Mersacidin, a new antibiotic from Bacillus. In vitro and in vivo antibacterial activity.

Mersacidin is a new peptide antibiotic of the proposed lantibiotic family. It is active in vitro and in vivo against Gram-positive bacteria including the methicillin-resistant Staphylococci. Its in vitro activity is less than those of vancomycin and erythromycin but it shows much higher activity in the in vivo system than can be expected from the in vitro testing results. A water soluble potassium salt has been prepared which has an activity profile similar to that of mersacidin, but has better in vivo activity against Streptococcus pyogenes than the parent compound.     

Antimycotic efficacy of bifonazole in vitro and in vivo

The new imadozolyl derivative 1-(p, alpha-diphenyl-benzyl)imidazole (bifonazole, Bay h 4502, Mycospor) shows in vitro the broad spectrum of activity characteristic of azole antimycotics. The intensity of activity under conventional test conditions is equivalent to that of clotrimazole. Further, concentrations of less than or equal to 5 micrograms/ml bifonazole have a fungicidal effect on dermatophytes, and a MIC value of less than or equal to 0.25 micrograms/ml has a maximal effect on Torulopsis glabrata. In ng concentrations bifonazole is effective on proliferating dermatophytes and pseudomycelia of Candida albicans. The resistance situation regarding bifonazole is favourable--as is typical of azole antimycotics. In animal experiments, topical application of concentrations of between 0.05 and 1% bifonazole as a cream or solution are extremely effective on guinea-pig trichophytosis. This is attributed to the therapeutically achievable fungicidal effect on dermatophytes and the long period of time the substance is retained in the skin. The sum of the experimental properties of bifonazole make it possible to recommend the active drug to be applied, once every 24 h, as a 1% cream or solution and the duration of therapy for these indications being reduced to 2-3 weeks.     

In vitro and in vivo antibacterial activities of meropenem, a new carbapenem antibiotic.

The in vitro and in vivo antibacterial activities of meropenem were compared with those of imipenem, ceftazidime, flomoxef, cefuzonam and cefotiam. Meropenem showed a broad antibacterial spectrum against clinical isolates of Gram-positive and Gram-negative bacteria. Against Gram-negative bacteria, with the exception of Acinetobacter calcoaceticus, meropenem exhibited the most potent activity among the drugs tested. It inhibited all 330 strains of Enterobacteriaceae at 0.78 mg/l. Meropenem was sensitive against several cephem-resistant strains of Enterobacteriaceae. Against Pseudomonas aeruginosa, meropenem was four-fold more active than imipenem and eight-fold more active than ceftazidime, with an MIC90 of 0.78 mg/l. The therapeutic effect of meropenem on systemic infection in mice was ten to twenty-fold less than that of imipenem against Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae. However, meropenem was as effective as imipenem on infections of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Acinetobacter calcoaceticus and Pseudomonas aeruginosa. Meropenem was eliminated from mice plasma two-fold faster than imipenem, with a plasma half-life of 7.6 min. From the above results the authors concluded that meropenem is a promising drug for clinical use.     

Cispentacin, a new antifungal antibiotic. II. In vitro and in vivo antifungal activities

Cispentacin [-)-(1R,2S)-2-aminocyclopentane-1-carboxylic acid) is a new antifungal antibiotic possessing potent anti-Candida activity. The 50% inhibitory concentration (IC50) and IC100 values of cispentacin against clinical isolates of Candida albicans were in the ranges 6.3 approximately 12.5 and 6.3 approximately 50 micrograms/ml, respectively, by turbidimetric measurement in yeast nitrogen base glucose medium. No significant activity was seen against any yeasts and molds when tested by the agar dilution method using three different agar media: KNOPP's agar, yeast extract-glucose-peptone agar and Sabouraud dextrose agar. This antibiotic demonstrated good therapeutic efficacy against a systemic Candida infection in mice by both parenteral and po administrations. The 50% protection dose (PD50) values after single iv and po administrations were 10 and 30 mg/kg, respectively. It was also effective in a systemic infection with Cryptococcus neoformans and in both lung and vaginal infections with C. albicans in mice. Cispentacin did not induce acute lethal toxicity at 1,000 mg/kg by iv injection and 1,500 mg/kg by ip and po administrations in mice.     

In vivo antibacterial activity of cefodizime, a new cephalosporin antibiotic

The in vivo activity of cefodizime (HR 221) was compared with that of cefotaxime (CTX), cefmenoxime, latamoxef, cefazolin and cefmetazole (CMZ). The protective effects of HR 221 on experimental infections in mice caused by Staphylococcus aureus Smith, Escherichia coli C-11, Proteus vulgaris GN-76 and Serratia marcescens No. 2 were directly related to its in vitro activity against these strains. In contrast, the compound showed the smallest ED50 values, among the 5 antibiotics tested (not including CMZ), for Klebsiella pneumoniae 3K-25 and Pseudomonas aeruginosa PI 67 against which it had relatively low in vitro activity, and its ED50 for Citrobacter freundii GN-346 was as small as 1.821 mg/mouse in spite of its MIC of greater than 100 micrograms/ml. HR 221 exerted potent bactericidal activity against Streptococcus pneumoniae Sp-1 inoculated into the mouse lung; the duration of action was prolonged. When tested against the E. coli Ec-89 infection induced in the rat uterus, the activity of HR 221 given to rats once daily was equal to that of CTX or CMZ given at the same dose twice daily.     

新氨基糖苷类抗生素vertimicin的体内抗菌活性研究

目的 评价新氨基糖苷类抗生素vertimicin（VTM）的体内抗菌活性。方法 采用小鼠全身感染模型，观察VTM对临床分离大肠埃希菌（E．coli）、肺炎克雷伯菌（K．pneumoniae）、铜绿假单胞菌（Ps．aeruginosa）和金葡菌（S．aureus）腹腔感染小鼠的体内疗效；采用兔皮肤烫伤感染模型、小鼠泌尿道上行性感染模型观察VTM对临床分离大肠埃希菌局部感染的体内疗效，并与对照药进行比较。结果 VTM皮下或静脉给药对E．coll96-12、K．pneumonlae93-5、Ps．aeruglnosa94-17和S．aureus93-44腹腔感染小鼠具有相似的体内疗效，皮下给药的ED50值分别为0．67、0．29、2．41和0．99mg／kg，静脉给药的ED50值分别为0．46、0．23、0．99和1．52mg／kg，体内疗效与奈替米星相近。兔皮肤烫伤感染模型中，VTM各剂量组兔皮肤组织活菌落数明显低于对照组（P〈0．05或0．01）。小鼠泌尿道上行性感染模型中，VTM各剂量组肾组织活菌落数明显低于对照组，肾剖面盖印细菌阴性率明显高于对照组（P〈0．01），抗菌活性优于庆大霉素。结论 VTM对全身和局部感染动物均显示较好保护作用，体内疗效与奈替米星相近。     

Rapamycin (AY-22,989), a new antifungal antibiotic. III. In vitro and in vivo evaluation.

The activity of rapamycin, a new anti-Candida antibiotic, was not affected by pH values between 6 and 8; at pH 4, however, activity was abolished. The MIC of rapamycin did not vary drastically with the size of inoculum: a ten-fold dilution of the inoculum reduced the MIC only two-fold. Serum binding was extensive. Serum levels obtained in mice were higher on subcutaneous injection than with oral administration. Dogs absorbed rapamycin after oral administration. Rapamycin cured systemic candidosis in mice: PD50 s.c. was 9.5 mg/kg: PD50 p.o. was 11 mg/kg. In the same experimental infections amphotericin B and nystatin exhibited PD50 values of less than 0.25 mg and greater than 4,000 units/kg respectively. Rapamycin and amphotericin B, administered at 1, 4 and 24 hours after infection, gave approximately the same percent survival after 30 days of observation. When the above treatment was extended by an additional daily treatment for 6 days, rapamycin by the subcutaneous route yielded a higher percentage of survival than either rapamycin or amphotericin B, administered orally, after a 30-day observation period. Vaginal candidosis in female rats was treated efficiently (91% cure) by rapamycin administered orally. No increase of resistance of C. albicans was observed during treatment.