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。     

In vitro efficacy of imipenem in combination with six antimicrobial agents against Mycobacterium abscessus

Antimicrobial therapy of Mycobacterium abscessus infection is difficult because there are relatively few effective treatment regimens and single-agent therapy frequently fails clinically. In light of the lack of data on the susceptibility profile of M. abscessus strains recovered from infections in Japan, the in vitro activity of imipenem in combination with clarithromycin, levofloxacin, moxifloxacin, minocycline, amikacin or tobramycin was investigated by the checkerboard method and compared with the combination amikacin and cefoxitin. The combination of imipenem with moxifloxacin, levofloxacin or clarithromycin had a higher synergistic and/or additive effect than amikacin and cefoxitin. A decrease in the MIC(90) value (minimum inhibitory concentration for 90% of the organisms) was observed in the presence of imipenem for clarithromycin, minocycline, levofloxacin and moxifloxacin. The data suggest that a combination regimen including imipenem may be a good choice in empirical treatment of M. abscessus infection.     

抗菌药物联用对耐甲氧西林金黄色葡萄球菌体外抗菌活性研究

目的了解万古霉素与头孢哌酮/舒巴坦、亚胺培南、左氧氟沙星联用对MRSA的体外抗菌活性,指导临床合理用药。方法常规方法培养分离细菌,用VITEK微生物自动分析仪或API系统鉴定到种。MRSA鉴定应用乳胶凝集试剂盒,药敏试验采用肉汤倍比稀释法和琼脂平板稀释法。结果万古霉素对40株MRSA的MIC90为4mg/L,而与头孢哌酮/舒巴坦、亚胺培南、左氧氟沙星联用MIC90降为0.25～1mg/L。结论万古霉素与上述三种药物联用以协同作用为主,抗菌活性提高4倍以上。临床上治疗由MRSA引起的重症感染应根据药敏试验结果采用万古霉素与亚胺培南或头孢哌酮/舒巴坦或其它抗菌药物联合应用。     

8-Hydroxyquinolines are bactericidal against Mycobacterium tuberculosis

There is an urgent need for new treatments effective against Mycobacterium tuberculosis, the causative agent of tuberculosis. The 8-hydroxyquinoline series is a privileged scaffold with anticancer, antifungal, and antibacterial activities. We conducted a structure–activity relationship study of the series regarding its antitubercular activity using 26 analogs. The 8-hydroxyquinolines showed good activity against M. tuberculosis, with minimum inhibitory concentrations (MIC90) of <5 μM for some analogs. Small substitutions at C5 resulted in the most potent activity. Substitutions at C2 generally decreased potency, although a sub-family of 2-styryl-substituted analogs retained activity. Representative compounds demonstrated bactericidal activity against replicating M. tuberculosis with >4 log kill at 10× MIC over 14 days. The majority of the compounds demonstrated cytotoxicity (IC₅₀ of <100 μM). Further development of this series as antitubercular agents should address the cytotoxicity liability. However, the 8-hydroxyquinoline series represents a useful tool for chemical genomics to identify novel targets in M. tuberculosis.     

头孢硫脒与其他6种抗菌药物对表皮葡萄球菌体外联合药敏的研究

目的 :评价头孢硫脒分别与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧沙星和加替沙星等 6种抗菌药物联合用药 ,对于表皮葡萄球菌 (Staphylo coccusepidermidis ,SE)的体外联合抗菌效应。方法 :采用棋盘法设计 ,微量肉汤稀释法测定不同浓度组合的 6组抗菌药物对 30株临床分离的表皮葡萄球菌的最低抑菌浓度 (MIC) ,并计算部分抑菌指数 (FIC指数 )。结果 :头孢硫脒对表皮葡萄球菌的MIC50 、MIC90 为 1、6 4mg·L-1;与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧沙星、加替沙星联合应用后 ,其MIC50 分别降低至 0 .12 5、0 .12 5、0 .12 5、0 .12 5、0 .2 5、0 .12 5mg·L-1,MIC90 分别降低至 1、1、1、2、1、1mg·L-1。结论 :6种抗菌药物与头孢硫脒联合用药后 ,对表皮葡萄球菌球菌基本表现为协同或相加作用 ,并以协同作用为主 ,无关作用较少 ,无拮抗作用。     

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.     

5种抗菌药物对厌氧菌的体外抗菌活性研究

测定了罗红霉素、ａｚｉｔｈｒｏｍｙｃｉｎ、头孢西丁、托舒沙星对６０株厌氧菌的体外抗菌活性，并同甲硝唑比较，发现托舒沙星对厌氧菌的体外抗菌活性最好，ＭＩＣ_（５０）和ＭＩＣ_（９０）为０．１２５和２ｍｇ／Ｌ优于甲硝唑（０．２５和１６ｍｇ／Ｌ）；罗红霉素（０．５、１６ｍｇ／Ｌ）与甲硝唑相似，ａｚｉｔｈｒｏｍｙｃｉｎ、头孢西丁的体外抗菌活性比甲硝唑略差，ＭＩＣ_（５０）和ＭＩＣ_（９０）分别为４和３２、２和３２ｍｇ／Ｌ，它们对脆弱拟杆菌的体外抗菌活性优于对其它拟杆菌的体外抗菌活性，对短真杆菌、变形链球菌、普氏消化链球菌等也具有较好的体外抗菌活性。     

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.     

Comparative in vitro activity of phenothiazines against multidrug-resistant Mycobacterium tuberculosis

The comparative activity of five phenothiazines against multidrug-resistant strains of Mycobacterium tuberculosis (MDRTB) was studied using the Bactec 460 system. The order of antimycobacterial activity of the phenothiazines was: chlorpromazine = thioridazine > promethazine > promazine = desipramine. However, the levels required for an MIC 50 exceeded 1 mg/l and are beyond those that are clinically achievable. As phenothiazines are concentrated by macrophages that phagocytose and have in situ activity against mycobacteria, these agents may be considered for use as adjuvants for the management of freshly diagnosed tuberculosis in patients from populations with a high prevalence of MDRTB.     

In vitro activity of four fluoroquinolones against Mycobacterium tuberculosis

The in vitro activity of ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin against strains of Mycobacterium tuberculosis was studied. Moxifloxacin and levofloxacin showed the greatest activity having an MIC(90) of 1 mg/l. The MIC(90) for ofloxacin was 2 mg/l and for ciprofloxacin 4 mg/l. Further studies should be made to determine the role played by these compounds in the treatment of tuberculosis.     

Comparative in vitro activities of several antimicrobial agents against Helicobacter pylori

Comparative in vitro activities of several antimicrobial agents against Helicobacter pylori were evaluated. Minimum inhibitory concentrations against 41 strains of H. pylori were determined by using E test. All 41 strains were isolated from gastric mucosa of patients suspected to have gastric ulcer. The ranges of MIC of amoxicillin was from 0.016 microgram/ml and less to 0.064 microgram/ml. The ranges of MIC of clarithromycin, erythromycin, and azithromycin were from 0.016 microgram/ml and less to 64 micrograms/ml, from 0.016 microgram/ml and less to more than 256 micrograms/ml, from 0.064 to more than 256 micrograms/ml, respectively. The ranges of MIC of ciprofloxacin, sparfloxacin, levofloxacin, norfloxacin were from 0.016 microgram/ml and less to 32 micrograms/ml, from 0.002 microgram/ml and less to more than 32 micrograms/ml, from 0.002 microgram/ml and less to more than 32 micrograms/ml, from 0.064 to more than 32 micrograms/ml, respectively.     

In vitro synergy of ciprofloxacin and three other antibiotics against Bacteroides fragilis

The potential in vitro synergistic effect of ciprofloxacin associated with mezlocillin, cefoxitin and clindamycin was evaluated against 30 strains of Bacteroides fragilis. All bacteria were clinical isolates, identified by gas chromatography and fermentation of carbohydrates. MICs of the drugs were determined by a miniaturized dilution broth method. Resistance or susceptibility to the drugs was not a criterion for the selection of the strains. Antibacterial combinations were tested by a checkerboard method utilizing brain hearth infusion broth and a bacterial inoculum of 10(6) CFU/ml. Microtitre plates were incubated at 37 degrees C for 48 h in anaerobic jars (BBL). Prereduced chopped meat carbohydrate broth was used to store and culture the strains. The effect of antimicrobial combinations was defined on the basis of the fractionary inhibitory concentration (FIC) indexes. We considered: synergistic effect FIC less than or equal to 0.5; additive effect FIC = 0.5-0.75; indifferent effect FIC = 0.76-2.0; antagonism FIC greater than or equal to 2. Ciprofloxacin + clindamycin showed synergistic activity against 10 strains out of 26 (38%); ciprofloxacin + mezlocillin against 9 strains out of 30 (30%); and ciprofloxacin + cefoxitin against 8 out of 29 strains (28%). Each antibiotic combination showed an additive or indifferent effect against all remaining bacteria. The synergistic effect of ciprofloxacin represents an important advantage in allowing the reduction of the dosage of associated drugs such as aminoglycosides or beta-lactams that can potentially be responsible for damage or side-effects.     

In vitro activity of linezolid against multidrug-resistant Mycobacterium tuberculosis isolates

Information in the literature regarding the activity of linezolid against multidrug-resistant (MDR) Mycobacterium tuberculosis strains is scarce. We therefore tested the in vitro activity of this drug against 39 MDR M. tuberculosis strains isolated from clinical specimens using the Bactec 460 TB system. All strains were inhibited by < or = 8 mg/L (minimum inhibitory concentration (MIC); MIC50 = 4 mg/L, MIC90 = 8 mg/L). Although the MIC values are higher than in other studies, based on proposed breakpoints all strains were found to be susceptible to linezolid. Further investigations to prove its usefulness in the treatment of MDR tuberculosis should be carried out.     

18种抗菌药物体外抗解脲枝原体活性的比较

采用微量稀释法，比较了１８种抗菌药物对６２株解脲枝原体的体外抑制作用。结果显示解脲枝原体对青霉素、氨苄西林、利福平、多粘菌素Ｂ、林可霉素、磺胺嘧啶钠、呋喃妥因不敏感，其ＭＩＣ_（９０）＞１０２４μｇ／ｍｌ；对红霉素、头孢唑林、大观霉素、庆大霉素、卡那霉素、链霉素、诺氟沙星有一定的耐药性，其ＭＩＣ_（９０）在１６～６４μｇ／ｍｌ之间，对盐酸四环素、氯霉素、氧氟沙星和多西环素有较高的敏感性，其ＭＩＣ_（９０）≤８μｇ／ｍｌ，尤以多西环素为著，其对四环素耐药的解脲枝原体株都有较强的抑制作用。     

帕司烟肼介入凝胶体外抗结核活性及安全性研究

目的 观察帕司烟肼凝胶体外抗结核作用和支气管介入的安全性。方法 手工法、仪器法分别测定帕司烟肼及其凝胶的最小抑菌浓度和最小杀菌浓度及家兔经支气管介入的安全性试验。结果 帕司烟肼凝胶对H37Rv标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为0．1、0，1、0．4mg／L，MBC值分别为0，2、0．2和1．6mg／L；帕司烟肼凝胶与帕司烟肼单体MIC、MBC值无显著差异；动物实验表明该药应用安全。结论 帕司烟肼凝胶具有与帕司烟肼单体相同的抗结核菌药效，卡波姆基质不影响帕司烟肼的抗菌活性；以卡波姆为基质的帕司烟肼凝胶应用安全。     

In vitro activities of fourteen antimicrobial agents against obligately anaerobic bacteria

The in vitro activities of fourteen antimicrobial agents were tested against 292 clinical isolates of obligately anaerobic bacteria using the broth microdilution technique. Taking all strains as a group the MIC(50/90) (mg/l) values were metronidazole and imipenem 0.25/1, meropenem 0.25/0.5, trovafloxacin 0.25/1, gatifloxacin and moxifloxacin 0.5/2, levofloxacin 2/16, ciprofloxacin 4/32, clindamycin 0.5/8, amoxycillin/clavulanate 1/4, doxycycline and chloramphenicol 2/4, erythromycin 4/>32 and penicillin G 16/>32.     

In vitro activity of linezolid against Mycobacterium tuberculosis complex, including multidrug-resistant Mycobacterium bovis isolates

The activity of linezolid was studied against 55 Mycobacterium tuberculosis (42 susceptible, 3 isoniazid resistant and 10 isoniazid and rifampicin resistant), one Mycobacterium bovis and two multidrug-resistant M. bovis isolates using the standard 7H10 agar proportion and the ESP Culture System II methods. Both methods displayed similar MIC(90) values (minimum inhibitory concentrations for 90% of the organisms) of 0.5mg/L; however, the former method yielded slightly lower MIC(50) values (MICs for 50% of the organisms) (0.25mg/L) compared with the latter method (0.5mg/L). No differences were observed between susceptible and resistant isolates, including multidrug-resistant M. bovis isolates, with a MIC range of 0.12-0.5mg/L. The potential role of linezolid in tuberculosis patients requires further in vivo evaluation.     

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.