Changes in molecular epidemiology of community-associated and health care-associated methicillin-resistant Staphylococcus aureus in Korean children

Widespread emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the epidemiology of S. aureus infections. We examined the molecular types and antibiotic susceptibility of CA-MRSA and health care-associated MRSA (HA-MRSA) among Korean children. MRSA isolates were obtained from patients admitted to university-affiliated tertiary hospitals in Korea, between 2006 and 2010. Molecular studies including multilocus sequence typing, SCCmec typing, and polymerase chain reaction amplification of PVL genes and antibiotic susceptibility tests were performed. SCCmec type IV was most frequently found for both CA-MRSA (80.0%) and HA-MRSA (56.4%). ST72-MRSA-SCCmec type IV and its single-locus variants were the most prevalent MRSA clones in the Korean pediatric population, both in community and in health care settings. The PVL genes were detected in 10% (4/40) of CA-MRSA isolates. Most of the clinical MRSA isolates showed vancomycin MIC ≥1.0 μg/mL. In conclusion, the molecular characteristics of HA-MRSA have been changing and CA-MRSA genotype overtook HA-MRSA genotype in health care settings.     

In vitro activities of 28 antimicrobial agents against Staphylococcus aureus isolates from tertiary-care hospitals in Korea: a nationwide survey

Staphylococcus aureus, one of the most frequently isolated pathogens in both hospitals and the community, has been particularly efficient at developing resistance to antimicrobial agents. As methicillin-resistant S. aureus (MRSA) has prevailed and, furthermore, as S. aureus with reduced susceptibility to vancomycin has emerged, the therapeutic options for the treatment of S. aureus infections have become limited. To update the current status of antibiotic resistance, clinical S. aureus isolates were collected from eight university-affiliated hospitals from June 1999 to January 2001. Susceptibility tests with 28 antibiotics were performed by the disk diffusion method. Among a total of 682 isolates, the methicillin resistance rate was 64% (439 of 682), and most of the MRSA isolates were resistant to multiple classes of antibiotics. Although a constitutive macrolide-lincosamide-streptogramin B resistance phenotype was common, no isolates were resistant to quinupristin-dalfopristin or linezolid. Rifampin, fusidic acid, trimethoprim-sulfamethoxazole, and arbekacin showed superior in vitro activity compared with the other antibiotics against the MRSA isolates. No isolates showed reduced susceptibility to vancomycin.     

Is methicillin-resistant Staphylococcus aureus replacing methicillin-susceptible S. aureus?

Despite extensive research on the emergence of and treatments for methicillin-resistant Staphylococcus aureus (MRSA), prior studies have not rigorously evaluated the impact of methicillin resistance on the overall incidence of S. aureus infections. Yet, there are direct clinical and research implications of determining whether methicillin-susceptible S. aureus (MSSA) infection rates remain stable in the face of increasing MRSA prevalence or whether MSSA will be replaced over time. A synthesis of prior studies indicates that the emergence of healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) has led to an increase in the overall incidence of S. aureus infections, with MRSA principally adding to, rather than replacing, MSSA. However, colonization with CA-MRSA may at least partially replace colonization with MSSA. So far, evidence indicates that MSSA still accounts for many infections. Therefore, eradication of MRSA alone is not sufficient to address the public health burden of S. aureus.     

康替唑胺体外抗菌作用研究

目的 评价唑烷酮类新药康替唑胺对临床分离菌的体外抗菌作用.方法 收集全国19所医院1321株的临床分离菌,以琼脂对倍稀释法测定康替唑胺对分离菌的最低抑菌浓度(MIC)并与有关抗菌药物进行比较,测定康替唑胺的杀菌活性、抗菌药物后效应(PAE)以及不同培养条件对康替唑胺抗菌作用的影响.结果 康替唑胺对革兰阳性菌中葡萄球菌...     

In vitro antimicrobial activity of GSQ1530, a new heteroaromatic polycyclic compound

GSQ1530 is a compound derived from a newly identified class of antibiotics referred to as heteroaromatic polycyclic (HARP) antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of GSQ1530. By using an NCCLS broth microdilution assay, the activities of GSQ1530 and other antibiotics were coevaluated against 215 clinical isolates. The MICs at which 90% of isolates are inhibited (MIC(90)s) of GSQ1530 for methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) were 2 and 4 micro g/ml, respectively. The MIC(90)s of GSQ1530 for the streptococci tested were 2 micro g/ml or less, regardless of their susceptibilities to other antibiotics. The MIC(90) of GSQ1530 for the enterococci tested (including vancomycin-resistant enterococci) was 4 micro g/ml. No cross-resistance was found between GSQ1530 and other known antibiotics. In a separate assay, GSQ1530 demonstrated excellent activity against vancomycin-intermediate-susceptible staphylococci (MIC(90), 1 micro g/ml). The minimal bactericidal concentration test was conducted with 73 clinical isolates; GSQ1530 was cidal against streptococci and staphylococci but static against enterococci. An in vitro killing kinetic study revealed a time-dependent profile, with at least a 3-log reduction of bacterial growth within 6 h after exposure to four times the MICs of GSQ1530 for both S. aureus and Streptococcus pneumoniae. The checkerboard study showed that GSQ1530 had a synergistic interaction with rifampin against MRSA. The test medium was found to have little effect on in vitro antimicrobial potency. The MICs of GSQ1530 for gram-positive cocci were 4- to 32-fold higher in the presence of serum proteins. GSQ1530 has high levels of plasma protein binding (91 and 89% for rat and human plasma, respectively). These preliminary results demonstrate that GSQ1530, a representative compound of our novel HARP antibiotics, has broad-spectrum activity against gram-positive bacteria. This novel class of antibacterial compounds is profiled in vivo to assess the therapeutic potential in humans. Ongoing in vivo studies will assess whether this class of molecules has promising in vivo efficacy and safety profiles.     

Efficacy of linezolid versus comparator therapies in Gram-positive infections

Treatment of Gram-positive bacterial infections is currently a therapeutic challenge because many of these pathogens are now resistant to standard antimicrobial agents. The emergence of multidrug-resistant, Gram-positive pathogens emphasizes the need for new antimicrobial therapy. Linezolid is an oxazolidinone antibiotic with a novel mechanism of action that works by inhibiting bacterial protein synthesis by blocking formation of the initiation complex. It is active against Gram-positive organisms resistant to other antibiotics, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant enterococci (VRE). Results are encouraging from several large-scale, randomized, Phase III trials comparing the efficacy and safety of linezolid with standard comparator agents for the treatment of nosocomial pneumonia, community-acquired pneumonia, skin and skin structure infections, and infections due to MRSA and VRE. Intravenous/oral linezolid is a promising antimicrobial agent and provides the clinician with an additional treatment option, particularly among the limited therapies for resistant Gram-positive bacterial infections.     

Development of new antibiotic resistance in methicillin-resistant but not methicillin-susceptible Staphylococcus aureus.

The frequency of infections caused by multidrug-resistant Staphylococcus aureus continues to increase while the numbers of alternative therapeutic agents remain limited. To investigate the changing patterns of in-vitro susceptibility of S. aureus to 16 antibiotics, 190 clinical isolates from two different years were studied. The MICs of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains isolated in 1987 were compared with those of similar numbers of strains isolated in 1989. For MRSA > or = 90% of isolates from both years were resistant to clindamycin, gentamicin and erythromycin. These strains remained highly susceptible to vancomycin (100%), minocycline (90%) and rifampicin (100%). The greatest increase in resistance was observed for ofloxacin (2% in 1987 vs 62% in 1989); cross-resistance to all of the quinolones tested was demonstrated. MSSA strains remained susceptible to vancomycin (100%), minocycline (98%), rifampicin (100%), clindamycin (90%), gentamicin (90%) and ciprofloxacin (98%). It is concluded that methicillin susceptibility is a useful marker for selecting potential agents for the treatment of infections caused by S. aureus. A combination of minocycline and rifampicin may be a useful alternative to vancomycin for treating MRSA infections.     

Community-associated MRSA (CA-MRSA): an emerging pathogen in infective endocarditis

Over the last decade, a novel methicillin-resistant Staphylococcus aureus (MRSA) has emerged, primarily associated with healthy individuals within the community. This organism is distinct from healthcare-associated MRSA (HA-MRSA) in terms of epidemiology, microbiology and clinical manifestation and as such has been defined as community-associated MRSA (CA-MRSA). Given that S. aureus is a major aetiological agent of infective endocarditis (IE), particularly associated with the iv drug user population, reports of IE attributed to CA-MRSA are now emerging in the literature. The aims of this article are to (i) define and contrast CA-MRSA with HA-MRSA; (ii) review the published cases of CA-MRSA IE to date; and (iii) evaluate the current international recommendations for antibiotic prophylaxis and treatment regimens for IE in relation to CA-MRSA.     

In vitro activity of linezolid,quinupristin-dalfopristin,vancomycin, teicoplanin,moxifloxacin and mupirocin against methicillin-resistant Staphylococcus aureus: comparative evaluation by the E test and a broth microdilution method

The E test and broth microdilution showed comparable accuracy for the susceptibility testing of methicillin-resistant S. aureus (MRSA). All of the 109 primary clinical MRSA isolates were fully susceptible to the glycopeptides vancomycin and teicoplanin, the oxazolidinone linezolid, and the streptogramin quinupristin-dalfopristin. Nine out of the 109 MRSA isolates (8.3 percent) demonstrated resistance to moxifloxacin and 5 out of the 109 strains (4.6 percent) were resistant to the topical agent mupirocin. Linezolid and quinupristin-dalfopristin may prove useful alternatives for the treatment of patients with MRSA infections. MRSA isolates should be screened for in vitro susceptibility against mupirocin prior to the topical application.     

Antimicrobial susceptibility and molecular characterization of community-acquired methicillin-resistant Staphylococcus aureus

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing. Since most published data are on nosocomial MRSA, our goal was to identify the antimicrobial susceptibility profile and resistance mechanisms of pretreatment MRSA isolates obtained from adult subjects participating in recent clinical treatment trials of community respiratory infections. Out of 465 S. aureus isolates, 43 were identified as MRSA. Antimicrobial susceptibility testing indicated susceptibility rates to: vancomycin (100%), gentamicin (86%), clindamycin (39%), quinolones (49%), and erythromycin (12%). Among our MRSA isolates, the MLS constitutive phenotype and ermA were more prevalent than the MLS inducible phenotype and ermC. No isolates had ermB or msrA. All ciprofloxacin resistant isolates had an amino acid change in GyrA and GrlA. The relatedness of our MRSA strains was assessed by ribotyping. Our results indicate that MRSA from adult subjects with community respiratory infections have similar antimicrobial susceptibility profiles and resistance mechanisms as nosocomial MRSA, and represent a genetically diverse group.     

In vitro and in vivo antibacterial activities of SM-216601, a new broad-spectrum parenteral carbapenem

SM-216601 is a novel parenteral 1beta-methylcarbapenem. In agar dilution susceptibility testing, the MIC of SM-216601 for 90% of the methicillin-resistant Staphylococcus aureus (MRSA) strains tested (MIC(90)) was 2 microg/ml, which was comparable to those of vancomycin and linezolid. SM-216601 was also very potent against Enterococcus faecium, including vancomycin-resistant strains (MIC(90) = 8 microg/ml). SM-216601 exhibited potent activity against penicillin-resistant Streptococcus pneumoniae, ampicillin-resistant Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, with MIC(90)s of less than 0.5 microg/ml, and intermediate activity against Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa. The therapeutic efficacy of SM-216601 against experimentally induced infections in mice caused by S. aureus, E. faecium, E. coli, and P. aeruginosa reflected its in vitro activity and plasma level. Thus, SM-216601 is a promising candidate for nosocomial bacterial infections caused by a wide range of gram-positive and gram-negative bacteria, including multiresistant pathogens.     

Quinupristin-dalfopristin resistance among gram-positive bacteria in Taiwan

To understand quinupristin-dalfopristin resistance among clinical isolates of gram-positive bacteria in Taiwan, where this agent is not yet available for clinical use, we evaluated 1,287 nonduplicate isolates recovered from January 1996 to December 1999 for in vitro susceptibility to quinupristin-dalfopristin and other newer antimicrobial agents. All methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to quinupristin-dalfopristin. High rates of nonsusceptibility to quinupristin-dalfopristin (MICs, >/=2 microg/ml) were demonstrated for the following organisms: methicillin-resistant S. aureus (MRSA) (31%), coagulase-negative staphylococci (CoNS) (16%), Streptococcus pneumoniae (8%), viridans group streptococci (51%), vancomycin-susceptible enterococci (85%), vancomycin-resistant Enterococcus faecalis (100%), vancomycin-resistant Enterococcus faecium (66%), Leuconostoc spp. (100%), Lactobacillus spp. (50%), and Pediococcus spp. (87%). All isolates of MSSA, MRSA, S. pneumoniae, and viridans group streptococci were susceptible to vancomycin and teicoplanin. The rates of nonsusceptibility to vancomycin and teicoplanin were 5 and 7%, respectively, for CoNS, ranging from 12 and 18% for S. simulans to 0 and 0% for S. cohnii and S. auricularis. Moxifloxacin and trovafloxacin had good activities against these isolates except for ciprofloxacin-resistant vancomycin-resistant enterococci and methicillin-resistant staphylococci. In Taiwan, virginiamycin has been used in animal husbandry for more than 20 years, which may contribute to the high rates of quinupristin-dalfopristin resistance.     

临床常见革兰阳性球菌的耐药性分析

目的了解我院临床分离的革兰阳性球菌对常用抗菌药物的敏感性。方法用K-B法检测2003年~2004年我院临床分离的革兰阳性球菌对常用抗菌药物的敏感性,按照美国国家临床实验室标准委员会(NCCLS)2004的标准进行。结果耐甲氧西林的金黄色葡萄球菌(MRSA)和耐甲氧西林的凝固酶阴性的葡萄球菌(MRCNS)的感染呈上升趋势,MRSA的检出率为63.2%,MRCNS的检出率79.8%,对于肠球菌,屎肠球菌的耐药率明显高于粪肠球菌,万古霉素对肠球菌有较高的抗菌活性。结论革兰阳性球菌的感染已经变得非常普遍,MRSA、MRCNS和肠球菌对于常用抗菌药物出现了较高的耐药率,因此,依据药敏实验的结果合理选用抗生素是非常必要的。     

Vancomycin: does it still have a role as an antistaphylococcal agent?

The recognition of the shortcomings of vancomycin as an antistaphylococcal agent, together with the burgeoning availability of alternative effective antistaphylococcal antibiotics, has led to a reassessment of the role of this glycopeptide antimicrobial in clinical therapeutics. Evidence indicates that vancomycin is inferior to semisynthetic penicillins in the treatment of infections due to methicillin-susceptible Staphylococcus aureus. Additional evidence suggests that vancomycin may be inferior to some comparator agents in the treatment of infections due to methicillin-resistant S. aureus (MRSA). While high-level resistance remains rare, data from some centers suggest an evolutionary change in S. aureus, evidenced by reduced susceptibility to vancomycin. This, together with the problem of heteroresistance to vancomycin, as well as poor tissue penetration after its systemic administration, presents potential obstacles to the successful therapy of S. aureus infections with this glycopeptide. While it has been suggested that these problems may be overcome by administration of vancomycin in much higher doses, the efficacy and safety of this approach remains to be determined and will require randomized clinical trials for its demonstration. A number of novel agents with activity against MRSA have been introduced to clinical practice in the last 2 years and others are still in the investigational stage. Despite the fact that these newer agents have been compared with vancomycin in trials only designed to demonstrate noninferiority, some potential evidence of superiority over vancomycin has emerged. While the relative roles of each of these newer agents and vancomycin can only be determined definitively by performance of adequately powered randomized clinical trials, current evidence suggests that vancomycin may be an inferior therapeutic agent.     

Comparison of community-associated and health care-associated methicillin-resistant Staphylococcus aureus in Canada: results of the CANWARD 2007-2009 study

This study assessed the demographics, antimicrobial susceptibility, and molecular epidemiology of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and health care-associated MRSA (HA-MRSA) in Canadian hospitals between 2007 and 2009. Among 3589 S. aureus, 889 (24.8%) were MRSA; 224 (25.2%) were CA-MRSA genotypes and 644 (72.4%) were HA-MRSA genotypes. The prevalence of CA-MRSA genotypes increased from 19.5% in 2007 to 31.9% in 2009 (P < .001). CMRSA10/USA300 (73.7%) was the predominant CA-MRSA epidemic type; the most common HA-MRSA epidemic type was CMRSA2/USA100/800 (83.5%). CA-MRSA genotypes carried SCCmec type IVa (98.2%) and were largely agr type I (73.2%). Most HA-MRSA genotypes were SCCmec type II (81.2%) and agr type II (83.4%). Panton-Valentine leukocidin was detected in 201/224 (89.7%) CA-MRSA genotypes and 3/644 (0.5%) HA-MRSA genotypes. An increase in vancomycin minimum inhibitory concentration (MIC) was observed in HA-MRSA genotypes overall, with 1.3% (4/305) of strains in 2007 and 4.6% (7/152) in 2009 exhibiting vancomycin MICs of 2 μg/mL. No MRSA resistance occurred with linezolid, daptomycin, or tigecycline. In conclusion, CA-MRSA genotypes represented 25.2% of all MRSA and continue to increase in prevalence in Canadian hospitals.     

Susceptibility of gram-positive cocci from 25 UK hospitals to antimicrobial agents including linezolid. The Linezolid Study Group

The prevalence of antibiotic resistance amongst Gram-positive cocci from 25 UK hospitals was studied over an 8 month period in 1999. A total of 3770 isolates were tested by the sentinel laboratories using the Etest; these bacteria comprised 1000 pneumococci, 1005 Staphylococcus aureus, 769 coagulase-negative staphylococci (CNS) and 996 enterococci. To ensure quality, 10% of the isolates were retested centrally, as were any found to express unusual resistance patterns. The prevalence of penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci and methicillin-resistant S. aureus (MRSA) varied widely amongst the sentinel laboratories. The resistance rates to methicillin among S. aureus and CNS were 19.2 and 38.9%, respectively, with MRSA rates in individual sentinel sites ranging from 0 to 43%. No glycopeptide resistance was seen in S. aureus, but 6.5% of CNS isolates were teicoplanin resistant and 0.5% were vancomycin resistant. Vancomycin resistance was much more frequent among Enterococcus faecium (24.1%) than E. faecalis (0.5%) (P<0.05), with most resistant isolates carrying vanA. The rate of penicillin resistance in pneumococci was 8.9%, and this resistance was predominantly intermediate (7.9%), with only six hospitals reporting isolates with high level resistance. The prevalence of erythromycin resistance among pneumococci was 12.3%, with the majority of resistant isolates having the macrolide efflux mechanism mediated by mefE. All the organisms tested were susceptible to linezolid with MICs in the range 0.12-4 mg/L. The modal MICs of linezolid were 1 mg/L for CNS and pneumococci, and 2 mg/L for S. aureus and enterococci. Linezolid was the most potent agent tested against Gram-positive cocci, including multiresistant strains, and as such may prove a valuable therapeutic option for the management of Gram-positive infections in hospitals.     

中医院临床分离菌株耐药性观察

目的调查中医院临床分离菌株分布及其耐药性,为合理使用抗菌药物提供参考。方法以临床标本分离菌株为对象,采用纸片扩散法测定其对常用抗菌药物耐药感性。结果该医院在2007-2010年间从病人标本中共分离出细菌20 725株,其中革兰阴性菌占84.3%,革兰阳性菌占15.7%。革兰阴性菌以大肠埃希菌和肺炎克雷伯菌居多,其中产超广谱β内酰胺酶的大肠埃希菌和肺炎克雷伯菌检出率分别为58.5%和29.1%。革兰阳性菌以金黄色葡萄球菌为主,其中MRSA分离率由2007年的44.6%增加到2010年的72.7%。临床分离菌株多数具有耐药,屎肠球菌对多数抗菌药物的耐药率超过80%,铜绿假单胞菌和鲍曼不动杆菌对多数抗菌药物的耐药率超过90%,4年共检出耐万古霉素的肠球菌15株。结论临床分离细菌以革兰阴性菌为主,耐药率呈逐年升高趋势,MRSA菌株检出率呈现增加趋势。     

痰标本中金黄色葡萄球菌的耐药性监测

目的回顾性分析痰标本中金葡菌的临床分布和耐药情况,为制订预防控制措施提供依据。方法对2009年1月至2012年9月临床分离的276株金葡菌进行分析,细菌鉴定采用VITEK 2 Compact全自动细菌培养鉴定仪,药敏试验结果按CLS1标准判断。结果耐甲氧西林金葡菌（MRSA）的检出率为79.0%（218/276）;临床分离的金葡菌主要分布为神经内科76株（27.5%）、ICU 70株（25.4%）、神经外科50）株（18.1%）、呼吸内科25株（9.1%）。金葡菌对万古霉素、替考拉宁和奎奴普丁-达福普汀的耐药率均〈0.5%;MRSA对甲氧苄啶-磺胺甲噁唑的耐药率低于甲氧西林敏感金葡菌（MSSA）;MRSA对其他大多数抗菌药物的耐药率高于MSSA。结论 MRSA的检出率和耐药率较高,临床应依据药敏试验结果合理选择抗菌药物。     

Therapeutic efficacy of J-111,225, a novel trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenem, against experimental murine systemic infections

In a murine model of systemic infection with methicillin-resistant Staphylococcus aureus (MRSA), J-111,225 showed an ED(50) value of 5. 83 mg/kg, which was comparable to vancomycin (ED(50) 4.84 mg/kg), whereas imipenem failed to cure infected mice (ED(50) >100 mg/kg). Against a mixed infection caused by MRSA and Pseudomonas aeruginosa, monotherapy with J-111,225 showed an ED(50) value of 7.23 mg/kg, whereas combined treatment with vancomycin plus imipenem (1:1) had an ED(50) of 20.86 mg/kg. J-111,225 showed good therapeutic efficacy against methicillin-susceptible S. aureus, penicillin-resistant Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and P. aeruginosa. The unusually broad spectrum suggests that monotherapy with this novel carbapenem may be suitable for polymicrobial infections associated with MRSA.     

耐甲氧西林金黄色葡萄球菌的SPA基因分型研究与耐药性分析

目的 探讨鄂尔多斯地区耐甲氧西林金黄色葡萄球菌(MRSA)分离株杀白细胞毒素(PVL)基因分布特点及药物敏感性。方法 收集2012年6月～2014年12月临床分离的SCCmecⅡ型和Ⅲ型MRSA菌株66株,应用聚合酶链反应对菌株进行PVL基因型检测,用琼脂稀释法测定PVL阳性菌株对常用抗菌药物的敏感性。结果 66例MRSA有6例PVL阳性,阳性率9.09%,其中Ⅱ型4株,Ⅲ型2株; 6株PVL阳性菌均对万古霉素、替考拉宁、利奈唑胺和对多种非β内酞胺类抗菌药敏感,对β内酞胺类、大环内酯类和克林霉素高度耐药。结论 在鄂尔多斯地区MRSA菌株中PVL阳性菌株较低,4株为CA-MRSA,2株为HA-MRSA,若以PVL阳性作为区分MRSA类型的标志有待进一步研究。