克林霉素诱导型耐药葡萄球菌体外抗菌活性研究

目的了解医院内感染可诱导克林霉素耐药葡萄球菌的发生率及常用抗菌药物对葡萄球菌的体外抗菌活性和联合药敏实验。方法细菌鉴定应用VITEK全自动细菌鉴定分析系统；药敏试验采用KB纸片法和琼脂平板稀释法，按CLSI规定的标准进行；用D-试验检测可诱导克林霉素耐药的发生率。结果2005年7月至2006年4月从临床各种感染标本中分离得到113株葡萄球菌，其中iMLSB表型（D-试验阳性）占34．5％；MSB表型（红霉素R，克林霉素S）占16．8％；cMLSB表型（红霉素R，克林霉素R）占41．6％；红霉素耐药克林霉素敏感表型葡萄球菌58株中D试验阳性率为67．2％；D-试验阳性葡萄球菌对万古霉素、左氧氟沙星、阿米卡星、头孢唑林的MIC90分别为2．0、8．0、4．0、16（mg／L），万古霉素与左氧氟沙星、阿米卡星、头孢唑林联合药敏结果MIC90均为1．0（mg／L）。结论医院内感染诱导型克林霉素葡萄球菌的发生率已越来越高，临床应根据细菌实验室的耐药表型检测合理应用抗菌药物。     

检出携带vanA基因耐万古霉素溶血葡萄球菌

目的 了解本院万古霉素敏感性减低葡萄球菌的流行情况,探讨其耐药机制.方法 分别采用菌谱分析法、万古霉素脑心浸液平板筛选法从临床分离菌株中筛选万古霉素敏感性减低葡萄球菌,并以琼脂稀释法、E-test法检测其最低抑菌浓度(MIC),以PCR方法检测耐药基因(van,mecA).结果 检出32株异质性万古霉素耐药葡萄球菌(h-VRS),1株万古霉素耐药溶血葡萄球菌(VRSH),对替考拉宁和万古霉素MIC分别为256μg/mL和128μg/mL.33株万古霉素敏感性减低葡萄球菌均检出mecA基因,32株h-VRS中均没有检出van基因;从VRSH菌株中检出vanA基因,该菌株从临床标本中检出,比较罕见.结论 万古霉素耐药葡萄球菌在我国已经出现,应当引起足够重视.     

夫西地酸对金黄色葡萄球菌抗菌活性研究

目的了解金黄色葡萄球菌对夫西地酸的耐药现状及耐药性改变。方法通过琼脂稀释法测定2007年连续收集的65株和2003年收集的55株金黄色葡萄球菌对夫西地酸的MIC值，用K—B纸片法测定这些菌株对万古霉素等7种抗生素的抑菌圈直径。结果120株金黄色葡萄球菌中对夫西地酸耐药的只有1株，耐药率为0．83％。2003年和2007年收集的菌株对夫西地酸的MIC50均为0．25mg／L，MIC90均为0．5mg／L，纸片法测定结果：所有菌株对万古霉素敏感，2003年的菌株57．8％耐甲氧西林，2007年的菌株76．9％耐甲氧西林。结论夫西地酸对金黄色葡萄球菌的体外抗菌活性很强，而且2003年和2007年菌株的抗菌活性无多大改变。     

万古霉素异质性耐药葡萄球菌的分离及其药物敏感性分析

目的 调查葡萄球菌对万古霉素异质性耐药亚群发生频率以及对常见抗生素的药物敏感性。方法 利用菌群分析法筛选万古霉素异质性耐药葡萄球菌亚群,Microscan Microbiology System对葡萄球菌分型和鉴定并分析对19种常用抗生素的药物敏感性。结果 115株耐甲氧西林的葡萄球菌,9株对万古霉素耐药亚群的MIC8－12mg/L,其发生频率为10^-4-10^-7,其中3株金葡球菌,6株溶血性葡萄球菌。传至7代后万古霉素MIC64mg/L。对19种抗生素药敏显示,万古霉素敏感2株、中介7株,敏感率22.2%;利福平敏感7株(MIC≤1mg/L）、中介1株（MIC＝2mg/L）及耐药1株（MIC＞2mg/L）、敏感率77.8%;SMZ／TMP敏感6株（MIC≤2/38mg/L）、耐药3株（MIC＞2／38mg/L）,敏感率66.7%;克林霉素敏感3株（MIC＝0.5或≤0.25）、耐药6株（MIC＞2mg／L）,敏感率33.3%;四环素敏感3株（MIC≤2mg/L）、耐药6株（MIC＞8mg/L）,敏感率33.3%;左氧氟沙星敏感1株（MIC≤2mg/L）、耐药8株（MIC＞4mg/L）,敏感率11.1%。其余13种抗生素耐药。结论 下呼吸道分离的葡萄球菌存在一定频率的对万古霉素异质性耐药株,可能是万古霉素治疗失败的原因之一,利福平、SMZ／TMP具有较好的敏感性,克林霉素和四环素次之,除了某些新型抗生素外,这些现有的药物可供临床治疗万古霉素异质性耐药葡萄球菌时参考。     

苯唑西林和万古霉素对金葡菌儿童株和成人株的体外抗菌活性差异

目的 分析苯唑西林和万古霉素对金葡菌儿童株和成人株的体外抗菌活性差异。方法用纸片扩散法检测苯唑西林和万古霉素对金葡菌的抑菌圈直径，用E-test法检测最低抑菌浓度（MIC），比较两种抗生素对金葡菌儿童株和成人株的抗菌活性。结果 纸片扩散法和E-test法检测金葡菌的药敏结果基本一致，E—test法结果显示儿童临床分离株对苯唑西林的敏感、中介和耐药率分别为88．2％、3．2％和8．6％，MIC50和MIC90分别为0．75和3．0μg／ml，成人临床分离株的敏感、中介和耐药率分别为28．2％、2．6％和69．2％。MIC50和MIC60均〉256ug／ml，成人株对苯唑西林的耐药率显著高于儿童株（r=107．1，P〈0．001）。所有菌株均对万古霉素敏感，其中儿童临床分离株的MIC50和MIC60分别为1．5和2．0μg／ml，成人临床分离株的MIC50和MIC60均为4．0μg／ml。结论 金葡菌成人株对万古霉索和苯唑西林的耐药性高于儿童株，临床应根据药敏试验结果合理选择抗生素，避免抗生素滥用。     

甲氧西林耐药溶血葡萄球菌大环内酯类和林可酰胺类耐药基因型与表型分析

目的研究甲氧西林耐药溶血葡萄球菌（MRSH）大环内酯类和林可酰胺类的耐药机制。方法琼脂稀释法测定3种抗菌药对63株溶血葡萄球菌的最低抑菌浓度（MIC），PCR技术检测mecA、ermA、ermB、ermC、msrA／msrB和linA／linA’耐药基因。结果62株MRSH均携带mecA，最常见大环内酯类和林可酰胺类耐药基因为msrA／msrB（59．7％），其次linA／linA’（50％）和ermC（32．3％），50％菌株携带2种耐药基因，3．2％菌株携带3种耐药基因；21株携带erm均对红霉素高耐（MIC≥256μg／ml），对克林霉素结构型MLSB或诱导型MLSB耐药；14株携带msrA／msrB对红霉素中度耐药（MIC=32或64μg／ml）；31株携带linA／linA’，3株对克林霉素耐药，其余均对克林霉素敏感。结论MRSH携带msrA／msrB、linA／linA’和ermC基因是其对大环内酯类和林可酰胺类产生耐药的主要原因。     

金黄色葡萄球菌对万古霉素的耐药性及耐药基因检测分析

目的 探讨金黄色葡萄球菌（SA）对万古霉素的耐药性及耐药基因分布情况。方法 收集平顶山市第一人民医院2020年4月至2022年3月临床送检样本分离的288株SA菌株,采用Vitek 2 Compact全自动细菌鉴定和药敏系统以及纸片扩散法进行菌落鉴定与药敏试验;采用聚合酶链反应检测pbp4、mgrA、agr、vraS、vraR、icaA、icaR基因表达。结果 288株SA菌株中筛选出25株万古霉素异质性耐药金黄色葡萄球菌（hVISA）菌株,hVISA阳性率为8.68%,未检测到万古霉素中介耐药金黄色葡萄球菌（VISA）菌株和万古霉素耐药金黄色葡萄球菌（VRSA）菌株;万古霉素敏感金黄色葡萄球菌（VSSA）菌株万古霉素最小抑菌浓度（MIC）主要分布在0.50 mg/L和0.75 mg/L,占比为41.83%和28.90%;hVISA菌株万古霉素MIC主要分布在1.50 mg/L和2.00 mg/L,占比为56.00%和28.00%;VSSA菌株pbp4、agr、icaR的相对表达量均低于hVISA菌株（P<0.05）,而mgrA、vraS、vraR、icaA的相对表达量均高于hV...     

头孢硫脒等6种抗菌药物对革兰氏阳性球菌体外抗菌活性研究

目的 对比研究头孢硫脒(CTM)、头孢唑林(CEZ)、头孢映辛(CXM)、头孢曲松(CRO)、苯唑西林(MPIPC)、万古霉素(VCM)对99株临床分离革兰氏阳性球菌的抗菌活性。方法采用琼脂平板稀释法测定最低抑菌浓度(MIC)。结果 CTM对32株金黄色葡萄球菌的MIC50、MIC90均为0．5mg/L，低于CRO，CTM对29株表皮葡萄球菌的MIC50、MIC90分别为0．125和8mg/L，是CRO的l／16，对9株甲氧西林耐药的葡萄球菌(MRS)的范围与CXM相近；CTM对粪肠球菌的抗菌活性与万古霉家相仿，强于CEZ、CXM、CRO、LGIPC。结论头孢硫腺对葡萄球菌和粪肠球菌具有很强的体外抗菌活性。     

左氧氟沙星联合万古霉素缩小金黄色葡萄球菌耐药突变选择窗的初步研究

目的:在体外初步探讨联合用药可缩小单药对细菌的耐药突变选择窗(MSW),为临床合理使用现有抗菌药物,防止细菌耐药产生提供理论依据。方法:应用肉汤法富集1010CFU/mL细菌,琼脂平板二倍稀释法测定左氧氟沙星、万古霉素单药和两药联用对金黄色葡萄球菌ATCC29213的最低药物浓度(MPC)和MSW。结果:左氧氟沙星、万古霉素单药对金黄色葡萄球菌ATCC29213的MSW分别为16和64。万古霉素和左氧氟沙星联合用药(1MIC 8MIC,2MIC 4MIC)使左氧氟沙星单药对ATCC29213的MSW缩小2～4倍。左氧氟沙星联合万古霉素用药(1MIC 16MIC,2MIC 8MIC)使万古霉素对ATCC29213的MSW缩小4～8倍。结论:万古霉素和左氧氟沙星联合用药可缩小各自单药对金黄色葡萄球菌ATCC29213的MSW。     

金黄色葡萄球菌167株耐药性分析

目的分析金黄色葡萄球菌的耐药性,为临床合理使用抗菌药物提供依据。方法对临床标本分离的金黄色葡萄球菌167株,采用K—B纸片法进行药敏试验,耐甲氧西林的金黄色葡萄球菌（MRSA）检测采用头孢西丁纸片扩散法。结果MRSA141株占84．4％,甲氧西林敏感金黄色葡萄球菌（MSSA）26株占15．6％。MRSA对万古霉素、呋喃西林的耐药率为0、18．4％,对其他抗菌药物呈多重耐药;除万古霉外,MRSA对其余11种抗菌药物的耐药率均高于MSSA,差异均有统计学意义（P〈0．05或P〈0．01）。结论MRSA已成为医院感染的重要病原菌,万古霉素、呋喃西林对MRSA有较高活性。重视临床微生物学检查,依据药敏结果优化选择抗菌药物,是提高感染治愈率的关键。     

替考拉宁对葡萄球菌的体外抗菌活性研究

目的 :测定替考拉宁对葡萄球菌的体外抗菌活性。方法 :采用琼脂二倍稀释法测定替考拉宁对 492株葡萄球菌的最低抑菌浓度 (MIC) ,其中金黄色葡萄球菌 3 2 4株 ,表皮葡萄球菌 1 68株。结果 :替考拉宁对葡萄球菌的MIC90 值均为 1mg·L-1,明显低于氧氟沙星、红霉素和苯唑西林 ,与万古霉素相当 ;替考拉宁对甲氧西林耐药金黄色葡萄球菌 (MR SA)和对甲氧西林耐药表皮葡萄球菌 (MRSE)的MIC90 分别为 4mg·L-1和 2mg·L-1,是万古霉素的1 / 2。抗菌活性明显高于氧氟沙星和红霉素。结论 :替考拉宁对葡萄球菌的体外抗菌活性是万古霉素的 2倍 ,明显强于氧氟沙星和红霉素     

Nosocomial infections due to methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci at a university hospital in Taiwan from 1991 to 2003: resistance trends, antibiotic usage and in vitro activities of newer antimicrobial agents

A rapid increase of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection (from 39% in 1991 to 75% in 2003) and vancomycin-resistant enterococci (VRE) (from 1.2% in 1996 to 6.1% in 2003) at a university hospital in Taiwan was found. The noticeable rise of MRSA and VRE was significantly correlated with the increased consumption of glycopeptides, beta-lactam-beta-lactamase inhibitor combinations, extended-spectrum cephalosporins, carbapenems and fluoroquinolones (Pearson's correlation coefficient, P < 0.05). Minimum inhibitory concentrations (MICs) of 100 non-duplicate blood isolates of MRSA (in 2003) and of 25 non-duplicate isolates of vancomycin-resistant Enterococcus faecalis and 172 vancomycin-resistant Enterococcus faecium (in 1996-2003) causing nosocomial infection recovered from various clinical specimens of patients treated at the hospital to nine antimicrobial agents were determined by the agar dilution method. All of these isolates were susceptible to linezolid and were inhibited by 0.5mg/L of tigecycline, and all MRSA isolates were inhibited by daptomycin 1mg/L, including two isolates of MRSA with heteroresistance to vancomycin. Daptomycin had two-fold better activity against vancomycin-resistant E. faecalis (MIC90, 2 mg/L) than against vancomycin-resistant E. faecium (MIC90, 4 mg/L). Decreased susceptibilities of vancomycin-resistant E. faecium and MRSA to quinupristin/dalfopristin (non-susceptibility 25% and 8%, respectively) were found. Telithromycin had poor activity against the isolates tested (MIC90, 8 mg/L). Linezolid, daptomycin and tigecycline may represent therapeutic options for infections caused by these resistant Gram-positive organisms.     

利奈唑胺、万古霉素对甲氧西林耐药的金黄色葡萄球菌的防耐药突变体选择浓度的研究

目的：比较利奈唑胺、万古霉素对耐甲氧西林金黄色葡萄球菌的防耐药突变选择能力;研究防耐药突变体选择浓度（MPC）和最低抑菌浓度（MIC）的相关性。方法：采用琼脂微量稀释法测定利奈唑胺、万古霉素对35株耐甲氧西林金黄色葡萄球菌（MRSA）临床分离菌株的MPC和MIC;采用线性回归法比较利奈唑胺、万古霉素对MRSA的MPC和MIC的相关性;结合人体药代动力学数据,预测利夺唑胺、万古霉素对MRSA的防耐药突变体选择能力。结果：利奈唑胺、万古霉素对35株MRSA的MPC90值（抑制90％的细菌发生细菌耐药的最低防耐药突变体选择浓度）分别为16.8μg／mL,选择指数（MPC90／MIC90）均为8。两药对MRSA的MPC和MIC的线性相关系数R^2分别为0．32和0．008。结合两药药代动力学参数,利奈唑胺药物浓度在整个给药间隔落在耐药突变选择窗理论（MSW）中,万古霉素药物浓度在大部分给药间隔落在MPC之上。结论：万古霉素对MRSA的防耐药选择能力强于利奈唑胺;MPC和MIC的相关性差。     

Antimicrobial resistance of Staphylococcus aureus isolated from skin infections

The antimicrobial susceptibility of 229 strains of Staphylococcus aureus isolated from various skin infections was determined against 22 antimicrobial agents by the agar dilution method. The clinical isolates were most sensitive to vancomycin, teicoplanin, mupirocin and fusidic acid. No strains were resistant to vancomycin or teicoplanin. Three strains were highly resistant (MIC > or =100 mg/l) to mupirocin and eight strains to fusidic acid. The MIC(50) of all antimicrobials, except for gentamicin, were below 3.13 mg/l. The incidence of resistance to penicillin, cephalosporins and clindamycin ranged from 20 to 30%. The occurrence of gentamicin, erythromycin and roxithromycin resistance was high at 55.2, 39.6 and 39.1%, respectively. Methicillin resistance occurred in 21.0% of strains. The incidence of organisms with MIC > or =3.13 mg/l to oxacillin was 24.3%. These results were comparable to the average rate of MRSA in Japanese dermatological specimens.     

In vitro antimicrobial activity of telavancin against methicillin-resistant Staphylococcus aureus clinical isolates from Japan (2006)

In vitro antimicrobial activity of telavancin, a rapidly bactericidal lipoglycopeptide, was evaluated against 1500 strains of MRSA recently isolated in Japan. Telavancin had potent activity, with MIC values that ranged from 0.12 microg/ml to 0.5 microg/ml and a MIC90 value of 0.5 microg/ml. The MIC90s of vancomycin and linezolid were 1.0microg/ml and 2 microg/ml, respectively. No vancomycin intermediate resistant or vancomycin-resistant MRSAs were detected in this surveillance study.     

Derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide as new antibacterial agents： synthesis and bioactivity

AIM: The aim of the present study was to design, synthesize, and evaluate novel antibacterial agents, derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide. METHODS: A total of 44 derivatives of aryl-4-guanidin-omethylbenzoate (series A) and N-aryl-4-guanidinomethylbenzamide (series B) were synthesized and their antibacterial activities were assessed in vitro against a variety of Gram-positive and Gram-negative bacteria by an agar dilution method. RESULTS: Twelve compounds showed potent bactericidal effects against a panel of Gram-positive germs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), vancomycin-intermediate Staphylococcus aureus (VISA), and methicillin-resistant coagulase-negative staphylococci (MRCNS), with minimum inhibitory concentrations (MIC) ranging between 0.5 and 8 microg/mL, which were comparable to the MIC values of several marketed antibiotics. They exhibited weak or no activity on the Gram-negative bacteria tested. In addition, these compounds displayed high inhibitory activities towards oligopeptidase B of bacterial origin. CONCLUSION: In comparison with the previously reported MIC values of several known antibiotics, the derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide showed comparable in vitro bactericidal activities against VRE and VISA as linezolid. Their growth inhibitory effects on MRSA were similar to vancomycin, but were less potent than linezolid and vancomycin against MRCNS. This class of compounds may have the potential to be developed into narrow spectrum antibacterial agents against certain drug-resistant strains of bacteria.     

硫肽类抗生素诺卡沙星抗革兰阳性菌的活性研究

目的：研究新型硫肽类抗生素诺卡沙星对临床常见革兰阳性致病菌的抗菌活性,探讨其抗菌机制,并与临床常用抗生素进行比较。方法：采用琼脂二倍稀释法测定最低抑菌浓度（Minimal Inhibition Concentration,MIC）,采用微量肉汤二倍稀释法测定最低杀菌浓度（Minimal Bactericidal Concentration,MBC）,采用小鼠体内抗菌保护实验测定体内抗菌活性。结果：诺卡沙星对甲氧西林耐药的葡萄球菌、青霉素耐药的肺炎球菌均显示较强的抗菌活性,对金黄色葡萄球菌MRSA、MSSA,表皮葡萄球菌MRSE、MSSE的MIC50值分别为0.016、0.016、0.0625、0.03125 mg· L-1,对肺炎球菌（PRSP/PISP）、化脓性链球菌、肠球菌的MIC50值为0.008、0.008、0.016 mg·L-1,其MIC50值为万古霉素的1/32-1/128,为莫西沙星的1/4-1/256,为利奈唑胺的1/32-1/256。注射用诺卡沙星经静脉给药后,对金黄色葡萄球菌感染小鼠均呈现体内保护作用,其ED50值明显低于对照药万古霉素和利奈唑胺,体内抗菌保护作用优于对照药。结论：诺卡沙星具有高效抗菌作用,明显优于万古霉素、利奈唑胺及莫西沙星,且与它们之间无交叉耐药现象。     

Enhancement of Vancomycin Activity by Phenothiazines against Vancomycin‐Resistant Enterococcus Faecium in vitro

Abstract: The antimicrobial and resistance‐reversal activities of seven phenothiazine derivatives were evaluated against vancomycin‐sensitive Enterococcus faecalis ATCC 29212, vancomycin resistant E. faecalis ATCC 51299 and ten vancomycin‐resistant E. faecium strains originating from human infections. Minimum inhibitory concentrations (MIC) of the compounds were determined by agar dilution method, and synergy between phenothiazines and vancomycin was investigated using Checkerboard (microbroth dilution) technique. We found that all enterococci strains, regardless of their susceptibility to vancomycin, were inhibited by phenothiazines at concentrations varying from 8 to 256 μg/ml, with thiethylperazine being the most potent inhibitory agent. Besides, all the phenothiazines showed partial synergy with vancomycin and could lessen MIC of vancomycin from 512 to 8 μg/ml at their sub‐inhibitory concentrations. The highest reduction in MIC was observed with chlorpromazine (32 times); however, thiethylperazine and promethazine stood next (24 times). Although resistance modification was observed at concentrations higher than those that phenothiazines reach in vivo, the potential offered by non‐antibiotics justify further animal experiments as well as clinical trials to establish their clinical relevance.     

2015-2018年四川地区无菌体液细菌的分布及耐药性分析

目的 对四川省细菌耐药监测网成员单位2015-2018年度无菌体液(未包括血液)的细菌分布及耐药情况进行统计分析，为本省临床合理应用抗菌药物提供依据。方法 按照监测方案，采用标准纸片扩散法、E-test法或自动化仪器检测法，依据美国临床实验室标准化研究协会(CLSI)2018年标准，用WHONET 5.6软件进行数据分析。结果 2015-2018年间四川地区无菌体液共分离出29754株非重复的细菌，其中革兰阳性菌11351株，占38.1%，革兰阴性菌18403株，占61.9%。无菌体液中最常见的细菌依次为大肠埃希菌、肺炎克雷伯菌、金黄色葡萄球菌、屎肠球菌和表皮葡萄球菌。耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的检出率分别为28.3%和63.9%。MRSA和MRCNS对绝大多数测试药物的耐药率均显著高于甲氧西林敏感株(MSSA和MSCNS)。屎肠球菌中分别检出0.5%(9株)对利奈唑胺耐药和2.2%(40株)对万古霉素耐药的菌株，粪肠球菌中发现1.7%(22株)对利奈唑胺耐药和0.3%(4株)对万古霉素耐药的菌株。耐万古霉素屎肠球菌(VRE)由4%降至1.8%，而耐利奈唑胺屎肠球菌由1.3%降至0。无菌体液标本中产ESBL大肠埃希菌和肺炎克雷伯菌的检出率分别为45.8%和25.6%，大肠埃希菌和肺炎克雷伯菌对碳氢霉烯类仍然保持较高的活性。非发酵菌对碳青霉烯类抗生素耐药率较高，其中鲍曼不动杆菌对亚胺培南的耐药率已大于65%。结论 四川地区无菌体液分离细菌对常见抗菌药物的耐药率部分仍呈增长趋势，尤其是耐碳青霉烯肺炎克雷伯菌。对万古霉素耐药的屎肠球菌分离率较高。非发酵菌特别是鲍曼不动杆菌的耐药形势严峻。应充分利用本地细菌耐药监测结果进行感控管理，促进抗菌药物合理应用。     

In vitro susceptibilities of clinical isolates of coagulase-negative staphylococci to glycopeptide antibiotics

Two hundred and thirteen clinical strains of coagulase-negative staphylococci isolated in Japan between 1980 and 1997 were analyzed for glycopeptide susceptibility by determining MIC using both Mueller-Hinton agar (MHA) and Brain Heart Infusion agar (BHIA) plates. Of 37 Staphylococcus epidermidis strains isolated between 1980 and 1981, all were susceptible to vancomycin and teicoplanin on both MHA and BHIA. However, of 122 isolates of Staphylococcus epidermidis isolated between 1994 and 1997, 1 (0.8%) was intermediate to vancomycin on MHA and 39 (32%) were intermediate on BHIA, while 3 (2.5%) and 27 (22.1%) were intermediate or resistant to teicoplanin on MHA and BHIA, respectively. It was demonstrated that the susceptibilities of the strains in 1990s to vancomycin and teicoplanin were significantly decreased compared with those in 1980s. Population analysis was performed with six strains each of Staphylococcus epidermidis and Staphylococcus haemolyticus (three with vancomycin MIC > or = 8 micrograms/ml and three with vancomycin MIC < or = 4 micrograms/ml using BHIA). The population curves of the Staphylococcus epidermidis strains showed a homogeneous pattern of susceptibility. Whereas, those for two Staphylococcus haemolyticus strains (vancomycin MIC = 8 micrograms/ml using BHIA) showed a typical heterogeneous pattern. Vancomycin-resistant mutants (MIC > or = 32 micrograms/ml) were obtained with a high frequency of 10(-4)-(-5) from the strains by one-step selection with 16 micrograms/ml of vancomycin.