耐甲氧西林金黄色葡萄球菌感染的现状和研究进展

近年来耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)的感染日益增多,其严重的耐药对人类造成巨大威胁,尤其是由于万古霉素的滥用,出现了万古霉素中敏的金黄色葡萄球菌(vancomycinintermediate staphylococcus aureus,VISA)。本文就其感染现状、基因分型和毒素、耐药性及防治作一综述。     

甲氧西林耐药金黄色葡萄球菌对氨基糖苷抗生素耐药机制的研究

为研究甲氧要耐药金黄色球菌（ＭＲＳＡ）对氨基糖苷类抗生素的耐药机制，应用氨基醭 抗生素耐药谱推测法、核素标记分析法、Ｓｏｕｔｈｅｍ印迹和斑点杂交试验对１００株ＭＲＳＡ进行了耐药研究。结果：根据细菌对氨基糖苷抗生素的耐药谱，１００株ＭＲＳＡ可以分成４类，６５株细菌产生ＡＡＣ（６）－ＡＰＨ（２）钝化酶，２４株产生ＡＡＣ（６）－ＡＰＨ（２）＋ＡＰＨ（３），１０株产生ＡＡＣ（６），还有１株产生ＡＡＣ（６）     

Plasmid fingerprinting of methicillin-resistant staphylococcus aureus strains isolated in Hamburg

Summary By means of restriction endonuclease digests and DNA/hybridisation studies we analysed ten representative methicillin-resistantStaphylococcus aureus strains of our collection for plasmid similarities and plasmid associated resistance determinants. We found that strains isolated at our laboratory contained identical or at least most similar plasmids. Isolates from another geographical origin showed different plasmid patterns. We found resistance determinants for gentamicin to be chromosomally encoded, whereas resistance to heavy metal ions and chloramphenicol was always plasmid associated. Resistance to trimethoprim, tetracycline and erythromycin was usually chromosomally mediated but could also reside on a plasmid. Our results indicate that methicillin-resistant strains from our collection may have a common origin. The clinical relevance of these results is discussed.

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Plasmid-Fingerprinting Hamburger Methicillin-resistenter Staphylococcus aureus-Isolate

Zusammenfassung Wir untersuchten zehn repräsentativeStaphylococcus aureus-Stämme unserer Sammlung mit Hilfe von Restriktionsanalysen und Hybridisierungsstudien auf Ähnlichkeiten in ihrem Plasmid-Gehalt sowie auf Plasmid-kodierte Resistenzen. Hamburger Isolate enthielten dabei sehr ähnliche, wenn nicht gleiche Plasmide. Stämme aus einem anderen Gebiet der Bundesrepublik zeigten dagegen ein stark abweichendes Plasmid-Muster. Die Gentamicinresistenz fanden wir chromosomal-kodiert, während Resistenzen gegenüber Schwermetallionen und Chloramphenicol immer Plasmid-assoziiert waren. Resistenzen gegenüber Trimethoprim, Tetrazyklin und Erythromycin waren normalerweise chromosomalkodiert, konnten aber auch auf Plasmiden gefunden werden. Unsere Ergebnisse legen einen gemeinsamen Ursprung Hamburger Stämme nah. Die klinische Bedeutung dieser Ergebnisse wird diskutiert.

     

509株金黄色葡萄球菌感染的临床分布和耐药性分析

目的了解北京安贞医院金黄色葡萄球菌(SAU)在2011~2014年中的临床分布和耐药情况,为临床合理用药提供指导。方法回顾性分析2011年1月至2014年12月临床标本分离的509株SAU的分布及耐药性。采用vitek-Compact系统和Phoenix 100系统进行细菌鉴定,MIC法进行体外抗菌药物敏感试验。结果临床分离金黄色葡萄球菌(SAU)509株。SAU中有耐甲氧西林金黄色葡萄球菌(MRSA)286株,占56.2%。标本来源依次为呼吸道(52.1%)、血液(13.6%)和伤口分泌物(11.8%)。科室依次是重症监护室(31.9%)、心脏外科病房(11.6%)和呼吸内科病房(9.0%)。SAU对16种抗菌药物耐药率排在前3位的是青霉素占97.4%、红霉素占74.1%及克林霉素占69.9%;对利奈唑胺、万古霉素、替加环素和奎奴普丁-达福普丁的敏感率约为100%。结论我院分离的SAU耐药严重,尤其是MRSA多药耐药严重,在治疗金黄色葡萄球菌感染时应根据实验室结果合理选用敏感的抗菌药物。     

The importance of incubation temperature for detecting beta-lactam-resistant staphylococcus aureus strains

Summary Sixty-six isolates of methicillin-resistantStaphylococcus aureus strains originating from Austria, Egypt, the Federal Republic of Germany and Switzerland were tested for their sensitivity to 12 -lactam antibiotics at both 30° and 37° C using the agar disk diffusion test. The MICs for six of the -lactam antibiotics were determined by the microdilution technique. Resistance to methicillin was always accompanied by resistance to several -lactam antibiotics. Resistance to all semi-synthetic penicillins and cephalosporins, including cefotaxime, was higher at 30° C than at 37° C. Cephalothin and cefamandole proved to be the most effective cephalosporin antibiotics against methicillin-resistantS. aureus strains. Newer cephalosporins, i. e. cefotaxime, cefoxitin and cefuroxime, exhibited only a low rate of activity against these strains. The occurrence of phage-type 85 inS. aureus strains from Austria, Egypt and Germany indicates that certain lysotypes are widespread.

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Die Bedeutung der Bebrütungstemperatur für die Erkennung Beta-Lactam-Antibiotika-resistenter Staphylococcus aureus-Stämme

Zusammenfassung Sechsundsechzig Methicillin-resistenteStaphylococcus aureus-Stämme aus Ägypten, der Bundesrepublik Deutschland, Österreich und der Schweiz wurden im Agardiffusionstest parallel bei 30° C und 37° C auf ihre Empfindlichkeit gegenüber zwölf -Lactam-Antibiotika geprüft. Bei sechs dieser Antibiotika wurden zusätzlich die MHK-Werte im Mikrodilutions-Verfahren bestimmt. Methicillin-Resistenz war ausnahmslos gekoppelt mit der Resistenz gegen mehrere andere -Lactam-Antibiotika. Gegenüber allen semi-synthetischen Penicillinen und Cephalosporinen einschließlich des Cefotaxims war die Resistenz bei 30° C stärker ausgeprägt als bei 37° C. Unter den Cephalosporin-Antibiotika zeigten Cephalotin und Cefamandol die stärkste Wirksamkeit gegen methicillinresistenteS. aureus-Stämme. Die neueren Cephalosporine wie Cefotaxim, Cefoxitin und Cefuroxim waren selten wirksam. Das Auftreten vonS. aureus-Stämmen mit dem Lysisbild 85 in Ägypten, in der Bundesrepublik Deutschland und in Österreich zeigt, daß gewisse Lysotypen weit verbreitet sind.

     

Properties of some staphylococcus aureus strains associated with spontaneous l-phase transformation.

Spontaneous L-phase production was found in 7 of 14 investigated Staphylococcus aureus strains. A common characteristic of the strains producing L-phase variants spontaneously was their ability to develop L-colonies on a solid medium with 1.0-1.5% NaCl by the action of methicillin, whereas other strains required higher NaCl concentrations. Further, in 6 of the 7 strains the ability for spontaneous L-phase production was associated with high L-phase productivity in the presence of methicillin. The pattern of alpha-, beta- and delta-hemolysin production in a strain was not correlated to spontaneous L-phase production.     

The research of the innate defense regulator peptide on the effects of methicillin resistant staphylococcus aureus biofilm

正Objective To investigate the destruction of the mature biofilm and the inhibitory effect of the biofilm formation of methicillin-resistant Staphylococcus aureus(MRSA)by different concentrations of the innate defense regulatory peptide(IDR-1018).Methods 1×10~5 CFU/ml MRSA was inoculated uniformly into 96 well     

In vitro activity of combinations of antibiotics against staphylococcus aureus resistant to gentamicin and methicillin

Summary Twenty clinical isolates ofStaphylococcus aureus, resistant to both gentamicin and methicillin, were testedin vitro for sensitivity to rifampicin, novobiocin, fusidic acid, vancomycin, teicoplanin and an extended range of aminoglycosides. Rifampicin was the most active compound tested, having an MIC of < 0.02 mg/l. All the strains were inhibited by 1 mg/l of novobiocin, vancomycin and teicoplanin, and only one strain was resistant to fusidic acid. 50% of the strains were inhibited by less than 1 mg/l of amikacin and netilmicin, but other aminoglycosides were of poor activity. Resistant mutants were selected when strains were grown in the presence of rifampicin, novobiocin or fusidic acid alone, but this did not occur when rifampicin was combined with either novobiocin or vancomycin. Pharmacokinetic and other considerations suggest that a combination of rifampicin and novobiocin deserves further assessment for the treatment of infections caused by this type of organism.

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In vitro-Aktivität von Antibiotika-Kombinationen gegen Gentamicin- und Methicillin-resistente Staphylococcus aureus-Stämme

Zusammenfassung 20 klinische Isolate vonStaphylococcus aureus, die sowohl gegen Gentmicin wie gegen Methicillin resistent waren, wurden auf ihre Empfindlichkeit gegen Rifampicin, Novobiocin, Fusidinsäure, Vancomycin, Teichoplanin und eine ganze Reihe von Aminoglykosiden geprüft. Rifampicin erwies sich als die aktivste der untersuchten Substanzen; die MHK lag unter 0,02 mg/l. Alle Stämme wurden von Novobiocin, Vancomycin und Teichoplanin bei einer Konzentration von 1 mg/l gehemmt. Gegen Fusidinsäure war nur ein einziger Stamm resistent. 50% der Stämme wurden durch Amikacin und Netilmicin in Konzentrationen von weniger als 1 mg/l gehemmt, andere Aminoglykoside waren dagegen nur schwach wirksam. Wenn die Stämme in Anwesenheit von Rifampicin, Novobiocin oder Fusidinsäure allein kultiviert wurden, wurden resistente Mutanten selektiert. Wenn Rifampicin mit Novobiocin oder Vancomycin kombiniert wurde, trat hingegen keine Selektion resistenter Mutanten auf. Unter anderem ist aus pharmakokinetischen Überlegungen eine weitere Untersuchung der Kombination von Rifampicin und Novobiocin für die Behandlung von Infektionen durch die untersuchte Erregerspezies gerechtfertigt.

     

Intrafamilial spread of highly virulent staphylococcus aureus strains carrying the gene for Panton-Valentine leukocidin

Necrotizing pneumonia caused by Staphylococcus aureus carrying the gene for Panton-Valentine leukocidin is a newly described disease entity. We report 2 cases with intrafamilial spread.     

社区相关耐甲氧西林金黄色葡萄球菌研究进展

以往由耐甲氧西林金黄色葡萄球菌(MRSA)所致感染多发生在医院环境,近年来社区相关MRSA的感染呈逐年上升趋势。社区相关MRSA与医院相关MRSA相比有着显著不同的特点:典型的社区相关MRSA菌株多携带SCCmecⅣ型基因;一般只对β-内酰胺类抗生素耐药;产生潘顿-瓦伦丁杀白细胞素(PVL);感染者多为既往身体健康的年轻人等。     

Meningitis due to staphylococcus aureus

A retrospective analysis of 10 adult patients with community-acquired Staphylococcus aureus meningitis was performed in order to elucidate the characteristics and treatment of this lethal disease. In all patients, a focus of infection outside the central nervous system was apparent at presentation. A poor prognosis was associated with severe underlying disease, greater degree of hyponatremia at presentation, development of seizures, failure of nuchal rigidity to develop, persistent or recurrent bacteremia, and the presence of concurrent S. aureus bronchopneumonia. Degree of deterioration in mental status and cerebrospinal fluid pleocytosis, protein levels, and glucose levels did not appear to have any prognostic significance. Therapy with rifampin and a semisynthetic penicillin effected a cure in all six patients treated with this regimen. In contrast, three of four patients treated with other antibiotic combinations died. On the basis of this experience, it is concluded that further trials with rifampin in combination with another anti-staphylococcal antibiotic for the treatment of S. aureus meningitis are warranted.     

A large outbreak of infections caused by a strain of staphylococcus aureus resistant to oxacillin and aminoglycosides

An extensive outbreak of nosocomial infections caused by oxacillinand aminoglycoside-resistant Staphylococcus aureus (OARSA) occurred over a 16 month period. A total of 349 isolates of OARSA were obtained from 174 patients. Colonization with OARSA was found in 92 patients. There were 120 infections in 82 patients; 50 were surgical wound infections, 13 were nonsurgical wound infections, six were pneumonias, 15 were urinary tract infections, 12 were intravenous site infections, and there were 19 episodes pf bacteremia (seven transient, 12 persistent). In patients with persistent bacteremia, the mortality rate was 33 percent. In patients treated for persistent bacteremia with vancomycin, the survival rate was 80 percent. Infections were highly associated with the surgical intensive care unit, and 90 percent of the isolates of OARSA tested had the same phage-type. Elderly patients with significant underlying disease, a history of previous surgery or of prior antimicrobial therapy appeared to be at increased risk for OARSA infections. OARSA were resistant to multiple antibiotics besides oxacillin, but all isolates were sensitive to vancomycin and rifampin. Three surgical intensive care unit nurses were found to be nasal carriers of OARSA, and one nurse had dermatitis of both hands colonized with OARSA. Following the removal of these nurses from the surgical intensive care unit and the institution of strict infection control measures, the number of OARSA infections and colonizations decreased to less than one per month. OARSA produces serious nosocomial disease, and epidemiologic intervention was effective in controlling this outbreak.     

糖尿病足溃疡中耐甲氧西林金黄色葡萄球菌感染情况与相应病情和预后

目的 了解糖尿病足感染中金黄色葡萄球菌的培养阳性率及耐药性,分析耐药性的相关危险因素及其对预后的影响.方法 取790例糖尿病足感染患者足部分泌物进行常规细菌培养,分析耐甲氧西林金黄色葡萄球菌(MRSA)感染的药敏情况和患者的临床特点并观察溃疡治愈率、截肢率、死亡率.结果 分泌物培养结果阳性的624例标本中共获得127株金黄色葡萄球菌,MRSA占金黄色葡萄球菌感染的51.2％,在所有足溃疡中检出率为9.1％,其中1例为耐万古霉素的菌株;MRSA主要对万古霉素、利福平、利奈唑胺、替考拉宁等药物敏感性较高.MRSA感染患者的3个月溃疡愈合率为47.7％,截肢率为47.7％,死亡率为9.2％,明显较非MRSA感染患者的预后差(P＜0.05).抗生素用药史可显著增加MRSA感染几率.结论 久治不愈的糖尿病足感染MRSA培养阳性率较高,MRSA感染提示患者预后较差.     

Some salient features of staphylococcus aureus endocarditis

Sixty-four cases of Staphylococcus aureus endocarditis between 1940 and 1971 were reviewed. There was no change in the incidence during these three decades. The over-all mortality was 41 and 86 per cent, respectively, in patients below and above age 50. The corresponding per cent mortality in the last decade of the study was lower, namely, 14 and 71 per cent. In four patients Staph. aureus endocarditis developed in the hospital. In two of these patients, endocarditis was associated with an infected indwelling intravenous catheter and in one, septic thrombophlebitis secondary to intravenous therapy was the presumed source. Endocarditis or bacteremia was not suspected clinically in 10 patients. Eight of them were over 70 years old; organic valvular heart disease was diagnosed in only one. A high index of suspicion is essential in the diagnosis of Staph, aureus endocarditis, since classic physical findings in subacute endocarditis are often absent. Endocarditis should be strongly suspected in the presence of Staph. aureus bacteremia.