Skip to main content
PMC home page
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1998 Oct;36(10):3105–3110. doi: 10.1128/jcm.36.10.3105-3110.1998

Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Strains Causing Nosocomial Outbreaks of Infection in the United Kingdom

Kevin Shannon 1,*, Paul Stapleton 1, Xiaoqin Xiang 1,†, Alan Johnson 2, Hamish Beattie 2, Fatima El Bakri 2,‡, Barry Cookson 2, Gary French 1
PMCID: PMC105128  PMID: 9738084

Abstract

Representative isolates from 10 distinct extended-spectrum β-lactamase-producing strains of Klebsiella pneumoniae that caused hospital outbreaks in the United Kingdom from 1991 to 1994 were examined for relationships between their enzymes and plasmids. The β-lactamases were identified by a combination of isoelectric focusing and gene sequencing. SHV-2 β-lactamase was produced by isolates from four outbreaks, SHV-5 was involved in three, and SHV-4, TEM-15, and TEM-26 were involved in one outbreak each. All of the extended-spectrum β-lactamases were encoded by self-transmissible plasmids, with sizes ranging from about 70 to 160 kb. No similarities between the restriction digest patterns of the extended-spectrum β-lactamase-encoding plasmids were detected, except to some extent between those that produced TEM-15 and TEM-26. Thus, outbreaks of hospital infection with these organisms in the United Kingdom from 1991 to 1994 involved distinct organisms and resistance plasmids and appeared to be unrelated.

Members of the family Enterobacteriaceae expressing extended-spectrum β-lactamases conferring resistance to ceftazidime and other cephalosporins and derived from TEM-1 or SHV-1 enzymes (15) have become an increasing problem during the past two decades. During the 1980s, occurrences were rare and most reports involved single isolates (32), although there were a few outbreaks, most notably of TEM-3-producing Klebsiella pneumoniae in France (38). However, in the 1990s there have been many outbreak reports, most frequently of single strains of Klebsiella spp., including SHV-5-producing Klebsiella strains, in Australia (25), Germany (3), Austria (33), Great Britain (10), Italy (31), and the United States (27, 41). In addition, an SHV-5-encoding plasmid has spread among several strains of Klebsiella in Greece (21) and Austria, where three outbreaks caused by distinguishable klebsiellae carrying the same plasmid were reported (33). Other outbreaks have included SHV-3-producing Klebsiella in Great Britain (17), Klebsiella and other Enterobacteriaceae producing the related β-lactamases TEM-10B, TEM-12B, and TEM-26B in Great Britain (13), Klebsiella producing an extended-spectrum β-lactamase that was not identified but that spread between two hospitals in Great Britain (9), SHV-3- and SHV-4-producing klebsiellae in France (2, 4, 7, 28), TEM-26-producing K. pneumoniae in the United States (27, 40), and TEM-10-plus-TEM-12-producing K. pneumoniae in the United States (6). Thus, no single extended-spectrum β-lactamase has predominated. However, interhospital spread of extended-spectrum β-lactamase-producing K. pneumoniae has been demonstrated in the United States (24).

Since 1991, outbreaks of infection or colonization with distinct strains of cephalosporin-resistant K. pneumoniae have occurred in a number of hospitals in the United Kingdom, in addition to those already reported (9, 10, 13, 17). The epidemiology of a number of these outbreaks is to be described by other workers (18a).

Organisms, outbreaks, and susceptibility.

In the present study, representative isolates of 10 distinct strains of cephalosporin-resistant K. pneumoniae producing hospital outbreaks in the United Kingdom between 1991 and 1994 were investigated to determine the relationships between their extended-spectrum β-lactamases and the plasmids encoding them. These organisms had been submitted to the Central Public Health Laboratory by hospitals who had epidemiological evidence of clinical outbreaks. All the outbreaks had been characterized by capsular serotyping and either bacteriophage typing or DNA fingerprinting by pulsed-field gel electrophoresis in the Laboratory of Hospital Infection. The isolates chosen for study were representative of the outbreaks and were distinct from each other by the typing methods used (18a).

MICs were determined by broth or agar dilution in Iso-Sensitest broth or agar (Oxoid, Basingstoke, United Kingdom) as described previously (17, 19, 35). National Committee for Clinical Laboratory Standards criteria were used to categorize strains as susceptible, intermediately resistant, or resistant (26). β-Lactamases were characterized by isoelectric focusing as described previously (22). Plasmids were extracted by use of either the method of Kado and Liu (18) or the alkaline lysis method of Birnboim and Doly (5). Extracted plasmids were digested with the restriction enzymes EcoRI, ClaI, BamHI, and HindIII (Life Technologies, Paisley, United Kingdom), and the resulting fragments were separated by agarose gel electrophoresis. Each clinical isolate was mated with the recipient strain, Escherichia coli K-12 J62.1 (nalidixic acid resistant), or a rifampin-resistant mutant of it, in broth as described previously (22). Transconjugants were selected on medium containing ceftazidime (4 μg/ml) plus nalidixic acid (100 μg/ml) or rifampin (200 μg/ml). Transconjugants were assessed for plasmid content and their antibiotic susceptibility.

Isolates from 10 distinct hospital outbreaks of infection or colonization with extended-spectrum β-lactamase-producing klebsiellas in the United Kingdom that occurred during the period 1991 to 1994 were investigated. Representative isolates (chosen on the basis of their typical antibiogram and serotype), which were all K. pneumoniae, were designated D1 to D10 and are listed in Table 1. The strains were considerably more resistant to ceftazidime, cefotaxime, and cefepime than were strains producing non-extended-spectrum β-lactamases. Clavulanic acid (2 μg/ml) substantially reduced the MICs of ceftazidime for all strains. Although the MICs of cefoxitin for some of the strains were higher than those usually found for Klebsiella, none was very high, and all strains were susceptible to carbapenems. The β-lactam resistance patterns of the transconjugants were similar to those of the corresponding donors, although sometimes with a lower degree of resistance (Table 1). Only one strain (D2) was susceptible to all the aminoglycosides tested (Table 2), but most strains were susceptible to amikacin. The strains were mostly susceptible to ciprofloxacin and trimethoprim but resistant to chloramphenicol and tetracycline.

TABLE 1.

MICs of β-lactam antibiotics and sizes of β-lactamase-encoding plasmids for Klebsiella outbreak strains and their E. coli transconjugants

Strain MICs (μg/ml) ofa:
β-Lactamase-encoding plasmids (kb)
Ampicillin Amox + Clav (2) Amox + Clav (2:1) Pip Pip + Taz (4) Temocillin Ceftaz Ceftaz + Clav (2) Cefotaxime Cefepime Cefoxitin Imipenem Meropenem
D1 >4,096 16 16 512 4 8 >64 1 1 4 2 0.25 0.06 78
D1 transconjugant 4,096 16 >64 1 1 4
D2 >4,096 32 16 512 128 16 32 1 16 16 32 0.06 0.06 70
D2 transconjugant 2,048 4 2 0.25 2 4
D3 4,096 8 4 128 4 8 64 0.5 16 2 16 0.06 0.06 130
D3 transconjugant 4,096 4 64 0.25 16 4
D4 >4,096 64 8 512 128 8 >64 0.5 64 8 16 0.06 0.03 150
D4 transconjugant >4,096 16 16 0.5 32 8
D5 4,096 8 8 256 2 4 16 0.5 8 1 4 0.06 0.03 85
D5 transconjugant 2,048 8 16 0.5 16 8
D6 >4,096 8 8 256 32 4 >64 0.5 8 2 4 0.06 0.06 125
D6 transconjugant 4,096 8 >64 0.5 16 16
D7 >4,096 256 32 >512 128 8 >64 1 16 1 8 0.06 0.03 125
D7 transconjugant 1,024 4 16 0.25 2 4
D8 4,096 8 8 128 4 4 8 0.5 4 0.5 8 0.06 0.03 150
D8 transconjugant >4,096 16 8 0.5 16 4
D9 >4,096 64 32 512 128 16 64 2 32 8 16 0.25 0.06 160
D9 transconjugant >4,096 16 32 1 32 4
D10 1,024 4 4 64 2 ≤2 32 0.25 2 0.5 2 0.12 0.03 150
D10 transconjugant 512 4 32 0.25 1 4
Open in a new tab
a

Antibiotic abbreviations: Amox, amoxicillin; Clav, clavulanic acid; Pip, piperacillin; Taz, tazobactam; Ceftaz, ceftazidime. 

TABLE 2.

MICs of aminoglycosides and other antibiotics for Klebsiella outbreak strains

Strain MICs (μg/ml) of:
Gentamicin Netilmicin Tobramycin Amikacin Streptomycin Ciprofloxacin Chloramphenicol Tetracycline Trimethoprim
D1 128 16 16 2 1 ≤0.25 8 >64 0.5
D2 0.5 ≤0.5 1 2 2 0.5 >128 8 0.5
D3 4 64 32 16 8 >8 16 4 >8
D4 32 16 128 32 4 1 >128 16 2
D5 1 64 32 16 1 1 32 >64 4
D6 128 16 16 ≤1 1 ≤0.25 128 8 >8
D7 128 128 64 32 256 >8 >128 >64 >8
D8 64 ≤0.5 32 ≤1 16 1 128 >64 4
D9 64 8 8 ≤1 64 4 >128 >64 >8
D10 32 16 128 64 2 ≤0.25 4 2 0.5
Open in a new tab

Single-plasmid transconjugants were obtained from each of the clinical strains, and their plasmids were extracted and compared by restriction endonuclease digestion with EcoRI, ClaI, BamHI, or HindIII. The plasmids in the transconjugants were large, 70 to 170 kb (Table 1). With each of these enzymes, the fragment patterns appeared distinct from the patterns for transconjugants obtained from donors D1 and D5. With EcoRI digestion, a number of common bands were noted for these two transconjugants (Fig. 1). However, greater diversity was noted with ClaI and HindIII digestion. Neither plasmid appeared to be digested by BamHI.

FIG. 1.

FIG. 1

Open in a new tab

Agarose gel electrophoresis of restriction digests of plasmids from the transconjugants of strains D1 and D5. Lane 1, D1 digested with ClaI; lane 2, D5 digested with ClaI; lane 3, D1 digested with EcoRI; lane 4, D5 digested with EcoRI; lane 5, D1 digested with HindIII; lane 6, D5 digested with HindIII; lane 7, molecular weight markers (with weights indicated, in thousands, to the right of the gel).

DNA sequences of β-lactamases.

PCR was used to amplify parts of SHV or TEM gene sequences in whole-cell DNA preparations as described previously (22). DNA preparations were made from the klebsiellae for detection of TEM gene sequences but from the transconjugants for detection of SHV gene sequences because of the chromosomal SHV-1 gene usually present in K. pneumoniae. An automated laser fluorescent DNA sequencer (Pharmacia Biotech, St. Albans, Hertfordshire, United Kingdom) was used to sequence the TEM PCR product, which had been labelled by the quick annealing method, as described previously (39). A similar procedure was used for SHV PCR products except that cycle sequencing was performed on 1 μg of purified PCR product obtained from transconjugants and with the reagents supplied in a Thermo Sequenase fluorescently labelled primer cycle sequencing kit (Amersham International, Buckinghamshire, United Kingdom). Reactions were performed as described in the manufacturer’s instructions, with 2 pmol of fluorescently labelled primer OS-1 (22) or a primer we have designated SHV-i (5′-CCAGATCGGCGAACAACGTCACC-3′; bases 447 to 468 of the SHV structural gene) and the following cycling conditions: 25 cycles of 30 s at 60°C and 30 s at 98°C.

Thermostable DNA polymerase from Thermus brockianus (DynaZyme), 10× polymerase buffer, and magnesium chloride were supplied by Flowgen (Lichfield, Staffordshire, United Kingdom). Nucleotides were obtained from Sigma (Poole, Dorset, United Kingdom). Sterile distilled water was molecular biology grade (Bio-Rad, Hemel Hempstead, Hertfordshire, United Kingdom). Synthetic oligonucleotide primers, AutoRead sequencing kits, and automated laser fluorescence-grade urea were supplied by Pharmacia Biotech. Hydrolink Long Ranger gel was obtained from Hoefer (Newcastle-under-Lyme, Staffordshire, United Kingdom). A Thermo Sequenase fluorescently labelled primer cycle sequencing kit with 7-deaza-dGTP was purchased from Amersham International. All other reagents were ANALAR grade obtained from BDH (Lutterworth, Leicestershire, United Kingdom).

The properties of the β-lactamases found in the outbreak strains are summarized in Table 3. Apart from strain D7, which produced TEM-1 in addition to an extended-spectrum β-lactamase, the strains possessed only one transferable β-lactamase. Two strains (D1 and D5) produced TEM-group extended-spectrum β-lactamases (TEM-26 and TEM-15, respectively). The other eight strains produced SHV-group extended-spectrum β-lactamases (SHV-2 by four, SHV-5 by three, and SHV-4 by one).

TABLE 3.

Isoelectric points and deduced amino acid sequence changes for β-lactamases from Klebsiella outbreak strains

Organism pI PCR results for:
Amino acid (codon)a,b at position:
Enzymea
TEM SHV 39 42 69 104 153 164 165 182 205 237 238 240 244 265 275 276
E. coli 5.4 Q A M E (GAG) H R (CGT) W M Q A G (GGT) E R T R N TEM-1c
Klebsiella D5 6.0 + 7.6 + K (AAG) S (AGT) TEM-15
D5 transconjugant 6.0
Klebsiella D1 5.5 + 7.6 + K (AAG) S (AGT) TEM-26
D1 transconjugant 5.5
E. coli 7.6 Q G M D R R W T R (CGG) A G (GGC) E (GAG) R L R N SHV-1c
Klebsiella D2 7.6 S (AGC) E (GAA) SHV-2
D2 transconjugant 7.6 +
Klebsiella D4 7.6 S (AGC) E (GAG) SHV-2
D4 transconjugant 7.6 +
Klebsiella D8 7.6 S (AGC) E (GAG) SHV-2
D8 transconjugant 7.6 +
Klebsiella D9 7.6 + 5.4 − S (AGC) E (GAG) SHV-2
D9 transconjugant 7.6 +
Klebsiella D3 7.75 L (CTG) S (AGC) K (AAA) SHV-4
D3 transconjugant 7.75 +
Klebsiella D6 7.6 + 8.2 S (AGC) K (AAG) SHV-5
D6 transconjugant 8.2 +
Klebsiella D7 5.4 + 7.6 + 8.2 + S (AGC) K (AAG) TEM-1 + SHV-5
D7 transconjugant 5.4 + 8.2 +
Klebsiella D10 7.6 + 8.2 S (AGC) K (AAG) SHV-5
D10 transconjugant 8.2 +
Open in a new tab
a

Sequence and enzyme data apply to the Klebsiella-transconjugant pair as a whole. 

b

Amino acid abbreviations: A, alanine; D, aspartic acid; E, glutamic acid; G, glycine; H, histidine; I, isoleucine; K, lysine; L, leucine; M, methionine; N, asparagine; P, proline; Q, glutamine; R, arginine; S, serine; T, threonine; V, valine; W, tryptophan. Nucleotide abbreviations: A, adenosine; C, cytosine; G, guanosine; T, thymidine. The consensus numbering scheme for group 2 (molecular class A β-lactamases) (1) is used. 

c

Data from Jacoby and Medeiros (15), Huletsky et al. (14), Knox (20), and Bush and Jacoby (8). 

In this study, we investigated the extended-spectrum β-lactamases and the plasmids encoding them in a series of distinct outbreak strains of K. pneumoniae isolated in the United Kingdom between 1991 and 1994. SHV-group extended-spectrum β-lactamases were more common than TEM-group enzymes. The identification of the former was straightforward, but the nomenclature of one of the TEM enzymes requires some comment. The amino acid changes detected in the enzyme from strain D5 were identical to those given by Jacoby and Medeiros (15) and Knox (20) for TEM-15 on the basis of oligotyping (23). However, this enzyme has been omitted from the most recently published list of TEM enzymes produced by Bush and Jacoby (8), presumably because it had not at that time been fully sequenced. However, it has been reinstated in their list, which is accessible on the World Wide Web (at http://www.lahey.org/studies/webt.htm), as an enzyme with changes of glutamic acid to lysine at position 104 and of glycine to serine at position 238. We found some variability in the codon corresponding to the amino acid at position 240 in SHV β-lactamases, with glutamic acid encoded by GAG or GAA and lysine encoded by AAA or AAG (Table 3); such variability has been reported previously (29).

Since most strains of K. pneumoniae synthesize a chromosomally encoded β-lactamase with an isoelectric point of 7.6 that is closely related to SHV-1 (11, 22), surveys of β-lactamases in this species that do not take the location of the gene encoding the enzyme into account are impossible to interpret. Consequently, there is little information on the frequencies of plasmid-encoded β-lactamases in this organism. Although extended-spectrum SHV β-lactamases appear to have evolved from SHV-1, it is not known whether their genes are derived from the chromosomal gene and have subsequently moved on to plasmids or whether mutation of plasmid genes has occurred.

Although TEM-1 and TEM-2 can be transposon encoded (34) as can plasmid-encoded SHV-1 (30), extended-spectrum β-lactamases have generally not been found on transposons (16). However, genes for TEM-12 (12) and TEM-16 (37) have been reported to be located on transposons. It is not known whether the β-lactamases from the outbreak strains reported in this paper are transposon encoded, but the apparent lack of relatedness of the plasmids suggests that they are not, except perhaps for the TEM-group enzymes.

On the basis of National Committee for Clinical Laboratory Standards criteria (26), eight of the strains were susceptible to cefotaxime and one had intermediate resistance (Table 1), although all the strains were less susceptible than typical klebsiellae that do not produce extended-spectrum β-lactamases. However, extended-spectrum β-lactamase producers can readily mutate to hyperproduction of the enzyme and higher degrees of resistance (42), so we believe that therapy of infections caused by such organisms would not be appropriate. Similarly, although most of the strains were susceptible or had intermediate resistance to amoxicillin-clavulanic acid, mutation to hyperproduction may result in resistance to this and other β-lactam–β-lactamase inhibitor combinations.

All of the strains were multiply drug resistant. As has been reported previously for extended-spectrum β-lactamase producers (16), they were usually resistant to the aminoglycosides, with only one strain, D2, being susceptible to all four aminoglycosides tested. Five of the 10 strains were fully amikacin susceptible, a proportion that is slightly higher than the 9 of 15 reported by Jacoby and Sutton (16). Resistance to streptomycin was uncommon; this contrasts with the situation 20 years ago, when 86% of gentamicin-resistant enterobacteria were also resistant to streptomycin (36), and presumably reflects the reduced selective pressure resulting in loss of genes encoding streptomycin resistance from plasmids. The carbapenems (imipenem and meropenem) were the only agents tested that were active against all the strains, but seven strains were ciprofloxacin susceptible. However, greater use of this and other quinolones may lead to selection of resistant mutants.

In conclusion, hospital outbreaks of K. pneumoniae producing extended-spectrum β-lactamases in the United Kingdom between 1991 and 1994 have been caused by distinct single strains. Two outbreak strains produced TEM enzymes (TEM-15 and TEM-26), three produced SHV-2, three produced SHV-5, and one produced SHV-4. These enzymes were encoded on large transferable plasmids that appeared to be distinct from each other. The organisms were variably multiply resistant to other antimicrobial agents and were usually resistant to gentamicin and sometimes to other aminoglycosides.

Acknowledgments

This study was supported in part by a grant (no. 804) from the Special Trustees of St. Thomas’ Hospital and by a Sino-British Friendship Scheme Scholarship (to X.X.).

REFERENCES

  • 1.Ambler R P, Coulson A F, Frère J M, Ghuysen J M, Joris B, Forsman M, Levesque R C, Tiraby G, Waley S G. A standard numbering scheme for the class A β-lactamases. Biochem J. 1991;276:269–270. doi: 10.1042/bj2760269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Arlet G, Rouveau M, Casin I, Bouvet P J M, Lagrange P H, Philippon A. Molecular epidemiology of Klebsiella pneumoniae strains that produce SHV-4 β-lactamase and which were isolated in 14 French hospitals. J Clin Microbiol. 1994;32:2553–2558. doi: 10.1128/jcm.32.10.2553-2558.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Bauernfeind A, Rosenthal E, Eberlein E, Holley M, Schweighart S. Spread of Klebsiella pneumoniae producing SHV-5 beta-lactamase among hospitalized patients. Infection. 1993;21:18–22. doi: 10.1007/BF01739303. [DOI] [PubMed] [Google Scholar]
  • 4.Bermudes H, Arpin C, Jude F, el-Harrif Z, Bebear C, Quentin C. Molecular epidemiology of an outbreak due to extended-spectrum β-lactamase-producing enterobacteria in a French hospital. Eur J Clin Microbiol Infect Dis. 1997;16:523–527. doi: 10.1007/BF01708236. [DOI] [PubMed] [Google Scholar]
  • 5.Birnboim H C, Doly J A. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979;7:1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Bradford P A, Cherubin C E, Idemyor V, Rasmussen B A, Bush K. Multiply resistant Klebsiella pneumoniae strains from two Chicago hospitals: identification of the extended-spectrum TEM-12 and TEM-10 ceftazidime-hydrolyzing β-lactamases in a single isolate. Antimicrob Agents Chemother. 1994;38:761–766. doi: 10.1128/aac.38.4.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Branger C, Bruneau B, Lesimple A L, Bouvet P J, Berry P, Secvali-Garcia J, Lambert-Zechovsky N. Epidemiological typing of extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates responsible for five outbreaks in a university hospital. J Hosp Infect. 1997;36:23–26. doi: 10.1016/s0195-6701(97)90088-8. [DOI] [PubMed] [Google Scholar]
  • 8.Bush K, Jacoby G. Nomenclature of TEM β-lactamases. J Antimicrob Chemother. 1997;39:1–3. doi: 10.1093/jac/39.1.1. [DOI] [PubMed] [Google Scholar]
  • 9.Cookson B, Johnson A P, Azadian B, Paul J, Hutchinson G, Kaufmann M, Woodford N, Malde M, Walsh B, Yousif A, Selkon J. International inter- and intrahospital spread of a multiple antibiotic-resistant strain of Klebsiella pneumoniae. J Infect Dis. 1995;171:511–513. doi: 10.1093/infdis/171.2.511. [DOI] [PubMed] [Google Scholar]
  • 10.French G L, Shannon K P, Simmons N. Hospital outbreak of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins and β-lactam/β-lactamase-inhibitor combinations by hyperproduction of SHV-5 β-lactamase. J Clin Microbiol. 1996;34:358–363. doi: 10.1128/jcm.34.2.358-363.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Hæggman S, Löfdahl S, Burman L G. An allelic variant of the chromosomal gene for class A β-lactamase K2, specific for Klebsiella pneumoniae, is the ancestor of SHV-1. Antimicrob Agents Chemother. 1997;41:2705–2709. doi: 10.1128/aac.41.12.2705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Heritage J, Hawkey P M, Todd N, Lewis I J. Transposition of the gene encoding a TEM-12 extended-spectrum β-lactamase. Antimicrob Agents Chemother. 1992;36:1981–1986. doi: 10.1128/aac.36.9.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Hibbert-Rogers L C, Heritage J, Gascoyne-Binzi D M, Hawkey P M, Todd N, Lewis I J, Bailey C. Molecular epidemiology of ceftazidime resistant Enterobacteriaceae from patients on a paediatric oncology ward. J Antimicrob Chemother. 1995;36:65–82. doi: 10.1093/jac/36.1.65. [DOI] [PubMed] [Google Scholar]
  • 14.Huletsky A, Couture F, Levesque R C. Nucleotide sequence and phylogeny of SHV-2 beta-lactamase. Antimicrob Agents Chemother. 1990;34:1725–1732. doi: 10.1128/aac.34.9.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Jacoby G A, Medeiros A A. More extended-spectrum β-lactamases. Antimicrob Agents Chemother. 1991;35:1697–1704. doi: 10.1128/aac.35.9.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Jacoby G A, Sutton L. Properties of plasmids responsible for production of extended-spectrum β-lactamases. Antimicrob Agents Chemother. 1991;35:164–169. doi: 10.1128/aac.35.1.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Johnson A P, Weinbren M J, Ayling-Smith B, Du Bois S K, Amyes S G B, George R C. Outbreak of infection in two UK hospitals caused by a strain of Klebsiella pneumoniae resistant to cefotaxime and ceftazidime. J Hosp Infect. 1992;20:97–103. doi: 10.1016/0195-6701(92)90111-x. [DOI] [PubMed] [Google Scholar]
  • 18.Kado C I, Liu S T. Rapid procedure for detection and isolation of large and small plasmids. J Bacteriol. 1981;145:1365–1373. doi: 10.1128/jb.145.3.1365-1373.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18a.Kaufmann, M. E., et al. Unpublished data.
  • 19.King A, Warren C, Shannon K, Phillips I. The in vitro antibacterial activity of cefotaxime compared with that of cefuroxime and cefoxitin. J Antimicrob Chemother. 1980;6:479–494. doi: 10.1093/jac/6.4.479. [DOI] [PubMed] [Google Scholar]
  • 20.Knox J R. Extended-spectrum and inhibitor-resistant TEM-type β-lactamases: mutations, specificity, and three-dimensional structure. Antimicrob Agents Chemother. 1995;39:2593–2601. doi: 10.1128/aac.39.12.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Legakis N J, Tzouvelekis L S, Hatzoudis G, Tzelepi E, Gourkou A, Pitt T L, Vatopoulos A C. Klebsiella pneumoniae infections in Greek hospitals. Dissemination of plasmids encoding an SHV-5 type beta-lactamase. J Hosp Infect. 1995;31:177–187. doi: 10.1016/0195-6701(95)90064-0. [DOI] [PubMed] [Google Scholar]
  • 22.Leung M, Shannon K, French G. Rarity of transferable β-lactamase production by Klebsiella species. J Antimicrob Chemother. 1997;39:737–745. doi: 10.1093/jac/39.6.737. [DOI] [PubMed] [Google Scholar]
  • 23.Mabilat C, Courvalin P. Development of “oligotyping” for characterization and molecular epidemiology of TEM β-lactamases in members of the family Enterobacteriaceae. Antimicrob Agents Chemother. 1990;34:2210–2216. doi: 10.1128/aac.34.11.2210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Monnet D L, Biddle J W, Edwards J R, Culver D H, Tolson J S, Martone W J, Tenover F C, Gaynes R P. Evidence of interhospital transmission of extended-spectrum β-lactam-resistant Klebsiella pneumoniae in the United States, 1986 to 1993. Infect Control Hosp Epidemiol. 1997;18:492–498. doi: 10.1086/647654. [DOI] [PubMed] [Google Scholar]
  • 25.Mulgrave L, Attwood P V. Characterization of an SHV-5 related extended broad-spectrum beta-lactamase in Enterobacteriaceae from Western Australia. Pathology. 1993;25:71–75. doi: 10.3109/00313029309068906. [DOI] [PubMed] [Google Scholar]
  • 26.National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 4th ed. Approved standard M7-A4. Villanova, Pa: National Committee for Clinical Laboratory Standards; 1996. [Google Scholar]
  • 27.Naumovski L, Quinn J P, Miyashiro D, Patel M, Bush K, Singer S B, Graves D, Palzkill T, Arvin A M. Outbreak of ceftazidime resistance due to a novel extended-spectrum β-lactamase in isolates from cancer patients. Antimicrob Agents Chemother. 1992;36:1991–1996. doi: 10.1128/aac.36.9.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Nouvellon M, Pons J-L, Sirot D, Combe M-L, Lemeland J-F. Clonal outbreaks of extended-spectrum β-lactamase-producing strains of Klebsiella pneumoniae demonstrated by antibiotic susceptibility testing, β-lactamase typing, and multilocus enzyme electrophoresis. J Clin Microbiol. 1994;32:2625–2627. doi: 10.1128/jcm.32.10.2625-2627.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Nüesch-Inderbinen M T, Kayser F H, Hächler H. Survey and molecular genetics of SHV β-lactamases in Enterobacteriaceae in Switzerland: two novel enzymes, SHV-11 and SHV-12. Antimicrob Agents Chemother. 1997;41:943–949. doi: 10.1128/aac.41.5.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Nugent M E, Hedges R W. The nature of the genetic determinant for the SHV-1 beta-lactamase. Mol Gen Genet. 1979;175:239–243. doi: 10.1007/BF00397222. [DOI] [PubMed] [Google Scholar]
  • 31.Pagani L, Ronza P, Giacobone E, Romero E. Extended-spectrum beta-lactamases from Klebsiella pneumoniae strains isolated at an Italian hospital. Eur J Epidemiol. 1994;10:533–540. doi: 10.1007/BF01719569. [DOI] [PubMed] [Google Scholar]
  • 32.Payne D J, Amyes S G B. Transferable resistance to extended-spectrum β-lactams: a major threat or a minor inconvenience? J Antimicrob Chemother. 1991;27:255–261. doi: 10.1093/jac/27.3.255. [DOI] [PubMed] [Google Scholar]
  • 33.Prodinger W M, Fille M, Bauernfeind A, Stemplinger I, Amann S, Pfausler B, Lass-Flörl C, Dierich M P. Molecular epidemiology of Klebsiella pneumoniae producing SHV-5 β-lactamase: parallel outbreaks due to multiple plasmid transfer. J Clin Microbiol. 1996;34:564–568. doi: 10.1128/jcm.34.3.564-568.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Saunders J R. Genetics and evolution of antibiotic resistance. Br Med Bull. 1984;40:54–60. doi: 10.1093/oxfordjournals.bmb.a071948. [DOI] [PubMed] [Google Scholar]
  • 35.Shannon K, King A, Phillips I. Prevalence of resistance to β-lactam antibiotics in Escherichia coli isolated from blood from 1969–1991. J Antimicrob Chemother. 1992;30:661–672. doi: 10.1093/jac/30.5.661. [DOI] [PubMed] [Google Scholar]
  • 36.Shannon K P, Phillips I, King B A. Aminoglycoside resistance among Enterobacteriaceae and Acinetobacter species. J Antimicrob Chemother. 1988;4:131–142. doi: 10.1093/jac/4.2.131. [DOI] [PubMed] [Google Scholar]
  • 37.Sirot D, De Champs C, Chanal C, Labia R, Darfeuille-Michaud A, Perroux R, Sirot J. Translocation of antibiotic resistance determinants including an extended-spectrum β-lactamase between conjugative plasmids of Klebsiella pneumoniae and Escherichia coli. Antimicrob Agents Chemother. 1991;35:1576–1581. doi: 10.1128/aac.35.8.1576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Sirot J, Chanal C, Petit A, Sirot D, Labia R, Gerbaud G. Klebsiella pneumoniae and other Enterobacteriaceae producing novel plasmid-mediated beta-lactamases markedly active against third-generation cephalosporins: epidemiologic studies. Rev Infect Dis. 1988;10:850–859. doi: 10.1093/clinids/10.4.850. [DOI] [PubMed] [Google Scholar]
  • 39.Stapleton P, Wu P-J, King A, Shannon K, French G, Phillips I. Incidence and mechanisms of resistance to the combination of amoxicillin with clavulanic acid in Escherichia coli. Antimicrob Agents Chemother. 1995;39:2478–2483. doi: 10.1128/aac.39.11.2478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Urban C, Meyer K S, Mariano N, Rahal J J, Flamm R, Rasmussen B A, Bush K. Identification of TEM-26 β-lactamase responsible for a major outbreak of ceftazidime-resistant Klebsiella pneumoniae. Antimicrob Agents Chemother. 1994;38:392–395. doi: 10.1128/aac.38.2.392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Venezia R A, Scarano F J, Preston K E, Steele L M, Root T P, Limberger R, Archinal W, Kacica M A. Molecular epidemiology of an SHV-5 extended-spectrum beta-lactamase in Enterobacteriaceae isolated from infants in a neonatal intensive care unit. Clin Infect Dis. 1995;21:915–923. doi: 10.1093/clinids/21.4.915. [DOI] [PubMed] [Google Scholar]
  • 42.Xiang X, Shannon K, French G. Mechanism and stability of hyperproduction of the extended-spectrum β-lactamase SHV-5 in Klebsiella pneumoniae. J Antimicrob Chemother. 1997;40:525–532. doi: 10.1093/jac/40.4.525. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES