This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yan, J.-J.
Right arrow Articles by Wu, J.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yan, J.-J.
Right arrow Articles by Wu, J.-J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2001, p. 2224-2228, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2224-2228.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Metallo-beta -Lactamases in Clinical Pseudomonas Isolates in Taiwan and Identification of VIM-3, a Novel Variant of the VIM-2 Enzyme

Jing-Jou Yan,1 Po-Ren Hsueh,2 Wen-Chien Ko,3 Kwen-Tay Luh,2 Shu-Huei Tsai,1 Hsiu-Mei Wu,4 and Jiunn-Jong Wu4,*

Department of Pathology, National Cheng Kung University Medical Center,1 and Departments of Medicine3 and Medical Technology,4 National Cheng Kung University Medical College, Tainan, Department of Laboratory Medicine, National Taiwan University Hospital, Taipei,2 Taiwan

Received 9 October 2000/Returned for modification 29 January 2001/Accepted 4 May 2001


    ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

A total of 209 clinical isolates of Pseudomonas (193 Pseudomonas aeruginosa, 10 P. putida, 4 P. stutzeri, and 2 P. fluorescens isolates) with reduced susceptibilities to imipenem and/or ceftazidime were subjected to PCR assays with primers specific for blaIMP-1, blaIMP-2, blaVIM-1, and blaVIM-2 and sequence analysis to identify the metallo-beta -lactamases (MBLs) prevalent among these organisms in Taiwan; and 21 isolates gave positive results. Five isolates including two P. putida and three P. stutzeri isolates were found to carry blaIMP-1, and six isolates including five P. putida and one P. stutzeri isolates harbored blaVIM-2. The remaining 10 isolates were P. aeruginosa, and all were found to carry a novel variant of blaVIM-2, designated blaVIM-3. There are only two nucleotide differences between blaVIM-2 and blaVIM-3, leading to two amino acid alterations. Our findings indicate that VIM-2 and its variant have become the most prevalent metalloenzymes in Pseudomonas in Taiwan. Southern hybridization with the blaVIM-2-, blaVIM-3-, and blaIMP-1 -specific probes revealed that only two VIM-2-producing P. putida isolates appeared to carry the MBL gene on plasmids. Pulsed-field gel electrophoresis showed that six VIM-3-producing P. aeruginosa isolates and two IMP-1-producing P. stutzeri isolates were genetically related, suggesting that the spread of these MBL genes in Taiwan could be due to clonal dissemination as well as genetic exchange between different clones.


    INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

Carbapenems are often used as antibiotics of last resort for the treatment of infections caused by gram-negative bacteria resistant to other beta -lactam agents because of their broad spectra of activity and stability to hydrolysis by most beta -lactamases including extended-spectrum beta -lactamases (4, 12, 26, 27). The mechanisms of resistance to carbapenems in Pseudomonas aeruginosa often result from reduced levels of drug accumulation or increased levels of expression of pump efflux (8, 15, 17). The resistance is occasionally due to production of metallo-beta -lactamases (MBLs), which can be either chromosomally encoded or plasmid mediated (8, 13, 22, 28, 32). IMP-1 was the first MBL identified in P. aeruginosa (28, 29). The enzyme has also been described in other nonfastidious, gram-negative nonfermenters and members of the family Enterobacteriaceae (9, 10, 20, 29). Several novel MBLs were identified recently, including VIM-1 from P. aeruginosa and IMP-2 from Acinetobacter baumannii in Italy (13, 25), VIM-2 from P. aeruginosa in France (22), and IMP-3 from Shigella flexneri in Japan (11). The spread of MBLs in gram-negative rods has been described in several other countries and is becoming an emerging threat (32; T. H. Koh, G. S. Babini, N. Woodford, L.-H. Sng, L. M. C. Hall, and D. M. Livermore, Letter, Lancet 353:2162, 1999; K. Lee, J. B. Lim, J. Yum, D. Yong, J. R. Choi, Y. Chong, J. M. Kim, and D. M. Livermore, Abstr. 40th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 2003, p. 123, 2000). It remains unknown whether these MBLs have appeared in Taiwan. Thus, the purpose of the present study was to determine the IMP- and VIM-type MBLs prevalent among clinical isolates of the genus Pseudomonas in Taiwan.


    MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

Bacterial strains. The isolates studied were selected from clinical isolates of Pseudomonas spp. randomly collected between January 1997 and May 2000 at two university hospitals in Taiwan. Since susceptibilities to imipenem for IMP-1 producers covered a wide range (9, 10, 28, 29), all isolates that showed reduced susceptibilities to imipenem (inhibition zone diameter, <16 mm) and/or ceftazidime (inhibition zone diameter, <18 mm) on the basis of the results of the disk diffusion method (19) were examined. Thus, a total of 209 isolates, including 164 Pseudomonas isolates (154 P. aeruginosa, 4 P. stutzeri, 4 P. putida, and 2 P. fluorescens isolates) from the National Cheng Kung University Medical Center, a 900-bed teaching hospital in southern Taiwan, and 45 Pseudomonas isolates (39 P. aeruginosa and 6 P. putida isolates) from the National Taiwan University Hospital, a 1,800-bed medical center in northern Taiwan, were selected. All these isolates were recovered from different patients and were identified by conventional techniques (6) and/or with the API 20NE system (bioMérieux, Marcy l'Etoile, France).

Screening tests for detection of MBL producers. The disk diffusion test for the screening of MBL producers was performed as described by Arakawa et al. (1). 2-Mercaptopropionic acid and 100 mM EDTA were used as MBL inhibitors.

PCR amplification and DNA sequencing. Plasmids from clinical isolates were prepared by a rapid alkaline lysis procedure (31). PCR assays were performed to amplify the entire sequences of the blaIMP-1, blaIMP-2, blaVIM-1, and blaVIM-2 genes with the oligonucleotide primers listed in Table 1. PCR conditions for all these genes were 3 min at 94°C; 35 cycles of 1 min at 94°C, 1 min at 55°C, and 2 min at 72°C; and finally, 7 min at 72°C. The amplicons were purified with PCR Clean Up Kits (Roche Molecular Biochemicals, Mannheim, Germany) and were sequenced on an ABI PRISM 377 sequencer analyzer (Applied Biosystems, Foster City, Calif.) with the primers listed in Table 1.

                              
View this table:
[in this window]
[in a new window]
  		TABLE 1.   Primers for PCR detection of MBL genes

Analytical IEF. Crude preparations of beta -lactamases were obtained by sonication (3) and were subjected to analytical isoelectric focusing (IEF) as described previously (18, 33). beta -Lactamase activity was detected by overlaying the gels with 0.5 mM nitrocefin (Oxoid, Basingstoke, United Kingdom) in 50 mM HEPES (pH 7.5) supplemented with 2 mM ZnCl2 (25). Extracts from TEM-1-, TEM-10-, SHV-1-, CMY-1-, SHV-5-, CTX-M-3-, and CMY-2-producing strains were used as standards for pls of 5.4, 5.6, 7.6, 8.0, 8.2, 8.4, and 9.0, respectively. In addition, the pI was also calculated by reference to a calibration curve constructed from the relative mobility of the IEF markers (Amersham Pharmacia Biotech, Hong Kong, China).

Transfer of resistance. Conjugation experiments were performed as described previously (23, 33) with streptomycin- and rifampin-resistant Escherichia coli C600 as the recipient (2). Tryptic soy agar plates supplemented with 500 µg of streptomycin (Sigma Chemical Company, St. Louis, Mo.) per ml or 64 µg of rifampin (Sigma) per ml and 10 µg of ceftazidime (Glaxo Group Research Ltd., Greenford, United Kingdom) per ml were used to select the transconjugants. To determine the sensitivity of the assay, direct transfer of the plasmid-encoded blaOXA-10 gene from a clinical isolate of P. aeruginosa into E. coli C600 was attempted, and transconjugant selection was performed on tryptic soy agar plates containing 100 µg of amoxicillin (SmithKline Beecham Pharmaceuticals, Surrey, United Kingdom) per ml and 64 µg of rifampin per ml.

Hybridization assays. In order to confirm negative PCR results, colony hybridization was performed for all 209 isolates studies, as described elsewhere (7). The PCR products of blaVIM-2, blaVIM-3, and blaIMP-1 were labeled with [alpha -32P]dCTP (Amersham Pharmacia Bitotech) by the random priming technique with a commercial kit (GIBCO BRL, Life Technologies, Gaithersburg, Md.). The blaVIM-1- and blaIMP-2-specific probes were the PCR-generated amplicons from VIM-1-containing P. aeruginosa VR-143/97 (13) and IMP-2-containing A. baumannii AC-54/97 (25), respectively.

Plasmids from the clinical isolates harboring the MBL genes were digested with BstEII (Roche Molecular Biochemicals) overnight. The digested DNA samples were electrophoresed on 0.8% agarose gels and subjected to Southern hybridization according to the original protocol (30) with the blaVIM-2-, blaVIM-3-, and blaIMP-1-specific probes prepared as described above.

Susceptibility tests. The MICs of the antimicrobial agents were determined by the agar dilution method according to the guidelines of the National Committee for Clinical Laboratory Standards (19). The antimicrobial agents and their sources are as follows: aztreonam, Bristol-Myers Squibb, New Brunswick, N.J.; ceftazidime, Glaxo Group Research Ltd.; cefotaxime, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, N.J.; imipenem, Merck Sharp & Dohme, West Point, Pa.; meropenem, Sumitomo Pharmaceuticals Ltd., Osaka, Japan; and piperacillin and tazobactam, Lederle Laboratories, Pearl River, N.Y.

PFGE analysis. Genomic DNAs prepared by the procedure of Piggot et al. (21) were digested overnight with 10 U of SpeI (New England Biolabs, Beverly, Mass.) and subjected to pulsed-field gel electrophoresis (PFGE) as described elsewhere (5, 33). The samples were electrophoresed with the Pulsaphor plus system (Amersham Pharmacia Biotech) at 200 V for 30 h, with pulse times ranging from 5 to 30 s.

Nucleotide sequence accession number. The nucleotide sequence of the novel MBL described in this paper has been assigned to the GenBank database under accession number AF300454.


    RESULTS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

Detection of MBL producers. Among the 209 Pseudomonas isolates tested, 21 (10 P. aeruginosa, 7 P. putida, and 4 P. stutzeri isolates) potentiated the inhibitory zones between ceftazidime disks and EDTA disks or 2-mercaptopropionic acid disks, suggesting production of MBLs, the activities of which were inhibited by EDTA and 2-mercaptopropionic acid, by these isolates.

PCR amplification and DNA sequencing. Of the 209 Pseudomonas isolates that were subjected to PCR assays, all 21 isolates positive by the screening test gave positive PCR results, while the remaining 188 isolates were negative. Sixteen isolates (10 P. aeruginosa, 5 P. putida, and 1 P. stutzeri isolates) were positive with the primers specific for blaVIM-2, and 5 (2 P. putida and 3 P. stutzeri isolates) were positive with the primers specific for blaIMP-1. Neither blaVIM-1 nor blaIMP-2 was amplified from any of the 209 isolates. The characteristics of these isolates are shown in Table 2. The sequence analysis revealed that 5 P. putida and 1 P. stutzeri isolates carried blaVIM-2 and that 2 P. putida and 3 P. stutzeri isolates harbored blaIMP-1. All 10 P. aeruginosa isolates were found to carry a variant blaVIM-2, designated blaVIM-3. The novel MBL gene differs from blaVIM-2 by replacement of a C with an A and an A with a G at nucleotides 178 and 443 of the structural gene, respectively, which results in Gly-to-Lys and Asn-to-Ser changes at amino acid positions 32 and 120 (24), respectively, according to the numbering for Bacillus cereus beta -lactamase II (24).

                              
View this table:
[in this window]
[in a new window]
  		TABLE 2.   Characteristics of the 21 Pseudomonas isolates carrying MBL genes

Hybridization assays and conjugation experiments. The results of colony hybridization assays were consistent with those obtained by PCR. All 10 VIM-3 and 6 VIM-2 producers that were recognized by PCR hybridized with both the blaVIM-3- and the blaVIM-2-specific probes, and the 5 IMP-1 producers hybridized with the blaIMP-1-specific probe. All other isolates showed negative results with the probes specific for blaVIM-1, blaVIM-2, blaVIM-3, blaIMP-1, and blaIMP-2.

Conjugation experiments failed to demonstrate transfer of carbapenem resistance from any of the isolates. Amoxicillin resistance was transferred from the control strain to E. coli C600 at a low frequency (10-8 to 10-10 per donor cell). Plasmid DNAs were isolated from three P. aeruginosa isolates (isolates NTU-39/00, PS-64/99, and PB-59) and three P. putida isolates (isolates NTU-91/99, NTU-93/00, and PB-166). For all three P. aeruginosa isolates the same restriction pattern was generated by BstEII digestion. The restriction patterns of the three P. putida isolates were different, and the blaVIM-2-specific probe hybridized to approximately 9-kb DNA fragments for two VIM-2 producers. The probes specific for blaVIM-2, blaVIM-3, and blaIMP-1 did hybridize significantly with contaminated chromosomal DNAs for the remaining four VIM-2 producers and all VIM-3 and IMP-1 producers, respectively. Therefore, the MBLs in most of these isolates seem to be chromosomally located.

Analytical IEF. The results of IEF are summarized in Table 2. Since VIM-type MBLs are acidic enzymes (13, 22) and all VIM-3-producing P. aeruginosa isolates contained one major band that focused at pH 5.1, the band of pl 5.1 was most likely contributed by VIM-3. The bands with pls of 5.0 and 8.7 were consistent with those of VIM-2 and IMP-1, respectively (16, 22). The bands with pls ranging from 8.0 to 8.9 were possibly contributed by AmpC-type beta -lactamases of Pseudomonas (4).

Susceptibility tests. The drug susceptibilities of the 21 isolates carrying MBL genes were determined and are shown in Table 2. All these isolates were resistant to cefotaxime and ceftazidime. The susceptibilities of these isolates to aztreonam, piperacillin, and carbapenems appeared to be diverse.

PFGE analysis. PFGE revealed that six MBL-producing P. aeruginosa isolates were closely or possibly genetically related and that two IMP-1-producing P. stutzeri isolates were genetically indistinguishable (Table 2 and Fig. 1).


View larger version (76K):
[in this window]
[in a new window]
  		FIG. 1.   PFGE profiles of SpeI-digested genomic DNAs from 21 Pseudomonas isolates carrying IMP- or VIM-type MBL genes. (A) Lanes 1 to 9 and 11, VIM-3-producing P. aeruginosa isolates NTU-23/99, PS-1205/00, PB-59, NTU-34/99, NTU-39/00, PS-64/99, NTU-26/99, NTU-33/99, NTU-43/00, and NTU-79/00, respectively; lane 10, VIM-2-producing P. putida isolate PS-693/00; lane M, a bacteriophage lambda ladder. (B) Lanes 1, 4, 6, 9, and 10, IMP-1 producer isolates PB-207, NTU-92/99, PB-166, PB-101, and PB-24, respectively; lanes 2, 3, 5, 7, and 8, VIM-2 producers isolates PS-1153/00, NTU-91/99, NTU-93/99, PS-579/00, and PS-679/00, respectively; lane M, a bacteriophage lambda ladder.


    DISCUSSION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

In the present study, 21 isolates of Pseudomonas spp. were found to produce MBLs. Only 5 (23.8%) of them carried IMP-1, while 16 (76.2%) isolates harbored the VIM-2-related enzymes. These data indicate that the VIM-2-related enzymes are the most prevalent MBLs among clinical isolates of Pseudomonas spp. in Taiwan. The countrywide spread of the IMP-1 enzyme in gram-negative bacilli was reported in Japan (9, 10, 28, 29). Shortly after VIM-1 and VIM-2 were identified in Europe (13, 22), VIM-type MBLs were also found in Pseudomonas and Acinetobacter spp. in Korea (Lee et al., 40th ICAAC). These findings together indicate that both IMP- and VIM-related MBLs are widespread in eastern Asian countries. The novel enzyme, VIM-3, identified in the present study had only two amino acid differences from VIM-2 Whether the amino acid changes lead to differences in the biochemical characteristics of these two MBLs needs further investigation.

Acquired MBL genes in P. aeruginosa are often carried on plasmids and are usually nontransferable by conjugation, at least to E. coli (10, 11, 13, 22). In the present study, the MBL genes in our isolates could not be transferred to E. coli by conjugation experiments. Southern hybridization showed that only two P. putida isolates carried the blaVIM-2 gene on plasmids. All other isolates seemed to carry these MBL genes on their chromosomes. In addition, clonal spread was suggested by PFGE for six P. aeruginosa and two P. stutzeri isolates (Fig. 1). Since the blaVIM and blaIMP genes were found to be on mobile gene cassettes inserted into integrons (11, 13, 22, 25), our findings suggest that the spread of these MBL genes in Taiwan could be due to clonal dissemination as well as to movement of the resistance genes between different clones.

Consistent with the findings reported previously (9, 10, 28, 29), all our MBL-producing isolates were resistant to the broad-spectrum cephems ceftazidime and cefotaxime, while their susceptibilities to carbapenems, ureidopenicillins, and aztreonam were diverse (Table 2). Expression of MBLs could be cryptic or could be suppressed in the strains demonstrating low-level carbapenem resistance (10). The different permeability coefficients of each beta -lactam may play an important role in resistance to each beta -lactam in gram-negative bacteria that produce metalloenzymes (15, 17). Active efflux also acts as a contributing factor to beta -lactam resistance in P. aeruginosa (14). Therefore, the lower MICs of piperacillin for some isolates could be due to their higher permeability coefficients or less efficient efflux pumps. Aztreonam is notable for its relatively low MICs for MBL-producing strains (13, 20, 22, 25). Therefore, reduced susceptibilities to aztreonam in a few isolates could be due to the presence of alternative resistance mechanisms. Isolate NTU-92/99, for which carbapenem MICs were notably low, had a relatively slow growth rate, although it possessed the biochemical and morphologic features characteristic of P. stutzeri. The slow growth rate and the difficulty in making suspensions might be partially responsible for the low carbapenem MICs for the isolate.

P. putida and P. stutzeri are environmental organisms and rarely cause human diseases (6). P. stutzeri has been reported to cause outbreaks of pseudobacteremia by contaminating antiseptics used to prepare skin (6). The medical records of the patients at the National Cheng Kung University Medical Center were reviewed. All these isolates were considered to be from the hospital environment. The three P. stutzeri and one P. putida isolates from blood samples and the P. putida isolate recovered from a drainage tube were of no clinical significance. They could originate from contaminated antiseptics, the patients' skin, blood culture bottles, or the drainage tube. The two P. putida and one P. stutzeri isolates from urine samples were all urinary catheterization related, and their clinical significance was not clear. Our findings suggest that the environmental organisms acquired the MBL genes under long-term selection pressure in the hospital environment.

Early detection of MBL-producing strains is important for clinicians for the selection of appropriate antimicrobial agents. PCR assays with primers specific for blaIMP-1 have been shown to be useful and reliable for detection of IMP-1 producers (29). Given that the numbers of metalloenzymes are increasing (11, 13, 22, 25), the use of multiple primers is needed. Since the PCR method is not cost-effective for use for daily testing in clinical laboratories, Arakawa et al. (1) have designed a simple disk diffusion test for screening for MBL-producing gram-negative rods; the test has a high degree of specificity and a high degree of sensitivity for the detection of IMP-1 producers. The results obtained by the screening test in the present study also correlated well with those obtained by the PCR method, indicating that the test is very useful for the detection not only of IMP-1-producing strains but also of VIM producers.

In conclusion, both IMP- and VIM-type MBLs have emerged in Pseudomonas spp. in Taiwan, and the VIM-2-related enzymes were the most prevalent types. The MBL genes were largely located on chromosomes, and their dissemination in Taiwan could be due to both mobilization of the resistance genes and clonal spread of the resistant strains.


    ACKNOWLEDGMENTS

We kindly thank G. M. Rossolini, Dipartimento di Biologia Molecolare, Sezione Di Microbiologia, Università di Siena, Siena, Italy, for provision of IMP-2-containing A. baumannii strain AC-54/97 and VIM-1-containing P. aeruginosa strain VR-143/97.

This work was partially supported by grants NCKUH89-054 from National Cheng Kung University Hospital and NSC89-2320-B-006-149 from the National Science Council of the Republic of China.


    FOOTNOTES

* Corresponding author. Mailing address: Department of Medical Technology, National Cheng Kung University Medical College, No. 1 University Rd., Tainan, Taiwan 70101. Phone: 886-6-2353535, ext. 5775. Fax: 886-6-2363956. E-mail: jjwu{at}mail.ncku.edu.tw.


    REFERENCES
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

1. Arakawa, Y., N. Shibata, K. Shibayama, H. Kurokawa, T. Yagi, H. Fugiwara, and M. Goto. 2000. Convenient test for screening metallo-beta -lactamase-producing gram-negative bacteria by using thio compounds. J. Clin. Microbiol. 38:40-43[Abstract/Free Full Text].
2. Bachmann, B. J., and K. B. Low. 1980. Linkage map of Escherichia coli K-12, edition 6. Microbiol. Rev. 44:1451-1456.
3. Bauernfeind, A., H. Grimm, and S. Schweighart. 1990. A new plasmidic cefotaximase in a clinical isolate of Escherichia coli. Infection 18:294-298[CrossRef][Medline].
4. Bush, K., G. A. Jacoby, and A. A. Medeiros. 1995. A functional classification scheme for beta -lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. 39:1211-1233[Medline].
5. Chu, G., D. Vollrath, and R. W. Davis. 1986. Separation of large DNA molecules by contour-clamped homogeneous electric fields. Science 234:1582-1585[Abstract/Free Full Text].
6. Gilligan, P. H., and S. Whittier. 1999. Pseudomonas and Burkholderia, p. 517-525. In P. R. Murray, E. J. Baron, M. A. Pfaller, F. C. Tenover, and R. H. Yolken (ed.), Manual of clinical microbiology, 7th ed. American Society for Microbiology, Washington, D.C.
7. Grunstein, M., and D. S. Hogness. 1975. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc. Natl. Acad. Sci. USA 72:3961-3965[Abstract/Free Full Text].
8. Hancock, R. E. W. 1998. Resistance mechanisms in Pseudomonas aeruginosa and other nonfermentative gram-negative bacteria. Clin. Infect. Dis. 27(Suppl. 1):S93-S99.
9. Hirakata, Y., K. Izumikawa, T. Yamaguchi, H. Takemura, H. Tanaka, R. Yoshida, J. Matsuda, M. Nakano, K. Tomono, S. Maesaki, M. Kaku, Y. Yamada, S. Kamihira, and S. Kohno. 1998. Rapid detection and evaluation of clinical characteristics of emerging multiple-drug-resistant gram-negative rods carrying the metallo-beta -lactamase gene blaIMP. Antimicrob. Agents Chemother. 42:2006-2011[Abstract/Free Full Text].
10. Ito, H., Y. Arakawa, S. Ohsuka, R. Wacharotayankun, N. Kato, and M. Ohta. 1995. Plasmid-mediated dissemination of the metallo-beta -lactamase gene blaIMP among clinical isolated strains of Serratia marcescens. Antimicrob. Agents Chemother. 39:824-829[Abstract].
11. Iyobe, S., H. Kusadokoro, J. Ozaki, N. Matsumura, S. Minami, S. Haruta, T. Sawai, and K. O'Hara. 2000. Amino acid substitutions in a variant of IMP-1 metallo-beta -lactamase. Antimicrob. Agents Chemother. 44:2023-2027[Abstract/Free Full Text].
12. Jacoby, G. A., and A. A. Medeiros. 1991. More extended-spectrum beta -lactamases. Antimicrob. Agents Chemother. 35:1697-1704[Free Full Text].
13. Lauretti, L., M. L. Riccio, A. Mazzariol, G. Cornaglia, G. Amicosante, R. Fontana, and G. M. Rossolini. 1999. Cloning and characterization of blaVIM, a new integron-borne metallo-beta -lactamase gene from a Pseudomonas aeruginosa clinical isolate. Antimicrob. Agents Chemother. 43:1584-1590[Abstract/Free Full Text].
14. Li, X. Z., D. Ma, D. M. Livermore, and H. Nikaido. 1994. Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: active efflux as a contributing factor to beta -lactam resistance. Antimicrob. Agents Chemother. 38:1742-1752[Abstract/Free Full Text].
15. Livermore, D. M. 1992. Interplay of impermeability and chromosomal beta -lactamase activity in imipenem-resistant Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 36:2046-2048[Abstract/Free Full Text].
16. Marumo, K., A. Takeda, Y. Nakamura, and K. Nakaya. 1995. Purification and characterization of metallo-beta -lactamase from Serratia marcescens. Microbiol. Immunol. 39:27-33[Medline].
17. Matsumura, N., S. Minami, Y. Watanabe, S. Iyobe, and S. Mitsuhashi. 1999. Role of permeability in the activities of beta -lactams against gram-negative bacteria which produce a group 3 beta -lactamase. Antimicrob. Agents Chemother. 43:2084-2086[Abstract/Free Full Text].
18. Matthew, M., M. Harris, M. J. Marshall, and G. W. Rose. 1975. The use of analytical isoelectric focusing for detection and identification of beta -lactamases. J. Gen. Microbiol. 88:169-178[Medline].
19. National Committee for Clinical Laboratory Standards. 1999. Performance standards for antimicrobial susceptibility testing; ninth informational supplement. M100-S9. National Committee for Clinical Laboratory Standards, Wayne, Pa.
20. Osano, E., Y. Arakawa, R. Wacharotayankun, M. Ohta, T. Horii, H. Ito, F. Yoshimura, and N. Kato. 1994. Molecular characterization of an enterobacterial metallo-beta -lactamase found in a clinical isolates of Serratia marcescens that shows imipenem resistance. Antimicrob. Agents Chemother. 38:71-78[Abstract/Free Full Text].
21. Piggot, P. J., M. Amjad, J. J. Wu, H. Sandoval, and J. Castro. 1990. Genetic and physical maps of Bacillus subtilis 168, p. 493-543. In C. R. Harwood, and S. M. Cutting (ed.), Molecular biology methods for bacillus. John Wiley & Sons Ltd., West Sussex, England.
22. Poirel, L., T. Naas, D. Nicolas, L. Collet, S. Bellais, J. D. Cavallo, and P. Nordmann. 2000. Characterization of VIM-2, a carbapenem-hydrolyzing metallo-beta -lactamase and its plasmid- and integron-borne gene from a Pseudomonas aeruginosa clinical isolate in France. Antimicrob. Agents Chemother. 44:891-897[Abstract/Free Full Text].
23. Provence, D. L., and R. Curtiss, III. 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.
24. Rasmussen, B. A., and K. Bush. 1997. Carbapenem-hydrolyzing beta -lactamases. Antimicrob. Agents Chemother. 41:223-232[Medline].
25. Riccio, M. L., N. Franceschini, L. Boschi, B. Caravelli, G. Cornaglia, R. Fontana, G. Amicosante, and G. M. Rossolini. 2000. Characterization of the metallo-beta -lactamase determinant of Acinetobacter baumannii AC-54/97 reveals the existence of blaIMP allelic variants carried by gene cassettes of different phylogeny. Antimicrob. Agents Chemother. 44:1229-1235[Abstract/Free Full Text].
26. Sanders, C. C. 1987. Chromosomal cephalosporinases responsible for multiple resistance to newer beta -lactam antibiotics. Annu. Rev. Microbiol. 41:573-593[CrossRef][Medline].
27. Schiappa, D. A., M. K. Hayden, M. G. Matushek, F. N. Hashemi, J. Sullivan, K. Y. Smith, D. Miyashiro, J. P. Quinn, R. A. Weinstein, and G. M. Trenholme. 1996. Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation. J. Infect. Dis. 174:529-536[Medline].
28. Senda, K., Y. Arakawa, K. Nakashima, H. Ito, S. Ichiyama, K. Shimokata, N. Kato, and M. Ohta. 1996. Multifocal outbreaks of metallo-beta -lactamase-producing Pseudomonas aeruginosa resistant to broad-spectrum-beta -lactams, including carbapenems. Antimicrob. Agents Chemother. 40:349-353[Abstract].
29. Senda, K., Y. Arakawa, S. Ichiyama, K. Nakashima, H. Ito, S. Ohsuka, K. Shimokata, N. Kato, and M. Ohta. 1996. PCR detection of metallo-beta -lactamase gene (blaIMP) in gram-negative rods resistant to broad-spectrum beta -lactams. J. Clin. Microbiol. 34:2909-2913[Abstract].
30. Southern, E. M. 1975. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98:503-517[CrossRef][Medline].
31. Takahashi, S., and Y. Nagano. 1984. Rapid procedure for isolation of plasmid DNA and application to epidemiological analysis. J. Clin. Microbiol. 20:608-613[Abstract/Free Full Text].
32. Tsakris, A., S. Pournaras, N. Woodford, M.-F. I. Palepou, G. S. Babini, J. Douboyas, and D. M. Livermore. 2000. Outbreak of infections caused by Pseudomonas aeruginosa producing VIM-1 carbapenemase in Greece. J. Clin. Microbiol. 38:1290-1292[Abstract/Free Full Text].
33. Yan, J. J., S. M. Wu, S. H. Tsai, J. J. Wu, and I. J. Su. 2000. Prevalence of SHV-12 among clinical isolates of Klebsiella pneumoniae producing extended-spectrum beta -lactamase and identification of a novel AmpC enzyme (CMY-8) in southern Taiwan. Antimicrob. Agents Chemother. 44:1438-1442[Abstract/Free Full Text].

Antimicrobial Agents and Chemotherapy, August 2001, p. 2224-2228, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2224-2228.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Tsakris, A., Poulou, A., Kristo, I., Pittaras, T., Spanakis, N., Pournaras, S., Markou, F. (2009). Large Dissemination of VIM-2-Metallo-{beta}-Lactamase-Producing Pseudomonas aeruginosa Strains Causing Health Care-Associated Community-Onset Infections. J. Clin. Microbiol. 47: 3524-3529 [Abstract] [Full Text]  
  • Strateva, T., Yordanov, D. (2009). Pseudomonas aeruginosa - a phenomenon of bacterial resistance. J Med Microbiol 58: 1133-1148 [Abstract] [Full Text]  
  • Siarkou, V. I., Vitti, D., Protonotariou, E., Ikonomidis, A., Sofianou, D. (2009). Molecular Epidemiology of Outbreak-Related Pseudomonas aeruginosa Strains Carrying the Novel Variant blaVIM-17 Metallo-{beta}-Lactamase Gene. Antimicrob. Agents Chemother. 53: 1325-1330 [Abstract] [Full Text]  
  • Qu, T.-t., Zhang, J.-l., Wang, J., Tao, J., Yu, Y.-s., Chen, Y.-g., Zhou, J.-y., Li, L.-j. (2009). Evaluation of Phenotypic Tests for Detection of Metallo-{beta}-Lactamase-Producing Pseudomonas aeruginosa Strains in China. J. Clin. Microbiol. 47: 1136-1142 [Abstract] [Full Text]  
  • Aschbacher, R., Doumith, M., Livermore, D. M., Larcher, C., Woodford, N. (2008). Linkage of acquired quinolone resistance (qnrS1) and metallo-{beta}-lactamase (blaVIM-1) genes in multiple species of Enterobacteriaceae from Bolzano, Italy. J Antimicrob Chemother 61: 515-523 [Abstract] [Full Text]  
  • Tokatlidou, D., Tsivitanidou, M., Pournaras, S., Ikonomidis, A., Tsakris, A., Sofianou, D. (2008). Outbreak Caused by a Multidrug-Resistant Klebsiella pneumoniae Clone Carrying blaVIM-12 in a University Hospital. J. Clin. Microbiol. 46: 1005-1008 [Abstract] [Full Text]  
  • Ikonomidis, A., Ntokou, E., Maniatis, A. N., Tsakris, A., Pournaras, S. (2008). Hidden VIM-1 Metallo- -Lactamase Phenotypes among Acinetobacter baumannii Clinical Isolates. J. Clin. Microbiol. 46: 346-349 [Abstract] [Full Text]  
  • Tseng, S.-P., Hsueh, P.-R., Tsai, J.-C., Teng, L.-J. (2007). Tn6001, a Transposon-Like Element Containing the blaVIM-3-Harboring Integron In450. Antimicrob. Agents Chemother. 51: 4187-4190 [Abstract] [Full Text]  
  • Leavitt, A., Navon-Venezia, S., Chmelnitsky, I., Schwaber, M. J., Carmeli, Y. (2007). Emergence of KPC-2 and KPC-3 in Carbapenem-Resistant Klebsiella pneumoniae Strains in an Israeli Hospital. Antimicrob. Agents Chemother. 51: 3026-3029 [Abstract] [Full Text]  
  • Queenan, A. M., Bush, K. (2007). Carbapenemases: the Versatile {beta}-Lactamases. Clin. Microbiol. Rev. 20: 440-458 [Abstract] [Full Text]  
  • Koh, T. H., Sng, L.-H., Wang, G. C. Y., Hsu, L.-Y., Zhao, Y. (2007). IMP-4 and OXA {beta}-lactamases in Acinetobacter baumannii from Singapore. J Antimicrob Chemother 59: 627-632 [Abstract] [Full Text]  
  • Tsakris, A., Ikonomidis, A., Spanakis, N., Poulou, A., Pournaras, S. (2007). Characterization of In3Mor, a new integron carrying VIM-1 metallo-{beta}-lactamase and sat1 gene, from Morganella morganii. J Antimicrob Chemother 59: 739-741 [Abstract] [Full Text]  
  • Yu, Y.-S., Qu, T.-T., Zhou, J.-Y., Wang, J., Li, H.-Y., Walsh, T. R. (2006). Integrons Containing the VIM-2 Metallo-{beta}-Lactamase Gene among Imipenem-Resistant Pseudomonas aeruginosa Strains from Different Chinese Hospitals. J. Clin. Microbiol. 44: 4242-4245 [Abstract] [Full Text]  
  • Horianopoulou, M., Legakis, N. J., Kanellopoulou, M., Lambropoulos, S., Tsakris, A., Falagas, M. E. (2006). Frequency and predictors of colonization of the respiratory tract by VIM-2-producing Pseudomonas aeruginosa in patients of a newly established intensive care unit.. J Med Microbiol 55: 1435-1439 [Abstract] [Full Text]  
  • Yan, J.-J., Hsueh, P.-R., Lu, J.-J., Chang, F.-Y., Ko, W.-C., Wu, J.-J. (2006). Characterization of acquired {beta}-lactamases and their genetic support in multidrug-resistant Pseudomonas aeruginosa isolates in Taiwan: the prevalence of unusual integrons. J Antimicrob Chemother 58: 530-536 [Abstract] [Full Text]  
  • Fiett, J., Baraniak, A., Mrowka, A., Fleischer, M., Drulis-Kawa, Z., Naumiuk, L., Samet, A., Hryniewicz, W., Gniadkowski, M. (2006). Molecular Epidemiology of Acquired-Metallo-{beta}-Lactamase-Producing Bacteria in Poland. Antimicrob. Agents Chemother. 50: 880-886 [Abstract] [Full Text]  
  • Peleg, A. Y., Franklin, C., Walters, L. J., Bell, J. M., Spelman, D. W. (2006). OXA-58 and IMP-4 Carbapenem-Hydrolyzing {beta}-Lactamases in an Acinetobacter junii Blood Culture Isolate from Australia. Antimicrob. Agents Chemother. 50: 399-400 [Full Text]  
  • Pournaras, S., Ikonomidis, A., Tzouvelekis, L. S., Tokatlidou, D., Spanakis, N., Maniatis, A. N., Legakis, N. J., Tsakris, A. (2005). VIM-12, a Novel Plasmid-Mediated Metallo-{beta}-Lactamase from Klebsiella pneumoniae That Resembles a VIM-1/VIM-2 Hybrid. Antimicrob. Agents Chemother. 49: 5153-5156 [Abstract] [Full Text]  
  • Ikonomidis, A., Tokatlidou, D., Kristo, I., Sofianou, D., Tsakris, A., Mantzana, P., Pournaras, S., Maniatis, A. N. (2005). Outbreaks in Distinct Regions Due to a Single Klebsiella pneumoniae Clone Carrying a blaVIM-1 Metallo-{beta}-Lactamase Gene. J. Clin. Microbiol. 43: 5344-5347 [Abstract] [Full Text]  
  • Pournaras, S., Maniati, M., Spanakis, N., Ikonomidis, A., Tassios, P. T., Tsakris, A., Legakis, N. J., Maniatis, A. N. (2005). Spread of efflux pump-overexpressing, non-metallo-{beta}-lactamase-producing, meropenem-resistant but ceftazidime-susceptible Pseudomonas aeruginosa in a region with blaVIM endemicity. J Antimicrob Chemother 56: 761-764 [Abstract] [Full Text]  
  • Nouer, S. A., Nucci, M., de-Oliveira, M. P., Pellegrino, F. L. P. C., Moreira, B. M. (2005). Risk Factors for Acquisition of Multidrug-Resistant Pseudomonas aeruginosa Producing SPM Metallo-{beta}-Lactamase. Antimicrob. Agents Chemother. 49: 3663-3667 [Abstract] [Full Text]  
  • Pitout, J. D. D., Gregson, D. B., Poirel, L., McClure, J.-A., Le, P., Church, D. L. (2005). Detection of Pseudomonas aeruginosa Producing Metallo-{beta}-Lactamases in a Large Centralized Laboratory. J. Clin. Microbiol. 43: 3129-3135 [Abstract] [Full Text]  
  • Quinteira, S., Ferreira, H., Peixe, L. (2005). First Isolation of blaVIM-2 in an Environmental Isolate of Pseudomonas pseudoalcaligenes. Antimicrob. Agents Chemother. 49: 2140-2141 [Full Text]  
  • Walsh, T. R., Toleman, M. A., Poirel, L., Nordmann, P. (2005). Metallo-{beta}-Lactamases: the Quiet before the Storm?. Clin. Microbiol. Rev. 18: 306-325 [Abstract] [Full Text]  
  • Castanheira, M., Toleman, M. A., Jones, R. N., Schmidt, F. J., Walsh, T. R. (2004). Molecular Characterization of a {beta}-Lactamase Gene, blaGIM-1, Encoding a New Subclass of Metallo-{beta}-Lactamase. Antimicrob. Agents Chemother. 48: 4654-4661 [Abstract] [Full Text]  
  • Mendes, R. E., Toleman, M. A., Ribeiro, J., Sader, H. S., Jones, R. N., Walsh, T. R. (2004). Integron Carrying a Novel Metallo-{beta}-Lactamase Gene, blaIMP-16, and a Fused Form of Aminoglycoside-Resistant Gene aac(6')-30/aac(6')-Ib': Report from the SENTRY Antimicrobial Surveillance Program. Antimicrob. Agents Chemother. 48: 4693-4702 [Abstract] [Full Text]  
  • Crespo, M. P., Woodford, N., Sinclair, A., Kaufmann, M. E., Turton, J, Glover, J., Velez, J. D., Castaneda, C. R., Recalde, M., Livermore, D. M. (2004). Outbreak of Carbapenem-Resistant Pseudomonas aeruginosa Producing VIM-8, a Novel Metallo-{beta}-Lactamase, in a Tertiary Care Center in Cali, Colombia. J. Clin. Microbiol. 42: 5094-5101 [Abstract] [Full Text]  
  • Nishio, H., Komatsu, M., Shibata, N., Shimakawa, K., Sueyoshi, N., Ura, T., Satoh, K., Toyokawa, M., Nakamura, T., Wada, Y., Orita, T., Kofuku, T., Yamasaki, K., Sakamoto, M., Kinoshita, S., Aihara, M., Arakawa, Y. (2004). Metallo-{beta}-Lactamase-Producing Gram-Negative Bacilli: Laboratory-Based Surveillance in Cooperation with 13 Clinical Laboratories in the Kinki Region of Japan. J. Clin. Microbiol. 42: 5256-5263 [Abstract] [Full Text]  
  • Koh, T. H., Wang, G. C. Y., Sng, L.-H. (2004). Clonal Spread of IMP-1-Producing Pseudomonas aeruginosa in Two Hospitals in Singapore. J. Clin. Microbiol. 42: 5378-5380 [Abstract] [Full Text]  
  • Peleg, A. Y., Franklin, C., Bell, J., Spelman, D. W. (2004). Emergence of IMP-4 metallo-{beta}-lactamase in a clinical isolate from Australia. J Antimicrob Chemother 54: 699-700 [Full Text]  
  • Koh, T. H., Wang, G. C. Y., Sng, L.-H. (2004). IMP-1 and a Novel Metallo-{beta}-Lactamase, VIM-6, in Fluorescent Pseudomonads Isolated in Singapore. Antimicrob. Agents Chemother. 48: 2334-2336 [Abstract] [Full Text]  
  • Yatsuyanagi, J., Saito, S., Harata, S., Suzuki, N., Ito, Y., Amano, K.-i., Enomoto, K. (2004). Class 1 Integron Containing Metallo-{beta}-Lactamase Gene blaVIM-2 in Pseudomonas aeruginosa Clinical Strains Isolated in Japan. Antimicrob. Agents Chemother. 48: 626-628 [Abstract] [Full Text]  
  • Toleman, M. A., Rolston, K., Jones, R. N., Walsh, T. R. (2004). blaVIM-7, an Evolutionarily Distinct Metallo-{beta}-Lactamase Gene in a Pseudomonas aeruginosa Isolate from the United States. Antimicrob. Agents Chemother. 48: 329-332 [Abstract] [Full Text]  
  • Giske, C. G., Rylander, M., Kronvall, G. (2003). VIM-4 in a Carbapenem-Resistant Strain of Pseudomonas aeruginosa Isolated in Sweden. Antimicrob. Agents Chemother. 47: 3034-3035 [Full Text]  
  • Yomoda, S., Okubo, T., Takahashi, A., Murakami, M., Iyobe, S. (2003). Presence of Pseudomonas putida Strains Harboring Plasmids Bearing the Metallo-{beta}-Lactamase Gene blaIMP in a Hospital in Japan. J. Clin. Microbiol. 41: 4246-4251 [Abstract] [Full Text]  
  • Pournaras, S., Maniati, M., Petinaki, E., Tzouvelekis, L. S., Tsakris, A., Legakis, N. J., Maniatis, A. N. (2003). Hospital outbreak of multiple clones of Pseudomonas aeruginosa carrying the unrelated metallo-{beta}-lactamase gene variants blaVIM-2 and blaVIM-4. J Antimicrob Chemother 51: 1409-1414 [Abstract] [Full Text]  
  • Yamasaki, K., Komatsu, M., Yamashita, T., Shimakawa, K., Ura, T., Nishio, H., Satoh, K., Washidu, R., Kinoshita, S., Aihara, M. (2003). Production of CTX-M-3 extended-spectrum {beta}-lactamase and IMP-1 metallo {beta}-lactamase by five Gram-negative bacilli: survey of clinical isolates from seven laboratories collected in 1998 and 2000, in the Kinki region of Japan. J Antimicrob Chemother 51: 631-638 [Abstract] [Full Text]  
  • Murphy, T. A., Simm, A. M., Toleman, M. A., Jones, R. N., Walsh, T. R. (2003). Biochemical Characterization of the Acquired Metallo-{beta}-Lactamase SPM-1 from Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 47: 582-587 [Abstract] [Full Text]  
  • Docquier, J.-D., Lamotte-Brasseur, J., Galleni, M., Amicosante, G., Frere, J.-M., Rossolini, G. M. (2003). On functional and structural heterogeneity of VIM-type metallo-{beta}-lactamases. J Antimicrob Chemother 51: 257-266 [Abstract] [Full Text]  
  • Pournaras, S., Tsakris, A., Maniati, M., Tzouvelekis, L. S., Maniatis, A. N. (2002). Novel Variant (blaVIM-4) of the Metallo-{beta}-Lactamase Gene blaVIM-1 in a Clinical Strain of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 46: 4026-4028 [Abstract] [Full Text]  
  • Lombardi, G., Luzzaro, F., Docquier, J.-D., Riccio, M. L., Perilli, M., Coli, A., Amicosante, G., Rossolini, G. M., Toniolo, A. (2002). Nosocomial Infections Caused by Multidrug-Resistant Isolates of Pseudomonas putida Producing VIM-1 Metallo-{beta}-Lactamase. J. Clin. Microbiol. 40: 4051-4055 [Abstract] [Full Text]  
  • Migliavacca, R., Docquier, J.-D., Mugnaioli, C., Amicosante, G., Daturi, R., Lee, K., Rossolini, G. M., Pagani, L. (2002). Simple Microdilution Test for Detection of Metallo-{beta}-Lactamase Production in Pseudomonas aeruginosa. J. Clin. Microbiol. 40: 4388-4390 [Abstract] [Full Text]  
  • Yong, D., Lee, K., Yum, J. H., Shin, H. B., Rossolini, G. M., Chong, Y. (2002). Imipenem-EDTA Disk Method for Differentiation of Metallo-{beta}-Lactamase-Producing Clinical Isolates of Pseudomonas spp. and Acinetobacter spp.. J. Clin. Microbiol. 40: 3798-3801 [Abstract] [Full Text]  
  • Yan, J.-J., Ko, W.-C., Chuang, C.-L., Wu, J.-J. (2002). Metallo-{beta}-lactamase-producing Enterobacteriaceae isolates in a university hospital in Taiwan: prevalence of IMP-8 in Enterobacter cloacae and first identification of VIM-2 in Citrobacter freundii. J Antimicrob Chemother 50: 503-511 [Abstract] [Full Text]  
  • Pellegrino, F. L. P. C., Teixeira, L. M., Carvalho, M. d. G. S., Aranha Nouer, S., Pinto de Oliveira, M., Mello Sampaio, J. L., D'Avila Freitas, A., Ferreira, A. L. P., Amorim, E. d. L. T., Riley, L. W., Moreira, B. M. (2002). Occurrence of a Multidrug-Resistant Pseudomonas aeruginosa Clone in Different Hospitals in Rio de Janeiro, Brazil. J. Clin. Microbiol. 40: 2420-2424 [Abstract] [Full Text]  
  • Bellais, S., Mimoz, O., Leotard, S., Jacolot, A., Petitjean, O., Nordmann, P. (2002). Efficacy of {beta}-Lactams for Treating Experimentally Induced Pneumonia Due to a Carbapenem-Hydrolyzing Metallo-{beta}-Lactamase-Producing Strain of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 46: 2032-2034 [Abstract] [Full Text]  
  • Prats, G., Miro, E., Mirelis, B., Poirel, L., Bellais, S., Nordmann, P. (2002). First Isolation of a Carbapenem-Hydrolyzing {beta}-Lactamase in Pseudomonas aeruginosa in Spain. Antimicrob. Agents Chemother. 46: 932-933 [Full Text]  
  • Yan, J.-J., Ko, W.-C., Tsai, S.-H., Wu, H.-M., Wu, J.-J. (2001). Outbreak of Infection with Multidrug-Resistant Klebsiella pneumoniae Carrying blaIMP-8 in a University Medical Center in Taiwan. J. Clin. Microbiol. 39: 4433-4439 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yan, J.-J.
Right arrow Articles by Wu, J.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yan, J.-J.
Right arrow Articles by Wu, J.-J.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»