Korean nationwide surveillance of antimicrobial resistance in 2000 with special reference to vancomycin resistance in enterococci,and expanded-spectrum cephalosporin and imipenem resistance in gram-negative bacilli

Antimicrobial resistance surveillance is necessary to determine the size of the problem and to guide empirical selection of antimicrobial agents for treating infected patients. The aim of this study was to analyze the results of susceptibility tests performed by hospitals participating in the Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) program. The rates of oxacillin-resistant staphylococci, penicillin-nonsusceptible pneumococci, and ampicillin-resistant E. faecium were over 70%. Ampicillin-resistant H. influenzae increased to 68%. Expanded-spectrum cephalosporin-resistant K. pneumoniae, fluoroquinolone-resistant E. coli, and imipenem-resistant P. aeruginosa remained at 16% through 27%, depending on the species. The proportions of vancomycin- resistant E. faecium and imipenem-resistant P. aeruginosa were 18 - 24% and 19-21%, respectively, indicating the seriousness of antimicrobial resistance. In conclusion, the increasing prevalence of resistant bacteria indicates that more concerted effort is required to conserve the usefulness of precious new antimicrobial agents.     

Korean Nationwide Surveillance of Antimicrobial Resistance of bacteria in 1997

Antimicrobial-resistant bacteria are known to be prevalent in tertiary-care hospitals in Korea. Twenty hospitals participated to this surveillance to determine the nationwide prevalence of resistance bacteria in 1997. Seven per cent and 26% of Escherichia coli and Klebsiella pneumoniae were resistant to 3rd-generation cephalosporin. Increased resistance rates, 19% of Acinetobacter baumannii to ampicillin/sulbactam, and 17% of Pseudomonas aeruginoa to imipenem, were noted. The resistance rate to fluoroquinolone rose to 24% in E. coli, 56% in A. baumannii and 42% in P. aeruginosa. Mean resistance rates were similar in all hospital groups: about 17% of P. aeruginosa to imipenem, 50% of Haemophilus influenzae to ampicillin, 70% of Staphylococcus aureus to methicillin, and 70% of pneumococci to penicillin. In conclusion, nosocomial pathogens and problem resistant organisms are prevalent in smaller hospitals too, indicating nosocomial spread is a significant cause of the increasing prevalence of resistant bacteria in Korea.     

Evolution of β-lactams resistance in Gram-negative bacteria in Tunisia

Antimicrobial resistance is a major health problem worldwide, but marked variations in the resistance profiles of bacterial pathogens are found between countries and in different patient settings. In Tunisia, the strikingly high prevalence of resistance of bacteria to penicillins and cephalorosporins drugs including fourth generation in clinical isolates of Gram negative bacteria has been reported. During 30 years, the emerging problem of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates is substantial, and some unique enzymes have been found. Recently, evidence that Gram-negative bacteria are resistant to nearly all available antimicrobial agents, including carbapenems, have emerged.     

Antibiotic resistance--bacteria fight back

Antibiotic resistance has become one of the leading problems in modern medicine. Resistance to antibiotics emerges in bacteria due to genetic mutations and consecutive selection of resistant mutants through selective pressure of antibiotics present in large amounts in soil, plants, animals and humans. Exchange of genetic material coding for resistance is possible even between unrelated organisms and further promotes the spread of resistance. Constantly evolving resistance mechanisms force experts to redefine breakpoint concentrations and interpretation of in vitro antibiotic sensitivity testing. Developing new antimicrobial agents does not seem to be enough to keep up pace with ever changing bacteria. Using antibiotics prudently and developing new approaches to the treatment of infections is vital for the future. The European Antimicrobial Resistance Surveillance System (EARSS) data clearly show that Scandinavian countries and The Netherlands have the lowest rates of resistance, while Southern and Eastern European countries have the highest prevalence of resistance. This is linked to the European Surveillance of Antimicrobial Consumption (ESAC) data that show very low consumption of antibiotics in Scandinavian countries and The Netherlands. Compliance with strict infection control policies related to multidrug resistant organisms is also high in these countries. Although it is important to be aware of the resistance problems worldwide, rational use of antibiotics should be based on the knowledge of local resistance patterns in common pathogens. Since 1996 there is a continuous surveillance of resistance in Croatia through the Croatian Committee for Antibiotic Resistance Surveillance. There is a particular concern about the rising penicillin and macrolide resistance in pneumococci. In Croatia, data for 2002 suggest that resistance to penicillin in pneumococci was 30% (low level) and 2% (high level). Among invasive isolates, 19% had reduced susceptibility to penicillin (< 1% high level resistance) as compared with 1% in The Netherlands and 53% in France. While methicillin-resistant Staphylococcus aureus (MRSA) has become endemic in many hospitals throughout the world, the most alarming event in 2002 was detection of Staphylococcus aureus fully resistant to vancomycin (VRSA). Of great concern is also reporting of MRSA community outbreaks in some parts of the world. Multiply resistant gram-negative pathogens, especially non-fermentative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumanii, have become dominant in many intensive care settings and some of these strains cannot be treated with any of the currently available systemic antibiotics. Raising awareness about the microbial resistance threat among health care workers and patients is essential if we are to preserve the efficacy of antibiotics for future generations.     

深圳市7家医院常见病原菌耐药性分析

目的了解深圳市区级、街道人民医院常见病原菌的耐药情况,为临床合理使用抗菌药物提供依据。方法对深圳市7家区级、街道二级甲等医院2009年1～9月分离的1765株病原菌进行药敏试验,用WHONET5.5软件对数据进行统计分析。结果大肠埃希菌对广谱青霉素、头孢呋辛、复方新诺明的耐药率均〉60%,肺炎克雷伯菌对广谱青霉素、第一和第二代头孢菌素的耐药率〉40%,两种菌对碳青酶烯类的敏感率为95%～100%,对氨基糖苷类阿米卡星敏感率达90%～95%,产ESBLs率分别为44.6%和29.0%。铜绿假单胞菌对氨苄西林、氨苄西林/舒巴坦、第一和第二代头孢菌素的耐药率〉90%,对氨基糖苷类阿米卡星的敏感率为91.4%,对碳青酶烯类和氟喹诺酮类药物敏感率为70%～80%。未发现耐万古霉素的葡萄球菌。结论深圳市区级、街道人民医院常见病原菌对抗菌药物的耐药性普遍存在,应长期开展对病原菌的耐药性监测。     

Emerging problems of antibiotic resistance in community medicine

Emergence of antimicrobial resistance in bacteria associated with community acquired infections has made the choice of empirical therapy more difficult and more expensive. The problems due to possible spread of MRSA to the community, emergence of penicillin resistance in S. pneumoniae, ampicillin resistance in H. influenzae, and multiresistance among common enteric pathogens are highlighted. Bacteria have a remarkable ability to develop resistance to many of the newly synthesized antimicrobial agents but the appropriate use of antibiotics will delay and in many cases prevent the emergence of resistance.     

Emergence and spread of antimicrobial resistance of Streptococcus pneumoniae in Korea

Pneumococcal resistance has become a global issue during the past three decades. One of the major foci of pneumococcal resistance worldwide is the Asian region including Korea, Japan, and Hong Kong. Korea had not been recognized as a focus of pneumococcal resistance until 1995, when serial reports documented the alarmingly high prevalence of penicillin resistance among clinical isolates. Serial reports on penicillin resistance among pneumococcal isolates in Korea ranged from 68% to 77% as of 1995. Multidrug resistance was also noted in 34% of Korean isolates. Penicillin-binding protein profile analysis, pulsed-field gel electrophoresis, ribotyping, and fingerprinting analysis of pbp genes showed that antibiotic-resistant pneumococci isolated in Korea were genetically related. Data documented the extensive spread of a resistant clone within Korea and between different countries. Besides the injudicious use of antimicrobial agents or the high prevalence of serotypes 23 and 19, the spread of a resistant clone may play an important role in the rapid increase of penicillin resistance in Korea.     

Multidrug-resistant Acinetobacter spp.: increasingly problematic nosocomial pathogens

Pathogenic bacteria have increasingly been resisting to antimicrobial therapy. Recently, resistance problem has been relatively much worsened in Gram-negative bacilli. Acinetobacter spp. are typical nosocomial pathogens causing infections and high mortality, almost exclusively in compromised hospital patients. Acinetobacter spp. are intrinsically less susceptible to antibiotics than Enterobacteriaceae, and have propensity to acquire resistance. A surveillance study in Korea in 2009 showed that resistance rates of Acinetobacter spp. were very high: to fluoroquinolone 67%, to amikacin 48%, to ceftazidime 66% and to imipenem 51%. Carbapenem resistance was mostly due to OXA type carbapenemase production in A. baumannii isolates, whereas it was due to metallo-β-lactamase production in non-baumannii Acinetobacter isolates. Colistin-resistant isolates were rare but started to be isolated in Korea. Currently, the infection caused by multidrug-resistant A. baumannii is among the most difficult ones to treat. Analysis at tertiary care hospital in 2010 showed that among the 1,085 isolates of Acinetobacter spp., 14.9% and 41.8% were resistant to seven, and to all eight antimicrobial agents tested, respectively. It is known to be difficult to prevent Acinetobacter spp. infection in hospitalized patients, because the organisms are ubiquitous in hospital environment. Efforts to control resistant bacteria in Korea by hospitals, relevant scientific societies and government agencies have only partially been successful. We need concerted multidisciplinary efforts to preserve the efficacy of currently available antimicrobial agents, by following the principles of antimicrobial stewardship.     

Korean Nationwide Surveillance of Antimicrobial Resistance of Bacteria in 1998

Antimicrobial resistance surveillance can provide information needed for empirical therapy of antimicrobial agents and for control of resistance. To determine the trend of antimicrobial resistance in Korea, in vitro susceptibility data in 1998 were collected from 25 hospitals participating to a program of Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR). The data were analyzed based upon hospital location and bed capacity. The results showed that cefoxitin-resistant E. coli and K. pneumoniae and 3rd-generation cephalosporin-resistant K. pneumoniae were prevalent, that 3rd-generation cephalosporin-resistant E. cloacae, S. marcesens and A. baumannii had increased, and ampicillin-resistant S. enterica were not rare. Oxacillin-resistant S. aureus, penicillin-non-susceptible pneumococci and beta-lactamase-producing H. influenzae were prevalent even smaller hospitals surveyed, and an increase of imipenem-resistant P. aeruginosa and vancomycin-resistant E. faecium is a new obvious threat. In general, resistance rates to some old antimicrobial agents, i.e., E. coli to ampicillin and S. aureus to oxacillin were high and did not vary greatly between the different levels of hospitals, while the rates to some of the newer ones, i.e., P. aeruginosa to imipenem, was quite variable and depended on the hospitals, probably reflecting difference in selective pressure.     

Vancomycin-resistant enterococcal infections in Korea

Enterococci recently became the second-to-third most commonly isolated organism from nosocomial infections. Enterococci are intrinsically more resistant to many antimicrobial agents and often show acquired resistance to many antimicrobial agents including high-level aminoglycosides. With the increased use of vancomycin, vancomycin-resistant enterococci (VRE) has become an important nosocomial pathogen. In Korea, the proportion of VRE among all enterococcal of VRE is no longer low in some settings and recent observations of a sudden increase of VRE isolation in several hospitals in Korea suggests that VRE infection may become a serious problem in the near future. The most important considerations are that vancomycin-resistant genes may spread to other highly virulent genera, such as MRSA, and that there are no approved and convincingly effective antibiotics for the treatment of VRE. Therefore, current efforts have concentrated on limiting the spread of these organisms within the hospital environment. Prudent use of antimicrobial agents and strict adherence to preventive measures such as aggressive communication, education, and infection control practices are essential to control the spread of this organism. However, hospital infection control protocols and the laboratory support they require are costly in terms of space and supplies, as well as in personnel resources. These factors add further pressure to already stretched hospital budgets. Nevertheless, policies or programs defining and managing VRE infection or colonization should be established and now is the time to enforce an overall management strategy against VRE.     

Increasing prevalence of vancomycin-resistant enterococci, and cefoxitin-, imipenem- and fluoroquinolone-resistant gram-negative bacilli: a KONSAR study in 2002

Continued antimicrobial resistance surveillance can provide valuable information for the empirical selection of antimicrobial agents for patient treatment, and for resistance control. In this 6th annual study for 2002, the susceptibility data at 39 Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) hospitals were analyzed. Resistance rates of S. aureus were 67% to oxacillin, and 58% to clindamycin. The ampicillin and vancomycin resistance rates of E. faecium were 89% and 16%, respectively. To penicillin, 71% of S. pneumoniae were nonsusceptible. Resistance rates of E. coli were 11% to cefotaxime, 8% to cefoxitin, and 34% to fluoroquinolone, and those of K. pneumoniae were 22% to ceftazidime, and 16% to cefoxitin. Lowest resistance rates to cephalosporins shown by E. cloacae and S. marcescens were to cefepime, 7% and 17%, respectively. This is the first KONSAR surveillance, which detected imipenem-resistant E. coli and K. pneumoniae. To imipenem, 22% of P. aeruginosa and 9% of Acinetobacter spp. were resistant. Trends of resistances showed a slight reduction in MRSA and in penicillin- nonsusceptible S. pneumoniae, but an increase in ampicillin-resistant E. faecium. Ampicillin-resistant E. coli and H. influenzae remained prevalent. Compared to the previous study, amikacin- and fluoroquinolone- resistant Acinetobacter spp. increased to 60% and 62%, respectively. Ceftazidime- resistant K. pneumoniae decreased slightly, and imipenem- resistant P. aeruginosa and Acinetobacter spp., and vancomycin-resistant E. faecium increased. In conclusion, vancomycin-resistant E. faecium, cefoxitin-resistant E. coli and K. pneumoniae, and imipenem-resistant P. aeruginosa and Acinetobacter spp. increased gradually, and imipenem- resistant E. coli and K. pneumoniae appeared for the first time. Continued surveillance is required to prevent further spread of these serious resistances.     

Is antimicrobial resistance also subject to globalization?

In recent years one of the more alarming aspects of clinical microbiology has been the dramatic increase in the incidence of resistance to antibacterial agents among pathogens causing nosocomial as well as community-acquired infections. There are profound geographic differences in the incidence of resistance among pathogens of the respiratory tract, only some of which can be explained by the local use of antibiotics. A high percentage of Moraxella catarrhalis strains produce β -lactamase and are thus resistant to many β -lactam antibiotics. In contrast, β -lactamase production among strains of Haemophilus influenzae rarely reaches more than 30% around the world. Methicillin-resistance in Staphylococcus aureus is a common and increasing problem in hospitals but its extent varies both locally and nationally. Resistance is usually associated with the local spread of resistant strains. High standards of hygiene in hospitals can prevent the spread of such strains but once established they can be difficult to eradicate. Although Streptococcus pyogenes remains highly susceptible to penicillins, even after many decades of their use, resistance to macrolides has occurred. This resistance can rise and fall. Although the increase of macrolide resistance in S. pyogenes can often be associated with an increase in the use of these drugs, this is not always so. In some cases it has been shown to be caused by the spread of one or more resistant clones. Eradication of these clones can reduce the level of resistance markedly. Resistance to both macrolides and penicillins among strains of Streptococcus pneumoniae is seen world-wide but is highly variable from country to country. Local habits of drug usage may play a part. In Italy, for example, there is preference for the use of parenteral third-generation cephalosporins for some severe infections and there is a corresponding low level of penicillin-resistance among pneumococci.     

Marked differences in antibiotic use and resistance between university hospitals in Vilnius, Lithuania, and Huddinge, Sweden

Antibiotic use and antimicrobial resistance was compared between Vilnius and Huddinge University hospitals. Drug use data were expressed in number of defined daily doses/100 bed-days; antimicrobial resistance were given as percentages of resistant isolates. Thirty-five and 48 different antibiotic drugs were used in Vilnius and Huddinge, respectively. The overall consumption of antibiotics was 15 DDD/100 bed-days in Vilnius and 43 DDD/100 bed-days in Huddinge. Benzylpenicillin, ampicillin, and aminoglycosides were the major antibiotics in Vilnius; beta-lactamase-resistant penicillins, cefalosporins, and quinolones in Huddinge. In Vilnius, gentamicin made up one-quarter of the use. Staphylococcus aureus and Gram-negative isolates from wounds and blood were more resistant to gentamicin in Vilnius. S. aureus was more often methicillin resistant in Vilnius than in Huddinge. There was no S. aureus-resistant to vancomycin in either hospital. The vancomycin-resistant enterococci made up from 4% to 10% in Vilnius hospital, but they were not detected in Huddinge hospital (0%). The majority of Streptococcus pneumoniae isolates were sensitive to benzylpenicillin in both hospitals. The higher resistance of microorganisms to some antibiotics in Vilnius may be explained by heavy use of few antibiotics. Lower level of hygiene procedures, sampling bias, and other methodological issues may also have contributed. Guidelines for antibiotic use and hygienic procedures are now under development in Vilnius.     

临床分离的4379株病原菌的分布特征及药敏结果分析

目的了解本院2008年临床分离的病原菌的分布特征及药敏结果,为合理使用抗菌药物提供依据。方法大多数细菌鉴定和药敏试验利用BD Phoenix仪,少数利用手工鉴定和K-B法药敏试验。念珠菌利用显色平板分离和鉴定,K-B法进行药敏试验。结果4379株细菌念珠菌中最常见的为大肠埃希菌（10.2%）、铜绿假单胞菌（9.4%）、金黄色葡萄球菌（7.7%）、鲍曼不动杆菌（7.7%）、白色念珠菌（7.0%）和肺炎克雷伯菌（6.2%）。大肠埃希菌和肺炎克雷伯菌产ESBLs比例分别为47.8%和41.3%。金黄色葡萄球菌、表皮葡萄球菌、溶血葡萄球菌和腐生葡萄球菌甲氧西林耐药率分别为58.1%、82.8%、83.6%和73.1%。G-杆菌中耐药率较低的为头孢哌酮/舒巴坦、亚胺培南、哌拉西林-他唑巴坦和阿米卡星。G＋球菌,万古霉素和替考拉宁的敏感率均为100.0%,其他抗菌药物耐药率较低的为氯霉素。念珠菌对两性霉素B和制霉菌素的耐药率均低于2.0%。结论本院临床分离大肠埃希菌和肺炎克雷伯菌产ESBLs水平、非发酵G-杆菌碳青霉烯类耐药率和葡萄球菌甲氧西林耐药率居高不下,应加强抗菌药物的合理使用,以降低耐药率。     

Saudi Arabian-American differences in antimicrobial resistance of Escherichia, Klebsiella, and Pseudomonas

Increasing microbial resistance to newly developed antibiotics has been a limiting factor in the therapeutic use of these agents. To determine the extent of the problem, in vitro antimicrobial susceptibility of 7,140 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa to seven commonly used antibiotics was established at the 1,700-bed Riyadh Central Hospital in Saudi Arabia and compared with 5,513 isolates at the Oklahoma Memorial Hospital and Veterans Administration Medical Center, Oklahoma City, Oklahoma. Escherichia coli and Pseudomonas aeruginosa at Riyadh Central Hospital were generally more resistant to ampicillin, carbenicillin, gentamicin, and trimethoprim-sulfamethoxazole than those at Oklahoma Memorial Hospital and the Veterans Administration Medical Center. All 1,022 isolates of Klebsiella pneumoniae at Oklahoma Memorial Hospital were more sensitive to the antibiotics than those at Riyadh Central Hospital or the Veterans Administration Medical Center. The sensitivity pattern of Klebsiella pneumoniae at Riyadh Central Hospital and the Veterans Administration Medical Centers was similar.     

Characteristics, epidemiology and clinical importance of emerging strains of Gram-negative bacilli producing extended-spectrum beta-lactamases

Beta-lactam antimicrobial agents represent the most common treatment for bacterial infections and continue to be the leading cause of resistance to beta-lactam antibiotics among Gram-negative bacteria worldwide. The persistent exposure of bacterial strains to a multitude of beta-lactams has induced dynamic and continuous production and mutation of beta-lactamases in these bacteria, expanding their activity even against the newly developed beta-lactam antibiotics. These enzymes are known as extended-spectrum beta-lactamases (ESBLs). The majority of ESBLs are derived from the widespread broad-spectrum beta-lactamases TEM-1 and SHV-1. There are also new families of ESBLs, including the CTX-M and OXA-type enzymes as well as novel unrelated beta-lactamases. In recent years, there has been an increased incidence and prevalence of ESBLs. ESBLs are mainly found in strains of Escherichia coli and Klebsiella pneumoniae but have also been reported in other Enterobacteriaceae strains and Pseudomonas aeruginosa. Infections with ESBL-producing bacterial strains are encountered singly or in outbreaks, especially in critical care units in hospitals, resulting in increasing cost of treatment and prolonged hospital stays. Not only may nursing home patients be an important reservoir of ESBL-containing multiple antibiotic-resistant organisms, but ambulatory patients with chronic conditions may also harbor ESBL-producing organisms.     

Why do antimicrobial agents become ineffectual?

Antibiotic resistance has evolved over the past 50 years from a merely microbiological curiosity to a serious medical problem in hospitals all over the world. Resistance has been reported in almost all species of gram-positive and -negative bacteria to various classes of antibiotics including recently developed ones. Bacteria acquire resistance by reducing permeability and intracellular accumulation, by alteration of targets of antibiotic action, and by enzymatic modification of antibiotics. Inappropriate use of an antibiotic selects resistant strains much more frequently. Once resistant bacteria has emerged, the resistance can be transferred to other bacteria by various mechanisms, resulting in multiresistant strains. MRSA is one of the typical multiresistant nosocomial pathogens. A study of the PFGE pattern of endonuclease-digested chromosomal DNA showed that MRSA of a few clones were disseminated among newborns in the NICU of a Japanese hospital. In this regard, it is important to choose appropriate antibiotics and then after some time, to change to other classes to reduce the selection of resistant strains. Since the development of epoch-making new antibiotics is not expected in the near future, it has become very important to use existing antibiotics prudently based on mechanisms of antibiotic action and bacterial resistance. Control of nosocomial infection is also very important to reduce further spread of resistant bacteria.     

Further increase of vancomycin-resistant Enterococcus faecium, amikacin- and fluoroquinolone-resistant Klebsiella pneumoniae, and imipenem-resistant Acinetobacter spp. in Korea: 2003 KONSAR surveillance

Monitoring temporal trends of antimicrobial resistance can provide useful information for the empirical selection of antimicrobial agents to treat infected patients and for the control of nosocomial infections. In this study, we analyzed antimicrobial resistance of clinically relevant bacteria in 2003 at Korean hospitals and at a commercial laboratory. The following organism-antimicrobial agent resistance combinations were very prevalent: oxacillin-resistant Staphylococcus aureus (68%), expanded-spectrum cephalosporin-resistant Klebsiella pneumoniae (25%), and fluoroquinolone-resistant Escherichia coli (33%), Acinetobacter spp. (58%), and Pseudomonas aeruginosa (40%). Moreover, gradual increases in vancomycin-resistant Enterococcus faecium (20%), cefoxitin-resistant E. coli (10%) and K. pneumoniae (23%), and imipenem-resistant P. aeruginosa (20%) and Acinetobacter spp. (13%) were also observed. The resistance rates of Acinetobacter spp. to most antimicrobial agents at hospitals and at the commercial laboratory were similar. Among the Acinetobacter spp. isolated at a tertiary-care hospital, 46.2% were multidrug-resistant to 9-12 of 13 antimicrobial agents, and 18.3% were panresistant. The exclusion of duplicate isolates at a tertiary-care hospital significantly lowered the proportion of oxacillin-resistant S. aureus, vancomycin-resistant E. faecium, and fluoroquinolone-resistant E. coli.