J Med Microbiol NEW Faster Access
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

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
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wei, Z.-Q.
Right arrow Articles by Li, L.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wei, Z.-Q.
Right arrow Articles by Li, L.-J.
Agricola
Right arrow Articles by Wei, Z.-Q.
Right arrow Articles by Li, L.-J.
J Med Microbiol 54 (2005), 885-888; DOI: 10.1099/jmm.0.46151-0
© 2005 Society for General Microbiology
ISSN 0022-2615

Nosocomial spread of multi-resistant Klebsiella pneumoniae containing a plasmid encoding multiple ß-lactamases

Ze-Qing Wei, Ya-Gang Chen, Yun-Song Yu, Wei-Xin Lu and Lan-Juan Li

Infectious Disease Dept, The First Affiliated Hospital, Medical School, Zhejiang University, The Key Laboratory of Infectious Diseases of Public Health Ministry, Zhejiang, Hangzhou, China

Correspondence Yun-Song Yu yvys119{at}163.com

Received May 10, 2005
Accepted June 17, 2005

Six Klebsiella pneumoniae isolates that exhibited resistance to a wide spectrum of antibiotics were recovered from the intensive care units in the First Affiliated Hospital, Zhejiang University, Hangzhou, China. All isolates contained two plasmids of approximately 95 kb and 200 kb. The 95 kb plasmid was shown to be transferable by conjugation experiments. Isoelectric focusing patterns of the ß-lactamases extracted from the six transconjugants were identical, displaying five pI bands: 5.4, 7.75, 8.0, 8.2 and 8.4. The band corresponding to a pI of 7.75 could be inhibited by cloxacillin but not clavulanic acid, while the other bands could be inhibited by clavulanic acid but not cloxacillin. The 95 kb plasmid was digested with HindIII and a recombinant plasmid pT948 was obtained. The insert was found to contain blaDHA–1, regulatory gene ampR and an insertion element (IS26), which was downstream of blaDHA–1. PCR and DNA sequencing results confirmed that the 95 kb plasmid encoded at least four ß-lactamase genes: blaTEM–1, blaSHV–12, blaCTX–M–3 and blaDHA–1. Epidemiological typing by PFGE of the six clinical isolates of K. pneumoniae demonstrated identical genotypic patterns. In conclusion, all results indicated that the six multi-drug resistant clinical isolates of K. pneumoniae most probably originated from one clone and caused a localized epidemic in the intensive care units.

Abbreviation: ESBL, extended-spectrum ß-lactamase.

The GenBank/EMBL/DDBJ accession number for the DHA-1 sequence described in this study is AY705809.


   INTRODUCTION
TOP
 INTRODUCTION
METHODS
 RESULTS AND DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Many ß-lactamase genes have been found in K. pneumoniae plasmids, including those encoding extended-spectrum ß-lactamases (ESBLs), AmpC ß-lactamases, inhibitor- resistant TEM ß-lactamases and metalloenzymes. These enzymes confer resistance to various antimicrobial agents including the third and fourth generation cephalosporins, cephamycins, monobactam ß-lactamase, ß-lactamase/inhibitor combinations and carbapenems (Essack et al., 2004; Hanson et al., 1999; Lemozy et al., 1995; Moland et al., 2003; Poirel et al., 2004; Yan et al., 2001). Most importantly, the number of resistance genes carried on the plasmids of multi-resistant K. pneumoniae is usually more than one, and occasionally as many as five genes are reported (Essack et al., 2004; Hanson et al., 1999; Poirel et al., 2004; Yan et al., 2001). In fact, coexistence of broad-spectrum ß-lactamases with ESBLs, ESBLs with AmpC ß-lactamase, multiple ESBLs or ESBLs with metallo-ß-lactamase has become common in multi-resistant K. pneumoniae (Essack et al., 2004; Hanson et al., 1999; Yan et al., 2001). Of these enzymes, ESBLs were the most prevalent in K. pneumoniae, frequently encoded on large plasmids with sizes of 80–160 kb.

DHA-1 is an AmpC-type ß-lactamase that shares 98.7 % amino acid similarity with the chromosomal AmpC enzyme from Morganella morganii and was originally described by Verdet et al. (2000) on a complex sulI-type integron. This integron was responsible for the transfer of blaDHA–1 and the corresponding ampR gene from the chromosome of M. morganii to Salmonella enteritidis (Verdet et al., 2000). In this study, we report the finding and characterization of a plasmid containing multiple resistance genes, including one encoding the plasmid-mediated AmpC ß-lactamase (DHA-1), and the downstream IS26 element, as well as those encoding a broad-spectrum ß-lactamase and two ESBLs.


   METHODS
TOP
 INTRODUCTION
 METHODS
RESULTS AND DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 
Bacterial strains.

Six multi-resistant K. pneumoniae isolates were obtained from five patients between May and August 2000 in the intensive care unit of Zhejiang University's First Affiliated Hospital. The isolates were identified by the API 20E system. The MICs of ceftazidime with or without clavulanic acid for these six isolates were all above 256 µg ml–1. Streptomycin-resistant Escherichia coli C600 was used as the recipient in conjugation experiments. E. coli DH5{alpha} and plasmid pGEM-T Easy (Promega) were used in cloning experiments as the host strain and vector, respectively.

Susceptibility testing.

The MICs of antimicrobial agents for clinical isolates of K. pneumoniae and transconjugants were determined by E-test (AB Biodisk) according to the manufacturer's instructions. The antimicrobial agents tested were imipenem, ceftazidime, ceftazidime/clavulanic acid, cefotaxime, cefotaxime/clavulanic acid, ceftriaxone, cefepime, cefoxitin, ticarcillin/clavulanic acid, piperacillin/tazobactam, cefoperazone/sulbactam, ciprofloxacin, gentamicin and amikacin. E. coli ATCC 25922 and E. coli ATCC 35218 were used as quality control strains.

PFGE.

Genomic DNA was analysed by PFGE after digestion with XbaI (Sangon), using the contour-clamped homogeneous electric field (CHEF) technique (Gouby et al., 1994). DNA fragments were separated by electrophoresis in 1 % agarose III (Sangon) in 0.5x TBE buffer (45 mM Tris, 45 mM boric acid, 1 mM EDTA, pH 8.0) with CHEF apparatus (CHEF MAPPER XA; Bio-Rad) at 14 °C and 6 V cm–1 and with alternating pulses at a 120° angle in a 2–40 s pulse time gradient for 22.5 h. DNA from {lambda} DNA-PFGE markers (Amersham) was used as size markers. Restriction patterns were interpreted by the criteria proposed by Tenover et al. (1995).

Transconjugation, plasmid extraction and plasmid fingerprints.

Conjugation was carried out by a broth method as described elsewhere (Yan et al., 2001). The plasmids of clinical isolates and transconjugants were extracted by the method of Kado and Liu (1981), with plasmids 40R646 (58 kb), 28R823 (221 kb), 40R448 (119 kb), 40R626 (61 kb), 40R268 (98 kb) and RT641 (91 kb) as plasmid size markers (Ling et al., 2000). Plasmid DNA of the six transconjugants was extracted with Qiagen Plasmid Maxi Kit (Qiagen) and digested with EcoRI and EcoO109I.

Isoelectric focusing.

Isoelectric focusing was performed according to a published protocol (Coudron et al., 2000). Isoelectric focusing was performed using the PhastSystem (Pharmacia) in an ampholine gel (pH 3.0–9.0; Pharmacia), and SHV-18 (pI 7.8), TME-12 (pI 5.25), SHV-1 (pI 7.6) and ACT-1 (pI 9.0) as pI markers. Filter paper containing either 0.5 mM clavulanic acid (Jiangsu Simcere) or 0.5 mM cloxacillin (Sigma) was used as an inhibitor for 30 s in isoelectric focusing test before staining with nitrocefin.

PCR amplification and sequencing.

Isolates of clinical K. pneumoniae and transconjugants were amplified by the standard PCR (Sambrook et al., 1989). Oligonucleotide primers for the TEM gene were designed according to the nucleotide sequence of TEM-1 (GenBank accession no. AF188200): TEM-3, 5'-TTAGACGTCAGGTGGCACTT-3' (nucleotides 76–95), and TEM-8, 5'-GGACCGGAGTTACCA ATGCT-3' (nucleotides 1065–1077). The SHV gene primers were designed from the nucleotide sequence of SHV-1 (GenBank accession no. X98100): SHV-12, 5'-TCGGCCTTCACTCAAGGATG-3' (nucleotides 44–63) and SHV-17, 5'-ATGCCGCCGCCAGTCATATC-3' (nucleotides 991–1010). P1C and P2D were the primers for the CTX-M-3 gene (Gniadkowski et al., 1998). DHA-1A and DHA-1B were the primers for blaDHA–1 (Yan et al., 2002). PCR products were purified and cloned into the pGEM-T Easy vector. Both strands of the cloned DNA fragments inserted into the recombinant plasmids were sequenced with an Applied Biosystems sequencer (ABI 377 or 3730).

Cloning and sequencing of the plasmid-mediated AmpC gene.

The plasmid of transconjugant KP6 was extracted by Qiagen Plasmid Maxi Kit and digested with HindIII. DNA fragments containing the AmpC gene were cloned into the pGEM-T vector. Recombinants were selected on MacConkey agar containing 10 µg cefoxitin ml–1. The entire inserted segment from the recombinant plasmid was completely sequenced by the walking method with an automated sequencer.

Nucleotide sequence accession numbers.

The nucleotide sequences described in this study can be found in GenBank under accession no. AY705809, a 6432 bp sequence containing DHA-1.


   RESULTS AND DISCUSSION
TOP
 INTRODUCTION
 METHODS
 RESULTS AND DISCUSSION
ACKNOWLEDGEMENTS
 REFERENCES
 
The six clinical isolates of K. pneumoniae all had a similar antibiotic-resistance pattern; they were resistant to ceftazidime, cefotaxime, ceftriaxone, gentamicin, amikacin, ciprofloxacin, aztreonam, cefoxitin and ticarcillin/clavulanic acid, and intermediately resistant to piperacillin/tazobactam, cefoperazone/sulbactam and cefepime. Among the test drugs, the isolates were susceptible to imipenem only.

Conjugation of each of the six K. pneumoniae isolates with E. coli C600 was successful, with a transfer frequency of 10–6–10–7. The plasmid patterns of the six clinical isolates were all identical, exhibiting two plasmids of approximately 95 kb and 200 kb (Fig. 1). Only the plasmid of approximately 95 kb was extracted from each of the six transconjugants. DNA fingerprints of plasmids from the six transconjugants digested with either EcoRI or EcoO109I were identical (Fig. 2). The drug-susceptibility profiles of the transconjugants were similar to the clinical isolates, except for the susceptibility to amikacin and ciprofloxacin.



View larger version (38K):
[in this window]
[in a new window]
  		Fig. 1. Plasmid profiles of six clinical isolates of K. pneumoniae and their corresponding transconjugants. Ma, 119 kb, 91 kb and 58 kb markers; Mb, 98 kb marker. Lanes 1, 3, 5, 7, 9 and 11, plasmids of transconjugants from clinical isolates of K. pneumoniae PK1, PK2, PK3, PK4, PK5 and PK6, respectively; lanes 2, 4, 6, 8, 10 and 12, plasmids from clinical isolates of K. pneumoniae PK1, PK2, PK3, PK4, PK5 and PK6, respectively.

 


View larger version (37K):
[in this window]
[in a new window]
  		Fig. 2. Agarose gel electrophoresis analysis of plasmids of six transconjugants digested with EcoRI and EcoO109I. Ma, {lambda}-HindIII digest DNA Marker; Mb, DNA Marker DL15000. Lanes 1–6, restriction patterns of EcoRI; lanes 7–12, restriction patterns of EcoO109I; lanes 1 and 7, pPK1; lanes 2 and 8, pPK2; lanes 3 and 9, pPK3; lanes 4 and 10, pPK4; lanes 5 and 11, pPK5; lanes 6 and 12, pPK6. (The plasmids extracted from the six transconjugants were designated pPK1 to pPK6.)

 

PCR and nucleotide sequence analysis found that the six clinical isolates of K. pneumoniae and their corresponding transconjugants carried blaTEM–1, blaSHV–12, blaCTX–M–3 and blaDHA–1. Isoelectric focusing patterns of the ß-lactamases extracted from the transconjugants were identical to the donor strains, displaying five pI bands: 5.4, 7.75, 8.0, 8.2 and 8.4. The band corresponding to a pI of 7.75 could be inhibited by cloxacillin but not clavulanic acid, while the other bands could be inhibited by clavulanic acid but not cloxacillin. Thus, the pI 7.75 band probably represented the DHA-1 ß-lactamase. The pI bands of 5.4, 8.2 and 8.4 accounted for the TEM-1, SHV-12 and CTX-M-3 enzymes, respectively. The band of pI 8.0 was relatively weak. To confirm its genotype, a set of primers was used to detect the ß-lactamase genes of OXA-15, OXA-23, CTX-M-2, CTX-M-8, CTX-M-9, TOHO-2 and VEB-1, but the PCR results were negative.

Since the first report of SHV-2 ESBLs in China in 1994, the frequency of ESBLs has been on the rise in this country (Cheng & Chen, 1994). In particular, ESBL-producing bacteria have become one of the most difficult clinical problems in recent years. CTX-M ß-lactamases are the predominant ESBLs in China, including CTX-M-3, CTX-M-9, CTX-M-13, CTX-M-14 and CTX-M-18 (Chanawong et al., 2003; Ji et al., 2004; Li et al., 2003; Wang et al., 2003). Moreover, some new CTX-M ß-lactamases have also been reported in China in recent years, including CTX-M-22 (AY080894), CTX-M-24 (AY143430), CTX-M-29 (AY267213) and CTX-M-32 (AY421962), which are included in GenBank (accession nos in parentheses). The main reason for the prevalence of CTX-M ß-lactamases in China may be the widespread use of certain third generation cephalosporins such as cefotaxime and ceftriaxone, whilst ceftazidime has been less frequently prescribed. Antibiotic selection pressure probably contributes to the increasing prevalence of cefotaxime- and ceftriaxone-hydrolysing CTX-M ß-lactamase in clinical settings. Another consideration may be the prevalence of CTX-M ß-lactamases, including TOHO-1 (Yagi et al., 2000), CTX-M-2, CTX-M-3 (Yamasaki et al., 2003) and CTX-M-14 (Pai et al., 2001), in neighbouring countries such as Japan and Korea, from where they may spread to China through international travel.

In the study, a recombinant plasmid pT948 containing a plasmid-mediated AmpC ß-lactamase gene was obtained from the 95 kb plasmid of a transconjugant. A 6432 bp DNA sequence was obtained by nucleotide sequencing. This fragment contained six ORFs, IS26, orf-2, blaDHA–1, ampR, qacE{Delta}1 and sulI (Fig. 3), which exhibited a high level of identity with pPON-1 of M. morganii (Poirel et al., 1999) and pSAL-1 of S. enteritidis (Verdet et al., 2000) (Fig. 3). The orf-2 in the inserted fragment in this study exhibited 98 % identity with the orf-1 in M. morganii, which is a conserved sequence in Morganella species with an unknown function. Fortineau et al. (2001) suggested that the reason why DHA-1 could be induced might be due to the large-size DNA fragment excised from M. morganii, involving not only ampC but also ampR. The presence of the orf-2 gene in this study indicated further that the plasmid-mediated DHA-1 may originate from the M. morganii chromosome. The qacE{Delta}1 and sulI genes were found in the upstream region of the blaDHA–1 genes. Frequently, these genes were found in the typical 3'-conserved sequence (3'-CS) of integron I. However, we were not able to identify the 5'-conserved sequence (5'-CS) in the upstream region by PCR. IS26 was found downstream of the blaDHA–1 gene; this is commonly related to the transmission of ß-lactamase genes such as CFE-1, ACC-1 and SHV-2a (Kim et al., 2002; Nadjar et al., 2000; Nakano et al., 2004).



View larger version (8K):
[in this window]
[in a new window]
  		Fig. 3. Comparison of the structural genes of (A) pPON-1 (M. morganii), (B) DHA-1 (this study) and (C) pSAL-1 (S. enteritidis).

 

The genotype and phenotype analysis suggested that the six prevalent K. pneumoniae isolates in the hospital originated from one clone. PFGE yielded identical profiles, consisting of 18 bands, when chromosomal DNA of each of the test isolates was digested with XbaI. Each of the six isolates had the same plasmid profile of two plasmids with sizes of 95 kb and 200 kb (Fig. 1). The plasmid profiles of their corresponding transconjugants were also identical. Furthermore, these isolates had similar antibiotic-resistance patterns.

Nucleotide sequence analysis of PCR products confirmed that the 95 kb plasmid in the transconjugants harboured at least four ß-lactamase genes including blaTEM–1, blaSHV–12, blaCTX–M–3 and blaDHA–1. Multi-resistant K. pneumoniae containing plasmids encoding multi-drug-resistance genes have been reported worldwide. The prevalence of such multi-resistant strains in intensive care units is a serious event even though these strains were not found in subsequent surveillance. Carbapenems were the antibiotic of choice for managing these bacteria. Unfortunately, a plasmid-mediated ß-lactamase conferring imipenem resistance has also been reported on the plasmid of K. pneumoniae (Moland et al., 2003; Poirel et al., 2004; Yan et al., 2001). These events must make clinicians highly aware of the problem of antibiotic resistance in K. pneumoniae.


   ACKNOWLEDGEMENTS
TOP
 INTRODUCTION
 METHODS
 RESULTS AND DISCUSSION
 ACKNOWLEDGEMENTS
REFERENCES
 
We are grateful to J. M. Ling, N. W. S. Lo, M. L. Chin and E. W. C. Chan, Department of Microbiology, The Chinese University of Hong Kong, The Prince of Wales Hospital, for technical assistance with plasmid extraction. We also thank B. Rowe, Division of Enteric Pathogens, Central Public Health Laboratory London, UK, for kindly providing the plasmid markers 40R646, 28R823, 40R448, 40R626, 40R268 and RT641. This work was supported in part by grant NSFC30270074 from the National Natural Science Foundation of China.


   REFERENCES
TOP
 INTRODUCTION
 METHODS
 RESULTS AND DISCUSSION
 ACKNOWLEDGEMENTS
 REFERENCES
 

  • Chanawong, A., M'Zali, F. H., Heritage, J., Xiong, J. H. & Hawkey, P. M. (2002). Three cefotaximases, CTX-M-9, CTX-M-13, and CTX-M-14, among Enterobacteriaceae in the People's Republic of China. Antimicrob Agents Chemother 46, 630–637.[Abstract/Free Full Text]

  • Cheng, Y. & Chen, M. (1994). Extended-spectrum ß-lactamases in clinical isolates of Enterobacter gergoviae and Escherichia coli in China. Antimicrob Agents Chemother 38, 2838–2842.[Abstract/Free Full Text]

  • Coudron, P. E., Moland, E. S. & Thomson, K. S. (2000). Occurrence and detection of AmpC beta-lactamases among Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolates at a veterans medical center. J Clin Microbiol 38, 1791–1796.[Abstract/Free Full Text]

  • Essack, S. Y., Hall, L. M. C. & Livermore, D. M. (2004). Klebsiella pneumoniae isolate from South Africa with multiple TEM, SHV and AmpC beta-lactamases. Int J Antimicrob Agents 23, 398–400.[CrossRef][Medline]

  • Fortineau, N., Poirel, L. & Nordmann, P. (2001). Plasmid-mediated and inducible cephalosporinase DHA-2 from Klebsiella pneumoniae. J Antimicrob Chemother 47, 207–210.[Abstract/Free Full Text]

  • Gniadkowski, M., Schneider, I., Palucha, A., Jungwirth, R., Mikiewicz, B. & Bauernfeind, A. (1998). Cefotaxime-resistant Enterobacteriaceae isolates from a hospital in Warsaw, Poland: identification of a new CTX-M-3 cefotaxime-hydrolyzing beta-lactamase that is closely related to the CTX-M-1/MEN-1 enzyme. Antimicrob Agents Chemother 42, 827–832.[Abstract/Free Full Text]

  • Gouby, A., Neuwirth, C., Bourg, G., Bouziges, N., Carles-Nurit, M. J., Despaux, E. & Ramuz, M. (1994). Epidemiological study by pulsed-field gel electrophoresis of an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a geriatric hospital. J Clin Microbiol 32, 301–305.[Abstract/Free Full Text]

  • Hanson, N. D., Thomson, K. S., Moland, E. S., Sanders, C. C., Berthold, G. & Penn, R. G. (1999). Molecular characterization of a multiply resistant Klebsiella pneumoniae encoding ESBLs and a plasmid-mediated AmpC. J Antimicrob Chemother 44, 377–380.[Abstract/Free Full Text]

  • Ji, S. J., Gu, Y. M., Tan, W. T., Wang, D. D., Feng, X. J., Zhou, Z. H., Yu, Y. S., Chen, Y. G. & Li, L. J. (2004). Genotype distribution of extended-spectrum ß-lactamases produced by Escherichia coli and Klebsiella pneumoniae in China. Chin J Lab Med 27, 590–593 (in Chinese).

  • Kado, C. I. & Liu, S. T. (1981). Rapid procedure for detection and isolation of large and small plasmids. J Bacteriol 145, 1365–1373.[Abstract/Free Full Text]

  • Kim, J., Shin, H. S., Seol, S. Y. & Cho, D. T. (2002). Relationship between blaSHV–12 and blaSHV–2a in Korea. J Antimicrob Chemother 49, 261–267.[Abstract/Free Full Text]

  • Lemozy, J., Sirot, D., Chanal, C., Huc, C., Labia, R., Dabernat, H. & Sirot, J. (1995). First characterization of inhibitor-resistant TEM (IRT) ß-lactamases in Klebsiella pneumoniae strains. Antimicrob Agents Chemother 39, 2580–2582.[Abstract]

  • Li, C. R., Li, Y. & Zhang, P. A. (2003). Dissemination and spread of CTX-M extended-spectrum ß-lactamases among clinical isolates of Klebsiella pneumoniae in central China. Int J Antimicrob Agents 22, 521–525.[CrossRef][Medline]

  • Ling, J. M., Lo, N. W. S., Ho, Y. M., Kam, K. M., Hoa, N. T. T., Phi, L. & Cheng, A. F. (2000). Molecular methods for the epidemiological typing of Salmonella enterica serotype Typhi from Hong Kong and Vietnam. J Clin Microbiol 38, 292–300.[Abstract/Free Full Text]

  • Moland, E. S., Hanson, N. D., Herrera, V. L., Black, J. A., Lockhart, T., Hossain, J. A., Johnson, J. A., Goering, R. V. & Thomson, K. S. (2003). Plasmid-mediated, carbapenem-hydrolysing ß-lactamase, KPC-2, in Klebsiella pneumoniae isolates. J Antimicrob Chemother 51, 711–714.[Abstract/Free Full Text]

  • Nadjar, D., Rouveau, M., Verdet, C., Donay, L., Herrmann, J., Lagrange, P. H., Philippon, A. & Arlet, G. (2000). Outbreak of Klebsiella pneumoniae producing transferable AmpC-type ß-lactamase (ACC-1) originating from Hafnia alvei. FEMS Microbiol Lett 187, 35–40.[Medline]

  • Nakano, R., Okamoto, R., Nakano, Y., Kaneko, K., Okitsu, N., Hosaka, Y. & Inoue, M. (2004). CFE-1, a novel plasmid-encoded AmpC-lactamase with an ampR gene originating from Citrobacter freundii. Antimicrob Agents Chemother 48, 1151–1158.[Abstract/Free Full Text]

  • Pai, H., Choi, E. H., Lee, H. J., Hong, J. Y. & Jacoby, G. A. (2001). Identification of CTX-M-14 extended-spectrum beta-lactamase in clinical isolates of Shigella sonnei, Escherichia coli, and Klebsiella pneumoniae in Korea. J Clin Microbiol 39, 3747–3749.[Abstract/Free Full Text]

  • Poirel, L., Guibert, M., Girlich, D., Naas, T. & Nordmann, P. (1999). Cloning, sequence analyses, expression, and distribution of ampC–ampR from Morganella morganii clinical isolates. Antimicrob Agents Chemother 43, 769–776.[Abstract/Free Full Text]

  • Poirel, L., Héritier, C., Tolün, V. & Nordmann, P. (2004). Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother 48, 15–22.[Abstract/Free Full Text]

  • Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.

  • Tenover, F. C., Arbeit, R. D., Goering, R. V., Mickelsen, P. A., Murray, B. E., Persing, D. H. & Swaminathan, B. (1995). Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33, 2233–2239.[Medline]

  • Verdet, C., Arlet, G., Barnaud, G., Lagrange, P. H. & Philippon, A. (2000). A novel integron in Salmonella enterica serovar Enteriditis, carrying the blaDHA–1 gene and its regulator gene ampR, originated from Morganella morganii. Antimicrob Agents Chemother 44, 222–225.[Abstract/Free Full Text]

  • Wang, H., Kelkar, S., Wu, W., Chen, M. & Quinn, J. P. (2003). Clinical isolates of Enterobacteriaceae producing extended-spectrum beta-lactamases: prevalence of CTX-M-3 at a hospital in China. Antimicrob Agents Chemother 47, 790–793.[Abstract/Free Full Text]

  • Yagi, T., Kurokawa, H., Shibata, N., Shibayama, K. & Arakawa, Y. (2000). A preliminary survey of extended-spectrum beta-lactamases (ESBLs) in clinical isolates of Klebsiella pneumoniae and Escherichia coli in Japan. FEMS Microbiol Lett 184, 53–56.[Medline]

  • Yamasaki, K., Komatsu, M., Yamashita, T. & 7 other authors (2003). Production of CTX-M-3 extended-spectrum ß-lactamase and IMP-1 metallo ß-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/Free Full Text]

  • Yan, J. J., Ko, W. C. & Wu, J. J. (2001). Identification of a plasmid encoding SHV-12, TEM-1, and a variant of IMP-2 metallo-ß-lactamase, IMP-8, from a clinical isolate of Klebsiella pneumoniae. Antimicrob Agents Chemother 45, 2368–2371.[Abstract/Free Full Text]

  • Yan, J. J., Ko, W. C., Jung, Y. C., Chuang, C. L. & Wu, J. J. (2002). Emergence of Klebsiella pneumoniae isolates producing inducible DHA-1 beta-lactamase in a university hospital in Taiwan. J Clin Microbiol 40, 3121–3126.[Abstract/Free Full Text]




    This article has been cited by other articles:


    		Home page
    		 Antimicrob. Agents Chemother.Home page
    Q. Wu, Y. Zhang, L. Han, J. Sun, and Y. Ni
    Plasmid-Mediated 16S rRNA Methylases in Aminoglycoside-Resistant Enterobacteriaceae Isolates in Shanghai, China
    Antimicrob. Agents Chemother., January 1, 2009; 53(1): 271 - 272.
    [Abstract] [Full Text] [PDF]

    		Home page
    		 J. Clin. Microbiol.Home page
    Y. Li, Q. Li, Y. Du, X. Jiang, J. Tang, J. Wang, G. Li, and Y. Jiang
    Prevalence of Plasmid-Mediated AmpC {beta}-Lactamases in a Chinese University Hospital from 2003 to 2005: First Report of CMY-2-Type AmpC {beta}-Lactamase Resistance in China
    J. Clin. Microbiol., April 1, 2008; 46(4): 1317 - 1321.
    [Abstract] [Full Text] [PDF]

    		Home page
    		 Proc. Natl. Acad. Sci. USAHome page
    S. A. Lujan, L. M. Guogas, H. Ragonese, S. W. Matson, and M. R. Redinbo
    Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase
    PNAS, July 24, 2007; 104(30): 12282 - 12287.
    [Abstract] [Full Text] [PDF]

    		Home page
    		 Antimicrob. Agents Chemother.Home page
    C. Verdet, Y. Benzerara, V. Gautier, O. Adam, Z. Ould-Hocine, and G. Arlet
    Emergence of DHA-1-Producing Klebsiella spp. in the Parisian Region: Genetic Organization of the ampC and ampR Genes Originating from Morganella morganii
    Antimicrob. Agents Chemother., February 1, 2006; 50(2): 607 - 617.
    [Abstract] [Full Text] [PDF]

    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
    Right arrow Citation Map
    Services
    Right arrow Email this article to a friend
    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 arrow reprints & permissions
    Citing Articles
    Right arrow Citing Articles via HighWire
    Right arrow Citing Articles via CrossRef
    Right arrow Citing Articles via Google Scholar
    Google Scholar
    Right arrow Articles by Wei, Z.-Q.
    Right arrow Articles by Li, L.-J.
    Right arrow Search for Related Content
    PubMed
    Right arrow PubMed Citation
    Right arrow Articles by Wei, Z.-Q.
    Right arrow Articles by Li, L.-J.
    Agricola
    Right arrow Articles by Wei, Z.-Q.
    Right arrow Articles by Li, L.-J.

    HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
    INT J SYST EVOL MICROBIOL J MED MICROBIOL MICROBIOLOGY J GEN VIROL ALL SGM JOURNALS