Vancomycin-resistant organisms on a burn unit

The incidence of infections due to vancomycin-resistant organisms has significantly increased during the past several years. This is important because vancomycin has been the drug of choice for treatment of infections due to methicillin-resistant Staphylococcus aureus (MRSA). Enterococci resistant to vancomycin are now emerging, and MRSA organisms with intermediate resistance to vancomycin have been identified in some centers. Cross transfer of resistance will eventually lead to the widespread development of organisms that are more difficult to eradicate. In our burn unit, we have encountered six patients (five with burns, one with necrotizing fasciitis) who had wound infections with vancomycin-resistant enterococci. Four patients died, and two recovered after prolonged hospital stays. Attempts to limit development of vancomycin-resistant enterococci are important.     

Activity of a novel cyclic lipopeptide, CB-183,315, against resistant Clostridium difficile and other Gram-positive aerobic and anaerobic intestinal pathogens

We evaluated the activity of CB-183,315 against Clostridium difficile, including strains that are resistant to fluoroquinolones and metronidazole and with elevated MICs to vancomycin as well as other Gram-positive intestinal pathogens. The MICs of CB-183,315 against all C. difficile isolates were ≤ 1 μg/ml. CB-183,315 had greater activity than vancomycin and metronidazole against C. difficile isolates and was more active than the comparators against vancomycin-resistant enterococcus (VRE). CB-183,315 also had excellent activity against methicillin-resistant Staphylococcus aureus (MRSA), other Clostridium spp., and Peptostreptococcus spp.     

Methicillin-resistant Staphylococcus aureus in critical care areas

In recent years the mainstay of treatment for hospital-associated MRSA infections has been vancomycin, but now vancomycin intermediate S aureus strains are beginning to emerge. Complete vancomycin resistant S aureus can develop, possessing the same vanA gene as vancomycin-resistant enterococcus. Four such isolates have been reported, three of which have been in the United States. There are new antibiotics being developed, but there is always a risk of resistance developing. There are some promising new ideas such as staphylococcal conjugate vaccines that reduce the rates of S aureus bacteremia for up to 10 months postimmunization in patients who have end stage renal disease receiving hemodialysis, but studies are ongoing. With all the uncertainty surrounding treatment, at least one medium has remained consistent and effective if used properly--infection control. But this requires complete support of all healthcare workers and hospital administration from the chief medical officer to doctors and nurses to environmental services personnel to take ownership of an effective infection control program. Who will advocate for more stringent infection control policies and for the equipment to successfully carry them out? Who will take the lead by ensuring implementation of infection control policies on a unit is effective? Who will hold themselves and other health care workers including physicians accountable to comply with these infection control policies every time they enter a patient's room? Nurses are on the front lines in the battle against antibiotic-resistant nosocomial infections such as MRSA, and we should not be apathetic or feel we are helpless. It is our duty as patient advocates not to take a spectator role but to answer these questions: "I will."     

铜陵市部分医院细菌耐药性监测与分析

目的了解安徽省铜陵市临床分离菌株耐药状况。方法2007年1～12月铜陵市临床分离菌株用Kirby-Bauer法进行药敏试验。结果1375株细菌中,革兰阳性菌399株,占29．0％;革兰阴性菌976株,占71．0％。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）分别占金黄色葡萄球菌和凝固酶阴性葡萄球菌（CNS）的18．4％和70．0％;MRSA和MRCNS对庆大霉素、环丙沙星、克林霉素和红霉素等均高度耐药,对利福平、氯霉素和呋喃妥因的耐药率均较低,未见耐万古霉素葡萄球菌。粪肠球菌对青霉素、氨苄西林、呋喃妥因、磷霉素和氯霉素的耐药率较低,未见耐万古霉素和替考拉宁粪肠球菌;屎肠球菌对磷霉素和氯霉素耐药率较低,发现2株耐万古霉素屎肠球菌。大肠埃希菌和克雷伯菌属中产超广谱β-内酰胺酶（ESBLs）株分别占49．3％和35．9％,产ESBLs株除对亚胺培南和美罗培南敏感外,对其他20种抗生素的耐药率均较不产ESBLs株高。非发酵菌对碳青霉烯类、头孢哌酮／舒巴坦、哌拉西林／三唑巴坦、头孢他啶、头孢吡肟、阿米卡星、环丙沙星等耐药率较低。结论革兰阳性菌对糖肽类抗生素耐药率低;革兰阴性菌对碳青霉烯类、头孢哌酮／舒巴坦、哌拉西林／三唑巴坦等耐药率低。加强细菌耐药性监测对合理使用抗生素、减少耐药菌株的产生和流行有重要临床指导价值。     

Effects of selective decontamination of digestive tract on mortality and antibiotic resistance in the intensive-care unit

PURPOSE OF REVIEW: Since its introduction in 1984 several small trials have studied the infection prevention regimen of selective decontamination of the digestive tract (SDD) in intensive care patients. Although meta-analyses of these studies suggested that SDD could reduce mortality, it continued to be a highly controversial strategy. There were not only serious doubts about the methodological quality of the meta-analyses, fear also existed that SDD would lead to increased antibiotic resistance. Recently, two new large randomized trials have been published that studied the effects of SDD on mortality and resistance. In this article, we will review the concept on which SDD is based and the present knowledge of the effects of SDD on mortality and antibiotic resistance. RECENT FINDINGS: In accordance with earlier meta-analyses of small studies, two recent randomized trials have confirmed that selective decontamination of the digestive tract significantly lowers mortality and decreases the emergence of antibiotic resistance. Limitation of these studies is the fact that they were conducted in intensive-care units (ICUs) with a low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). SUMMARY: There is convincing evidence that selective decontamination of the digestive tract (SDD) lowers mortality as well as resistance in circumstances with low prevalence of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococcus (VRE). SDD should still be considered experimental in area's where MRSA and VRE are endemic. However, given the important potential benefits of SDD, more studies are urgently needed to adapt SDD in a way that proves effective in those settings.     

Vancomycin-induced deletion of the methicillin resistance gene mecA in Staphylococcus aureus

OBJECTIVE: To elucidate factors that contribute to the development of vancomycin resistance in methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Forty-nine MRSA isolates were subjected to passage selection with vancomycin to isolate mutants with reduced susceptibility to vancomycin. One mutant was chosen for detailed molecular and biochemical characterization. RESULTS: Five vancomycin-resistant mutants (vancomycin MICs, 6-12 mg/L) were obtained in vitro from five MRSA parent isolates. Upon acquisition of vancomycin resistance, all mutants showed a concomitant decrease in oxacillin resistance. In one particular MRSA strain, selection for vancomycin resistance repeatedly produced deletions and rearrangements, including loss of the mecA gene. Pleiotropic phenotypical changes, such as yellow pigment formation, loss of haemolysis, thickened cell wall, increased resistance to lysostaphin and reduced cell wall turnover were observed in this mutant. CONCLUSION: Acquisition of vancomycin resistance in one MRSA strain triggered mecA deletion suggesting that this deletion, coupled to other rearrangements and/or mutations, may be responsible for the increased vancomycin resistance phenotype.     

Ultrastructural Effects of Oritavancin on Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus

The ultrastructural effects of the lipoglycopeptide oritavancin on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE) were examined by transmission electron microscopy. Oritavancin but not vancomycin induced aberrant septum formation and loss of staining of nascent septal cross walls in MRSA. Septal distortions were also observed in VRE exposed to oritavancin.     

2006-2010年浙江省萧山地区金黄色葡萄球菌临床分离与耐药变迁

目的 调查医院金黄色葡萄球菌(SAU)临床分离和分布情况及其对常用抗菌药物的耐药率,分析SAU耐药性变迁,并比较儿科组和重症监护病房(ICU)、耐甲氧西林金黄色葡萄球菌(MRSA)和甲氧西林敏感金黄色葡萄球菌(MSSA)耐药率,为临床合理使用抗菌药物提供依据。 方法 对浙江萧山医院2006年1月至2010年12月检出的SAU药敏结果回顾性分析。 结果 共检出SAU 857株,菌株的主要来源为痰213株(24.9%)、脓液189株(22.1%)、泌尿生殖道分泌物166株(19.4%);菌株分布前3位的科室是妇产科165株(19.3%)、儿科155株(18.1%)、ICU 103株(12.0%);其中MRSA 252株(29.4%)。SAU对利奈唑胺、万古霉素和呋喃妥因具有很高的敏感性,未检出万古霉素耐药株;氨苄西林/舒巴坦和莫西沙星的耐药率呈上升趋势;MRSA 对青霉素、苯唑西林、头孢唑林、氨苄西林/舒巴坦、庆大霉素、利福平、左旋氧氟沙星、莫西沙星、呋喃妥因、克林霉素、红霉素和四环素耐药率都明显高于MSSA 耐药率,差异有统计学意义(PP结论 MRSA检出率升高,应加强对SAU检测及其耐药性监测;通过分析SAU耐药率的变迁,有利于采取措施控制医院内MRSA的流行和指导临床用药。     

In vitro activities of LTX-109, a synthetic antimicrobial peptide, against methicillin-resistant, vancomycin-intermediate, vancomycin-resistant, daptomycin-nonsusceptible, and linezolid-nonsusceptible Staphylococcus aureus

LTX-109 and eight other antimicrobial agents were evaluated against 155 methicillin-resistant Staphylococcus aureus (MRSA) isolates, including strains resistant to vancomycin and strains with decreased susceptibility to daptomycin and linezolid, by microdilution tests to determine MICs. Time-kill assays were performed against representative MRSA, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus (VRSA) isolates. LTX-109 demonstrated a MIC range of 2 to 4 μg/ml and dose-dependent rapid bactericidal activity against S. aureus. This activity was not influenced by resistance to other antistaphylococcal agents.     

Emergence in Asian countries of Staphylococcus aureus with reduced susceptibility to vancomycin

To investigate the prevalence of Staphylococcus aureus with reduced susceptibility to vancomycin among methicillin-resistant S. aureus (MRSA) strains in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12 Asian countries were screened by using brain heart infusion agar plates containing 4 mg of vancomycin per liter. The presence of strains that were heterointermediately resistant to vancomycin (hVISA) was confirmed by population analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58 isolates (4.3%) were hVISA. hVISA strains were found in India, South Korea, Japan, the Philippines, Singapore, Thailand, and Vietnam. However, neither vancomycin-intermediate S. aureus nor vancomycin-resistant S. aureus isolates were found among MRSA isolates from Asian countries in this survey.     

A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital

One hundred methicillin-resistant Staphylococcus aureus (MRSA) strains, isolated between 1983 and 1999, were tested alongside the vancomycin hetero-resistant S. aureus (hVRSA) strain Mu 3, and vancomycin-resistant S. aureus (VRSA) strain Mu 50, for their resistance to vancomycin. This was achieved using the screening method described by Hiramatsu, gradient plates, agar incorporation, standard Etest, macrodilution Etest and a modified population analysis. Using Hiramatsu's screening method, 5% of the 100 MRSA were identified as VRSA and 5% identified as hVRSA, the gradient plates identified 7% hVRSA, and the standard and macrodilution Etests identified no hVRSA. Mu 3 appeared to be vancomycin-susceptible using both the agar incorporation and standard Etest methods, but was classified as hVRSA using the macrodilution Etest. The modified population analysis reliably detected vancomycin hetero-resistance in Mu 3 and identified no hVRSAs within the 100 MRSA sample.     

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.     

Occurrence of vancomycin-intermediate-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> in Japan

The Clinical and Laboratory Standards Institute (CLSI) amended the criteria for vancomycin susceptibility and resistance of Staphylococcus aureus in 2006. The earlier criteria had established that S. aureus with minimum inhibitory concentrations (MICs) of vancomycin of < or =4 microg/ml, 8 to 16 microg/ml, and > or =32 microg/ml were vancomycin-susceptible, -intermediate-resistant and -resistant, respectively. The revised recommendation states that bacteria showing vancomycin MICs of < or =2 microg/ml, 4 to 8 microg/ml, and > or =16 microg/ml are -susceptible, -intermediate-resistant, and -resistant, respectively. We examined, based on these new criteria, the vancomycin susceptibility of methicillin-resistant S. aureus (MRSA) strains isolated in Japan from 1978 through 2005 at 17 general hospitals. The results showed that, among 2446 MRSA isolates tested, 8 were classified as intermediate-vancomycin-resistant (VISA). Re-examination of vancomycin susceptibility in these 8 strains in 2006 revealed that 6 strains showed a vancomycin MIC of 4 microg/ml, as tested by the agar dilution method, broth dilution methods, and E-test; the 2 other strains had lost the vancomycin resistance. Pulsed-field gel electrophoresis (PFGE) of the chromosomal DNA of these strains exhibited five unique profiles; 2 strains isolated from the same hospital were identical. These results revealed that at least five different types of VISA strains could be identified in Japan so far according to the new CLSI criteria. All these VISA strains had type II staphylococcal cassette chromosome, mec. This study revealed, for the first time in Japan, the presence of intermediate vancomycin-resistant MRSA in this country.     

Spontaneous deletion of the methicillin resistance determinant, mecA, partially compensates for the fitness cost associated with high-level vancomycin resistance in Staphylococcus aureus

Treatment of infections caused by Staphylococcus aureus is often confounded by the bacterium's ability to develop resistance to chemotherapeutic agents. Methicillin-resistant S. aureus (MRSA) arises through the acquisition of staphylococcal chromosomal cassette mec (SCCmec), a genomic island containing the methicillin resistance determinant, mecA. In contrast, resistance to vancomycin can result from exposure to the drug, a mechanism that is not dependent upon a gene acquisition event. Here we describe three MRSA strains that became resistant to vancomycin during passage in the presence of increasing concentrations of the drug. In each case two derivative strains were isolated, one that had lost mecA and one that retained mecA during passage. Strain 5836VR lost mecA by the site-specific chromosomal excision of SCCmec, while the other two strains (strains 3130VR and VP32) deleted portions of their SCCmec elements in a manner that appeared to involve IS431. Conversion to vancomycin resistance caused a decrease in the growth rate that was partially compensated for by the deletion of mecA. In mixed-culture competition experiments, vancomycin-resistant strains that lacked mecA readily outcompeted their mecA-containing counterparts, suggesting that the loss of mecA during conversion to vancomycin resistance was advantageous to the organism.     

金黄色葡萄球菌临床分离株对万古霉素敏感性的监测

目的检测金黄色葡萄球菌（金葡菌）对万古霉素药物敏感情况,以监控对万古霉素敏感性降低金葡菌[vaneomyein-intermediate Staphylococcus aureus（S．aureus）,VISA]或耐万古霉素金葡菌（vancomycin-resistant S．aureus,VRSA）的出现,防止其暴发流行。方法对石家庄市区2家三级甲等医院分离自痰液、支气管肺泡灌洗液等临床标本的55株金葡菌应用苯唑西林纸片和头孢西丁纸片检测是否为耐甲氧西林的金葡菌（methieilin-resistant S．aureus,MRSA）;对检出的MRSA,再用胶乳凝集试验检测青霉素结合蛋白2a（PBp-2a）进一步确认。应用Kirb-Bauer纸片法和琼脂稀释法测定万古霉素对55株金葡菌的抑菌环大小和最低抑菌浓度（MIC值）,并比较MRSA与对甲氧西林敏感的金葡菌（methieilin-suseeptibility S．aureus,MSSA）的MIC差异。同时对2004～2005年河北医科大学第二医院分离金葡菌的耐药性状况进行了回顾分析。结果55株金葡菌的万古霉素抑菌环直径15～21mm,MIC≤1mg／L,且MRSA与MSSA两组之间差异无统计学意义（P〉0．05）。河北医科大学第二医院2004年、2005年MRSA的检出率分别为56．8％和64．5％。结论石家庄市区医院分离的55株金葡菌中未检出VISA或VRSA,但部分菌株已经接近耐药折点,应密切关注其发展动向;MRSA的耐药机制可能与金葡菌对糖肽类抗生素耐药无直接相关性。     

United States geographic bacteria susceptibility patterns. 1997 ASCP Susceptibility Testing Group

Antimicrobial drug resistance in bacterial pathogens continues, with 1997 seeing reports of Staphylococcus aureus no longer fully susceptible to vancomycin occurring in the United States. To better deal with this rapidly developing problem, we present the third year of United States national data that highlights the geographic nature of increasing resistance to antimicrobial agents. In 1997, we observed increasing numbers of vancomycin-resistant Enterococcus faecium, more methicillin-resistant Staphylococcus aureus (MRSA), and an apparent spreading of penicillin resistance in pneumococci. The majority of reporting sites now indicates that over 20% of Pseudomonas aeruginosa are fully resistant to ciprofloxacin, the only oral agent available for treating this pathogen. With increasing resistance coming at a time of decreasing available resources, it is more clear than ever before that the future of infectious diseases and clinical microbiology remains filled with challenge.     

Sitafloxacin in the treatment of patients with infections caused by vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus

Sitafloxacin is a new quinolone active against multi-resistant Gram-positive pathogens. An open study was conducted in patients with serious systemic infections with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococcus (VRE). Patients with MRSA were recruited if treatment with glycopeptides had failed. Of 11 patients with MRSA infection, four were cured, six failed treatment and one was indeterminate. Of nine patients with VRE infection (one patient had both pathogens), five were cured and four failed. Fifteen adverse events in 12 patients were potentially related to the study drug. Sitafloxacin was effective in VRE and some recalcitrant MRSA infections.     

Isolates with low-level vancomycin resistance associated with persistent methicillin-resistant Staphylococcus aureus bacteremia

Low-level vancomycin-resistant Staphylococcus aureus (vancomycin-intermediate S. aureus [VISA] and heterogenous VISA [hVISA]) is increasingly reported and leads to glycopeptide treatment failure. Various phenotypic features have been reported for these isolates, but the genetic changes leading to hVISA and VISA have yet to be clearly determined. We assessed phenotypic, antibiotic resistance, and genomic changes by using genomic DNA microarray comparison and sequencing of selected loci in five pairs of clinical hVISA/VISA strains and the initial methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained prior to vancomycin therapy. The isolates were from adult patients in Australia and New Zealand who had persistent MRSA bacteremia (>7 days) while receiving vancomycin therapy. In all cases, the initial isolates were found to be fully vancomycin-susceptible Staphylococcus aureus (VSSA). The hVISA/VISA phenotype was associated with increased cell wall thickness, reduced autolytic activity in four of five hVISA/VISA strains, and a striking reduction in biofilm formation compared to the parent strains in all pairs. All five pairs appeared to be isogenic, and genomic DNA microarray comparison suggested that major genetic changes are not required for the development of the resistant phenotype in these strains. No sequence differences were found in the agr locus or the tcaRA genes for any pair, but a marked reduction in RNAIII expression was found in four pairs. In summary, hVISA/VISA arises from fully VSSA during persistent infection that fails to respond to glycopeptide therapy and is associated with significant phenotypic changes, including a marked reduction in biofilm-forming ability. These clinically derived pairs of isolates will be a useful resource to elucidate the genetic mechanism of resistance in hVISA/VISA strains.     

132株耐甲氧西林金黄色葡萄球菌的临床分布及耐药性变迁分析

目的：了解本院临床标本中分离出的耐甲氧西林金黄色葡萄球菌（MRSA）的科室分布及耐药性变迁情况。方法：收集本院2009年1月-2011年1月共3年间临床分离到的MRSA,统计分析MRSA的分布及药敏试验结果。结果：3年内共分离出金黄色葡萄球菌（SA）249株,其中MRSA132株。分离出SA的标本中以呼吸道标本为主,占51．5％,其次为分泌物和脓液。检出率较高的科室是外科,占36．9％,其次为呼吸内科和老年科。除万古霉素、利福平、复方新诺明及呋喃妥因外,MRSA对其余的抗茵药物的耐药率均高于MSSA（对甲氧西林敏感金黄色葡萄球菌）,耐药率均保持在40％以上,而且耐药率呈逐年上升趋势。结论：MRSA对大部分抗菌药物仍维持较高的耐药率,应定期监测临床标本中分离的MRSA耐药率,合理使用抗茵药物,延缓临床株耐药性的增长,控制医院感染的发生及暴发流行。     

Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia

OBJECTIVES: To evaluate microbiological properties of methicillin-resistant Staphylococcus aureus (MRSA) during prolonged vancomycin therapy. METHODS: We evaluated vancomycin susceptibility and heteroresistance, accessory gene regulator (agr) function, autolysis, biofilm production and in vitro vancomycin killing in serial MRSA bloodstream isolates obtained over a 30 month period from a patient with a chronic endovascular infection. RESULTS: Despite the fact that the MRSA in this patient had the same genetic background as other clinical glycopeptide intermediate-resistant S. aureus (GISA) isolates, vancomycin administered for 9 months, maintaining serum concentrations >10 mg/L, did not select for GISA. Minimal changes in vancomycin susceptibility were detected using agar dilution and population analysis methods. We noted increases in delta haemolysin production, autolysis and the bactericidal effects of vancomycin in vitro against the MRSA obtained after prolonged vancomycin suppressive therapy was discontinued. CONCLUSIONS: Despite the lack of development of detectable resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop vancomycin tolerance and decreased autolysis. In addition, suppression of agr function appears to end after vancomycin is stopped. Whether these changes are prerequisites for attenuated vancomycin efficacy and the development of glycopeptide resistance warrants further study. The development of vancomycin resistance may be more difficult under conditions where vancomycin serum concentrations are maintained >10 mg/L.