Studies on penem antibiotics. II. In vitro activity of SUN5555, a new oral penem

The new oral penem antibiotic SUN5555 shows broad antibacterial activity against both aerobic and anaerobic Gram-positive and Gram-negative bacteria. SUN5555 is highly stable against various beta-lactamases. It binds preferentially to the penicillin-binding proteins 2 and 1A of Escherichia coli.     

In vitro antimicrobial activity of cefpirome, a new cephalosporin with a broad antimicrobial spectrum

The in vitro activity of cefpirome (HR 810), a new cephalosporin antibiotic having a 2,3-cyclopentenopyridine group in the 3-position side chain, was compared with in vitro activities of 5 other cephalosporins. HR 810 showed a broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria when tested using 71 standard strains and 876 clinical isolates. HR 810 inhibited 70% of the clinically isolated Staphylococcus aureus and Staphylococcus epidermidis strains when used at 0.59-0.84 microgram/ml, 2- to 25-fold lower than values of reference antibiotics, and the compound was also highly effective against Enterococcus faecalis which is relatively resistant to most of the existing cephem antibiotics. The activity of HR 810 against Enterobacteriaceae members (11 species), based on its minimal inhibitory concentrations inhibiting 90% of bacterial growth (MIC90S), was the highest among the cephalosporins used. Especially against Enterobacter species and Citrobacter freundii, the MIC90S of the compound were 4- to 64-fold lower than the values of the other antibiotics. Against Pseudomonas aeruginosa, HR 810 was as active as cefoperazone, an antipseudomonal agent. The minimal bactericidal concentrations (MBCs) of HR 810 were equal to or only 2-fold greater than the MICs for most of 12 standard strains tested. The compound markedly decreased viable bacterial counts at its MICs, thus showing strong bactericidal activities. The in vitro activity of HR 810 was not affected by pH or human serum content of agar media, but the activity against Gram-negative bacteria was lowered as the inoculum size increased.     

In vitro antibacterial activity of faropenem, a novel oral penem antibiotic, against enterohemorrhagic Escherichia coli O157 strains

Against enterohemorrhagic Escherichia coli (EHEC) O157 clinically isolated, the effects of faropenem (FRPM), a novel oral penem antibiotic, on the MICs, bactericidal activity, verotoxin (VT)-release, and lipopolysaccharide (LPS)-release were investigated in vitro and compared with those of other types of antibacterial agents. The MICs of FRPM in aerobic and anaerobic culture condition, were 0.78 and 0.39 microgram/ml, respectively. In aerobic condition, FRPM was more active than ampicillin, amoxicillin (AMPC), fosfomycin (FOM), kanamycin (KM), minocycline (MINO), and clarithromycin (CAM), but was slightly less active than cefdinir (CFDN), cefditoren (CDTR), and norfloxacin (NFLX) against O157 clinical isolates. In anaerobic condition, however, FRPM showed as strong activity as CFDN, CDTR, and NFLX. FOM, NFLX, and KM as well as the beta-lactams including FRPM indicated the powerful bactericidal activity against one strain of O157 clinical isolates. The effects of MINO and CAM were bacteriostatic. FOM and the beta-lactams including FRPM promoted verotoxin type 1 (VT1)-release, but rather suppressed verotoxin type 2 (VT2)-release from the same isolate. NFLX, however, promoted VT1-release and vast amount of VT2-release. In the case of KM, MINO, and CAM, the release suppression of both VT1 and VT2 was observed. FRPM, AMPC, and FOM had very weak activity on LPS-release, while CFDN, CDTR, and NFLX released a large amount of LPS from the strain. KM, MINO, and CAM had relatively weak activity. In these in vitro experiments, FRPM demonstrated the effective profile to the treatment for EHEC infection, except for the effect on VT1-release. These results suggest the possibility that FRPM shows good clinical efficacy for EHEC infection.     

In vitro activity of antimicrobial agents against mycobacteria

The aims of this study were to investigate the possible effects of new antimicrobial agents, the conventional antituberculosis drugs and several combinations of these agents against 190 clinical isolates of Mycobacterium tuberculosis and 30 of M. avium.     

喹诺酮类抗菌药物的体外抗菌活性测定和分析

测定１９９１年９月至１９９３年９月收集到的８９２株临床分离菌株对诺氟沙星，依诺沙星，氧氟沙星，洛美沙星及环丙沙星的敏感性，将结果进行归纳总结，并用部分菌株作体外抗菌活性测定，结果在８９２株菌中，对５种喹诺酮类药物敏感６７５株，耐药２１７株，耐药率为２４．３％，耐１种药者１６．９％耐２种药者４．７％，耐３种药者２．２％，耐４种药者０．４％，对５种喹诺酮类药物的耐药率分别为：诺氟沙星２９．９％，依诺沙     

溴莫普林体内和体外抗菌活性研究

目的：本文对二氢叶酸还原酶抑制剂溴莫普林（ＢＤＰ）的抗菌活性进行了研究。方法：ＢＤＰ的最小抑菌浓度（ＭＩＣ）检测采用试管肉汤稀释法，其半数有效量（ＥＤ５０）的检测通过对感染小鼠的试验性治疗来实现。结果：ＢＤＰ对６９０株临床分离株的ＭＩＣ５０为４ｍｇ·Ｌ－１，低于单次口服６００ｍｇＢＤＰ在血浆中可能达到的峰浓度。ＢＤＰ的ＭＩＣ与甲氧苄氨嘧啶（ＴＭＰ）相似，但ＥＤ５０仅为ＴＭＰ的１／２左右。结论：ＢＤＰ的体内药效明显优于ＴＭＰ。     

In vitro activity of antimicrobial agents against Acinetobacter calcoaceticus

The aim of this study was to evaluate the in vitro activity of several new microbial agents against 96 Acinetobacter calcoaceticus isolates. Among several new beta-lactams, imipenem, a new, broad-spectrum, highly potent penem, was the most active drug in vitro against these strains, with a geometric mean MIC of about 0.3 mg/l. Ceftazidime and ceftizoxime also demonstrated good in vitro activity with geometric mean MICs of 6 mg/l and 7 mg/l respectively. Among new quinolones, ciprofloxacin, ofloxacin and pefloxacin were substantially active in vitro: geometric means were 0.8, 0.9 and 1.5 mg/l respectively. A progressive increase in resistance to aminoglycosides has been observed and 80 to 90% of isolates were resistant to all but amikacin, tobramycin and habekacin, which showed geometric mean MICs of 7.0, 6.0 and 1.2 mg/l.     

In vitro antimicrobial activity of new 1,10-phenantroline derivatives

The antimicrobial and antifungical activities of some 1,10-phenanthroline derivatives are described. The test was performed using the diffusimetric method with stainless steel cylinders based on diffusion of the substances on the gelose surface for bacteria and Sabouraud field for Candida Albicans yeast. The comparative analysis of the obtained data leads to the following conclusions concerning the relation between structure and activity     

克林沙星在体内外的抗菌活性

目的：对克林沙星的抗菌活性进行研究。方法：克林沙星的最小抑菌浓度（ＭＩＣ）检测采用试管肉汤稀释法,其半数有效量（ＥＤ５０）的检测通过对感染小鼠的试验性治疗来实现。结果：克林沙星对嗜麦芽窄食单胞菌以外的全部实验菌的ＭＩＣ９０为０．０３～２．０ｍｇ．Ｌ＾－１,低于单次口服克林沙星２００ｍｇ在血浆中的峰浓度（２．５ｍｇ．Ｌ＾－１）;克林沙星的ＭＩＣ值为环丙沙星的１／８～１／２,ＥＤ５０为环丙沙星的１＝３     

国产氟罗沙星体外抗菌活性研究

测定国产氟罗沙星对４９３株临床分离细菌的最低抑菌浓度（ＭＩＣ），并与氧氟沙星、洛美沙星、环丙沙星和几种头孢菌素、氨基糖苷类抗生素作了比较。结果表明：氟罗沙星对革兰氏阴性细菌有强大抗菌活性，对肠杆菌科细菌的ＭＩＣ９０≤１μｇ／ｍｌ。对铜绿假单胞菌亦有较强抗菌活性，其ＭＩＣ５０、ＭＩＣ９０分别为２和４μｇ／ｍｌ。金葡球菌（含ＭＲＳＡ菌株）对氟罗沙星亦很敏感，ＭＩＣ９０≤１μｇ／ｍｌ。链球菌属对其基本耐药，ＭＩＣ９０为８～１６μｇ／ｍｌ。对大多数常见致病菌，氟罗沙星体外抗菌活性与氧氟沙星、洛美沙星相近，稍逊于环丙沙星。对革兰氏阴性菌，氟罗沙星与头孢噻肟、头孢他啶、阿米卡星相当，优于头孢唑林、氨苄西林、哌拉西林、庆大霉素。耐庆大霉素、头孢菌素菌株对氟罗沙星仍敏感。细菌对氟罗沙星单步自发耐药突变频率极低，但通过连续传代培养可以培育出对氟罗沙星高度耐药菌株。     

Rufloxacin体内和体外抗菌活性研究

检测了ｒｕｆｌｏｘａｃｉｎ（ＲＦＬＸ）对１０４０株致病菌的ＭＩＣ，其总的ＭＩＣ５０为２ｍｇ／Ｌ，低于该药在体内可能达到的峰浓度（Ｃｍａｘ）。与诺氟沙星比较其体外抗菌活性与之相近或略低。体内药效研究显示ＲＦＬＸ对金葡球菌、伤寒沙门氏菌、大肠埃希氏菌和不动杆菌等引起的小鼠感染有明显的治疗效果，其疗效与氧氟沙星和洛美沙星相近或略优。建议建立体内药效指数ＥＤ５０／ＭＩＣ，以比较ＭＩＣ不同时不同药物的体内疗效。     

In vitro antimicrobial activity of o-phenylenediamine-tert-butyl-N-1,2,3-triazole carbamate analogs

In an attempt to design and synthesize effective antimicrobial agents using click chemistry, mono- and di-alkyne-substituted monoboc protected o-phenylenediamines were reacted with different substituted aryl azides which yielded 18 new compounds (4a–4k and 5a–5f, 5l). Structures of all newly synthesized compounds were established by ¹H and ¹³C NMR analysis. The intermediate compound 1 was also confirmed by X-ray crystallography. The title compounds were screened for their antibacterial activity against Gram +ve bacteria (Staphylococcus aureus and Enterococcus faecalis), Gram ?ve bacteria (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), and their antifungal profile were tested on (Candida tropicalis, Candida albicans, Candida krusei, and Cryptococcus neoformans) as well as on molds such as (Aspergillus niger, Aspergillus fumigatus). The compounds 4k and 5f both showed maximum potency against S. aureus (ATCC 25323) strain with MIC value of 6.25 µg/ml, which is comparable with standard drug ciprofloxacin (MIC 6.25 µg/ml) while remaining compounds showed moderate to weak activity. Further, all compounds showed average antifungal activity in the range of 100–200 µg/ml.     

Amiloride, a diuretic with in vitro antimicrobial activity

The effect of amiloride, an inhibitor of passive sodium influx in animal cells, was investigated on the in vitro bacterial growth. Amiloride blocked the growth of different bacterial strains at concentrations ranging from 25 to 1,300 micrograms/ml. While generally the block was bacteriostatic and bacteria, on amiloride removal, recovered their ability to growth, the drug showed a killing activity on hemolytic streptococci. Gram-positive bacteria revealed a greater susceptibility to amiloride than gram-negative ones. Although an hitherto unknown effect of amiloride cannot be excluded, from the known mechanism of action of amiloride on animal cells it might be suggested that sodium permeability plays a critical role on bacterial multiplication.     

阿洛西林及其它常用抗菌药物对京沪两地898株细菌的体外抗菌活性测定

目的研究阿洛西林及其它8种临床常用抗菌药物对常见病原体的体外抗菌活性。方法采用琼脂稀释法测定阿洛西林、美洛西林、哌拉西林、头孢呋辛、头孢曲松、头孢他啶、头孢哌酮、左氧氟沙星和阿奇霉索9种药物对上海、北京两地898株临床分离细菌的最低抑菌浓度（MIC）。结果阿洛西林对肺炎链球菌、流感嗜血杆菌和甲氧西林敏感的金黄色葡萄球菌（MSSA）的MIC50／MIC90分别为0．06／2、0．06／0．5和2／8，三种细菌对阿洛西林的敏感率均高达100％。粪肠球菌、屎肠球菌、铜绿假单胞菌和不动杆菌对阿洛西林的敏感率分别为91％、13％、68％和38％。阿洛西林分别列于9种受试药物的第一、第一和第三位。大肠埃希菌、肺炎克雷伯菌和阴沟肠杆菌对阿洛西林的敏感率分别为41％、65％和39％，低于第三代头孢菌素但优于美洛西林和哌拉西林。结论阿洛西林的抗菌谱广，对革兰阳性菌、阴性菌均有较为理想的抗菌活性，是目前用于社区及医院感染治疗的重要选择药物之一。     

Comparative anti-anaerobic activity of Men 10700, a penem antibiotic

The in vitro activity of Men 10700, a new penem, has been compared with that of metronidazole, clindamycin, ciprofloxacin, co-amoxiclav, imipenem and three third generation cephalosporins against 120 strains of anaerobes. The organisms tested comprised Clostridium perfringens, Clostridium difficile, Bacteroides fragilis and speciated members of the genera Fusobacterium, Veillonella and Peptostreptococcus. Men 10700 showed activity similar to that of imipenem, and was more potent than metronidazole against all species except C. difficile and P. anaerobius. The spectrum of activity of Men 10700 suggests this agent may be useful for treating infections caused by anaerobes.     

司帕沙星衍生物(YH37)体外抗微生物活性研究

采用微量稀释法测定了5-氨基-1-环丙基-6，8-二氟-1，4-二氢-7-（3-甲基-1-哌嗪基）-4-氧代喹啉-6-羧酸（YH37）对临床分离的人型支原体（Mh）、解脲脲原体（Uu）以及细菌标准菌株的体外敏感性。结果显示，YH37对Mh的抑制活性较强，MIC90为0．25mg／L，是司帕沙星的1／8；对Uu的MIC90为1mg／L，是司帕沙星的1／4。YH37对Mh、Uu的喹诺酮耐药株有一定的抑制活性，其MIC分别为CPLX的1／4～1／16。YH37对被测细菌的抑制活性是左氧氟沙星的1／8～1／16，是司帕沙星的1／2。     

联合用药对鲍曼不动杆菌体外抗菌活性考察

目的:初步探究12种临床常用抗菌药物对鲍曼不动杆菌的体外抗菌活性以及几种抗菌药物的体外联合抗菌活性,为临床治疗鲍曼不动杆菌提供联合用药的实验依据。方法:河北医科大学第二医院检验科分离自临床感染患者的40株耐药鲍曼不动杆菌,采用微量肉汤稀释法测定12种临床常用抗菌药物及异帕米星与头孢哌酮钠/舒巴坦钠、头孢吡肟、比阿培南两两联用药的最低抑菌浓度(MIC)。结果:12种临床常用抗菌药物中除异帕米星对鲍曼不动杆菌显示一定的体外抗菌活性外,其余11种全部表现为强耐药;而联合用药的实验结果显示:异帕米星与头孢哌酮钠/舒巴坦钠联合后FIC均小于1,表现为协同和相加作用,比阿培南的联合抑菌指数(FIC)>1占40%,头孢吡肟的FIC>1占30%,表现为无关作用。结论:鲍曼不动杆菌对临床常用抗菌药物已经产生了很强的耐药性,临床可优先选择异帕米星与头孢哌酮钠/舒巴坦钠,也可根据患者具体情况选用头孢吡肟、比阿培南的联合进行治疗,以防耐药株的产生和医院感染的扩散,并注意消毒与隔离,防止交叉感染。