本研究從2003 年 3 月到 8 月收集 7 家醫學中心共 291 株大腸桿菌 (Escherichia coli) 臨床菌株，這些菌株對第三代頭孢子菌素抗生素具有較高的抗性。利用最小抑制濃度及紙錠擴散確認法等方法分析這些菌株中總共有 60.5% (176/291) 可產生超廣效性乙內醯胺酶。利用聚合酶連鎖反應及最小抑制濃度分析這些菌株中有 43.6% 擁有 plasmid-mediated AmpC 酵素。根據等電點電泳與聚合酶連鎖反應結果發現每一測試菌株中可能同時含有2或3種乙內醯胺酶對廣效性頭孢子菌素具有抗性。 291株大腸桿菌分離株中具 TEM, CTX-M, SHV ESBLs及CMY-2相關性酵素基因分別佔 81.7, 54.3, 9.3及43.6%。利用核酸序列定序發現 blaCTX-M 基因存在 5 種subtypes， blaCTX-M-3、blaCTX-M-9 、 blaCTX-M-14、 blaCTX-M-15、 blaCTX-M-19 等基因，其中以blaCTX-M-3 和 blaCTX-M-14 最為常見。而blaCTX-M-19 基因則首次在台灣被發現。從不同醫院隨機選取具 blaCTX-M-3 或 blaCTX-M-14基因菌株，以 隨機放大基因多型性圖譜分析可分別將其分為 14 種blaCTX-M-3 與 16 種 blaCTX-M-14 types。 根據此結果發現， 在不同醫院的分離株中 blaCTX-M-3 或 blaCTX-M-14 基因存在不同的基因圖譜。以同種接合實驗及質體分析發現該具有乙內醯胺酶質體可在相同種細菌間傳遞，且相似的抗藥性質體也可在不同醫院間傳播。

A total of 291 Escherichia coli isolates were collected from seven medical centers between March and August 2003. These isolates showed highly resistant to third generation of cephalosporins. The extended-spectrum β-lactamases (ESBLs) production was detected in 60.5% (176/291) of E. coli isolates by minimum inhibitory concentration (MIC) and disk diffusion confirmatory tests, and 43.6% of the E. coli isolates exhibited plasmid-mediated AmpC enzymes by PCR and MIC analysis. According the results of isoelectric focusing electrophoresis and PCR showed these isolates harbored two or three β-lactamases involved in resistance to extended-spectrum cephalosporins. In 291 isolates of E. coli, TEM (81.7%), CTX-M (54.3%), SHV ESBLs (9.3%), and CMY-2-related enzymes (43.6%) were detected. Nucleotide sequencing of blaCTX-M genes revealed the presence of 5 subtypes, which were blaCTX-M-3, blaCTX-M-9, blaCTX-M-14, blaCTX-M-15, and blaCTX-M-19 genes. Among them，blaCTX-M-3 and blaCTX-M-14 were predominant in E. coli. The blaCTX-M-19 genes were firstly identified in Taiwan. The blaCTX-M-3- or blaCTX-M-14-positive strains were randomly selected from different hospitals. Fourteen types of blaCTX-M-3 and 16 types of blaCTX-M-14 were classified by randomly amplified polymorphic DNA (RAPD) analysis from these isolates. The results exhibited blaCTX-M-3 or blaCTX-M-14 genetic diversity among the isolates from different hospitals. The transconjugation experiments and plasmid analysis suggested these bla–positive plasmids could transfer to same species and interhospital spreading.

參考文獻
Ambler, R. P. 1980. The structure of beta-lactamases. Philos Trans R Soc Lond B Biol Sci. 289:321-331.

Asbel, L. E., and M. E. Levison. 2000. Cephalosporins, carbapenems, and monobactams. Infect. Dis. Clin. North Am. 14:435-447.

Barnaud, G., G. Arlet, C. Verdet, and O. Gaillot. 1998. Lagrange, PH. Philippon, A. Salmonella enteritidis: AmpC plasmid-mediated inducible -lactamase (DHA-1) with an ampR gene from Morganella morganii. Antimicrob. Agents Chemother. 42:2352-2358.

Barthélémy, M., J. Péduzzi, and R. Labia. 1985. Distinction entre les structures primaries des-lactamases TEM-1 et TEM-2. Ann Inst Pasteur Microbiol. 136A:311-321.

Bauernfeind, A., Y. Chong, and S. chweighart. 1989. Extended broad spectrum -lactamase in Klebsiella pneumoniae including resistance to cephamycins. Infection 17:316–321.

Bauernfeind, A., H. Grimm, and S. Schweighart. 1990a. A new plasmidic cefotaximase in a clinical isolate of Escherichia coli. Infection. 18:294-298.

Bauernfeind, A., S. Schweighart, K. Dornbusch, and H. Giamarellou. 1990b. A transferable cephamycinase in Klebsiella pneumoniae, abstr. A190. In Program and abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.

Bauernfeind, A., S. Wagner, and R. Jungwirth. 1997. A novel Class C β-lactamases (FOX-2) in Escherichia coli conferring resistance to cephamycins. Antimicrob. Agents Chemother. 41: 2041-2046.

Bell, J. M., J. D. Turnidge, A. C. Gales, M. A. Pfaller, and R. N. Jones. SENTRY 2006. APAC Study Group Longitudinal farm study of extended-spectrum beta-lactamase-mediated resistance. J. Clin. Microbiol. 44:1630-1634.

Bicknell, R., V. Knott-Hunziker, and S. G. Waley. 1983. The pH-dependence of class B and class C beta-lactamases. Biochem. J. 213:61-66.

Birch, M., D. W. Denning, and D. Law. 1996. Rapid genotyping of Escherichia coli O157 isolates by random amplification of polymorphic DNA. Eur. J. Clin. Microbiol. Infect. Dis. 15:297-302.

Bonnet, R. 2004. Growing group of extended-spectrum-lactamases: the CTX-M enzymes. Antimicrob. Agents Chemother. 48:1-14.

Bradford, P. A. 2001. Extended-spectrum lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin. Microbiol. Rev. 14:933-951.

Bradford, P. A., C. Urban, N. Mariano, S. J. Projan, J. J. Rahal, and K. Bush. 1997. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC -lactamase, and the loss of an outer membrane protein. Antimicrob. Agents Chemother. 41:563-569.

Bradford, P. A., Y. Yang, D. Sahm, I. Grope, Gardovska, D. and Storch, G. 1998. CTX-M-5, a novel cefotaxime-hydrolyzing -lactamase from an outbreak of Salmonella typhimurium in Latvia. Antimicrob. Agents Chemother. 42:1980-1984.

Bush, K., C. Macalintal, B. A. Rasmussen, V. J. Lee, and Y. Yang. 1993. Kinetic interactions of tazobactam with beta-lactamases from all major structural classes. Antimicro. Agents Chemother. 37:851-858.

Bush. K., G. A. Jacoby, and A. A. Medeiros. 1995. A functional classification scheme for -lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. 39:1211-1233.

Cao, V., T. Lambert, and P. Courvalin. 2002. ColE1-like plasmid pIP843 of Klebsiella pneumoniae encoding extended-spectrum beta-lactamase CTX-M-17. Antimicrob. Agents Chemother, 46:1212-1217.

Chaibi, E. B., D. Sirot, G. Paul, and R. Labia. 1999. Inhibitor-resistant TEM--lactamases: phenotypic, genetic and biochemical characteristics. J. Antimicro. Chemother. 43:447-458.

Chayakulkeeree, M., P. Junsriwong, A. Keerasuntonpong, C. Tribuddharat, and V. Thamlikitkul. 2005. Epidemiology of extended-spectrum beta-lactamase producing gram-negative bacilli at Siriraj Hospital, Thailand, 2003.Southeast Asian. J. Trop. Med. Public Health. 36(6):1503-1509.

Chia, J. H., C. Chu, L. H. Su, C. H. Chiu, A. J. Kuo, C. F. Sun, and T. L. Wu. 2005. Development of a Multiplex PCR and SHV Melting-Curve Mutation Detection System for Detection of Some SHV and CTX-M ß-Lactamases of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae in Taiwan. J. Clinical. Microbiology. 43:4486-4491.
Chow, J. W., M. J. Fine, and D. M. Shlaes. 1991. Enterobacter bacteremia: clinical features with emergence of antibiotic resistance during therapy. Ann. Intern. Med. 115:585-590.

Christopher, W. 2005. Antibiotics:Actions, Origin, Rsistance. ASM Press.
Cooperman., 1977. Identification of binding sites on the E. coli ribosome by affinity labeling. Adv. Exp. Med. Biol. 86A:595-609. Review.

Datt, N., and P. Kontomichalou. 1965. Penicillinase synthesis controlled by infectious R-factor in Enterobacteriaceae. Nature 208:239-241.

Giamarellou, H. 2005. Multidrug resistance in Gram-negative bacteria that produce extended-spectrum ß-lactamases (ESBLs). Clin. Microbiol. Infect. 11:1-16.

Girlich, D., L. Poirel, A. Leelaporn, A. Karim, C. Tribuddharat, M. Fennewald, and P. Nordmann. 2001. Molecular epidemiology of the integron located VEB-1 extended-spectrum ß-lactamase in nosocomial enterobacterial isolates in Bangkok, Thailand. J. Clin. Microbiol. 39:175–182.

Gniadkowski, M., I. Schneider, A. Palucha, R. Jungwirth, B. Mikiewicz, and A. Bauernfeind. 1998. Cefotaxime-resistant Enterobacteriaceae isolates from a hospital in Warsaw, Poland: Identification of a new CTX-M-3 cefotaxime-hydrolyzing ß-lactamase that is closely related to the CTX-M-1/MEN-1 enzyme. Antimicrob. Agents Chemother. 42:827-832.

Golemi, D., L. Maveyraud, S. Vakulenko, J. P. Samama, and S. Mobashery. 2001. Critical involvement of a carbamylated lysine in catalytic function of class D beta-lactamases. Proc. Natl. Acad. Sci. USA. 98:14280-14285.

Gouby, A., C. Neuwirth, G. Bourg, N. Bouziges, M. J. Carles-Nurit, E. Despaux, and M. Ramuz. 1994. Epidemiological study by pulse-field gel electrophoresis of an outbreak of extended-spectrum β-lactamase-producing Klebsiella pneumoniae in a geriatric hospital. J. Clin. Microbiol. 32:301-305.

Greenwood, D. 1995. Sixty years on: Antimicrobial drug resistance comes of age, Lancet 346 (Suppl.)

Hawkey, K. M. 1998. The origins and molecular basis of antibiotic resistance. BMJ 317:657-660.

Hawkey, P. M. 1997. Resistance to carbapenems. J. Med. Microbiol. 46:451-454.

Hirakata, Y., J. Matsuda, Y. Miyazaki, S. Kamihira, S. Kawakamim, Y. Miyazawa, Y. Ono, N. Nakazaki, Y. Hirata, M. Inoue, J. D. Turnidge, J. M. Bell, R. N. Jones, and S. Kohno. 2005. Asia-Pacific Participants Regional variation in the prevalence of extended-spectrum beta-lactamase-producing clinical isolates in the Asia-Pacific region (SENTRY 1998-2002). Diagn. Microbiol. Infect. Dis. 52:323-329.

Jacoby, G. A., and A. A. Medeiros. 1991. More extended-spectrum -lactamases. Antimicrob. Agents Chemother. 35:1697-1704.

Jacoby, G. A., and L. Suton. 1991. Properties of plasmids responsible for extended β-lactamase production. Antimicro. Agents Chemother. 35:164-169.
Jantausch, B. A. 2003. Peripheral brain: cephalosporins. Pediatr. Rev. 24:128-136.

Jeong, S. H., I. K. Bae, S. B. Kwon, J. H. Lee, H. I. Jung, J. S. Song, B. C. Jeong, S. J. Kim, and S. H. Lee. 2004. Investigation of extended-spectrum β-lactamases produced by clinical isolates of Klebsiella pneumoniae and Escherichia coli in Korea. Lett. Appl. Microbiol. 39:41-47.

Jeong, S. H., I. K. Bae, J. H. Lee, S. G. Sohn, G. H. Kang, G. J. Jeon, Y. H. Kim, B. C. Jeong, and S. H. Lee. 2004. Molecular Characterization of Extended-Spectrum Beta-Lactamases Produced by Clinical Isolates of Klebsiella pneumoniae and Escherichia coli from a Korean Nationwide Survey. J. Clinical. Microbiology. 42:2902-2906.

Jitsurong, S., and J. Yodsawat. 2006. Prevalence of extended-spectrum beta-lactamases (ESBLs) produced in blood isolates of gram-negative bacteria in a teaching hospital in southern Thailand. Southeast Asian J. Trop Med. Public Health. 37:131-135.

Jones, R. N., A. L. Barry, and C. Thornsberry. 1983. In vitro evaluation of three new macrolide antimicrobial agents, RU28965, RU29065, and RU29702, and comparisons with other orally administered drugs. Antimicrob. Agents Chemother. 24: 209–215.

Kariuki, S., J. E. Corkill, G. Revathi, R. Musoke, and C. A. Hart. 2001. Molecular characterization of a novel plasmid-encoded cefotaximase (CTX-M-12) found in clinical Klebsiella pneumoniae isolates from Kenya. Antimicro. Agents Chemother. 45:2141-2143.

Kim, J., Y. M. Lim, I. Rheem, Y. Lee, J. C. Lee, S. Y. Seol, Y. C. Lee, and D. T. Cho. 2005. CTX-M and SHV-12 beta-lactamases are the most common extended-spectrum enzymes in clinical isolates of Escherichia coli and Klebsiella pneumoniae collected from 3 university hospitals within Korea. FEMS Microbiol. Lett. 245:93-98.

Kimura, S., M. Ishiguro, Y. Ishii, J. Alba, and K. Yamaguchi. 2004. Role of a mutation at position 167 of CTX-M-19 in ceftazidime hydrolysis. Antimicrob. Agents Chemother. 48:1454-1460.

Knothe, H., P. Shah, V. Krcmery, M. Antal, and S. Mitsuhashi. 1983. Transferable resistance to cefotaxime, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens. Infection 11:315-317.

Larson, L. L., and R. Ramphal. 2002. Extended-spectrum β-lactamases. Semin Respir Infect. 17:189-194.

Levy, S. B. 1995. Antimicrobial resistance: A global prespective, Adv. Exp. Med. Biol. 390:1-13.

Liu, P. Y., JC. Tung, S. C. Ke, and S. L. Chen. 1998. Molecular epidemiology of extended-spectrum -lactamase-producing Klebsiella pneumoniae isolates in a district hospital in Taiwan. J. Clin. Microbiol. 36:2759-2762.

Livermore D. M. 1995. -Lactamases in laboratory and clinical resistance. Clin. Microbiol. Rev. 8:557-584.

Mabilat, C., and S. Goussard. 1993. PCR detection and identification of genes for extended-spectrum β-lactamases, In D. H. Persing, T. F. Smith, F. C. Tenover, and T. J. White (ed.), Diagnostic molecular microbiology: principles and applications. ASM Press. p.553-559.

Mandell, G. L., J. E. Bennett, and R. Dolin. 2000. Principles and Practice of Infectious Diseases, 5th ed. New York: Churchill Livingstone.

Martinez, L., S. Hernandez-Alles, S. Alberti, J. Tomas, V. Benedi, and G. Jacoby. 1996. In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum cephalosporins. Antimicrob. Agents Chemother. 40:342-348.

Massova, I., and S. Mobashery. 1998. Kinship and diversification of bacterial penicillin-binding proteins and beta-lactamases. Antimicrob. Agents Chemother. 42:1-17.

Matar, G. M., S. Al. Khodor, M. El-Zaatari, and M. Uwaydah. 2005. Prevalence of the genes encoding extended-spectrum -lactamases, in Escherichia coli resistant to -lactam and non- -lactam antibiotics. Ann. Trop Med. Parasitol. 99:413-7.

Matthew, M., M. Harris, M. J. Marshall, and G. W. Rose. 1975. The use of analytical isoelectric focusing for detection and identification of-lactamases. J. Gen. Microbiol. 88:169-178.

Maveyraud, L., D. Golemi, L. P. Kotra, S. Tranier, S. Vakulenko, S. Mobashery, and J. P. Samama. 2000. Insights into class D beta-lactamases are revealed by the crystal structure of the OXA10 enzyme from Pseudomonas aeruginosa. Struct. Fold Des. 8:1289-1298.

Naohiro, Shibata., Doi. Yohei, Yamane. Kunikazu, Yagi. Tetsuya, Kurokawa. Hiroshi, Shibayama. Keigo, Kato. Haru, Kai. Kumiko, and Arakawa. Yoshichika. 2003. PCR Typing of Genetic Determinants for Metallo-β-Lactamases and Integrases Carried by Gram-Negative Bacteria Isolated in Japan, with Focus on the Class 3 Integron. J. Clin. Microbiol. 41: 5407–5413.

National Committee for Clinical Laboratory Standards. 2000. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved Standard M7-A5 and Informational Supplement M100-S10. National Committee for Clinical Laboratory Standards, Wayne, Pa.

Neu, H. C. 1992. The crisis in antibiotic resistance. Science 257:1046-1073

Nüesch-Inderbinen, M. T., H. Hächler, and F. H. Kayser. 1996. Detection of genes coding for extended-spectrum SHV beta-lactamases in clinical isolates by a molecular genetic method, and comparison with the E test. Eur. J. Clin. Microbiol. Infect. Dis. 15:398-402.

Okeke, I. N., S. T. Fayinka, and A. Lamikanra. 2000. Antibiotic resistance in Escherichia coli from Nigerian students, 1986-1998. Emerg. Infect. Dis. 6: 393-6.

Orskov, I., F. Orskov, B. Jann, and K. Jann. 1977. Serology, chemistry, and genetics of O and K antigens of Escherichia coli. Bacteriol. Rev. 41: 667–710.

Pagani, L., E. D. Amico, and R. Migliavacca. 2003. Multiple CTX-M-Type Extended-spectrum β-lactamases in nosocomial isolates of Enterobacteriaceae from a hospital in northern Italy. J. Clin. Microbiol. 41:4264-4269.

Paterson, D. L., K. M. Hujer, A. M. Hujer, B. Yeiser, M. D. Bonomo, L. B. Rice, and R. A. Bonomo. 2003. International Klebsiella Study Group. Extended-spectrum -lactamases in Klebsiella pneumoniae bloodstream isolates from seven countries: dominance and widespread prevalence of SHV- and CTX-M-type -lactamases. Antimicrob. Agents Chemother. 47:3554-3560.

Philippon, A., G. Arlet, and G. A. Jacoby. 2002. Plasmid-determined AmpC-type -lactamases. Antimicrob. Agents Chemother. 46:1-11.

Poirel, L., C. Heritier, V. Tolun, and P. Nordmann. 2004. Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob. Agents Chemother. 48:15-22.

Poirel, L. Le., I. Thomas, T. Naas, A. Karim, and P. Nordmann. 2000. Biochemical sequence analyes of GES-1, a novel class A extended-spectrum β-lactamase, and the class I integron In52 from Klebsiella pneumoniae. Antimicro. Agents Chemother. 44:622-632.

Poirel, L., O. Menuteau, N. Agoli, C. Cattoen, and P. Nordmann, 2003. Outbreak of extended-spectrum β-lactamase VEB-1-producing isolates of Acinetobacter baumannii in a French hospital. J. Clin. Microbiol. 41:3542-3547.

Poirel, L., I. Le. Thomas, T. Naas, A. Karim, E. Bingen, and P. Nordmann. 2001b. CTM-X-type extended-spectrumβ-lactamase that hydrolyzes ceftazidime through a single amino acid substitution in the omega loop. Antimicrob. Agents Chemother. 45:3355-3361.

Provence, D. L., and III. R. Curtiss. 1994. Gene transfer in gram-negative bacteria, p. 319-347. In P. Gerhardt, R. G. E. Murray, W. A. Wood, and N. R. Krieg (ed.), Methods for general and molecular bacteriology. American Society for Microbiology, Washington, D. C.

Reguera, J. A., F. Baquero, J. C. Perez-Diaz, and J. L. Martinez. 1991. Factors determining resistance to beta-lactam combined with beta-lactamase inhibitors in Escherichia coli. J. Antimicrob. Chemother. 27:569-575.

Saladin, M., VTB. Cao, T. Lambert, J. L. Donay, J. L. Herrmann, Z. Ould-Hocine, C. Verdit, F. Delisle, A. Philippon, and G. Arlet. 2002. Diversity of CTX-M β-lactamases and their promoter regions from Enterobacteriaceae isolated in three Parisian hospitals. FEMS Microbiol. Lett. 209:161-168.

Salyers, A. A., and D. D. Whitt. 2002. Antimicrobial Compounds. pp. 150-167. In Bacterial pathogenesis: a molecular approach, 2nd ed. American Society for Microbiology Press, Washington, DC.

Salyers, A. A., and D. D. Whitt. 2002. How Bacteria Become Resistant to Antibiotics. pp. 168-184. In Bacterial pathogenesis: a molecular approach, 2nd ed. American Society for Microbiology Press, Washington, DC.

Sanders, C. C., and W. E. Sanders. 1995. Resistance to antibacterial agents, Adv. Exp. Med. Biol. 390:15-23.

Shah, A. A., F. Hasan, and S. Ahmed. 2004. Extended spectrum β-lactamase (ESBL): characterization, epidemiology and detection. Crit. Rev. Microbiol. 30:25-32.
Siu, L. K., P. L. Lu, P. R. Hsueh, and F. M. Lin. 1999. Bacteremia due to extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a pediatric oncology ward: clinical features and identification of different plasmids carrying both SHV-5 and TEM-1 genes. J. Clin. Microbiol. 37:4020-4027.

Smith, Moland. E., N. D. Hanson, V. L. Herrera, J. A. Black, T. J. Lockhart, A. Hossain, J. A. Johnson, R. V. Goering, and K. S. Thomson. 2003. Plasmid-mediated, carbapenem-hydrolysingβ-lactamase, KPC-2, in Klebsiella pneumoniae isolates. J. Antimicrob. Chemother. 51:711-714.

Song, W., J. S. Kim, H. S. Kim, S. H. Jeong, D. Yong, and K. M. Lee. 2006. Emergence of Escherichia coli isolates producing conjugative plasmid-mediated DHA-1 β-lactamase in a Korean university hospital J Hosp Infect.

Sougakoff, W., S. Goussard, and P. Courvalin. 1988. TEM-3 β-lactamase, which hydrolyzes broad-spectrum cephalosporins, is derived from the TEM-2 penicillinase by two amino acid substitutions. FEMS Microbiol. Lett. 56:343-348.

Stürenburg, E., and D. Mack. 2003. Extended-spectrum -lactamases: implications for the clinical microbiology laboratory, therapy, and infection control. J. Infect. 47:273-295.

Susic, E. 2004. Mechanisms of resistance in Enterobacteriaceae towards beta-lactamase antibiotics. Acta. Med. Croatica. 58:307-12.

Tipper, D. J., and J. L. Strominger. 1965. Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc. Natl. Acad. Sci. USA. 54:1133-1141.

Tranier, S., AT. Bouthors, L. Maveyraud, V. Guilet, W. Sougakoff, and J. P. Samama. 2000. The high resolution crystal structure for class A beta-lactamase PER-1 reveals the bases for its increase in breadth of activity. J Biol. Chem. 275:28075-28082.

Tzelepi, E., P. Giakkoupi, D. Sofianou, V. Loukova, A. Kemeroglou, and A. Tsakris. 2000. Detection of extended-spectrum -lactamases in clinical isolates of Enterobacter cloacae and Enterobacter aerogenes. J. Clin. Microbiol. 38:542-546.

Tzouvelekis, L. S., E. Tzelepi, P. T. Tassios, and N. J. Legakis. 2000. CTX-M-type -lactamases: an emerging group of extended-spectrum enzymes. Int. J. Antimicrob. Agents. 14:137-142.

Vahaboglu, H., S. Dodanli, C. Eroglu, R. Öztürk, G. Soyletir, I. Yildirim, and V. Avkan. 1996. Characterization of multiple-antibiotic-resistant Salmonella typhimurium strains: Molecular epidemiology of PER-1-producing isolates and evidence for nosocomial plasmid exchange by a clone. J. Clin. Microbiol. 34:2942-2946.

Van, Bambeke. F., and P. M. Tulkens. 2001. Macrolides: pharmacokinetics and pharmacodynamics. Int. J. Antimicrob. Agents. 18 (Suppl 1):S17-S23.

Versalovic, J., T. Koeuth, and J. R. Lupski. 1991. Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. Nucleic Acids Res. 19:6823-6831.

Walther-Rasmussen, J., and N. Høiby. 2004. Cefotaximases (CTX-M-ases), an expanding family of extended-spectrum -lactamases. Can. J. Microbiol. 50:137-165.

Weinstein, D. L., M. P. Jackson, J. E. Samuel, R. K. Holmes, and A. D. O'Brien. 1988. Cloning and sequencing of a Shiga-like toxin type II variant from Escherichia coli strain responsible for edema disease of swine. J. Bacteriol. 170:4223-4230

Winokur, P. L., A. Brueggemann, D. L. Desalvo, L. Hoffmann, M. D. Apley, E. K. Uhlenhopp, M. A. Pfaller, and G. V. Doern. 2000. Animal and human multidrug-resistant, cephalosporin-resistant Salmonella isolates expressing a plasmid-mediated CMY-2 AmpC β-lactamase. Antimicrob. Agents Chemother. 44:2777-2783.

Winokur, P. L., R. Canton, J. M. Casellas, and N. Legakis. 2001. Variations in the prevalence of strains expressing an extended-spectrum beta-lactamase phenotype and characterization of isolates from Europe, the Americas, and the Western Pacific region. Clin. Infect.Dis. 32 (Suppl. 2):S94-103.

Wu, T. L., J. H. Chia, L. H. Su, A. J. Kuo, and C. H. Chiu. 2003. Dissemination of extended-spectrum-lactamase-producing Enterobacteriaceae in pediatric intensive care units. J. Clin. Microbiol. 41:4836-4838.

Wu, T. L., W. S. Hung, C. Y. Chuang, E. H. Chen, R. N. Jones, and L. W. Yu. 2005. Identification of a novel cephalosporinase (DHA-3) in Klebsiella pneumoniae isolated in Taiwan. Clin. Microbiol. Infect. 11:893-897.

Yamaguchi, K., M. Murakami, AIshii. Takahashi, Y. Iwata, K. MItoh, T. Oohara, N. Watanabe, N. Uehara, N. Fomura, M. Watanabe, M. Yasujima, T. Kasai, H. Kanno, M. Aihara, A. Suwabe, K. Yamahata, S. Maesaki, G. Hashikita, M. Kaku, K. Kanemitsu, K. Miyake, and T. Oguri. 2005. Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2004. Jpn. J. Antibiot. 58:655-89.

Yan, J. J., W. C. Ko, Y. C. Jung, C. L. Chuang, and J. J. Wu. 2002. Emergence of Klebsiella pneumoniae isolates producing inducible DHA-1 beta-lactamase in a university hospital in Taiwan. J. Clin. Microbiol. 40:3121-3126.

Yan, J. J., W. C. Ko, S. H. Tsai, H. M. Wu, Y. T. Jin, and J. J. Wu. 2000a. Dissemination of CTX-M-3 and CMY-2 -lactamases among clinical isolated of Escherichia coli in southern Taiwan. J. Clin. Microbiol. 38:4320-432.

Yan, J. J., S. M. Wu, S. H. Tsai, J. J. Wu, and I. J. Su. 2000b. Prevalence of SHV-12 among clinical isolates of Klebsiella pneumoniae producing extended-spectrum -lactamases and identification of a novel AmpC enzyme (CMY-8) in southern Taiwan. Antimicrob. agents Chemother. 44:1438-1442.

Yu, W. L., K. C. Cheng, and L. T.Wu. 2004. Emergence of two Klebsiella pneumoniae isolates harboring plasmid-mediated CTX-M-15 β-lactamase in Taiwan. Antimicrob. Agents Chemother. 48:362-3.

Yu, W. L., R. N. Jones, R. J. Hollis, S. A. Messer, D. J. Biedenbach, L. M. Deshpande, and M. A. Pfaller. 2002. Molecular epidemiology of extended-spectrum beta-lactamase-producing, fluoroquinolone-resistant isolates of Klebsiella pneumoniae in Taiwan. J. Clin. Microbiol. 40:4666-4669.