广东东莞地区葡萄球菌对红霉素和克林霉素诱导耐药性的调查

目的了解广东东莞地区葡萄球菌大环内酯类药物的耐药情况及耐药机制。方法按美国临床实验室标准化研究所（CLSI）推荐的纸片扩散法测定葡萄球菌对红霉素及克林霉素的耐药性，并以D试验测定红霉索对克林霉素的诱导耐药表型。结果719株葡萄球菌红霉素及克林霉素同时耐药为45．5％，D试验阳性占所检的葡萄球菌的18.6％。在单一纸片红霉素耐药而克林霉素敏感的葡萄球菌中，D试验阳性即对克林霉索具有诱导型耐药的为50．8％。结论开展D试验检测葡萄球菌中红霉素对克林霉素的诱导耐药性可帮助临床医生正确选用大环内酯类、林可霉素类抗生素。     

葡萄球菌耐药性和红霉素诱导克林霉素耐药状况

目的了解本地葡萄球菌耐药率以及红霉素诱导克林霉素耐药的发生率。方法采用试管法血浆凝固酶试验检测凝固酶阴性葡萄球菌（CONS）和金黄色葡萄球菌（Sa），头孢西叮纸片扩散法检测耐甲氧西林葡萄球菌（MRS），Kirby-Bauer法检测88株葡萄球菌对11种抗菌药物的耐药性，D-test双纸片法检测红霉素诱导克林霉素耐药。结果88株葡萄球菌中，CONS和Sa的构成比是83．0％（73／88）比17．0％（15／88），MRS的检出率是71．6％（63／88）。在CONS中，MRCONS的检出率是71．2％（52／73），Sa中MRSA的检出率是73．3％（11／15），二者差异无统计学意义。对环丙沙星、红霉素、克林霉素、复方新诺明和庆大霉素的耐药率，Sa明显高于CONS、MRS明显高于MSS，二者差异有统计学意义（P〈0．05）。11种抗生素中，青霉素和红霉素对所有菌株的耐药率均〉50％，万古霉素、利福平、呋南妥因和氯霉素对所有菌株耐药率均〈50％，未检出万古霉素耐药菌株。在22株红霉素耐药、克林霉素敏感的葡萄球菌中，D-test阳性的葡萄球菌共10株，阳性率为45．5％（10／22）。结论88株临床分离的葡萄球菌中主要以凝固酶阴性的葡萄球菌为主，MRS的检出率已超过70％，Sa和MRS的耐药率较CONS和MSS高，除万古霉素和呋南妥因外，本地区临床分离的葡萄球菌对常用抗生素的耐药性均较高。红霉素耐药、克林霉素敏感的葡萄球茼中，红霉素诱导克林霉素耐药的菌株已接近一半（45．5％），对于药敏实验中表现为红霉素耐药、克林霉素敏感的葡萄球菌， 必须加作D-test确定克林霉素的敏感性。     

259例金黄色葡萄球菌对红霉素、克林霉素的诱导耐药性研究

目的了解金黄色葡萄球菌对红霉素及克林霉素的耐药性,应用D-试验检测红霉素对克林霉素的诱导耐药率。方法按照美国临床实验室标准化委员会（NCCLs）推荐的纸片扩散方法测定并判读金黄色葡萄球菌对红霉素和克林霉素的耐药性,并以D-试验测定红霉素对克林霉素的诱导耐药表型。结果红霉素和克林霉素同时耐药在耐甲氧西林金黄色葡萄球菌和甲氧西林敏感型金黄色葡萄球菌中分别占61.00%和38.00%,对红霉素耐药而克林霉素敏感的MRSA和MSSA中D-试验阳性即对克林霉素具有诱导耐药性者分别为64.81%和63.89%。D-试验阳性占所测金黄色葡萄球菌的22.4%,占红霉素耐药而克林霉素敏感菌株的64.44%。结论临床微生物室开展D-试验,检测金黄色葡萄球菌中克林霉素诱导性耐药可以指导临床医师合理选用大环内酯类,克林霉素类抗菌药物。     

216例金黄色葡萄球菌中红霉素对克林霉素诱导耐药检测

目的：了解金黄色葡萄球菌（SA）对红霉素和克林霉素的耐药性,检测红霉素对克林霉素诱导耐药的发生率。方法采用美国临床实验室标准化协会（CLSI）推荐的纸片扩散法,用红霉素和克林霉素双纸片法（D-试验）和VITEK 2 Compact AES分析红霉素对克林霉素诱导耐药表型。结果216株SA中有76株（MSSA22株, MRSA54株）呈红霉素耐药、克林霉素敏感,其中29株D-试验阳性（MSSA 8株, MRSA 21株）,检出率分别为36.4%、38.9%。结论临床微生物实验室应加强对SA中克林霉素诱导耐药的检测,以指导临床医生合理选用大环内酯类、林可酰胺类抗菌药物。     

In vitro activity of linezolid,synercid and telithromycin against genetically defined high level fluoroquinolone-resistant methicillin-resistant Staphylococcus aureus

The in vitro activity of levofloxacin, moxifloxacin, gatifloxacin, erythromycin, telithromycin, linezolid, synercid and vancomycin was measured against 36 genetically defined, gyrA/grlA double mutant MRSA clinical strains with an MIC to ciprofloxacin > or = 8 mg/l. The three newer fluoroquinolones tested were more active than ciprofloxacin. Resistance rates for levofloxacin and gatifloxacin were high (44.5 and 36.1%, respectively). All the strains were moxifloxacin-susceptible, though most of them had MICs close to the break point. All the strains were intermediate or resistant to erythromycin and most were also resistant to telithromycin. No strains were resistant to linezolid, synercid or vancomycin (MIC(90): 2, 1 and 2 mg/l, respectively).     

In vitro activity of moxifloxacin,levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis

The in vitro activity of moxifloxacin, gatifloxacin, levofloxacin and linezolid was evaluated against 234 strains of Mycobacterium tuberculosis isolated in the Southeast of Spain. All drugs tested showed good activity, with an MIC₉₀ of less than 1 mg/l, and were active against isociacide and rifampicin resistant strains. Three strains were resistant to isoniazid and to the fluoroquinolones, which suggested the existence of mechanisms of resistance not yet described. These new compounds may prove to be therapeutic alternatives for treatment of multi-resistant tuberculosis and further studies should be done to demonstrate their true usefulness.     

Susceptibility of Streptococcus pneumoniae to penicillin, azithromycin and telithromycin (PROTEKT 1999-2003)

Isolates of Streptococcus pneumoniae collected over the first 4 years of the PROTEKT study were tested for susceptibility to penicillin, azithromycin and telithromycin. A total of 20 750 isolates were collected from 39 countries. Penicillin non-susceptibility rates were stable over the study period; overall, 21.8% of isolates were resistant. Azithromycin resistance increased from 31.0% in Year 1 to 36.3% in Year 4. Resistance rates for penicillin and azithromycin varied between countries and were highest in France, Spain, South Africa, USA and the Far East. Multidrug resistance in S. pneumoniae did not change significantly over the 4 years, with an overall rate of 38.6%. Telithromycin retained good activity against S. pneumoniae (0.1% of isolates resistant), including multidrug-resistant isolates.     

利奈唑胺、替考拉宁和万古霉素等抗菌药物对常见需氧革兰阳性球菌的体外抗菌活性

目的评价利奈唑胺、替考拉宁和万古霉素等抗菌药物的体外抗菌活性。方法采用琼脂稀释法对临床收集的132株革兰阳性球菌进行抗菌活性测定,记录其各自的MIC并进行比较。结果利奈唑胺、替考拉宁及万古霉素3药对革兰阳性球菌均有较大抗菌活性,敏感率均为100%,包括其中的耐甲氧西林葡萄球菌和青霉素中介肺炎链球菌均有良好抗菌作用。3药在部分革兰阳性球菌的抗菌作用中与利福平相仿,但比氨基糖苷类抗生素和氟喹诺酮类抗菌药强。在对甲氧西林敏感金葡萄的抗菌活性中,替考拉宁的MIC90均为利奈唑胺和万古霉素的4倍;在对甲氧西林敏感凝固酶阴性葡萄球菌的抗菌活性中,替考拉宁的MIC90分别均为利奈唑胺和万古霉素的8倍;而在青霉素敏感和中介肺炎链球菌的抗菌活性中,替考拉宁的MIC90为利奈唑胺的1/16,为万古霉素的1/8;在肠球菌属的抗菌活性中,万古霉素的MIC90分别为利奈唑胺的2倍,是替考拉宁的4倍和8倍。结论利奈唑胺、替考拉宁以及万古霉素等三药对革兰阳性球菌有较大的抗菌作用,对部分革兰阳性菌的抗菌作用与利福平相仿,但比其他如氨基糖苷类抗生素和氟诺酮类抗菌药更优,是临床革兰阳性球菌严重感染的有效药物。     

In vitro activity of ABT-773, telithromycin and eight other antimicrobials against erythromycin-resistant Streptococcus pneumoniae respiratory isolates of children.

The activity of the ketolide ABT-773 against 180 erythromycin-resistant Streptococcus pneumoniae obtained from children was compared with telithromycin, azithromycin, clarithromyin, roxithromycin, clindamycin, penicillin, levofloxacin and gatifloxacin. Ketolide MICs were all ≤1 mg/l, with ABT-773 being the most potent of all drugs tested. MIC₉₀s for macrolides and azithromycin in mefE+ isolates were 16–32 compared with >128 mg/l for ermB+ isolates. ABT-773 and telithromycin MIC₉₀s for mefE+ isolates were 0.125 and 0.5, compared with 0.032 and 0.016 mg/l for ermB+ isolates and 0.5 and 1 mg/l, respectively, for isolates containing both genes. Clindamycin was active against mefE+ but not ermB+ isolates. 155 isolates were resistant to penicillin. All fluoroquinolone MICs were <1 mg/l. Further studies of ketolides for treatment of paediatric S. pneumoniae infections are warranted.     

三种局部抗菌药物对甲氧西林耐药金黄色葡萄球菌的抗菌活性研究

目的：研究分析三种局部抗菌药物对甲氧西林耐药金黄色葡萄球菌的抗菌活性研究。方法：回顾性分析我院于2014年3月～2015年3月收治的100例烧伤患者的病历资料,对烧伤创面分泌物制作标本,共分离100株非重复并连续的MRSA,应用棋盘格法对磺胺嘧啶银、莫匹罗星、克霉唑单用以及联用时对MRSA的抗菌活性予以分析。结果：磺胺嘧啶银对MRSA的MIC为8μg/mL, MIC50为9μg/mL,MIC90为16μg/mL,莫匹罗星对MRSA的MIC为2μg/mL,MIC50为16μg/mL,MIC90为64μg/mL,克霉唑对MRSA的MIC分别为2μg/mL,MIC50为3μg/mL,MIC90为4μg/mL。莫匹罗星和克霉唑联用,和磺胺嘧啶银单用比较,MIC50降低75%,MIC90降低87.5%;和莫匹罗星单用比较,MIC50降低87.5%,MIC90降低96.9%;和克霉唑单用比较,MIC50降低50%,MIC90降低50.0%;磺胺嘧啶银和莫匹罗星联用,有70例相同,20例相加,10例无关,没有拮抗现象。磺胺嘧啶银和克霉唑联用,92例抗菌效果相加,8例无关,没有协同和拮抗现象。两种药物联用的抗菌活性明显优于单用。结论：MRSA感染的烧伤创面,就要应用较低剂量的磺胺嘧啶银联合其他药物,不仅可以实现感染的有效控制,也能将药物对创面愈合的一种不良反应降低,值得临床推广。     

In vitro activity of ABT-773, telithromycin and eight other antimicrobials against erythromycin-resistant Streptococcus pneumoniae respiratory isolates of children

The activity of the ketolide ABT-773 against 180 erythromycin-resistant Streptococcus pneumoniae obtained from children was compared with telithromycin, azithromycin, clarithromyin, roxithromycin, clindamycin, penicillin, levofloxacin and gatifloxacin. Ketolide MICs were all ≤1 mg/l, with ABT-773 being the most potent of all drugs tested. MIC₉₀s for macrolides and azithromycin in mefE+ isolates were 16–32 compared with >128 mg/l for ermB+ isolates. ABT-773 and telithromycin MIC₉₀s for mefE+ isolates were 0.125 and 0.5, compared with 0.032 and 0.016 mg/l for ermB+ isolates and 0.5 and 1 mg/l, respectively, for isolates containing both genes. Clindamycin was active against mefE+ but not ermB+ isolates. 155 isolates were resistant to penicillin. All fluoroquinolone MICs were <1 mg/l. Further studies of ketolides for treatment of paediatric S. pneumoniae infections are warranted.     

Prevalence of mupirocin resistance in clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis: results of the Antimicrobial Resistance Surveillance Study of the Paul-Ehrlich-Society for Chemotherapy, 2001

A multicentre surveillance study comprising 26 laboratories located in Austria, Germany, and Switzerland was carried out in November 2001. A total of 787 isolates of Staphylococcus aureus and 456 isolates of Staphylococcus epidermidis mainly recovered from hospitalised patients, were tested. MICs for mupirocin were determined using the broth microdilution procedure. Breakpoints were ≤4 mg/l (susceptible), 8–256 mg/l (low-level resistance) and ≥512 mg/l (high-level resistance). Rates of low- and high-level resistances were 2.9 and 0.9% in S. aureus, and 9.4 and 3.3% in S. epidermidis, respectively. Mupirocin resistance was almost exclusively observed in oxacillin-resistant isolates of S. aureus (MRSA) and S. epidermidis (MRSE). High-level mupirocin resistance was detected in 3.1 and 4.5% of MRSA and MRSE, respectively.     

In vitro activity of mupirocin and amoxicillin-clavulanate alone and in combination against staphylococci including those resistant to methicillin

Mupirocin and amoxicillin-clavulanate were synergistic against 9 of 49 (18%) strains of methicillin-resistant and methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci (CNS). A pattern of enhanced killing was also found using time-kill studies. Time-kill assays were more discriminatory than chequerboard titration assays in demonstrating synergy. These results suggest that combinations of amoxicillin-clavulanate and mupirocin may have therapeutic benefits in prophylaxis against staphylococcal infections.     

Activity of ceftobiprole against methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to daptomycin,linezolid or vancomycin,and strains with defined SCCmec types

Ceftobiprole is a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative pathogens including Pseudomonas aeruginosa. The aim of this study was to evaluate the activity of ceftobiprole against MRSA isolates with decreased susceptibility to daptomycin, linezolid or vancomycin as well as isolates from staphylococcal chromosome cassette mec (SCCmec) types I, II, III and IV. Overall, ceftobiprole demonstrated high potency against the 216 isolates tested, with MIC₅₀ and MIC₉₀ values (minimum inhibitory concentrations required to inhibit 50% and 90% of the isolates, respectively) of 1 mg/L and 2 mg/L (97.2% susceptible). The MIC₉₀ for ceftobiprole was 2 mg/L against the linezolid-non-susceptible, daptomycin-non-susceptible and vancomycin-intermediate (VISA and hVISA) subsets and was 1 mg/L against the vancomycin-resistant (VRSA) strains. The MIC_50/90 values for ceftobiprole were 2/4, 1/2, 2/2 and 1/1 mg/L against SCCmec types I, II, III and IV, respectively. SCCmec type I strains had the highest MICs, with six strains exhibiting a ceftobiprole MIC of 4 mg/L and 15 strains at 2 mg/L. Ceftobiprole demonstrated potent activity against MRSA, including subsets of isolates with reduced susceptibility to daptomycin, linezolid and vancomycin. The activity of ceftobiprole against these resistant phenotypes indicates that it may have clinical utility in the treatment of infections caused by multidrug-resistant S. aureus and across strains from prevalent SCCmec types.     

益生菌与红霉素治疗早产儿喂养不耐受临床疗效对比分析

目的观察益生菌与红霉素治疗早产儿喂养不耐受的临床疗效、不良反应发生情况,探讨早产儿喂养不耐受的治疗方法。方法将93例喂养不耐受的早产儿随机分为常规组30例、红霉素组32例和益生菌组31例。常规组单纯给予常规治疗,红霉素组在常规治疗基础上加用红霉素治疗,益生菌组在常规治疗基础上加用益生菌治疗。观察并比较3组临床有效率、胃肠道症状消失时间、达到全胃肠喂养时间、恢复至出生体质量时间及腹泻、便秘发生情况。结果益生菌组和红霉素组有效率高于常规组,胃肠道症状消失时间、达到全胃肠喂养时间、恢复至出生体质量时间短于常规组;益生菌组腹泻、便秘发生率低于红霉素组和常规组,差异均有统计学意义(P<0.05和P<0.01)。除腹泻、便秘发生率外,益生菌组和红霉素组其他观察指标比较差异均无统计学意义(P>0.05)。结论益生菌与红霉素治疗早产儿喂养不耐受均有较好疗效,但红霉素在治疗过程中腹泻、便秘相对明显,在无胃肠道发育畸形的情况下,益生菌更有利于早产儿胃肠系统的生长发育。     

'In vitro' development of metronidazole, erythromycin, amoxicillin and gentamicin resistance in Helicobacter pylori

Serial passage of 37 Helicobacter pylori clinical isolates on increasing concentrations of metronidazole rapidly produced five strains with MICs up to 512 fold higher than those for the original strains. For these five metronidazole-resistant strains the MICs of erythromycin, gentamicin and amoxicillin were unchanged. When they were submitted to the same technique for these last antimicrobial agents, only one strain developed high level resistance to erythromycin and gentamicin having MIC values respectively up to 32 and 64-fold increased. Finally, no amoxicillin-resistant Helicobacter pylori could be obtained.     

红霉素对糖尿病胃轻瘫患者胃动素胃泌素及肠道菌群的影响

目的 观察红霉素对糖尿病胃轻瘫(DGP)患者胃动素、胃泌素及肠道菌群的影响.方法 将2011年9月至2013年9月本院消化内科门诊及住院收治的78例DGP患者按随机法分为观察组和对照组,对照组患者给予莫沙必利片治疗,观察组患者给予红霉素胶囊治疗.比较两组患者的疗效、血浆胃动素(MTL)和血清胃泌素(GAS)水平及肠道菌群数量.结果 治疗后观察组患者总有效率显著高于对照组患者(x2=12.889,P＜0.05),而两组患者血浆胃动素和血清胃泌素水平显著下降(均P＜0.05),且观察组中血浆胃动素和血清胃泌素水平显著低于对照组,差异均有统计学意义(t=13.865、6.272,均P＜0.05);治疗前后两组患者肠道内大肠杆菌、肠球菌、双歧杆菌、乳酸杆菌数量比较差异均无统计学意义(t=1.540、1.093、1.790、1.946,均P＞0.05);而治疗后观察组中拟杆菌数量明显多于对照组,差异具有统计学意义(t=8.073,P＜0.05).结论 红霉素治疗糖尿病胃轻瘫临床效果显著,能降低胃动素、胃泌素的分泌,对患者肠道菌群影响较小,具有良好应用价值,值得临床推广使用.     

Comparative pharmacokinetics of dirithromycin and erythromycin in normal volunteers with special regard to accumulation in polymorphonuclear leukocytes and in saliva

Objective: In a randomized cross-over study, we assessed pharmacokinetics and intracellular concentrations in polymorphonuclear leukocytes (PMN) and saliva of erythromycin and erythromycylamine, the active metabolite of dirithromycin. Methods: Ten healthy volunteers received 1 g erythromycin b.i.d. or 500 mg dirithromycin qd for 5 days (wash out period, 35 days). Concentrations of erythromycin and erythromycylamine were measured in serum, urine, saliva, and granulocytes by bioassay and high-performance liquid chromatography (HPLC) on days 1, 3, and 5 of each study period, respectively. Results: While maximal serum concentrations (C_max) and the area under the data (AUD_tot) of erythromycin were significantly higher (C_max 1.44 mg · l⁻¹, AUD_tot 5.66 mg · h · l⁻¹) than those of erythromycylamine (C_max 0.29 mg · l⁻¹, AUD_tot 1.96 mg · h · l⁻¹), erythromycylamine had a significantly higher mean residence time (21 h) than erythromycin (5.5 h). Erythromycylamine accumulated significantly more in PMN than erythromycin;␣the accumulation factor of erythromycylamine was 100 with a maximal intracellular concentration of 13.4 mg · l⁻¹, whereas the maximal accumulation factor of erythromycin was 4 with a maximal intracellular concentration of 6.1 mg · l⁻¹. There were no significant differences in maximal saliva concentrations (erythromycin 0.35 mg · l⁻¹, erythromycylamine 0.31 mg · l⁻¹). Received: 16 September 1996 / Accepted in revised form: 12 February 1997     

利奈唑胺、去甲万古霉素等抗菌药物对耐甲氧西林金黄色葡萄球菌的抗菌活性

目的:研究北京市三家医院耐甲氧西林金黄色葡萄球菌(MRSA)耐药现状,评价利奈唑胺、去甲万古霉素等药物的抗菌活性。方法:收集解放军总医院、北京医院、北京协和医院三家医院分离的非重复MRSA111株,头孢西丁纸片法确认MRSA,采用琼脂稀释法测定抗菌药物的最低抑菌浓度(MIC)。结果:111株MRSA,对β-内酰胺类的耐药率为100%,对红霉素的耐药率为92.8%,对氨基糖苷类(奈替米星、庆大霉素)的耐药率为99.1%,对氟喹酮类(加替沙星、莫西沙星、左氧氟沙星)的耐药率为91.9%~99.1%,对氯霉素的耐药率为3.6%,对去甲万古霉素、利奈唑胺全部敏感,对去甲万古霉素MIC50和MIC90分别为0.5和1μg/mL,对利奈唑胺的MIC50和MIC90均为2μg/mL。结论:北京三家医院分离的MRSA对本研究的大多数抗菌药物均耐药,去甲万古霉素和利奈唑胺对于MRSA有很高的抗菌活性。