Evaluation of Ceftriaxone Utilization at Multicenter Study

BACKGROUND/AIMS: As bacterial resistance to antimicrobial agents has grown due to the increasing use of antimicrobial agents, we sought to evaluate the suitability of ceftriaxone usage (representative of third generation cephalosporins) at 10 university hospitals in Korea. METHODS: We prospectively evaluated the appropriateness of antibiotic usage in 400 adult patients who received ceftriaxone between February 1, 2006 and June 30, 2006. Drug utilization evaluation (DUE) methods were based on standards set forth by the American Society of Hospital Pharmacists. The DUE criteria used in this study were modified to be more suitable in our hospital setting: justification of drug use, critical and process indications, complications, and outcome measures. RESULTS: The average patient age was 64.4 years. The utilization of ceftriaxone was appropriate in 262 cases (65.5%) for the justification of use, while inappropriate use was observed in 138 cases (34.5%). Common reasons for inappropriate use of ceftriaxone included continued empiric use for presumed infections, prophylactic perioperative injection, and empiric therapy for fever. Most of the critical indications showed a high rate of suitability (66.5-98.5%). Complications occurred in 37 cases (9.3%). With respect to outcome measures, clinical responses were observed in 60.7% of cases, while only 15.7% of cases showed evidence of infection eradication via negative cultures. CONCLUSIONS: Appropriate use (65.5%) of ceftriaxone was higher than inappropriate use (34.5%) at university hospitals in Korea. Inappropriate utilization, however, including continued empiric use for presumed infections and prophylactic perioperative injection remained high. Intensification of educational programs and antibiotic control systems for ceftriaxone is needed to improve the suitability of antimicrobial use.

Mechanism of VanB Phenotype in Vancomycin-Resistant Enterococci carrying vanA gene / 대한진단검사의학회지

BACKGROUND: Recently, vancomycin-resistant enterococci (VRE) with the vanA genotype that are susceptible to teicoplanin have been described in Japan, Taiwan, and Korea. The investigators suggested three point mutations in the putative sensor domain of vanS or impairment of accessory proteins VanY and VanZ as an explanation for the VanB phenotype-vanA genotype VRE. In this study, we analyzed Tn1546-like elements to determine the molecular mechanisms responsible for the impaired glycopeptide resistance of clinical VRE isolates with VanB phenotype-vanA genotype from Korea. METHODS: From 2001 to 2004, 28 clinical isolates of Enterococcus faecium with VanB phenotypevanA genotype were collected from 8 different university hospitals in diverse geographic areas in Korea. For structural analysis of Tn1546-like elements, PCR amplifications for internal regions of Tn1546 were performed. The purified PCR products were directly sequenced with an ABI Prism 3100 DNA sequencer. RESULTS: The sequence data of the vanS regulatory gene revealed that none of the isolates had any point mutations in this gene. All 28 isolates had a complete or incomplete deletion of vanY gene. Of these, 13 strains represented a complete deletion of vanZ, and 2 strains showed the deletion of nucleotides near the end point of vanX. CONCLUSIONS: The mechanism of VanB phenotype-vanA genotype in VRE isolates from Korea is not point mutations of vanS but the rearrangements of vanX, vanY and vanZ.

Emergence of CTX-M-12, PER-1 and OXA-30 beta-Lactamase-Producing Klebsiella pneumoniae / 대한임상미생물학회지

BACKGROUND: The aim of this study was to determine a nation-wide prevalence of Ambler class A and D extended-spectrum-lactamases (ESBL) in Klebsiella pneumoniae isolates in Korea. METHODS: During the period of April to May 2005, 189 isolates of K.pneumoniae were collected from 11 Korean hospitals. Antimicrobial susceptibilities to ceftazidime and cefotaxime were tested by the disk diffusion method, and ESBL production was determined by double-disk synergy test. Determinants of ceftazidime or cefotaxime-resistance were transferred to Escherichia coli J53 (azide-resistant) by transconjugation. Genotypes of class A and D ESBL genes were determined by PCR amplification and sequencing. RESULTS: One hundred-sixty isolates of K.pneumoniae showed positive results in double-disk synergy test. The most prevalent ESBL was SHV-12 (n=148). Also detected were genes encoding ESBLs including TEM-52 (n=1), SHV-2a (n=2), CTX-M-3 (n=15), CTX-M-9 (n=6), CTX-M-12 (n=2), CTX-M-14 (n=9), CTX-M-15 (n=1), PER-1 (n=1), GES-5 (n=3), and OXA-30 (n=2) beta-lactamases. CONCLUSION: With the emergence of CTX-M-12, PER-1, and OXA-30 beta-lactamases, the ESBLs in K.pneumoniae isolates are becoming more diverse in Korea.

Emergence of CTX-M-12 and A Novel CTX-M Type Extended-Spectrum beta-Lactamaseproducing Klebsiella pneumoniae / 대한진단검사의학회지

BACKGROUND: The aims of this study were to survey the nation-wide susceptibilities of Klebsiella pneumoniae isolates against ceftazidime and cefotaxime and to determine the prevalence of class A extended-spectrum beta-lactamases (ESBLs). METHODS: During the period of February to July 2004, K. pneumoniae isolates intermediate or resistant to ceftazidime and/or cefotaxime were collected from 12 hospitals in Korea. Antimicrobial susceptibilities were determined by the disk diffusion and the agar dilution methods and ESBL-production was by double-disk synergy test. Ceftazidime or cefotaxime-resistance determinants of the ESBLproducers were transfered to Escherichia coli J53 by transconjugation. Searches for class A ESBL genes were performed by PCR amplication. RESULTS: Among 212 clinical K. pneumoniae isolates, 172 (81%) isolates showed positive results in double-disk synergy test; the most prevalent ESBL was SHV-12 (n=104). Genes encoding ESBLs including SHV-2 (n=6), SHV-2a (n=17), CTX-M-3 (n=18), CTX-M-9 (n=6), CTX-M-12 (n=1), CTX-M- 14 (n=27), CTX-M-15 (n=3), and a novel CTX-M-type beta-lactamases were also detected. CONCLUSIONS: It is concluded that diversity of ESBLs in K. pneumoniae isolates are increasing in Korea. CTX-M-12 has never been reported in Asia, and a novel CTX-M-type ESBL has emerged.

Dissemination of CTX-M Type Extended-Spectrum beta-Lactamases and Emergence of CTX-M-12 in Escherichia coli / 대한진단검사의학회지

BACKGROUND: Clinical isolates of Escherichia coli were evaluated to determine the prevalence and genotypes of Ambler class A extended-spectrum beta -lactamases (ESBLs). METHODS: Clinical isolates of E. coli were collected from 12 hospitals from February through July, 2004. Antimicrobial susceptibility was tested by disk diffusion and agar dilution methods, and ESBLproduction was determined by double-disk synergy test. TEM, SHV, CTX-M, PER-1, VEB, IBC, GES, and TLA type ESBL genes were detected by PCR amplifications, and the PCR products were subjected to direct sequencing. RESULTS: The double-disk synergy test was positive in 90.9% (149 in 164) of the ceftazidime- or cefotaxime-resistant E. coli isolates. The most prevalent types of Ambler class A ESBLs in E. coliisolates were CTX-M-15 (n=53). CTX-M-14 (n=24), CTX-M-3 (n=9), CTX-M-9 (n=3), CTX-M-12 (n=3), SHV-2a (n=1), SHV-12 (n=5) and TEM-52 (n=3) were also found. CTX-M-12 ESBL had never been reported before in Korea. CONCLUSIONS: CTX-M type ESBL-producing E. coli isolates are spreading and CTX-M-12 is emerging in Korea.

Prevalence of Ambler Class A Extended-Spectrum beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates in Korea / 대한임상미생물학회지

BACKGROUND: The aim of this study is to determine the nationwide prevalence of Ambler class A extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and to characterize genotypes of ESBLs. METHODS: During the period of February through July, 2003, E.coli and K.pneumoniae isolates were collected from 12 hospitals in Korea. Antimicrobial susceptibilities were tested by disk diffusion method, and ESBL-production was determined by the double-disk synergy test. MICs of beta-lactam antibiotics were tested by agar dilution method. Searches for bla TEM, bla SHV, bla CTX-M, bla PER-1, bla VEB, bla IBC, bla GES and bla TLA genes were performed by PCR amplification, and the genotypes of ESBLs were determined by direct nucleotide sequence analysis of amplified products. RESULTS: Resistance rates of E.coli (n=246) and K.pneumoniae (n=239) isolates to ceftazidime were 8.5% and 20.1%, respectively. Most prevalent Ambler class A ESBL genotypes in E.coli isolates were bla CTX-M-15 (n=4) and bla CTX-M-3 (n=3), and each of bla CTX-M-14, bla SHV-12, and bla TEM-52 gene was also found in one isolate. Most prevalent ESBL genotypes in K.pneumoniae were bla SHV-12 (n=30) and bla CTX-M-3 (n=13), and bla CTX-M-14 (n=5). bla SHV-2a (n=3), bla SHV-5 (n=2), bla TEM-52 (n=1), bla GES-3 (n=2) genes were also found. CONCLUSION: CTX-M-type ESBL-producing E.coli and K.pneumoniae isolates are spreading, and a GES-type ESBL has emerged in Korea.

Antimicrobial Resistance of Clinically Important Bacteria Isolated from 12 Hospitals in Korea in 2004 / 대한임상미생물학회지

BACKGROUND: A rapid increase in antimicrobial-resistant bacteria has become a serious problem in many countries including Korea, but the rate and pattern of antimicrobial resistance may vary significantly depending on countries and even on hospitals. The aim of this study was to determine the nationwide prevalence of resistance among frequently isolated bacterial pathogens in Korea. METHODS: Routine susceptibility data for medically important bacterial pathogens from 12 university hospital and general hospital laboratories in Korea were analysed by patient group. These pathogens had been isolated during the period from April to November in 2004. RESULTS: The proportion of methicillin-resistant Staphylococcus aureus (MRSA) was 67%. Van-comycin-resistance rate of Enterococcus faecalis was 1% and that of E.faecium was 20%. The resistance rates of Streptococcus pneumoniae to penicillin and Haemophilus influenzae to ampicillin were 70% and 54%, respectively. The resistant rates of Escherichia coli and Klebsiella pneumoniae were 7-10% and 26-31% to the 3rd generation cephalosporin, respectively. The resistance rates to 3rd generation cephalosporin were 22-30% in Citrobacter freundii, 35-44% in Enterobacter cloacae and 15-22 % in Serratia marcescens. Imipenem resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii were 26% and 17%. Cotrimoxazole and levofloxacin resistance rates of Stenotrophomonas maltophilia were 46% and 44%, respectively. CONCLUSION: Antimicrobial resistance rates of clinically important pathogens in Korea were still high and were generally higher among the bacteria isolated from the intensive care unit patients. Strict infection control and continuous nationwide surveillance program will be required to manage the antimicrobial resistance problem.

Drug Use Evaluation of Intravenous Ciprofloxacin in University Hospitals in Korea

BACKGROUND: To evaluate the appropriateness of intravenous (IV) ciprofloxacin usage in university hospitals in Korea. MATERIALS AND METHODS: We prospectively evaluated the appropriateness of drug usage in 290 consecutive adult patients who received IV ciprofloxacin in eight teaching hospitals during the period from September 25, 2003 to November 15, 2003. Drug use evaluation (DUE) in this study was based on the modified standard by the American Society of Hospital Pharmacy with regard to the justification of drug use, critical and process indications, complications, and outcome measures. RESULTS: Average age of the patients was 54 years. The use of IV ciprofloxacin was appropriate only in 33 cases (26.9%). Common reasons for inappropriate use of IV ciprofloxacin include perioperative uses or prophylactic injection before urologic procedures, and empirical therapy for febrile episodes. Most of the "critical indications" and "process indications" showed high rate of appropriateness (82.4-100%). However, the rate of taking culture and sensitivity test before (73.8%) and during ciprofloxacin use (68.6%) were low. Complications with ciprofloxacin use were rare. In 93.3% of cases, ciprofloxacin treatment was clinically effective. CONCLUSION: Use of intravenous ciprofloxacin is frequently inappropriate in tertiary care hospitals in Korea. Implementation of education program and antibiotic control system is critical in improving the appropriateness of antimicrobial use.

Drug Use Evaluation of Intravenous Ciprofloxacin in University Hospitals in Korea

BACKGROUND: To evaluate the appropriateness of intravenous (IV) ciprofloxacin usage in university hospitals in Korea. MATERIALS AND METHODS: We prospectively evaluated the appropriateness of drug usage in 290 consecutive adult patients who received IV ciprofloxacin in eight teaching hospitals during the period from September 25, 2003 to November 15, 2003. Drug use evaluation (DUE) in this study was based on the modified standard by the American Society of Hospital Pharmacy with regard to the justification of drug use, critical and process indications, complications, and outcome measures. RESULTS: Average age of the patients was 54 years. The use of IV ciprofloxacin was appropriate only in 33 cases (26.9%). Common reasons for inappropriate use of IV ciprofloxacin include perioperative uses or prophylactic injection before urologic procedures, and empirical therapy for febrile episodes. Most of the "critical indications" and "process indications" showed high rate of appropriateness (82.4-100%). However, the rate of taking culture and sensitivity test before (73.8%) and during ciprofloxacin use (68.6%) were low. Complications with ciprofloxacin use were rare. In 93.3% of cases, ciprofloxacin treatment was clinically effective. CONCLUSION: Use of intravenous ciprofloxacin is frequently inappropriate in tertiary care hospitals in Korea. Implementation of education program and antibiotic control system is critical in improving the appropriateness of antimicrobial use.

Prevalence of CTX-M-type Extended-Spectrum beta-Lactamase-Producing Esherichia coli and Klebsiella pneumoniae Isolates in Korea / 대한임상미생물학회지

BACKGROUND: The aim of this study was to survey the nation wide susceptibilities of Esherichia coli and Klebsiella pneumoniae against cefotaxime and to determine the prevalence of CTX-M-type extended-spectrum beta- lactamases(ESBLs). METHODS: During the period of April to June, 2002, E. coli and K. pneumoniae isolates were collected from 13 hospitals. Antimicrobial susceptibilities to cefotaxime were tested by the disk diffusion method. ESBL production was determined by double disk synergy test. Cefotaxime-resistance of the ESBL-producers was transferred to azide-resistant E. coli J53 by conjugation. MICs of beta- lactam antibiotics were determined by agar dilution method. Searches for blaCTX-M genes were performed by PCR amplication. pIs of beta-lactamases were determined by isoelectric focusing. RESULTS: Ten percents of E. coli and 35 percents of K. pneumoniae isolates among 260 strains of each were intermediate or resistant to cefotaxime. Twenty-three isolates of E. coli and 78 K. pneumoniae isolates showed positive results in the double disk synergy test. One isolate of E. coli and 2 K. pneumoniae isolates harbored blaCTX-M-3 gene, 2 E. coli isolates harbored blaCTX-M-15 gene, and 2 E. coli and 2 K. pneumoniae isolates harbored blaCTX-M-14 gene. CONCLUSION: E. coli and K. pneumoniae isolates producing CTX-M-type ESBLs are not uncommon in Korean hospitals. The spread of CTX-M-type ESBL genes could compromise the future usefulness of 3rd generation cephalosporins and aztreonam for the treatment of E. coli and K. pneumoniae infections.

Antimicrobial Resistance of Clinically Important Bacteria Isolated from 12 Hospitals in Korea / 대한임상미생물학회지

BACKGROUND: A rapid increase in antimicrobial-resistant bacteria has become a serious problem in Korea. Moreover, the antibiotic resistance problem has worsened noticeably during the past several years. The aim of this study was to determine the prevalence of resistance among frequently isolated gram-positive and -negative bacteria in Korea. METHODS: Routine susceptibility data for medically important bacteria isolated during 6 months of 2003 were collected from 12 university and general hospital laboratories in Korea. RESULTS: The proportion of methicillin-resistant Staphylococcus aureus (MRSA) was 66%; however, vancomycin-resistant strains were not detected. The rates of vancomycin-resistant Enterococcus faecium and penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) were 22% and 73%, respectively. The resistance rates to 3rd generation cephalosporins and monobactam were: Escherichia coli 8-12%, Klebsiella pneumoniae 18-22%, Citrobacter freundii 22-32%, Enterobacter cloacae 34-37%, and Serratia marcescens 12-21%, respectively. Imipenem resistance rates of Acinetobacter baumannii and Pseudomonas aeruginosa were 23% and 25%, respectively. CONCLUSIONS: Antimicrobial resistant strains were already prevalent among the clinically important isolates, especially, MRSA, PNSP, and extended-spectrum cephalosporin resistant gram-negative bacilli in Korea. The imipenem-resistant rates of A. baumannii and P. aeruginosa increased, respectively, from 13% and 20% in 2002 to 23% and 25% in 2003. The results of this study will provide a basis for proper treatment of bacterial infections and prevention of spread of resistant bacteria. A continuous nationwide surveillance of antimicrobial resistance is very important and should be performed.

Prevalence of CTX-M-type Extended-Spectrum beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates in Korea, 2003 / 대한임상미생물학회지

BACKGROUND: The aims of this study were to survey nationwide susceptibilities of Escherichia coli and Klebsiella pneumoniae isolates against cefotaxime and to determine the prevalences of CTX-Mtype extended-spectrum beta-lactamases(ESBLs). METHODS: During the period of February to July, 2003, E. coli and K. pneumoniae isolates were collected from 12 hospitals. Antimicrobial susceptibilities to cefotaxime were tested by the disk diffusion method. ESBL production was determined by the double disk synergy test. Cefotaxime-resistance of the ESBL-producers was transfered to E. coli DH5alphaand E. coli Top10-F by transformation. MICs of beta-lactam antibiotics were determined by the agar dilution method. Searches for blaCTX-M genes was performed by PCR amplication; pIs of beta-lactamases were determined by isoelectric focusing. RESULTS: Among 230 isolates of E. coli and 232 isolates of K. pneumoniae, 27 (11.7%) and 79 (34.1%) were intermediate or resistant to cefotaxime, respectively. Twenty-four (10.4%) isolates of E. coli and 58 (25.0%) K. pneumoniae isolates showed positive results in the double disk synergy test. Three isolates of E. coli and 13 K. pneumoniae isolates harbored blaCTX-M-3 gene, 4 E. coli isolates harbored blaCTX-M-15 gene, and 1 E. coli and 5 K. pneumoniae isolates harbored blaCTX-M-14 gene. CONCLUSION: E. coli and K. pneumoniae isolates producing CTX-M-type ESBLs were not uncommon in Korean hospitals. It is thought that periodical surveys are necessary for inspecting the spread of CTX-M-type ESBL genes are necessary.