A为原料 ,经 9位酮基肟化 ,9位肟羟基 ,2′位羟基和 3′位二甲胺基同时苄基化 ,6位羟基甲基化 ,水解去 3位克拉定糖 ,氢化还原脱苄基 ,对甲基苄基或邻氯苄基取代 9位肟羟基等 6步反应 ,制得 3 羟基 6 O 甲基红霉素 9 肟基衍生物 ,其结构经1 3 CNMR ,FAB MS确证。结果　共制得 7个化合物 ,对其中 4个 (5 - 8)未见报道的化合物进行了体外抗菌活性测定。结论　 5 ,7,8对部分红霉素诱导耐药菌有一定的活性     

(9S)-9-羟基-12-亚甲基红霉素A衍生物的合成

为了合成具有抗菌活性的红霉素衍生物,本文以红霉素A为原料,合成了6-位烯丙基取代中间体12,21-双键-2′-O,4″-O-二苯甲酰基-(9S)-9-O,11-O-异丙基-6-O-烯丙基红霉素A 12,得到(9S)-9-羟基-12-亚甲基衍生物6和6,7-去氢-(9S)-9-羟基-12-亚甲基衍生物11。经¹³C NMR,FAB-MS确证产物结构。所得化合物进行了体外抗菌活性测定。6和11均显示出较弱的抑菌活性。     

(9S)-12-亚甲基红霉素衍生物的合成及体外抗菌活性

目的合成新的具有抗菌活性的红霉素衍生物。方法以红霉素为原料，合成中间体2′-O,4″-O-二苯甲酰基-(9S)-9-O,11-O-异丙基-12-亚甲基红霉素与6,7-去氢-2′-O,4″-O-二苯甲酰基-(9S)-9-O,11-O-异丙基-12-亚甲基红霉素，进而合成相应(9S)-9-O,11-O-亚乙基-12-亚甲基衍生物。产物结构经¹³C NMR,FAB-MS确证。对所得化合物进行体外抗菌活性测定。结果制备11个红霉素衍生物，其中5个未见文献报道。化合物9和12进行了体外抗菌活性测定。结论化合物9和12表现出较弱的抗菌活性。     

9-肟基-3-酮基-6-O-甲基红霉素的合成

以红霉素为原料，经肟化、苄基化、甲基化、水解、氧化和氢化还原等6步反应，制得9-肟基-3-酮基-6-O-甲基红霉素。总收率41％。     

2′,4″-二乙酰基红霉素-9-O-杂环烷基肟衍生物的合成及体内抗菌活性

目的设计合成2′,4″-二乙酰基红霉素-9-O-杂环烷基肟衍生物,并对其体内抗菌活性进行评价。方法以红霉素为原料,经9位羰基肟化、肟羟基烷基化、2′,4″-二羟基乙酰化3步反应制得目标化合物;选取有代表性的8个化合物评价其对小鼠感染所致败血症的治疗作用。结果与结论共制得18个未见文献报道的目标化合物,经MS1、H-NMR确证结构;该类化合物具有较好的抗菌活性,其中化合物9n的活性优于对照药罗红霉素和克拉霉素。     

2',4″-二乙酰基红霉素-9-O-杂环烷基肟衍生物的合成及体内抗菌活性

目的 设计合成2',4"-二乙酰基红霉素-9-O-杂环烷基肟衍生物,并对其体内抗菌活性进行评价.方法 以红霉素为原料,经9位羰基肟化、肟羟基烷基化、2',4"-二羟基乙酰化3步反应制得目标化合物;选取有代表性的8个化合物评价其对小鼠感染所致败血症的治疗作用.结果与结论 共制得18个未见文献报道的目标化合物,经MS、1H-NMR确证结构;该类化合物具有较好的抗菌活性,其中化合物9 n的活性优于对照药罗红霉素和克拉霉素.     

2’，4＂-二乙酰基红霉素-9-O-杂环烷基肟衍生物的合成及体内抗菌活性

目的设计合成2’，4＂-二乙酰基红霉素-9-O-杂环烷基肟衍生物，并对其体内抗菌活性进行评价。方法以红霉素为原料，经9位羰基肟化、肟羟基烷基化、2’，4＂-二羟基乙酰化3步反应制得目标化合物；选取有代表性的8个化合物评价其对小鼠感染所致败血症的治疗作用。结果与结论共制得18个未见文献报道的目标化合物，经MS,^1H—NMR确证结构；该类化合物具有较好的抗菌活性，其中化合物9n的活性优于对照药罗红霉素和克拉霉素。     

5α-△9(11)-16β-甲基-3β,17α,21-三羟基-孕甾烯-3β,21-双醋酸酯-20酮和5α,17α-甲基-17β-羟基-雄甾-3酮的微生物转化

用诺卡氏菌与节杆菌混合菌种转化从蕃麻皂素制得的中间体5α-△⁹⁽¹¹⁾-16-16β-甲基-3β,17α,21三羟基孕甾烯-3β,21-双醋酸酯-20酮(Ⅰ)得50%的16β-甲基-△^1,4,9(11)-孕甾三烯-20酮(Ⅱ)和少量的16β-甲基-9,11α环氧-△¹,4孕甾二烯-20酮(Ⅲ)。另外,又用同样的混合菌种转化从剑麻皂素制得的中间体5α,17α甲基-17β羟基-雄甾-3酮(Ⅳ)得50%17α甲基-17β羟基-△^1,4-雄甾二烯-3酮(Ⅴ)。如改变培养基则得3,17β-羟基-17α-甲基-9酮基-9,10开环-1,3,5(10)雄甾三烯化合物。     

3-(4-氨基-5-甲基-均三唑-3-硫基)-1-苯丙-1-酮-O-(5-取代苯基-［1,3,4］噁二唑-2-甲基)肟的合成及抗菌活性

目的研究氨基杂环肟类化合物的合成方法和抗菌活性。方法用4-氨基-3-甲基-5-巯基-［1,2,4］三唑与β-氯苯丙酮缩合、肟化、醚化得3-(4-氨基-5-甲基-均三唑-3-硫基)-1-苯丙-1-酮-O-(5-取代苯基-［1,3,4］噁二唑-2-甲基)肟醚目标化合物。用二倍试管稀释方法研究了目标化合物的体外抑菌活性。结果合成了12个新化合物，其结构经MS，IR，¹H NMR和元素分析确证。10个目标化合物在体外有一定的抗菌活性。结论该类杂环化合物有待进一步的结构优化研究。     

3-(3′-甲基-4′-取代苯基-1′,3′-丁二烯基)吲哚类衍生物的合成及其抗癌活性

目的　研究3-(3′-甲基-4′-取代苯基-1′,3′-丁二烯基)吲哚类衍生物的合成及其抗癌活性。方法　通过亲电取代、羟醛缩合、选择性还原、相转移Wittig反应和水解反应合成目的化合物,利用几种药理模型进行抗癌和抗炎活性筛选。结果　设计合成了11个3-(3′-甲基-4′-取代苯基-1′,3′-丁二烯基)吲哚化合物,均为新化合物。生物活性实验结果表明,化合物8对HL-60,HCT-8和Bel7402癌细胞株有效,且在浓度为10^-5mol·L^-1时,其抗炎抑制率可达100％。结论　化合物8显示了抑癌作用和抗炎活性,值得进一步研究。     

3-Keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A synthesis and in vitro activity

A series of 3-keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A were prepared with a novel synthetic route, which include 6 reaction steps--oximation, protection, hydrolysis, oxidation, deprotection and addition. The antibacterial activity of these compounds were tested in vitro against both erythromycin-susceptible and erythromycin-resistant organisms. Several of these derivatives showed improved antibacterial activity against some erythromycin-resistant organisms as compared to erythromycin A.     

Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among bacteria were also evaluated with the bacterial resistance ratio calculated from the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter Iwoffii, Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group, and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against M. (B.) catarrhalis (MIC90: 4 micrograms/mL) and showed comparable activity to carbapenems against H. influenzae (MIC90: 1 microgram/mL). The antibacterial activity of CZOP against E. coli was preferable (MIC90: 0.125 microgram/mL) and comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The MIC90 of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 microgram/mL, respectively. The MIC90 of CZOP against E. cloacae increased during 6 years (32 to 128 micrograms/mL). The antibacterial activity of CZOP against E. aerogenes was preferable (MIC90: 1 microgram/mL). The antibacterial activities of CZOP against S. marcescens and S. liquefaciens were relatively potent (MIC90: 0.5 and 0.25 microgram/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP preserved comparable antibacterial activity to CPR against C. freundii and C. koseri (MIC90: 8 and 0.125 micrograms/mL). The MIC90 of CZOP against P. mirabilis, P. vulgaris, and M. morganii was 0.25, 16, and 2 micrograms/mL, respectively. The antibacterial activity of CZOP against Providencia spp. was moderate (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against P. aeruginosa was the most potent (MIC90: 16 micrograms/mL) among the test agents and comparable to those CFPM, IPM, and MEPM. CZOP had low activity against P. fluorescens and P. putida (MIC90: 128 micrograms/mL). The antibacterial activity of CZOP against A. baumannii was comparable to those of ceftazidime (CAZ), CPR and CFPM (MIC90: 32 micrograms/mL) and against A. lwoffii was moderate (MIC90: 64 micrograms/mL). Most of the test agents including CZOP had low antibacterial activity against B. cepacia, S. maltophilia, and B. fragilis group. The MIC90 of CZOP against Prevotella/Porphyromonas was 64 micrograms/mL. Bacterial cross-resistance ratio between CZOP and other agents was low in most of the species, ranging from 0.0 to 15.1%. In non-glucose fermentative bacteria, however, the bacterial cross-resistance ratio between CZOP and CFPM, CAZ, CPR, or IPM was high, being 36.8%, 28.0%, 38.7%, or 31.1%, respectively. In conclusion, the 6-year duration study suggested that the antibacterial activity of CZOP against E. cloacae possible decreased, but against other Gram-negative bacteria was consistent with the study results obtained until the new drug application approval.     

Synthesis and antibacterial activity of 6-O-arylbutynyl ketolides with improved activity against some key erythromycin-resistant pathogens

A series of novel 6-O-substituted homopropargyl ketolides was synthesized and evaluated against various erythromycin-resistant pathogens. Promising in vitro antibacterial activity was demonstrated for compounds bearing this structural motif.     

Combination effect of teicoplanin and beta-lactams on MRSA

In vitro combination effect of teicoplanin and beta-lactams was investigated against 109 MRSA strains isolated from a variety of clinical specimens at the Social Health Insurance Medical Center during the period from January 1994 through February 2000. TEIC + panipenem (PAPM) was revealed by microbroth dilution method-based checkerboard method, to exhibit synergistic effect of min. FIC index < or = 0.5 against all the 109 strains. The combination of TEIC and flomoxef (FMOX) was shown to have synergistic effect on 108 strains (99.1%). The combination of TEIC and cefepime (CFPM) was shown to have synergistic effect on 96 strains (88.1%). The combination of TEIC and cefmetazole (CMZ) was shown to have synergistic effect on all the 109 strains (100%). The mean value of min. FIC indices obtained from each of the combinations was 0.1259 as to TEIC + PAPM, 0.2019 as to TEIC + FMOX, 0.3257 as to TEIC + CFPM and 0.1995 as to TEIC + CMZ, in other words, the combination of TEIC + PAPM showed the lowest value of all the combinations. While MIC80 was 2.0 micrograms/ml when TEIC was used alone, it was < or = 0.06 microgram/ml when used together with PAPM, and 0.13 microgram/ml when used together with FMOX, respectively. While MIC80 was 3.2 micrograms/ml when PAPM was used alone, it was 0.5 microgram/ml when used together with TEIC. Meanwhile, the value for FMOX was changed from > or = 128 micrograms/ml to 4.0 micrograms/ml. When TEIC was used in combination with CFPM, MIC80 was found to be 0.5 microgram/ml. Similar to the case of the concurrent use with FMOX, the value obtained by combination with CMZ was 0.13 microgram/ml. While MIC80 was 128 micrograms/ml when CFPM was used alone, it was 8.0 micrograms/ml when used together with TEIC, whereas the value for CMZ was decreased from 64 micrograms/ml to 2.0 micrograms/ml. In conclusion, TEIC's antibacterial activity was shown to be accentuated by any of the combinations.     

Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--I. Gram-positive bacteria

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, and carbapenems. Changes in the bacterial susceptibility for CZOP were also evaluated with the resistance ratio calculated with breakpoint MIC. Sixteen species (2,363 strains) of Gram-positive bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), methicillin-resistant Staphylococcus epidermidis (MRSE), Staphylococcus haemolyticus, Staphylococcus saprophyticus, Enterococcus faecalis, Enterococcus faecium, Enterococcus avium, Streptococcus pyogenes, Streptococcus agalactiae, penicillin-susceptible Streptococcus pneumoniae (PSSP), penicillin-intermediate resistant S. pneumoniae (PISP), penicillin-resistant S. pneumoniae (PRSP), Streptococcus milleri group and Peptostreptococcus spp. The antibacterial activity of CZOP either against MSSA or MSSE was preferable (MIC90: 2 or 0.5 micrograms/mL) and comparable to those of other cephems. CZOP was also effective on MRSE (MIC90: 16 micrograms/mL) but not on MRSA. CZOP and other cephems had low antibacterial activity against S. haemolyticus (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against S. saprophyticus was comparable to or higher than those of other cephems, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (32 vs 1-2 micrograms/mL). The antibacterial activity of CZOP against E. faecalis was comparable to that of cefpirome (CPR; MIC90: 16 micrograms/mL) and higher than those of other cephems. No antibacterial activity of CZOP against E. faecium and E. avium was observed, like other drugs. The antibacterial activity of CZOP against S. pyogenes was as potent as those of cefotiam and CPR (MIC90: < or = 0.063 microgram/mL), and, against S. agalactiae, was also preferable (MIC90: 0.125 microgram/mL). CZOP indicated preferable antibacterial activity either against PSSP, PISP, or PRSP (MIC90: 0.25, 1, or 2 micrograms/mL). The antibacterial activity of CZOP against S. milleri group was also preferable, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (4 vs 0.5 micrograms/mL). The antibacterial activity of CZOP against Peptostreptococcus spp. was preferable but weaker than those of cefazolin and cefmetazole. The resistance ratio estimated from breakpoint MIC of CZOP was 95.9% in MRSA, 93.5% in PRSP, 63.3% in PISP, 35.8% in S. haemolyticus, 27.9% in E. faecalis, and 13.3% MRSE. Those resistance ratios were comparable to those for cefepime (CFPM), but E. faecalis showed 91.2% for CFPM. The difference in the resistance ratio of E. faecalis demonstrated that CZOP successfully maintained its antibacterial activity against these species. In correlation of drug susceptibility, 40.3% of PRSP was not inhibited at breakpoint MIC either CZOP or CFPM while 69.2% at breakpoint MIC either CZOP or ceftazidime. In conclusion, the antibacterial activities of CZOP against the Gram-positive bacteria obtained from the 6-year duration study were consistent with the results from the studies performed until the new drug application approval. A decline in the sensitivities of S. saprophyticus, S. milleri group, PISP, and PRSP to CZOP, however, was suggested.     

Antibacterial activities of piperacillin in several fresh clinical isolates

We investigated activity of piperacillin (PIPC) in comparison with 8 antibacterial reference drugs against several fresh clinical strains isolated from patients with infectious diseases in the respiratory tract and after surgical interventions in 1999. The following results were obtained: 1. PIPC had its MIC90 of 0.12-6 micrograms/ml in Gram-positive bacteria (Methicillin susceptible Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecalis) and showed its MIC of 1 microgram/ml or higher in 9 possible PRSP strains out of 38 isolates of S. pneumoniae but there were no possible isolates with evident resistance in other species of bacteria. 2. PIPC showed favorable antibacterial activities as its MIC90 were 2-8 micrograms/ml in Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Pseudomonas aeruginosa, Moraxella (Branhamella) catarrhalis, Haemophilus influenzae), except for P. mirabilis in which its MIC90 was as high as 64 micrograms/ml. 11 out of 39 isolates of P. mirabilis were resistant to other drugs such as PIPC, ABPC, CTM and CZOP. 3. PIPC had its MIC90 of > 128 micrograms/ml in Bacteroides fragilis. From these results, PIPC was considered highly effective in several infections in view of maintaining its favorable antibacterial activities in several causative bacteria even today when 20 years had passed since its first application to clinical practice.     

7-[(2S)-2-羟甲基-4-氨基-1-吡咯烷基]氟喹诺酮类化合物的合成及体外抗菌活性

用反式-L-羟脯氨酸经对甲苯磺酰氯保护、甲酯化、氧化、肟化、四氢铝锂还原、叔丁氧基羰基保护后脱除对甲苯磺酰保护基,与不同的氟喹诺酮中间体缩合,最后经脱除叔丁氧基羰基等反应得到目标物,结构经1HNMR和FAB-MS确证,并进行了体外抗菌活性试验.结果表明,除化合物13对供试的大部分菌株,特别是对链球菌的体外活性相当于或优于对照药加替沙星和环丙沙星外,其余3个目标物总体活性均低于对照品.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1986). I. Susceptibility distribution

Susceptibilities to various antibacterial and antibiotic agents of bacterial strains isolated from urinary tract infections at 8 hospitals in Japan from July to October in 1986 are summarized as follows. 1. Enterococcus faecalis was susceptible to sulfamethoxazole/trimethoprim (ST) and imipenem (IPM) with MIC90s of 0.78 and 1.56 microgram/ml. Minocycline had the strongest activity against Staphylococcus aureus; the MICs for all strains tested were lower than 0.39 microgram/ml. The MIC80s of dicloxacillin, and arbekacin (HBK) were 0.20 and 0.78 microgram/ml, respectively. Among the cephems, the MIC80 of flomoxef was 25 micrograms/ml, whereas those of cefmenoxime (CMX) and cefotiam (CTM) were 50 micrograms/ml. 2. Escherichia coli was most susceptible to ofloxacin (OFLX) among the oral antibacterial and antibiotic agents tested. OFLX showed the minimum inhibitory concentration against 90% (MIC90) of the 274 strains of E. coli tested to be lower than 0.10 microgram/ml. The antibacterial activities of the third generation cephems such as CMX and latamoxef (LMOX) were the strongest among the injectable antibiotics tested. The MIC90s of CMX and LMOX were lower than 0.10 and 0.20 microgram/ml, respectively. CTM and cefmetazole, the second generation cephems, were also highly active against E. coli with MIC90s of 0.39 and 1.56 micrograms/ml, respectively. 3. Among the oral antibacterial and antibiotic agents tested, OFLX was the most active against Klebsiella pneumoniae. Its MIC90 was 0.78 microgram/ml. Among the injectable antibiotics tested, CMX was the strongest with an MIC90 of 0.20 microgram/ml; MIC90 of CTM and LMOX were 0.39 microgram/ml. 4. The tested antibacterial and antibiotic agents were generally less active against Citrobacter freundii than against other bacteria. The MIC80 of OFLX was 0.39 microgram/ml. Gentamicin (GM) and ST were slightly active against C. freundii. Among the cephems, CMX had the MIC80 of 25 micrograms/ml. 5. Enterobacter cloacae was less susceptible to the cephems tested. OFLX, GM, and mecillinam were active against this bacteria with MIC80s of 0.78, 0.78 and 1.56 micrograms/ml, respectively. 6. Among the oral antibacterial and antibiotic agents and penicillins examined, piperacillin (PIPC) was the most active against Proteus mirabilis. Its MIC90 was 0.39 microgram/ml. Those of sulbenicillin, cefaclor, ampicillin, OFLX, and ST were 0.78, 0.78, 1.56, 3.13 and 3.13 micrograms/ml, respectively. CMX was highly active against P. mirabilis with an MIC90 of less than or equal to 0.10 microgram/ml; LMOX followed with an MIC90 of 0.20 microgram/ml among the injectable antibiotics tested. CTM was also active against this bacterium; the MIC90 was 0.39 microgram/ml. 7. The antibacterial and antibiotic agents were generally only slightly active against Proteus vulgaris.(ABSTRACT TRUNCATED AT 400 WORDS)     

In vitro and in vivo antidermatophytic activity of saperconazole, a new fluorinated triazole.

The in vitro activity of saperconazole against selected isolates of dermatophytes and its in vivo efficacy in a guinea pig dermatophytic infection model using Trichophyton mentagrophytes were evaluated. Susceptibility testing was determined with an agar dilution method in three media: yeast nitrogen base agar (YNBA), brain heart infusion agar (BHIA) and Sabouraud dextrose agar (SDA). An inoculum of 1 x 10(5) CFU of T. mentagrophytes spores was placed onto the surface of these agars. Incubation was at 32 degrees C for 72 h. The MIC of saperconazole against all isolates was less than 1 microgram/ml, whereas the MIC ranged from 0.1 to > 128 micrograms/ml for fluconazole. The MIC range of saperconazole against Trichophyton species was < or = 0.002 to 0.25 micrograms/ml; against Microsporum species it was < 0.001 to 0.1 microgram/ml; and against Epidemophyton species was < or = 0.002 to 0.25 micrograms/ml. These data showed that saperconazole was the most active compound tested against these selected dermatophytes. The activities of saperconazole against T. mentagrophytes, T. rubrum and M. canis were not affected by the medium. The MICs against these organisms were < or = 0.008 micrograms/ml in SDA, YNBA or BHIA. There were 2- to 4-fold decreases in activity for fluconazole at the same conditions. In vivo, topical treatment with saperconazole at concentrations of 0.125% and 0.25% resulted in 50% and 75% microbiological cure rates, respectively, in the guinea pig topically infected with T. mentagrophytes.     

Susceptibility of clinical isolates to aztreonam

In vitro antibacterial activities of 9 antibiotics including aztreonam (AZT) against clinically isolated Gram-negative bacteria were determined using MIC-2000 plus system. Bacteria were isolated from clinical materials in Saga Medical School during a period from May 1987 to March 1988. Summarized results were as follows: 1. AZT showed excellent antibacterial activities against Escherichia coli, Klebsiella pneumoniae, Proteus sp. and Haemophilus influenzae, and MIC80 values of AZT against these organisms were lower than 0.20 microgram/ml. 2. Antibacterial activities of AZT were superior to cephem antibiotics compared against Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii and Serratia marcescens. 3. The MIC50 and MIC80 of AZT against Pseudomonas aeruginosa were 12.5 micrograms/ml and 25 micrograms/ml, respectively. 4. AZT did not show any antibacterial activity against Acinetobacter sp. and Xanthomonas maltophilia.