硫脒头孢菌素、氨苄青霉素单独及联合艮他霉素对肠球菌的杀菌作用的研究

作者比较硫脒头孢菌素(Cefathiami-dine)和氨苄青霉素、头孢菌素Ⅱ及唑啉头孢菌素等的体外抗肠球菌的活性。在一系列含对倍稀释抗生素的平皿上,采用多点接种器和 Iso-sensitest 琼脂,37℃过夜培养。其结果检得硫脒头孢菌素2mg/l、氨苄青霉素4mg/l(除对一株菌8mg/l)、头孢菌素Ⅱ16mg/l 或唑啉头孢菌素32mg/l 能抑制全部56株被试粪链球菌。对三株粪链球菌的作用:二株临床分离菌对四种抗生素均耐药(MIC≥128mg/l),另一株为粪链球菌标准菌株 NCTC7171,上述四种抗生素的 MIC 则分别为4、2、2和64mg/l。用试管法(1株菌)和平皿法(21株菌)证实接种量变化(10~2～10~7)对硫脒头孢菌素的 MIC 值影响不大。用四种方法比较研究硫脒头孢菌素与氨苄青霉素对同一株粪链球菌的杀菌效果,结果相似。10株菌试管法显示两药的 MBC 均大于256mg/l,即     

Ciprofloxacin对耐甲氧西林金葡菌的活性

作者采用肉汤二倍稀释法测定了 Cipr-ofloxacin 及万古霉素等六种抗生素对54株临床分离的耐甲氧西林金葡菌(MRSA)的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)所有菌株对三个耐酶青霉素——甲氧西林、乙氧萘青霉素和苯唑青霉素全部耐药;许多菌株对庆大霉素也耐药;45%菌株对氯林霉素耐药;但全部菌株对 Ciprofloxacin 和万古霉素敏感。Ciprofloxacin 对这些 MRSA 的MIC_(50)为0.25μg/ml,MIC_(90)为0.5μg/ml。Ciprofloxacin 和万古霉素对所有被试菌呈现杀菌作用,MBC_(90)分别为1.0和2.0μg/ml。对15株 MRSA 杀菌动力学的研究指出,当接种菌量为5.0×10~5CFU/ml 时,Cipro-floxacin 和万古霉素的杀菌率没有显著不     

β-内酰胺酶抑制剂CP-45899体外抗菌活性的研究

CP-45899是一个化学合成的β-内酰胺酶抑制剂,其体内外抗菌协同作用国外已有报道。1981年我所合成了CP-45899,本文介绍它与青霉素、氨苄青霉素在体外对耐青霉素、氨苄青霉素的革兰氏阳性、阴性菌的协同抗菌作用。 实验用菌株均为1979年至1982年在四川地区收集的临床致病菌共106株。最小抑菌浓度(MIC)及最小杀菌浓度(MBC)是用肉汤二倍稀释法测定,菌接种量约为10~6个/ml。做MIC时肉眼未见生长管,吸0.1ml作平皿培养,37℃培养24小时,无菌落生长为MBC。β-内酰胺酶由四川制药厂提供的腊样芽孢杆菌63503菌株所产生,每毫升约80万单位。CP-45899与酶作用时间以及加入青霉素的时间各为30分钟,金黄色葡萄球菌209P为检     

磺苄西林对粘液型和非粘液型绿脓杆菌的体外抗菌活性

用试管双倍稀释法测定磺苄西林(Sulbenicil-lin)、羧苄青霉素、氨苄青霉素、哌拉西林(Piperacil-lin)和头孢噻肟对20株粘液型和50株非粘液型绿脓杆菌的体外抗菌活性。结果表明,细菌接种量为10~(-4)CF U/ml 时,磺苄西林的抗菌活性较羧苄青霉素强,但较哌拉西林和头孢噻肟弱。显然,这些细菌对受试的β-内酰胺抗生素具高度耐药性,尤当细菌接种量为10~7CF U/ml 时更为明显。哌拉西林和头孢噻肟在接种量为10~7 CFμ/ml 时的抗菌活性较10~4时为小,这在杀菌浓度时更为明显。磺苄西林、羧苄青霉素和头孢噻肟的MBC/MIC 比率范围为1～2,而哌拉西林则为3～     

头孢吡肟对质粒介导产AmpC β-内酰胺酶大肠埃希菌的接种效应研究

目的本实验研究了临床分离的质粒介导AmpC β-内酰胺酶大肠埃希菌,在两种接种浓度下(标准浓度105CFU/ml和高浓度107CFU/ml)测定头孢吡肟、头孢噻肟、头孢他啶、头孢哌酮/舒巴坦和亚胺培南的MIC值。方法19株血培养的质粒介导的AmpC β-内酰胺酶大肠埃希菌,其中10株单产ACT型,5株单产DHA型,4株产ACT DHA型。采用琼脂稀释法测定头孢吡肟等5种抗生素在两种接种浓度下的MIC值。高接种浓度下测得的MIC值较标准接种浓度下的MIC值≥8倍时定义为有接种效应。结果在标准接种浓度下,亚胺培南的敏感率为100%,头孢吡肟也有84.2%的高敏感率,头孢哌酮/舒巴坦的敏感率为5.3%,头孢噻肟和头孢他啶的敏感率为0。在两种接种浓度下,头孢吡肟MIC值增加从32倍到100多倍不等,100%有接种效应,而亚胺培南几乎没有接种效应。结论头孢吡肟有明显的接种效应,尽管本文结果为实验室的体外实验结果,但仍建议:头孢吡肟不推荐为临床上治疗由质粒介导AmpC β-内酰胺酶大肠埃希菌引起的严重感染的药物。     

三种新喹诺酮对厌氧菌的体外活性

作者应用布鲁氏菌深红色血培养基琼脂稀释技术,测定了三种新喹诺酮类药物司帕沙星(Sparfloxacin)、替马沙星和WIN57273对厌氧菌的抗菌活性。其它抗菌药物包括:环丙沙星、Imipenem、氯霉素、甲硝唑、头孢替坦、头孢西丁和羟氨苄青霉素加克拉维酸。由于研究是分别进行的,应避免直接对照,本文是三项研究的摘要。实验中使用的细菌是Wadsworth医疗中心最近临床分离的菌株中随机采集的,并按规定程序鉴定。MICs测定用10~5CFU的接种菌和布鲁氏菌深红色血培养基。平皿在GasPak瓶(BBL,Cockeysville,Md)中,或是一个厌氧室(Anaerobe Systems,San Jose,Calif)中孵育37℃48h。以细菌未生长,或未见单一     

氨噻三嗪头孢菌素的药理与临床应用

氨噻三嗪头孢菌素(Cefatriaxon,商品名 Rocephin)对临床分离的大多数肠细菌属与氨噻肟头孢菌素有相似的抗菌活性。对绿脓杆菌的抗菌活性比氨噻肟头孢菌素强二倍,比羧噻吩青霉素强三倍,MIC 为7.2μg/ml;当浓度为17.2μg/ml 时可抑制对羧噻吩青霉素耐药的菌株。对流感嗜血杆菌的活性比氨苄青霉素强四倍,对β-内酰胺酶产生菌的抗菌活性与氨苄青霉素相当。对青霉素 G     

甲磺酸加替沙星与其他4种氟喹诺酮类药物对临床分离菌的体外抗菌活性比较

目的 :比较甲磺酸加替沙星与氧氟沙星、左氧沙星、环丙沙星、司帕沙星对 182株临床分离菌的体外抗菌活性。方法 :采用琼脂平板二倍稀释法测定加替沙星等 5种氟喹诺酮类药物对 182株临床试验分离菌株的最低抑菌浓度 (MIC)。结果 :加替沙星对葡萄球菌属的MIC90 比其他 4种氟喹诺酮类药物低。葡萄球菌属对加替沙星的敏感率显著高于其他4种氟喹诺酮类药物 ;对其他G 球菌的MICR 也较其他氟喹诺酮类药物低。G-杆菌中埃希菌属、肠杆菌属对加替沙星的敏感率明显高于其他 4种氟喹诺酮类药物 ,加替沙星对埃希菌属、肠杆菌属的MIC90比左氧沙星低 2倍 ,比其他 3种抗菌药物低 8倍 ;假单胞菌属、克雷伯菌属和其他G-杆菌对加替沙星的敏感率与左氧沙星的差异无统计学意义 ,与其他 3种氟喹诺酮类药物的差异有统计学意义。结论 :甲磺酸加替沙星具有广谱而强大的体外抗菌活性。     

一种作为β-内酰胺酶抑制剂的β-内酰胺砜化合物

CP—45899是一种青霉烷酸砜,结构式如图。它是一种许多革兰氏阳性菌和阴性菌及厌氧菌产生的β-内酰胺酶抑制剂。CP—45899对金葡菌或表皮葡萄球菌等大部份革兰氏阳性球菌及大多数肠杆菌科和绿脓杆菌抗菌活力很低。但对淋病双球菌和脑膜炎奈瑟氏菌0.1—6.2μg/ml 有效。对从临床分离的283个菌株活力试验,CP—45899与氨苄青霉素联用,对含β-内酰胺酶菌株66%有完全协同作用(即两种药物 MIC 值减少四倍)和25%有部份     

志贺菌主动外排系统对氟喹诺酮类抗生素耐药性的影响

目的 探讨主动外排系统AcrAB-TolC在志贺菌对氟喹诺酮类抗生素耐药性中的作用.方法 K-B纸片扩散法及MIC测定2009-2011年天津地区临床分离的144株志贺菌的药敏情况;加入泵抑制剂CCCP(羰基氰氯苯腙)检测耐药菌株对氟喹诺类抗生素敏感性的变化;应用定量PCR研究外排泵基因acrAB-tolC表达以探讨外排泵在菌株对氟喹诺酮耐药中的作用.结果 144株志贺菌中,共有5株志贺菌对环丙沙星等氟喹诺酮类抗生素耐药,均为福氏志贺菌.加入泵抑制剂后,5株志贺菌对5种氟喹诺酮类抗生素的MIC下降了4～16倍,而对照菌株对上述药物的MIC没有变化或仅下降至原值的1/2.实时定量PCR结果表明耐药菌株外排泵基因acrA、acrB和tolC的mRNA水平显著高于敏感野生株(P＜0.05).结论 本地区志贺菌临床株对氟喹诺酮类抗生素环丙沙星及氧氟沙星耐药率最高,为3.47％.AcrAB-TolC外排泵基因的高表达是导致志贺菌对氟喹诺酮类抗生素耐药的主要原因之一.     

Antimicrobial activity of oral quinolones against clinical isolates of Bifidobacterium group and Clostridium difficile

Administrations of antimicrobial agent influence human intestinal flora, and sometimes lead to cause Clostridium difficile colitis (CDC). It has been well known that antimicrobial agents, such as clindamycin (CLDM), ampicillin (ABPC) and cephems, frequently cause C. difficile colitis, however, recently some respiratory quinolones, such as garenoxacin (GRNX) and moxifloxacin (MFLX), have paid to attention. Bifidobacterium species would be highly associated with the preservation of normal intestinal flora, while C. difficile would be associated with diarrhea related with antibiotics administration. We investigated antimicrobial activity of GRNX, MFLX and levofloxacin (LVFX) by agar dilution methods based on CLSI recommendations. Forty-seven strains Bifidobacterium species isolated from healthy human intestinal flora and 51 strains of C. difficile isolated from C. difficile colitis patients between 2004 and 2006 were subjected to this study. MIC ranges of Bifidobacterium species for GRNX, MFLX and LVFX were 0.5-16, 0.06-2, and 0.5-8 microg/mL, respectively. MIC50 s of GRNX, MFLX and LVFX against Bifidobacterium species were 2, 0.5 and 4 microg/mL, respectively. MIC90 s of GRNX, MFLX and LVFX against Bifidobacterium species were 8, 2 and 8 microg/mL, respectively. MIC ranges of C. difficile for GRNX, MFLX and LVFX were 0.5 - > 64, 1-64, and 0.125-32 microg/mL, respectively. MIC50s of GRNX, MFLX and LVFX against C. difficile were 2, 2 and 0.5 microg/mL, respectively. MIC90 s of GRNX, MFLX and LVFX against C. difficile were 64, 16 and 8 microg/mL, respectively. LVFX would preserve Bifidobacterium species, and also would be bactericidal for C. difficile, which might lead to the low rate of gastrointestinal disorder in LVFX. GRNX would preserve Bifidobacterium species, however, might be lead to CDC in some cases, since antimicrobial activity for C. difficile has been weak compared with LVFX. Since MFLX would be bactericidal for Bifidobacterium species and antibacterial activity of MFLX for C. difficile would be weak compared with LVFX, we have to pay attention to antibiotics associated diarrhea in MFLX treatment.     

Antibacterial activity of aztreonam: a synthetic monobactam. A comparative study with thirteen other antibiotics

The in vitro activity of aztreoman (SQ 26, 776), a new monocyclic beta-lactam antimicrobial agent, was determined against 1720 bacteria, all clinical isolates, and compared with that of thirteen beta-lactam and aminoglycoside antibiotics. Aztreonam inhibited 90% of Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, E. coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii, Proteus rettgeri, Proteus vulgaris and Salmonella sp. by less than or equal to 0.4 micrograms ml-1. This activity was superior to moxalactam, piperacillin, cefamandole, cefoperazone, cefoxitin, cefsulodin, ceftazidime and aminoglycoside antibiotics. Aztreonam was as active as moxalactam against Enterobacter aerogenes, Enterobacter cloacae and Shigella species. Pseudomonas aeruginosa strains resistant to moxalactam, piperacillin, cefamandole, cefoperazone, cefotaxime, cefoxitin, cefsulodin and ceftazidime were inhibited by aztreonam 50% by 6.3 micrograms ml-1 and 90% by 16 micrograms ml-1. Aztreonam was as active as ceftazidime against Serratia marcescens, all strains were inhibited by 3.1 micrograms ml-1 and 90% by 1.6 micrograms ml-1. There was no major difference between MBC and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU.     

Comparative in vitro activity of aztreonam and other antimicrobial agents against Salmonella species

The in vitro activity of aztreonam, the first monobactam antibiotic, was compared with that of 17 other antimicrobial agents against 79 strains of Salmonella species. The microorganisms were isolated from hospitalized patients, surface waters and seafoods during the decade 1975-1984. They included the following species: Salmonella typhi 63, Salmonella typhimurium 5, Salmonella wien 5, Salmonella heidelberg 2, Salmonella arizonae 2, Salmonella paratyphi B 1 and Salmonella enteritidis 1. The minimum inhibitory concentration (MIC) values of the antibiotics were determined using a serial dilution method in agar. A final inoculum size of 10(5) colony-forming units (CFU) X ml-1 of the tested microorganisms was used. Aztreonam exhibited a superior antimicrobial activity to that of the other antibiotics tested. Aztreonam inhibited 90% of the strains by 0.8 micrograms X ml-1 (MIC range was 0.05 to 1.56 micrograms X ml-1). There was no major difference between minimum bactericidal concentration and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU X ml-1.     

Antibacterial activity of gatifloxacin against various fresh clinical isolates in 2002

Antibacterial activities of gatifloxacin (GFLX) and other antibacterial drugs against various fresh clinical strains (800 isolates) isolated from specimens of patients in 2002 were compared. GFLX was more active than levofloxacin and ciprofloxacin against Gram-positive bacteria such as methicillin susceptible Staphylococcus aureus and Streptococcus pneumoniae. For these isolates, clarithromycin and azithromycin were less active (MIC90; > 16- > 64 micrograms/mL), GFLX was more active than cefdinir. For Escherichia coli, Klebsiella pneumoniae, Acinetobacter species, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis, three quinolones including GFLX were potently active (MIC90; < or = 0.06-0.5 microgram/mL). Pseudomonas aeruginosa isolated from urinary tract infections were resistant to three quinolones including GFLX (MIC90; 32-64 micrograms/mL), however P. aeruginosa isolated from respiratory and otolaryngological infections were more susceptible (MIC90; 0.5-2 micrograms/mL). Quinolones were less active against Neisseria gonorrhoeae as compared with the cephem antibiotics tested, but GFLX was the most active against N. gonorrhoeae among the quinolones tested. In this study, we investigated activity of GFLX against fresh clinical strains isolated early in 2002, GFLX is widely and potently active against S. aureus, S. pneumoniae and various Gram-negative bacteria.     

Activity-bioavailability balance in oral drug development for a selected group of 6-fluoroquinolones

A nomogram is proposed to select the best candidate in drug development studies with quinolones and is intended to substitute other possible models. The nomogram is referred to as an activity-bioavailability balance (ABB) because it includes the following two criteria: ABB = [(1/gm MIC drug candidate)/ (1/gm MIC ciprofloxacin)].[(F(calc) drug candidate)/( F(calc) ciproflaxacin)]. The in vitro activity of a group of 4'N-alkyl-ciprofloxacin derivatives was determined together with that of ciprofloxacin, initially against some reference strains and subsequently against 159 clinical isolates of eight selected species. The inverse of the geometric mean of the lowest concentration of drug at which the original inoculum was reduced to no more than two colonies (1/gm MIC), as an antimicrobial activity parameter, and the absolute oral bioavailability index (F(calc)), as predicted from in situ intestinal absorption rate constants, were used for calculation of the ABB values, which ranged from 0.1 to 17 for the species and compounds tested. Ciprofloxacin was the best candidate only against Escherichia coli, whereas 4'N-methyl- and/or 4'N-ethyl-ciprofloxacin showed better or much better ABB values than the model drug, and can be selected as potential drug candidates against the remaining clinical strains. The procedure described could be a useful technique for further drug development studies.     

Studies on susceptibility of isolated organisms from pediatric infections against various antimicrobial agents

Twelve oral antimicrobial agents were tested for their antimicrobial activities against causative organisms isolated from pediatric infections. Activities of these antimicrobial agents against Streptococcus pyogenes were also examined in relation to T-antigen typing of the species. The results of the investigation are summarized as follows. 1. Against Staphylococcus aureus, rokitamycin (RKM), josamycin, ofloxacin, minocycline exhibited strong antimicrobial activities, and few strains of S. aureus showed resistance to these antimicrobial agents. More strains exhibited resistance to erythromycin (EM) than to other macrolide antibiotics (MLs) examined. Amoxicillin (AMPC)-resistance was often observed also. 2. Against S. pyogenes, beta-lactam antibiotics (beta-lactams) and RKM had MIC80 of 0.20 microgram/ml or below, and no resistant strains of this organism were observed against these antibiotics. Only 2 resistant strains (2.0%) of S. pyogenes to MLs were detected, but resistance to tetracyclines (TCs) was observed at a high frequency, with 71.4% or more strains among T-4, T-6, T-12 and T-28 antigen types exhibited resistance to TCs. Among the 21 strains of T-12 antigen type examined, only one strain (4.8%) was found resistant to MLs. These observations suggested that the reduction in the frequency of ML-resistant strains was not due to the reduction in the number of T-12 antigen type strains but due to losses of resistance factors against MLs of plasmids. 3. Antibacterial activities of beta-lactams and MLs against Streptococcus pneumoniae strains were good, similarly to activities against S. pyogenes. But many strains of S. pneumoniae were resistant to TCs. 4. New quinolone antimicrobial agents (quinolones) showed excellent activities against Branhamella catarrhalis strains with EM and RKM showing the next best activities. The number of resistant strains against quinolones, however, seemed to be on an increase. 5. Quinolones had strong antimicrobial activities against Haemophilus influenzae, few strains of which showed resistance to quinolones. AMPC had the next best activity, but approximately 10% of H. influenzae exhibited resistance to this antibiotic. 6. Against Campylobacter spp., quinolones and MLs showed the best activities with MIC80 values at or below 0.25 microgram/ml, and no resistant strains of the species against these antimicrobial agents were observed. Fosfomycin and TCs showed somewhat inferior activities to quinolones and MLs, with beta-lactams showing still lower activities. 7. Only few strains of Mycoplasma pneumoniae and Chlamydia trachomatis were examined, but MLs and TCs appeared to be effective against these organisms.(ABSTRACT TRUNCATED AT 400 WORDS)     

Susceptibility of Brucella melitensis to fluoroquinolones

In vitro activity of four fluoroquinolones and four other antibacterial agents was tested against clinical isolates of Brucella melitensis. Initially all the 146 isolates studied were inhibited by 0.06-0.5 mg/l of ciprofloxacin and fleroxacin and 0.12-0.5 mg/l of pefloxacin or norfloxacin. One of these isolates developed resistance during therapy with ciprofloxacin, with a rise in MIC from 0.06 mg/l to more than 5.0 mg/l. This strain also showed cross-resistance to all other quinolones. All the isolates remained susceptible to tetracycline, gentamicin, rifampicin and trimethoprim-sulfamethoxazole. None of the quinolones showed in vitro synergy with other antibiotics.     

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.     

Piperacillin (T-1220), a new semisynthetic penicillin: in vitro antimicrobial activity comparison with carbenicillin, ticarcillin, ampicillin, cephalothin, cefamandole and cefoxitin

Piperacillin (T-1220) is a new semisynthetic penicillin with an unusually broad spectrum of antimicrobial activity. In vitro comparisons of this drug with 6 other beta-lactam antimicrobics (ticarcillin, carbenicillin, ampicillin, cephalothin, cefamandole and cefoxitin) were conducted. These included minimal inhibitory concentrations (MIC) against 394 bacterial isolates, the minimal lethal concentrations (MLC) against 79 of those, as well as the effect of inoculum size on the MIC and MLC of the drugs. Piperacillin had significantly greater activity than did the other penicillins against Pseudomonas species and Klebsiella pneumoniae. Against P. aeruginosa piperacillin was 8- and 16-fold more active than ticarcillin and carbenicillin, respectively. The MLC of piperacillin rarely differed from the MIC by more than one log2 dilutions except against P. aeruginosa in which the MLC was 4-fold greater or more than the MIC of 45% of isolates tested. Ticarcillin, carbenicillin and cefoxitin showed minimal inoculum size effects. Cefamandole results showed the greatest inoculum size variation with 55% and 37% of isolates showing an 8-fold increase in MIC and MLC respectively by increasing inoculum from 10(5) to 10(7) CFU/ml. Piperacillin was intermediately effected having 25% of strains greater than 8-fold increase in MIC.