Methicillin-resistant Staphylococcus aureus (MRSA) is a typical pathogen of nosocomial infection, and has recently emerged as an important community-acquired pathogen. MRSA is notorious as a multidrug-resistant organism. Its resistance to all beta-lactams is mediated by PBP2a which is encoded by mecA, and it is also resistant to many antimicrobials of other classes due to frequently co-carrying resistance genes, which accounts for becoming a clinical and laboratory issue. This article reviews the microbiological characteristics, surveillance methods, and molecular epidemiology of MRSA.
Adenosine ; beta-Lactams ; Carrier State ; Cross Infection ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Molecular Epidemiology

Staphylococcal cassette chromosome mec (SCCmec) type and coagulase serotype are important epidemiologic factors in methicillin-resistant Staphylococcus aureus (MRSA). To investigate correlation between SCCmec type and coagulase serotype of MRSA, we analyzed SCCmec types of MRSA strains isolated from clinical sources and compared the results to coagulase serotypes and antimicrobial susceptibility patterns. A total of 108 MRSA isolates were classified into four SCCmec types: II (55.6%), IV (21.3%) III (13.0%) and IIIA (8.3%), and five coagulase serotypes: II (54.6%), IV (21.3%), V (18.5%) and VII (2.8%). All of coagulase type II, IV and V strains belonged to SCCmec type II, III/IIIA and IV, respectively. SCCmec types II, III and IIIA were multidrug resistant, whereas SCCmec type IV strains were non-multidrug resistant except beta-lactams and erythromycin. The data provide that there is a significant correlation between SCCmec types and phenotypic characteristic of coagulase serotypes.
beta-Lactams ; Coagulase ; Epidemiologic Factors ; Erythromycin ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus

BACKGROUND: Extended-spectrum beta-lactamases (ESBLs) confer resistance to extended-spectrum cephalosporin (e.g., cefotaxime, ceftazidime) and aztreonam. But the diversity of ESBLs results in various susceptibility profiles with different beta-lactams. To study the relative in vitro activities of various beta-lactams and non-beta-lactam antibiotics against the clinical isolates of ESBL-producing K. pneumoniae, we determined the MIC (minimum inhibitory concentration) of various antimicrobials. METHODS: Fifty-seven isolates of K. pneumoniae which produced ESBL and 63 isolates which did not produce ESBL from 3 university hospitals in Korea were tested. The MIC values of antimicrobials were determined by agar dilution method and detection of ESBL production was performed by double disk synergy test. RESULTS: The MIC values of beta-lactams against K. pneumoniae which produced ESBLs exhibited heterogeneous susceptability profiles. In differentiation of ESBL production, MIC value of 8 ug/mL (breakpoint of intermediate resistance) of ceftazidime was more sensitive and more specific than that of cefotaxime or aztreonam. MIC50 values of gentamicin, amikacin and ciprofloxacin against K. pneumoniae that produced ESBL were significantly higher than those against Non-ESBL producing isolates (P<0.001), suggesting that ESBL producing isolates are multi-drug resistant. CONCLUSION: The level of resistance to various beta-lactams of K. pneumoniae which produced ESBL was heterogeneous. ESBL-producing K. pneumoniae showed higher resistance to aminoglycoside and quinolone antibiotics. Ceftazidime was the most appropriate antibiotic to differentiate ESBL production.
Agar ; Amikacin ; Anti-Bacterial Agents* ; Aztreonam ; beta-Lactamases* ; beta-Lactams ; Cefotaxime ; Ceftazidime ; Ciprofloxacin ; Gentamicins ; Hospitals, University ; Klebsiella pneumoniae* ; Klebsiella* ; Korea ; Pneumonia

Antibiotics are prescribed to prevent infection and to treat established or presumptive infections. In choosing the appropriate antibiotics, a number of factors must be considered. First, the identity of the infecting organism must be known. Second, the information about the antibiotic susceptibility of the infecting organism must be as accurate as possible. Finally, host factors must be taken into consideration. The pharmacokinetics and pharmacodynamics of antibiotics in children are different from those in adults and are important host factors. The antibiotics may be classified into several groups : the beta-lactams (i.e., penicillins, cephalosporins, carbacephems, and monobactam), glycopeptides (i.e., vancomycin), aminoglycosides, macrolides, and quinolones. This article describes the clinical application of selected antibiotics to infectious diseases with newly available agents in children. The development of new oral agents prescribed as once or twice per day achieves enhanced compliance. These include cefprozil, cefpodoxime, loracarbef, azithromycin, clarithromycin, and fluoroquinolones. Meropenem is also a newly available carbacephem approved for use in children. Antibiotics available but not approved for use in children are imipenem-ci-lastatin, aztreonam, quinolones, and several cephalosporins including "fourth"-generation such as cefipime. Recently the use of once-daily dosing of aminoglycosides has been evaluated in pediatric populations, which appears to be safe and effective, although further studise are warranted. The emergence of antibiotic-resistant bacteria has generally been correlated with the rise of specific antibiotic use in clinical practice. Although the development of resistance may be inevitable, the rate at which it develops may be diminished by the rational use of antibiotics.
Adult ; Aminoglycosides ; Anti-Bacterial Agents ; Azithromycin ; Aztreonam ; Bacteria ; beta-Lactams ; Cephalosporins ; Child ; Clarithromycin ; Communicable Diseases ; Compliance ; Fluoroquinolones ; Glycopeptides ; Humans ; Macrolides ; Penicillins ; Pharmacokinetics ; Quinolones

BACKGROUND: Recently, new plasmid-mediated extended-spectrum beta-lactamases have been reported. These are not derived from TEM or SHV enzymes but are related to cephalosporins of Enterobacteriaceae (AmpCenzymes), that confer to all cephalosporins including cefoxitin. METHODS: Fifteen clinical isolates of cefoxitin-resistant Klebsiella pneumoniae were charaterized. Antimicroilutin method. Crude beta-lactamases were prepared by sonication and isoelectric focusing of the enzyme preparations was performed in polyacrylamide gel. The transmissibility of resistance was tested by mating to E. coli J53. We performed PCR and hybridization for further characterization of the AmpC-type beta-lactamse. RESULTS: Seven strains were found to have the plasmid-mediated AmpC type beta-lactamase as a pI of 8.0 and this was confirmed to be cmy-1 beta-lactamase by PCR and hybridization analysis. These strains were resistant to ampicillin and piperacillin with MICs above 128microgram/ml. Cefoxitin resistance could be transferred from 4 strains via a large plasmi with molecular sizes approximately 77 or 130 kb. The molecular weight of CMY-1 enzyme is approximately 38kDa. We analyzed the OMP of six cefoxitin-resistance K. pneumoniae. Two of six strains were lacking a major OMP of approximately 40 kDa, but four of them showed another 39 kDa sized band just below the 40 kDa major OMP, which were thought to be a modified 40 kDa OMP. CONCLUSION: With these results, we conclude that resistance to cefoxitin in K. pneumoniae isolated from Korean patients is either associated with the productin of CMY-a, a plasmid-mediated AmpC type beta-lactamase, of altered expressin of an outer membrane protein.
Ampicillin ; beta-Lactamases* ; beta-Lactams ; Cefoxitin ; Cephalosporins ; Enterobacteriaceae ; Humans ; Isoelectric Focusing ; Klebsiella pneumoniae* ; Klebsiella* ; Membrane Proteins ; Molecular Weight ; Piperacillin ; Pneumonia ; Polymerase Chain Reaction ; Sonication

BACKGROUND: Resistance to beta-lactams in E. coli is mostly via acquisition of plasmid-mediated beta-lactamase gene. Among the plasmid-mediated beta-lactamases, TEM-1 beta-lactamase is by far the most prevalent among ampicillin-resistant E. coli. The prevalence of TEM-1 or TEM-2 ranged from 61% to 98% across the surveys. Klebsiella species generally have class A chromosomal beta-lactamases, which differ greatly from the class C types. Most K. pneumoniae isolates have chromosomally mediated SHV-1 beta-lactamase in most surveys. There has been only one report of prevalence and types of beta-lactamases in E. coli and K. pneumoniae in Korea. We performed this study to determine the prevalence and types of beta-lactamases in E. coli and K. pneumoniae isolated in Korea. METHODS: Ampicillin resistance was determined by disk diffusion test (E. coli) and agar dilution method (K. pneumoniae). Fifty five isolates of E. coli and 92 isolates of K. pneumoniae which were derived from patients in 2 university hospitals in Korea during 1996 were tested by TEM- and SHV-specific PCR. RESULTS: The ampicillin resistance rate in E. coli and K. pneumoniae was 82% and 94.6%, respectively. TEM-type beta-lactamase gene was found in 53% of E. coli isolates. 93.5% of K. pneumoniae isolates was found to have SHV-type beta- lactamase gene. CONCLUSION: In Korea TEM-type beta-lactamase gene was most prevalent in E. coli, but its prevalence rate was relatively low compared with those in other country. For K. pneumoniae, the isolates with SHV type beta-lactamase gene were predominant.
Agar ; Ampicillin Resistance ; beta-Lactamases* ; beta-Lactams ; Diffusion ; Escherichia coli* ; Escherichia* ; Hospitals, University ; Humans ; Klebsiella pneumoniae* ; Klebsiella* ; Korea* ; Penicillinase ; Pneumonia ; Polymerase Chain Reaction ; Prevalence*

BACKGROUND: Enterococci exhibit intrinsic resistance or high-level minimum inhibitory concentration (MIC) to beta-lactams than other streptococci. This appears to be due to low affinity of penicillin-binding proteins and rarely production of beta-lactamase, which gives the reason of testing beta-lactamase for blood and cerebrospinal fluid isolates. Ampicillin is more effective than penicillin in vitro, and MIC of ampicillin is generally 1 dilution lower than that of penicillin. The purpose of this study is to detect beta-lactamase producing enterococci an6 to compare MICs of ampicillin and penicillin by Vitek system (bioMerieux, Hazelwood, MO, USA) with those by agar dilution method. METHODS: We collected 110 isolates of Enterococcus faecalis and 51 isolates of E. faecium from clinical specimens in 1998. MICs of antibiotics were determined by agar dilution method and Vitek system. We also performed beta-lactamase test by the Cefinase (Becton Dickinson, USA) for 512 isolates of E. faecalis and 189 isolates of E. faecium collected in 1998. RESULTS: The most common sites of isolates were blood, bile, surgical/traumatic wounds, closed and open pus and urine. MICs of ampicillin were 1 to 2 dilution lower than those of penicillin for E. faecalis (P=0.03). But there were no significant differences in MICs for E. faecium (P=0.19). Five isolates (4 E. faecalis and 1 E. faecium) were susceptible to ampicillin but resistant to penicillin. There were no beta-lactamase producing enterococci among 701 isolates tested. CONCLUSIONS: MIC by Vitek system tends to be 1 to 2 dilution lower than MIC by agar dilution method to beta-lactams, and MIC of ampicillin is 1 to 2 dilution lower than MIC of penicillin, which could result in discrepancy in interpretation of susceptibilty tests. A beta-lactamase test for enterococci is not recommeneded for routine test in Korea.
Agar ; Ampicillin ; Anti-Bacterial Agents* ; beta-Lactamases ; beta-Lactams ; Bile ; Cerebrospinal Fluid ; Enterococcus faecalis ; Enterococcus* ; Korea ; Microbial Sensitivity Tests ; Penicillin-Binding Proteins ; Penicillins ; Suppuration ; Wounds and Injuries

BACKGROUND: Recently Escherichia coli isolates with extended-spectrum beta-lactamase(ESBL) have been increased in Korea. ESBLs confer variable levels of resistance to cefotaxime, ceftazidime and other broad-spectrum cephalosporins as well as to monobactams such as aztreonam, but they have no detectable activity against cephamycins and carbapenems. The aim of this study was to characterize the ESBL produced by E. coli strains isolated from clinical specimens. METHODS: From March to July, 1998, a total of 93 clinical isolates of E. coli, which was produced ESBL, were collected from patients of the Asan Medical Center. The isolates flagged as ESBL producers by microbroth dilution antibiotic susceptibility test were confirmed by the double disk synergy test. Minimal inhibitory concentration(MIC) of beta-lactams were determined by agar dilution method. The presence of TEM, SHV or CMY-1 gene was determined by polymerase chain reaction. The types of beta-lactamase gene were determined by isoelectric focusing and nucleotide sequence analysis. RESULTS: Sixty-two strains carried plasmid-mediated TEM-52 gene, which sequence showed the substitution of 3 amino acids compared to that of TEM-1. Seventeen strains produced SHV-12, six strains produced SHV-2a, three strains produced TEM-52 and SHV-12, three strains produced TEM-52 and SHV-2a, and one strain produced SHV-2a and SHV-12. One out of twenty-seven strains of cefoxitin-resistant E. coli was confirmed to have CMY-1 beta-lactamase by PCR and nucleotide sequence analysis. CONCLUSIONS: TEM-52 was the most prevalent in E. coli isolates. The most common SHV-types of ESBL in Korea are SHV-12 and SHV-2a in E. coli isolates. In Korea, widespread use of oxyimino-cephalosporins in the hospitals has dramatically increased the prevalence of ESBL-producers in E. coli. Therefore, more prudent use of antibiotics is necessary to reduce the spread of these resistant organisms.
Agar ; Amino Acids ; Anti-Bacterial Agents ; Aztreonam ; Base Sequence ; beta-Lactamases* ; beta-Lactams ; Carbapenems ; Cefotaxime ; Ceftazidime ; Cephalosporins ; Cephamycins ; Chungcheongnam-do ; Escherichia coli* ; Escherichia* ; Humans ; Isoelectric Focusing ; Korea ; Monobactams ; Polymerase Chain Reaction ; Prevalence

BACKGROUND: In 2010, the Clinical and Laboratory Standards Institute (CLSI) revised breakpoints for cephalosporins and carbapenems and indicated that extended-spectrum beta-lactamase (ESBL) testing is no longer necessary for Enterobacteriaceae. We compared the results of the CLSI 2010 and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC breakpoints for Enterobacteriaceae producing ESBL and/or plasmid-mediated AmpC beta-lactamase (PABL). METHODS: A total of 94 well-characterized clinical isolates of Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Salmonella spp., Shigella spp., Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, and Serratia marcescens were analyzed. Of them, 57 were ESBL producers, 24 were PABL producers, and 13 were ESBL plus PABL co-producers. Broth microdilution MIC tests were performed for cefotaxime, ceftazidime, aztreonam, cefepime, and imipenem. RESULTS: Among the 94 isolates containing ESBL and/or PABL, the number of isolates that were susceptible to cefotaxime, ceftazidime, aztreonam, cefepime, and imipenem according to the CLSI 2010 vs. the EUCAST breakpoints were 4 (4.3%) vs. 4 (4.3%); 26 (27.7%) vs. 8 (8.5%); 37 (39.4%) vs. 14 (14.9%); 71 (75.5%) vs. 31 (33.0%); and 76 (80.9%) vs. 90 (95.7%), respectively. Of the 18 isolates that were not susceptible to imipenem according to the CLSI 2010 breakpoints, 13 isolates (72.2%) were P. mirabilis. CONCLUSION: The CLSI 2010 MIC breakpoints without tests to detect ESBL and/or PABL for Enterobacteriaceae could be unreliable. Thus, special tests for ESBLs and AmpC beta-lactamases are required to detect the resistance mechanisms involved.
Aztreonam ; Bacterial Proteins ; beta-Lactamases ; beta-Lactams ; Carbapenems ; Cefotaxime ; Ceftazidime ; Cephalosporins ; Citrobacter freundii ; Enterobacter aerogenes ; Enterobacter cloacae ; Enterobacteriaceae ; Escherichia coli ; Imipenem ; Klebsiella oxytoca ; Klebsiella pneumoniae ; Proteus mirabilis ; Salmonella ; Serratia marcescens ; Shigella

BACKGROUND: Increased isolation of extended-spectrum beta-lactamase (ESBL)-producing Entero bacteriaceae resistant to third generation cephalosporins and aztreonam has been noted recently. This study was to determine the prevalence of resistance to these drugs and ESBL in Enterobacteriaceae and to evaluate the methods for de tection. METHODS: During the period of October, 1997 and March, 1998, a total of 731 clinical isolates of Enterobacteriaceae were collected from patients of the Kosin Medical Center, Pusan, Korea. Antimicrobial susceptibility test by disk diffusion method and double disk synergy test were performed. MICs of beta-lactams were determined by agar dilution method. And ESBL genotypes were determined by polymerase chain reaction. RESULTS: About 10% of Escherichia coli isolates and 20% of Klebsiella pneumoniae isolates were intermediate or resistant to the third generation cephalosporins or aztreonam. Sensitivities of cefotaxime, ceftazidime, ceftriaxone and cefpodoxime disks for the detection of ESBL- producing strains of E. coli and K. pneumoniae by NCCLS standards were 100%, respectively, but that of aztreonam disk was 97%. Positive predictive value of the ceftazidime disk was higher than those of other disks. Twenty strains of E. coli, 20 K pneumoniae, 19 Enterobacter spp., six Citrobacter freundii, and eight Serratia marcescens showed positive results in double disk synergy test. The transconjugant strain of K. pneumoniae K20482 had blaSHV, and remains of transconjugants of ESBL-producing K. pneumoniae, Enterobacter spp. and S. marcescens had blaTEM. CONCLUSIONS: In this study, many strains of Enterobacteriaceae isolated in Korea were resistant to third generation cephalosporins and aztreonam. Some of the strains of Enterobacter spp. and S. marcescens as well as E. coli and K. pneumoniae produced ESBL, and majority of these strains had blaTEM. In the detection of ESBL-producing strains of E. coli and K. pneumoniae by NCCLS standards, all of the antimicrobial agent disks tested were useful, but ceftazidime disk was most effective because of its highest positive predictive value.
Agar ; Aztreonam ; beta-Lactamases ; beta-Lactams ; Busan ; Cefotaxime ; Ceftazidime ; Ceftriaxone ; Cephalosporins ; Citrobacter freundii ; Diffusion ; Enterobacter ; Enterobacteriaceae* ; Escherichia coli ; Genotype ; Humans ; Klebsiella pneumoniae ; Korea ; Pneumonia ; Polymerase Chain Reaction ; Prevalence* ; Serratia marcescens