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Epidemiology

Emergence of Klebsiella pneumoniae Isolates Producing Inducible DHA-1 β-Lactamase in a University Hospital in Taiwan

Jing-Jou Yan, Wen-Chien Ko, Yun-Chih Jung, Chin-Luan Chuang, Jiunn-Jong Wu
Jing-Jou Yan
1Departments of Pathology
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Wen-Chien Ko
2Internal Medicine
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Yun-Chih Jung
3Department of Pathology, Sinlau Christian Hospital, Tainan, Taiwan
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Chin-Luan Chuang
1Departments of Pathology
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Jiunn-Jong Wu
4Medical Technology, College of Medicine, National Cheng Kung University
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  • For correspondence: jjwu@mail.ncku.edu.tw
DOI: 10.1128/JCM.40.9.3121-3126.2002
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ABSTRACT

Ten nonrepetitive clinical isolates of Klebsiella pneumoniae exhibiting an unusual inducible β-lactam resistance phenotype were identified between January 1999 and September 2001 in a university hospital in Taiwan. In the presence of 2 μg of clavulanic acid, the isolates showed a one to four twofold concentration increase in the MICs of ceftazidime, cefotaxime, and aztreonam but remained susceptible to cefepime (MICs, ≤0.5 μg/ml) and imipenem (MICs, ≤0.5 μg/ml). PCR, sequence analysis, and isoelectric focusing revealed production by these isolates of TEM-1, SHV-11, and DHA-1, a plasmid-encoded inducible AmpC β-lactamase originally found in a Salmonella enterica serovar Enteritidis strain. Transfer of the resistance by conjugation experiments was not successful, but Southern hybridization showed that blaDHA-1 was located on 70-kb plasmids, suggesting that the blaDHA-1-containing plasmids in the K. pneumoniae isolates were non-self-transmissible. Five isolates were recovered from patients in two surgery wards and two intensive care units. Acquisition of the DHA-1 producers could be traced back to previous hospitalizations 1 to 5 months earlier for the other five patients. Six and seven patterns among the isolates were demonstrated by plasmid analysis and ribotyping, respectively, indicating that the spread of the DHA-1 producers was due to both horizontal transfer of blaDHA-1 and dissemination of endemic clones.

Chromosome-mediated AmpC β-lactamases have been described in a wide variety of gram-negative bacilli, such as Pseudomonas aeruginosa and Enterobacter spp. (8, 15, 16, 25). In most genera of the family Enterobacteriaceae, AmpC is inducible and, when overexpressed, can confer resistance to both oxyimino- and 7-α-methoxy-cephalosporins and monobactams (8, 15, 25). Many plasmid-mediated AmpC enzymes, such as CMY-type β-lactamases, have been found in bacterial species that naturally lack a chromosomal AmpC β-lactamase, such as Klebsiella pneumoniae, Proteus mirabilis, and Salmonella spp. (2, 4-6, 10-14, 21, 28, 30). It is believed that such β-lactamases arose through the transfer of chromosomal AmpC genes onto plasmids (21).

Unlike chromosome-mediated AmpC, plasmid-encoded AmpC enzymes are almost always expressed constitutively (4-6, 11-14, 21, 30). Plasmid-mediated inducible β-lactamases are extremely rare. DHA-1 from a clinical isolate of Salmonella enterica serovar Enteritidis from Saudi Arabia is the first identified plasmid-encoded inducible cephalosporinase (2). The counterpart of blaDHA-1 was the chromosomal AmpC gene of Morganella morganii (3, 22). The inducibility of DHA-1 is due to the presence of a regulator ampR gene, which is also related to that of M. morganii, upstream of blaDHA-1 on the same plasmid (2, 22, 29). A DHA-1-related β-lactamase, named DHA-2, was identified more recently from a K. pneumoniae isolate in France (10). The enzyme also confers an inducible β-lactam resistance phenotype.

Recently, the standard confirmatory test for the detection of extended-spectrum β-lactamases (19) revealed an unusual ceftazidime and cefotaxime resistance phenotype in clinical isolates of K. pneumoniae in a university hospital in Taiwan. Thus, a retrospective analysis was carried out to characterize these isolates and their various clinical and epidemiological features. We found inducible expression of DHA-1 by these isolates. To our knowledge, this is the first report of the appearance of DHA-1 in the Far East and is also the first report of fairly widespread of DHA-1-producing K. pneumoniae within a health care institution.

MATERIALS AND METHODS

Bacterial isolates and patients.The standard screening and confirmation methods for the detection of extended-spectrum β-lactamases (19) were routinely performed at the Department of Pathology, National Cheng Kung University Hospital, a 900-bed teaching hospital in southern Taiwan. Between January 1999 and September 2001, 10 nonrepetitive isolates of K. pneumoniae from 10 patients demonstrated reduced inhibition zone diameters for both ceftazidime and cefotaxime in combination with clavulanic acid versus those for ceftazidime and cefotaxime when tested alone (see Table 1), suggesting production of β-lactamases induced by clavulanic acid. All these isolates were identified by conventional techniques (9) and/or the API 20E system (bioMérieux, Marcy l'Etoile, France). The medical records of the patients from whom the isolates were recovered were reviewed.

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TABLE 1.

Susceptibility patterns of DHA-1-producing K. pneumoniae isolatesa

Antagonism testing.The disk antagonism method initially used to detect inducibility of chromosomal β-lactamases (16) was performed with a slight modification to test the 10 K. pneumoniae isolates. Disks of inducing agents and disks of cephalosporins were placed on the surface of Mueller-Hinton agar plates and separated by 25 mm (see Fig. 1). The cephalosporins used were cefotaxime, ceftazidime, aztreonam, and cefepime. Clavulanic acid (10 μg) and cefoxitin (30 μg) were used as inducing agents. The plates were examined after overnight incubation at 37°C.

FIG. 1.
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FIG. 1.

Double-disk antagonism tests with 30 μg of cefoxitin (A) and 10 μg of clavulanic acid (B). ATM, aztreonam; CAZ, ceftazidime; CLA, clavulanic acid; CTX, cefotaxime; FEP, cefepime; FOX, cefoxitin.

Susceptibility testing.MICs were determined by the standard agar dilution method (18). The antimicrobial agents and their sources were as follows: amoxicillin and clavulanic acid, SmithKline Beecham Pharmaceuticals, Surrey, United Kingdom; aztreonam and cefepime, Bristol-Myers Squibb, New Brunswick, N.J.; cefotaxime, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, N.J.; cefoxitin, Sigma Chemical Company, St. Louis, Mo.; ceftazidime, Glaxo Group Research Ltd., Greenford, United Kingdom; and imipenem, Merck Sharp & Dohme, West Point, Pa. The susceptibilities to six non-β-lactam agents were determined by the standard disk diffusion method (19). Antimicrobial disks were obtained from Becton Dickinson Microbiology Systems, Cockeysville, Md., including amikacin, ciprofloxacin, gentamicin, ofloxacin, tobramycin, and trimethoprim-sulfamethoxazole.

IEF.Crude preparations of β-lactamases were obtained from the isolates by sonication (7) and subjected to analytical isoelectric focusing (IEF) as described previously (17, 30). Cells induced by 16 μg of cefoxitin per ml were incubated for 3 h before harvesting (2). β-Lactamase activity was detected by overlaying the gels with 0.5 mM nitrocefin in 0.1 M phosphate buffer, pH 7.0.

PCR and DNA sequencing.Plasmids from the isolates were extracted by a rapid alkaline lysis procedure (27) and used as templates in PCRs. The entire blaDHA-1 gene was amplified with the oligonucleotide primers DHA-1A (5′-CTGATGAAAAAATCGTTATC-3′) and DHA-1B (5′-ATTCCAGTGCACTCAAAATA-3′), corresponding to nucleotides −3 to 17 and 1138 to 1119, respectively, of the DHA-1 structural gene (2). The PCR conditions were as follows: 3 min at 94°C; 35 cycles of 1 min at 94°C, 1 min at 55°C, and 1 min at 72°C; and finally 7 min at 72°C. The entire sequences of blaTEM- and blaSHV-related genes were amplified with the primer pairs as described previously (30). The amplicons were purified with a commercial kit (Roche Molecular Biochemicals, Mannheim, Germany) and sequenced on an ABI Prism 310 sequencer analyzer (Applied Biosystems, Foster City, Calif.).

Transfer of resistance.Conjugation experiments were performed as described previously (24, 30) with streptomycin-resistant Escherichia coli C600 as the recipient (1). Tryptic soy agar plates supplemented with 500 μg of streptomycin (Sigma) per ml and 64 μg of cefoxitin per ml were used to select the transconjugants. K. pneumoniae strain W142 harboring blaCMY-8 was used as the control (30).

Plasmid analysis and Southern hybridization.Plasmids from the isolates were analyzed by electrophoresis on a 0.8% agarose gel. E. coli strain NCTC 50192 (National Collection of Type Cultures, London, United Kingdom), which contained four plasmids of 7, 36.3, 63.8, and 148.5 kb, was used as a source of molecular size markers. The gel was stained with ethidium bromide (Sigma), visualized under UV light, and subjected to Southern hybridization according to the original protocol (26). The blaDHA-1-specific probe was a PCR-generated amplicon labeled with [α-32P]dCTP (Amersham Pharmacia Biotech) by the random priming technique with a commercial kit (Gibco-BRL Life Technologies, Gaithersburg, Md.).

Ribotyping.The chromosomal DNA of the isolates was extracted and purified as described previously (23). The genomic DNA was restricted with EcoRI or BstEII (Roche Molecular Biochemicals) (20). The digests of chromosomal DNA were electrophoresed at 35 V for 18 h in a 0.8% agarose gel, transferred to a nylon membrane (Amersham Pharmacia Biotech), and then hybridized with a [α-32P]dCTP-labeled cDNA copy of E. coli rRNA (Roche Molecular Biochemicals) obtained by reverse transcription with avian myeloblastosis virus reverse transcriptase (Gibco-BRL) as described previously (23).

RESULTS

Inducibility of β-lactamases.In the standard extended-spectrum β-lactamases confirmatory test, the reduced zone diameters for ceftazidime and cefotaxime in combination with clavulanic acid versus those for ceftazidime and cefotaxime tested alone among the 10 K. pneumoniae isolates ranged from 2 to 10 mm (mean, 5.6 mm) and 3 to 8 mm (mean, 5.6 mm), respectively, suggesting production of β-lactamases induced by clavulanic acid (Table 1). Inducibility of the β-lactamases was further recognized by the disk antagonism test, which demonstrated blunting of the cephalosporin disks adjacent to the cefoxitin and clavulanic acid disks (Fig. 1).

Susceptibility testing.The results of the susceptibility tests are shown in Table 1. All 10 isolates exhibited high-level resistance to amoxicillin-clavulanic acid and cefoxitin. In the presence of clavulanic acid, a one to four twofold concentration increase in the MICs of ceftazidime, cefotaxime, and aztreonam was noted, while the changes after addition of clavulanic acid in the MICs of cefepime and imipenem were not obvious.

Identification of β-lactamases.IEF demonstrated that all 10 isolates displayed three bands of β-lactamase activity with pIs of 5.4, 7.6, and 7.8. The pI 7.6 band probably represented the chromosomal SHV-1 or SHV-11 type β-lactamase of K. pneumoniae (15, 30), the pI 5.4 band might represent the TEM-1 β-lactamase (15), and the pI 7.8 band might represent the β-lactamase responsible for the inducible resistance phenotype.

A 1,141-bp fragment was amplified by PCR with the blaDHA-1-specific primers for all 10 K. pneumoniae isolates. The amino acid sequences of the PCR products deduced from the sequence analysis were identical to the plasmid-mediated cephalosporinase DHA-1 from S. enterica serovar Enteritidis (2). The DHA-1 cephalosporinase was consistent with the pI 7.8 β-lactamase demonstrated by IEF (2). All the isolates also carried blaTEM-1 and blaSHV-11, which were identified by PCR with the blaTEM- and blaSHV-specific primers and sequence analysis.

Conjugation experiments and plasmid analysis.Conjugation experiments failed to demonstrate transfer of inducible cephalosporin resistance from any of the isolates. Cefoxitin resistance was transferred from the control strain to E. coli C600 at a frequency of 10−3 to 10−4 per donor cell. Six different profiles were demonstrated by plasmid analysis among the 10 isolates (Fig. 2). In all isolates analyzed, the presence of a plasmid of approximately 70 kb was detected. Southern hybridization with the blaDHA-1-specific probe showed that blaDHA-1 was located on the 70-kb plasmid (data not shown).

FIG. 2.
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FIG. 2.

Plasmid profiles of the 10 K. pneumoniae isolates. Lanes 1 to 10, isolates 387, 416, 1490, 1596, 197, 274, 281, 325, 397, and 1067, respectively; lane M, E. coli NCTC 50192, which contains four plasmids with molecular sizes of 7, 36.2, 63.8, and 148.5 kb.

Ribotyping.The genetic relationship among the 10 K. pneumoniae isolates was investigated by ribotyping with two different endonucleases. Patterns with at least two discordant bands were considered different (20). The results are listed in Table 2 and partially shown in Fig. 3. Both EcoRI and BstEII generated seven different patterns. Isolates 1490 and 1596, both of which were collected in early 2000, and isolates 197, 274, and 281, which were all collected in late 2000, had identical ribotypes, suggesting that they derived from two endemic clones.

FIG. 3.
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FIG. 3.

Ribotypes generated by EcoRI. Lane 1, molecular size marker kit II (Roche Molecular Biochemicals); lanes 2 to 11, isolates 387, 416, 1490, 1596, 197, 274, 281, 325, 397, and 1067, respectively; lane 12, 1-kb ladder (Promega Co., Madison, Wis.).

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TABLE 2.

Clinical data, plasmid profiles, and ribotypes of the 10 DHA-1-producing K. pneumoniae isolates

Clinical characteristics.Three isolates were recovered from sputum samples and were considered colonizers. The other seven isolates were associated with three urinary tract infections, two wound infections, one intra-abdominal infection, and one bloodstream infection. The clinical characteristics of the patients infected with or colonized by the DHA-1-producing isolates are summarized in Table 2. Six patients had undergone hemodialysis due to either chronic or acute renal failure before isolation. Five isolates were obtained >48 h after the patients were admitted to the hospital. Three of the five isolates were from the patients in the surgery wards, and two isolates were from the patients in the intensive care units. Although the remaining five isolates were obtained within 48 h after the current admission, all patients with these isolates had been hospitalized in the teaching hospital 1 to 5 months earlier. Notably, four of them had been on hemodialysis either in the university hospital or at community hospitals.

All nine patients for whom complete medical records were available had been exposed to β-lactam agents within 2 weeks before isolation of the DHA-1 producers. Patients 3, 4, 6, and 8 received no specific antimicrobial agents for the DHA-1 producers, and patient 7 was not treated for the urinary tract infection at the university hospital. Patients 2 and 9 received ciprofloxacin and trimethoprim-sulfamethoxazole, respectively, for 2 weeks, and the K. pneumoniae strains were not isolated from urine samples afterward. Patient 1 had received cefotaxime and ciprofloxacin, but his deep soft tissue infection was not eradicated until debridement was performed 1 month after admission. Patient 5 received cefotaxime after isolation and died of intra-abdominal hemorrhages and multiorgan failure due to his underlying diseases 1 week later. Whether the bacterial peritonitis was persistent before his death is not clear. Patient 10 was cured of the bloodstream infection with 2 weeks of meropenem and netilmicin therapy. Five patients died during hospitalization, and patient 7 died during the other hospitalization; however, none of the deaths were directly due to infections caused by the DHA-1 producers.

DISCUSSION

The plasmid-mediated inducible DHA-1 β-lactamase was first identified in Taiwan in the present study. PCR, sequence analysis, and IEF revealed production of three β-lactamases, TEM-1, SHV-11, and DHA-1, by all 10 K. pneumoniae isolates possessing inducible resistance to extended-spectrum β-lactamases. TEM-1 and SHV-11 are restricted-spectrum β-lactamases. Since DHA-1, originally found in an S. enterica serovar Enteritidis strain was inducible (2), the enzyme is believed to be responsible for the unusual inducible β-lactam resistance phenotype of our isolates. Transfer of the resistance by conjugation experiments was not successful; however, the blaDHA-1-specific probe was hybridized to a 70-kb plasmid in all isolates analyzed, suggesting that blaDHA-1 was on non-self-transmissible plasmids. Similar results have been described in reports of DHA-1-producing S. enterica serovar Enteritidis and DHA-2-producing K. pneumoniae (2, 10). To our knowledge, plasmid-mediated DHA-type β-lactamases have only been reported in isolates from Europe and the Middle East (2, 10, 29). Thus, this is also the first report of the appearance of a DHA-type β-lactamase in the Far East.

In the extended-spectrum β-lactamases confirmatory test, all K. pneumoniae isolates revealed decreased inhibition zone diameters for ceftazidime and cefotaxime in combination with clavulanic acid compared with those of these two agents tested alone, indicating that the test could also be used to screen for inducible β-lactamase-producing gram-negative bacilli that naturally lack inducible chromosome-mediated AmpC enzymes. All 10 K. pneumoniae isolates showed blunting of the cephalosporin disks adjacent to the cefoxitin and clavulanic acid disks in the antagonism test, indicating that the test can also be used to recognize plasmid-mediated β-lactamases.

In the Enterobacteriaceae, AmpC-hyperproducing derepressed strains appear frequently in infections caused by organisms naturally producing inducible AmpC enzymes when patients are treated with extended-spectrum β-lactams (16). Therefore, it has been recommended that the inducible-AmpC-producing Enterobacteriaceae species should be reported as resistant to all extended-spectrum β-lactams (16). The use of extended-spectrum β-lactams should be restricted accordingly. Studies on determining the therapeutic success or failure of extended-spectrum third-generation cephalosporins in treating infections with plasmid-mediated inducible AmpC producers, such as our DHA-1-producing K. pneumoniae isolates, are lacking. Therefore, whether such K. pneumoniae strains, like gram-negative organisms naturally producing inducible AmpC enzymes, should also be reported as resistant to all third-generation cephalosporins is not known and deserves further investigation.

The drugs of choice for the treatment of infections with such organisms are also undetermined. Based on MIC data (Table 1) and the confirmatory test for extended-spectrum β-lactamases, a majority of the DHA-1-producing K. pneumoniae isolates would not have been reported as resistant to all third-generation cephalosporins. However, after induction by clavulanic acid, these isolates showed reduced susceptibilities to these agents. Moreover, all these isolates remained susceptible to cefepime and imipenem even in the presence of clavulanic acid. Thus, fourth-generation cephalosporins and carbapenems could be better choices for the treatment of infections caused by DHA-1 producers. Alternatively, when the presence of inducible DHA-type enzymes is suspected or detected, physicians should be informed, and the use of strong AmpC-inducing agents, such as clavulanic acid and cephamycins, should be avoided.

Six plasmid patterns and seven ribotypes were found among the 10 DHA-1-producing isolates (Fig. 2 and 3), indicating that the spread of blaDHA-1 was due to both dissemination of endemic clones and horizontal transfer of the resistance gene. Most isolates in the university hospital were obtained from surgery wards and intensive care units. Five isolates were obtained within 48 h after admission; however, all patients from whom the isolates were obtained had been hospitalized in the same university hospital 1 to 5 months before the current admissions. It is not known exactly whether these isolates were from the university medical center or other hospitals. However, since isolates 274 and 281 had a ribotype identical to that of isolate 197, which was obviously from the university hospital, it is very likely that at least patients 6 and 7 had acquired the resistance strain during previous hospitalizations. Six of the 10 patients infected with DHA-1 producers had been on hemodialysis. Since this was a retrospective study, it is not clear whether the nosocomial infections were associated with the hemodialysis systems.

In conclusion, sporadic infections with K. pneumoniae possessing an unusual inducible β-lactam resistance phenotype were found in a university hospital in Taiwan. DHA-1 encoded by non-self-transferable plasmids conferred the resistance phenotype. The spread of the DHA-1 producers was due to dissemination of endemic clones and horizontal transfer of the resistance gene.

ACKNOWLEDGMENTS

This work was partially supported by grants DOH91-DC1050 from the Center for Disease Control, the Department of Health, the Executive Yuan, and NSC 91-2314-B-006-002 from the National Science Council, Taiwan.

FOOTNOTES

    • Received 26 March 2002.
    • Returned for modification 25 May 2002.
    • Accepted 22 June 2002.
  • Copyright © 2002 American Society for Microbiology

REFERENCES

  1. 1.↵
    Bachmann, B. J., and K. B. Low. 1980. Linkage map of Escherichia coli K-12, edition 6. Microbiol. Rev.44:1451-1456.
    OpenUrl
  2. 2.↵
    Barnaud, G., G. Arlet, C. Verdet, O. Gaillot, P. H. Lagrange, and A. Philippon. 1998. Salmonella enteritidis: AmpC plasmid-mediated inducible β-lactamase (DHA-1) with an ampR gene from Morganella morganii. Antimicrob. Agents Chemother.42:2352-2358.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    Barnaud, G., G. Arlet, C. Danglot, and A. Philippon. 1997. Cloning and sequencing of the gene encoding the AmpC β-lactamase of Morganella morganii. FEMS Microbiol. Lett.148:15-20.
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    Bauernfeind, A., I. Stemplinger, R. Jungwirth, R. Wilhelm, and Y. Chong. 1996. Comparative characterization of the cephamycinase blaCMY-1 gene and its relationship with other β-lactamase genes. Antimicrob. Agents Chemother.40:1926-1930.
    OpenUrlAbstract/FREE Full Text
  5. 5.
    Bauernfeind, A., I. Stemplinger, R. Jungwirth, and H. Giamarellou. 1996. Characterization of the plasmidic β-lactamase CMY-2, which is responsible for cephamycin resistance. Antimicrob. Agents Chemother.40:221-224.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    Bauernfeind, A., I. Schneider, R. Jungwirth, H. Sahly, and U. Ullmann. 1999. A novel type of AmpC β-lactamase, ACC-1, produced by a Klebsiella pneumoniae strain causing nosocomial pneumonia. Antimicrob. Agents Chemother.43:1924-1931.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    Bauernfeind, A., H. Grimm, and S. Schweighart. 1990. A new plasmidic cefotaximase in a clinical isolate of Escherichia coli. Infection18:294-298.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    Bush, K., G. A. Jacoby, and A. A. Medeiros. 1995. A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother.39:1211-1233.
    OpenUrlFREE Full Text
  9. 9.↵
    Farmer, J. J., III. 1995. Enterobacteriaceae: introduction and identification, p. 438-449. In P. R. Murray, E. J. Baron, M. A. Pfaller, F. C. Tenover, and R. H. Yolken (ed.), Manual of clinical microbiology, 6th ed. American Society for Microbiology, Washington, D.C.
  10. 10.↵
    Fortineau, N., L. Poirel, and P. Nordmann. 2001. Plasmid-mediated and inducible cephalosporinase DHA-2 from Klebsiella pneumoniae. J. Antimicrob. Chemother.47:207-210.
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.↵
    Gazouli, M., L. S. Tzouvelekis, A. C. Vatopoulos, and E. Tzelepi. 1998. Transferable class C β-lactamases in Escherichia coli strains isolated in Greek hospitals and characterization of two enzyme variants (LAT-3 and LAT-4) closely related to Citrobacter freundii AmpC β-lactamase. J. Antimicrob. Chemother.42:419-425.
    OpenUrlCrossRefPubMedWeb of Science
  12. 12.
    Gonzales Leiza, M., J. C. Perez-Diaz, J. Ayala, J. M. Casellas, J. Martinez-Beltran, K. Bush, and F. Baquero. 1994. Gene sequence and biochemical characterization of FOX-1 from Klebsiella pneumoniae, a new AmpC-type plasmid-mediated β-lactamase with two molecular variants. Antimicrob. Agents Chemother.38:2150-2157.
    OpenUrlAbstract/FREE Full Text
  13. 13.
    Horii, T., Y. Arakawa, M. Ohta, T. Sugiyama, R. Wacharotayankun, H. Ito, and N. Kato. 1994. Characterization of a plasmid-borne and constitutively expressed blaMOX-1 gene encoding AmpC-type β-lactamase. Gene139:93-98.
    OpenUrlCrossRefPubMedWeb of Science
  14. 14.↵
    Koeck, J. L., G. Arlet, A. Philippon, S Basmaciogullari, H. V. Thien, Y. Buisson, and J.-D. Cavallo. 1997. A plasmid-mediated CMY-2 β-lactamase from an Algerian clinical isolate of Salmonella senftenberg. FEMS Microbiol. Lett.152:255-260.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    Livermore, D. M. 1995. β-Lactamases in laboratory and clinical resistance. Clin. Microbiol. Rev.34:557-584.
    OpenUrl
  16. 16.↵
    Livermore, D. M., and D. F. J. Brown. 2001. Detection of β-lactamase-mediated resistance. J. Antimicrob. Chemother.48(Suppl. S1):59-64.
    OpenUrlCrossRefPubMedWeb of Science
  17. 17.↵
    Matthew, M., M. Harris, M. J. Marshall, and G. W. Rose. 1975. The use of analytical isoelectric focusing for detection and identification of β-lactamases. J. Gen. Microbiol.88:169-178.
    OpenUrlPubMed
  18. 18.↵
    National Committee for Clinical Laboratory Standards. 2000. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 5th ed. Approved standard M7-A5. National Committee for Clinical Laboratory Standards, Wayne, Pa.
  19. 19.↵
    National Committee for Clinical Laboratory Standards. 2000. Performance standards for antimicrobial disk susceptibility tests, 7th ed. Approved standard M2-A7. National Committee for Clinical Laboratory Standards, Wayne, Pa.
  20. 20.↵
    Pai, H., S. Lyu, J. H. Lee, J. Kim, Y. Kwon, J.-W. Kim, and K. W. Choe. 1999. Survey of extended-spectrum β-lactamases in clinical isolates of Escherichia coli and Klebsiella pneumoniae: prevalence of TEM-52 in Korea. J. Clin. Microbiol.37:1758-1763.
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    Philippon, A., G. Arlet, and G. A. Jacoby. 2002. Plasmid-determined AmpC-type β-lactamases. Antimicrob. Agents Chemother.46:1-11.
    OpenUrlFREE Full Text
  22. 22.↵
    Poirel, L., M. Guibert, D. Girlich, T. Naas, and P. Nordmann. 1999. Cloning, sequence analyses, expression, and distribution of ampC-ampR from Morganella morganii clinical isolates. Antimicrob. Agents Chemother.43:769-776.
    OpenUrlAbstract/FREE Full Text
  23. 23.↵
    Popovic, T., C. A. Bopp, Ø. Olsvik, and J. A. Kiehlbauch. 1993. Ribotyping in molecular epidemiology, p. 573-594. In D. H. Persing, T. F. Smith, F. C. Tenover, and T. J. White (ed.), Diagnostic molecular microbiology: principles and applications. American Society for Microbiology, Washington, D.C.
  24. 24.↵
    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.
  25. 25.↵
    Sanders, C. C. 1987. Chromosomal cephalosporinases responsible for multiple resistance to newer β-lactam antibiotics. Annu. Rev. Microbiol.41:573-593.
    OpenUrlCrossRefPubMedWeb of Science
  26. 26.↵
    Southern, E. M. 1975. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol.98:503-517.
    OpenUrlCrossRefPubMedWeb of Science
  27. 27.↵
    Takahashi, S., and Y. Nagano. 1984. Rapid procedure for isolation of plasmid DNA and application to epidemiological analysis. J. Clin. Microbiol.20:608-613.
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    Thomson, K. S. 2001. Controversies about extended-spectrum and AmpC beta-lactamases. Emerg. Infect. Dis.7:333-336.
    OpenUrlCrossRefPubMedWeb of Science
  29. 29.↵
    Verdet, C., G. Arlet, G. Barnaud, P. H. Lagrange, and A. Philippon. 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.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    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 β-lactamase and identification of a novel AmpC enzyme (CMY-8) in southern Taiwan. Antimicrob. Agents Chemother.44:1438-1442.
    OpenUrlAbstract/FREE Full Text
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Emergence of Klebsiella pneumoniae Isolates Producing Inducible DHA-1 β-Lactamase in a University Hospital in Taiwan
Jing-Jou Yan, Wen-Chien Ko, Yun-Chih Jung, Chin-Luan Chuang, Jiunn-Jong Wu
Journal of Clinical Microbiology Sep 2002, 40 (9) 3121-3126; DOI: 10.1128/JCM.40.9.3121-3126.2002

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Emergence of Klebsiella pneumoniae Isolates Producing Inducible DHA-1 β-Lactamase in a University Hospital in Taiwan
Jing-Jou Yan, Wen-Chien Ko, Yun-Chih Jung, Chin-Luan Chuang, Jiunn-Jong Wu
Journal of Clinical Microbiology Sep 2002, 40 (9) 3121-3126; DOI: 10.1128/JCM.40.9.3121-3126.2002
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KEYWORDS

Anti-Bacterial Agents
Bacterial Proteins
Hospitals, University
Klebsiella Infections
Klebsiella pneumoniae
beta-lactamases

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