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 Martínez-Martínez, L.
Right arrow Articles by Jacoby, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martínez-Martínez, L.
Right arrow Articles by Jacoby, G. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 1999, p. 1669-1673, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Roles of beta -Lactamases and Porins in Activities of Carbapenems and Cephalosporins against Klebsiella pneumoniae

Luis Martínez-Martínez,1,2,* Alvaro Pascual,1,2 Santiago Hernández-Allés,3 Dolores Alvarez-Díaz,3 Ana Isabel Suárez,2 John Tran,4 Vicente Javier Benedí,3 and George A. Jacoby4

Department of Microbiology, School of Medicine, University of Seville,1 and Department of Microbiology University Hospital V. Macarena,2 Seville, and Area of Microbiology, Department of Biology and IMEDEA (CSIC-UIB), University of the Balearic Islands, Palma de Mallorca,3 Spain, and Veterans Affairs Medical Center, Bedford and Lahey Clinic, Burlington, Massachusetts4

Received 9 September 1998/Returned for modification 19 January 1999/Accepted 30 April 1999


    ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

Two clinical isolates of extended-spectrum beta -lactamase (ESBL)-producing Klebsiella pneumoniae were noted to be less susceptible than expected to imipenem. Both were missing outer membrane proteins that serve as channels for antibiotic entry. The role of beta -lactamase in resistance was investigated by eliminating the original ESBL and introducing plasmids encoding various ESBLs and AmpC beta -lactamase types, by studying the effect of an increased inoculum, and by evaluating interactions with beta -lactamase inhibitors. The contribution of porin deficiency was investigated by restoring a functional ompK36 gene on a plasmid. Plasmids encoding AmpC-type beta -lactamases provided resistance to imipenem (up to 64 µg/ml) and meropenem (up to 16 µg/ml) in strains deficient in porins. Carbapenem resistance showed little inoculum effect, was not affected by clavulanate but was blocked by BRL 42715, and was diminished if OmpK36 porin was restored. Plasmids encoding TEM- and SHV-type ESBLs conferred resistance to cefepime and cefpirome, as well as to earlier oxyimino-beta -lactams. This resistance was magnified with an increased inoculum, was blocked by clavulanate, and was also lowered by OmpK36 porin restoration. In addition, SHV-2 beta -lactamase had a small effect on carbapenem resistance (imipenem MIC, 4 µg/ml, increasing to 16 µg/ml with a higher inoculum) when porins were absent. In K. pneumoniae porin loss can thus augment resistance provided either by TEM- or SHV-type ESBLs or by plasmid-mediated AmpC enzymes to include the latest oxyimino-beta -lactams and carbapenems.


    INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

Carbapenems are usually active against extended-spectrum beta -lactamase (ESBL)-producing Klebsiella pneumoniae strains, including porin-deficient ones (13). The MICs of meropenem for clinical isolates of K. pneumoniae strains that produce ESBLs are usually 8 to 16 lower than the MICs of imipenem (4, 27). Carbapenems are also usually active against plasmid-mediated AmpC-type beta -lactamase-producing strains (10, 16). Imipenem-resistant K. pneumoniae strains that produce ACT-1 (an AmpC-type beta -lactamase) (3) or ESBL SHV-2 (18) and that are deficient in a major outer membrane protein, presumably a porin, have been reported recently.

Plasmid- or chromosome-encoded carbapenemases (17) or the association of reduced outer membrane permeability with increased chromosomal beta -lactamase production have been shown to be the major mechanisms of resistance to carbapenems in several species of enterobacteria, including Enterobacter spp. (5, 7, 9, 29), Serratia marcescens (25, 36), Citrobacter freundii (19), Providencia rettgeri (29), and Escherichia coli (6, 28). The association of porin loss and metallo-beta -lactamase production in laboratory-constructed strains of E. coli determined resistance to both imipenem and meropenem when a high bacterial inoculum was used (6).

As a part of a study of resistance to expanded-spectrum beta -lactams in enterobacteria, two clinical isolates of K. pneumoniae that were resistant to ceftazidime (MICs, >256 µg/ml for both strains) and that presented with reduced sensitivity to imipenem (MICs, 2 µg/ml) have been identified. The objectives of this work were to evaluate the mechanisms for the increased MIC of imipenem for these two clinical isolates and to evaluate the relative roles of porins and beta -lactamases (both plasmid-mediated ESBLs and plasmid-mediated AmpC-type enzymes) in the activities of imipenem, meropenem, and cephalosporins against K. pneumoniae.

(This study was presented in part in the 36th and 37th Interscience Conferences on Antimicrobial Agents and Chemotherapy, New Orleans, La. [20a], 15 to 18 September 1996 and Toronto, Ontario, Canada, 28 September to 1 October 1997 [21a], respectively.)


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

Bacterial strains. K. pneumoniae 143098-3 was cultured from sputum at the Massachussetts General Hospital, Boston, in December 1993. It was resistant to ceftazidime, cefotaxime, aztreonam, cefotetan, cefoxitin, chloramphenicol, ciprofloxacin, gentamicin, kanamycin, sulfonamide, tetracycline, tobramycin, and trimethoprim and had a 16-mm zone diameter around a 10-µg imipenem disk. On isoelectric focusing (22) K. pneumoniae 143098-3 had beta -lactamase bands at pIs 5.4, 7.6, and 8.2, consistent with TEM-1, SHV-1, and SHV-5 respectively, and could transfer a plasmid (designated pMG257) encoding the pI 5.4 and 8.2 beta -lactamases to E. coli J53 Rifr by selection with ceftazidime. Strain C1 was obtained from strain 143098-3 after overnight growth at 43°C by replica plating for a ceftazidime susceptible derivative. It was also cefotaxime and aztreonam sensitive but retained the parent's resistance to the other drugs except that the imipenem disk diameter was 24 mm. On isoelectric focusing, beta -lactamase bands at pIs 5.4 and 7.6 were retained, but the band at pI 8.2 was no longer present, suggesting that the putative SHV-5 enzyme was no longer expressed. Attempts to cure the entire resistance phenotype with acridine orange, ethidium bromide, novobiocin, or sodium dodecyl sulfate (SDS) were unsuccessful.

K. pneumoniae NEDH-1 is a urine isolate obtained at the New England Deaconess Hospital, Boston, Mass., in August 1994. The isolate was resistant to ceftazidime, cefotaxime, aztreonam, chloramphenicol, kanamycin, streptomycin, sulfonamide, tobramycin, and trimethoprim and could transfer a plasmid (named pMG258) encoding resistance to these drugs on mating to E. coli. On isoelectric focusing, beta -lactamase bands at pIs 5.4 and 7.6 consistent with TEM-1 and SHV-2, respectively, were present. C2 was derived from strain NEDH-1 by growth in ethidium bromide and screening for a ceftazidime-susceptible derivative. It lost the resistance of the parent to all drugs listed above and no longer produced beta -lactamase, suggesting that pMG258 had been completely eliminated.

Plasmids coding for different TEM- or SHV-type ESBLs or AmpC-type enzymes were introduced by conjugation, as described previously (14), into C1 and C2 (Table 1).

                              
View this table:
[in this window]
[in a new window]
  		TABLE 1.   Plasmids used in the study

The role of porin OmpK36 expression in the resistance of beta -lactamase-producing strains was tested by transformation with plasmid pSHA2, which encodes the OmpK36 porin and which contains a potassium tellurite resistance cassette (for selection purposes) (20). Plasmid pSHA4 (which also codes for resistance to tellurite and which is equivalent to pSHA2 but which has a truncated ompK36 gene) was used as a control. Transformants were obtained on Mueller-Hinton agar containing ceftazidime (20 µg/ml) and potassium tellurite (30 µg/ml).

E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were used as quality control strains for susceptibility testing.

Susceptibility testing. The following antimicrobial agents were tested: cefoxitin (Sigma, Madrid, Spain), ceftazidime (Sigma), cefepime (Bristol-Myers Squibb, Madrid, Spain), cefpirome (Hoescht Marion-Roussel, Romainville, France), imipenem (Merck Sharpe & Dohme, Madrid, Spain), meropenem (Zeneca Farma, Madrid, Spain), and ciprofloxacin (Sigma). All beta -lactams were tested alone or in combination with a fixed concentration (2 µg/ml) of clavulanic acid (SmithKline Beecham, Madrid, Spain), a well-known ESBL inhibitor. The combinations of cefoxitin, imipenem, and meropenem with the serine-beta -lactamase inhibitor BRL 42715 (SmithKline Beecham) were also tested against strains that express AmpC-type enzymes. BRL 42715 is able to inhibit not only class A beta -lactamases but also class C enzymes, and for this reason it was expected that it would inhibit the plasmid-mediated AmpC-type enzymes evaluated in the present study. MICs were determined in cation-adjusted Mueller-Hinton broth, according to the guidelines of the National Committee for Clinical Laboratory Standards (23). The activities of cefepime, cefpirome, imipenem, and meropenem were compared at inocula of 105 and 107 CFU/ml. The E test was also used for some assays. Media were supplemented with potassium tellurite (30 µg/ml) when strains carrying pSHA plasmids were studied in order to avoid plasmid loss.

Isoelectric focusing of beta -lactamases. Cells were grown to the logarithmic phase and were disrupted by sonication. After removal of nonbroken cells and debris, the supernatant was used to determine pIs by isoelectric focusing as described previously (20, 22). beta -Lactamases with known pIs (TEM-1, pI 5.4; TEM-3, pI 6.3; TEM-4, pI 5.9; TEM-26, pI 5.6; SHV-3, pI 7.0; SHV-2, pI 7.6; and SHV-5, pI 8.2) were used for comparison.

Isolation and analysis of OMPs. Outer membrane proteins (OMPs) were isolated as sodium lauryl sarcosinate (2%)-insoluble material from cell envelopes obtained by sonication of bacteria grown in nutrient broth (8). Electrophoretic analysis of OMPs was performed by SDS-polyacrylamide gel electrophoresis (PAGE) as described elsewhere (15, 20).

DNA manipulations. Plasmids pSHA2 and pSHA4 were transformed into the desired strains by electroporation. Standard procedures for agarose gel electrophoresis and plasmid transformation were used (32).


    RESULTS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

K. pneumoniae C1 and C2 were deficient in both OmpK35 and OmpK36 porins, as determined by SDS-PAGE (data not shown). Tables 2 and 3 show that introduction of TEM- or SHV-type ESBLs into these strains increased the MICs of ceftazidime, cefepime, and cefpirome but not that of cefoxitin. The MICs of imipenem and meropenem were not increased except for a fourfold increase with the SHV-2 beta -lactamase. Introduction of plasmids encoding AmpC-type beta -lactamases also increased the MICs of cefepime and cefpirome, but to a lesser extent, especially for cefepime. Cefoxitin MICs were higher by acquisition of AmpC-type enzymes, and all except the enzyme determined by pMG252 increased imipenem MICs as much as 64-fold and meropenem MICs up to 16-fold.

                              
View this table:
[in this window]
[in a new window]
  		TABLE 2.   MICs of antimicrobial agents determined by microdilution for ESBL- or AmpC-producing strains of K. pneumoniae at an inoculum of 105 or 107 CFU/ml


                              
View this table:
[in this window]
[in a new window]
  		TABLE 3.   MICs of cephalosporins and carbapenems alone and combined with clavulanic acid or BRL 42715 for K. pneumoniae strains producing different beta -lactamases

Table 2 shows that increasing the test inoculum from 105 to 107 CFU/ml resulted in higher MICs of cefepime and cefpirome for both ESBL- and AmpC-producing strains. The higher inoculum did not enhance the carbapenem resistance of the ESBL-producing strains except for those with SHV-2, for which the imipenem MIC reached 16 µg/ml. With AmpC strains carbapenem resistance showed a two- to fourfold inoculum effect, with MICs of 64 µg/ml for imipenem and 16 µg/ml for meropenem.

Clavulanic acid blocked resistance to ceftazidime, cefepime, and cefpirome produced by TEM- and SHV-type ESBLs in strains C1 and C2 (Table 3). The resistance to cefoxitin, imipenem, and meropenem produced by AmpC-type beta -lactamases was reduced by BRL 42715 but not by clavulanic acid (Table 3).

SDS-PAGE analysis documented that the missing OmpK36 porin was restored by transformation with plasmid pSHA2. Control strains transformed with plasmid pSHA4 (which encodes a truncated ompK36 gene) remained OmpK36 deficient (data not shown). Table 4 shows that restoration of OmpK36 lowered the MICs of ceftazidime, cefoxitin, cefepime, and cefpirome and, for AmpC-producing strains, the MICs of imipenem and meropenem. The MICs of imipenem (32 to 64 µg/ml) and meropenem (16 µg/ml) were reduced to 0.5 to 2 and 0.25 µg/ml, respectively, by a functional OmpK36 porin. The MICs of cefoxitin, imipenem, and meropenem in the presence of BRL 42715 for strain C1-AC248 that expressed or that did not express porin OmpK36 were 4 and 128 µg/ml, respectively, for cefoxitin, 1 and 1 µg/ml, respectively, for imipenem, and 0.25 and 4 µg/ml, respectively, for meropenem. The corresponding values for strain C2-AC248 that expressed or that did not express OmpK36 were 4 and 64 µg/ml, respectively, for cefoxitin, 0.125 and 0.25 µg/ml, respectively, for imipenem, and 0.03 and 0.25 µg/ml, respectively, for meropenem.

                              
View this table:
[in this window]
[in a new window]
  		TABLE 4.   MICs of antimicrobial agents for K. pneumoniae strains that produce different ESBLs and that express or do not express OmpK36 porin


    DISCUSSION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

Results from this study confirm previous observations (20, 35) indicating that resistance to expanded-spectrum cephalosporins increases in K. pneumoniae strains that produce TEM- or SHV-type ESBLs that lack the two major porins of the species (OmpK35 and OmpK36). The level of resistance further increased when a high inoculum (107 CFU/ml) was used, and this may be clinically relevant in situations in which the number of bacteria at the site of infection is particularly high.

Restoration of OmpK36 function in porin-deficient strains producing ESBLs caused significant decreases in the MICs of ceftazidime, cefepime, and cefpirome. In E. coli we have observed that the expression of OmpF in strains that are deficient in both OmpF and OmpC porins and that hyperproduce chromosomal beta -lactamase is more efficient than expression of OmpC in reverting the resistant phenotype (28). It has been previously shown that the OmpK36 porin of K. pneumoniae is homologous to OmpC of E. coli (1). Cloning of the ompK35 gene of K. pneumoniae is in progress and will allow evaluation of the role of this other porin, in comparison with that of OmpK36, in the resistance of K. pneumoniae to antimicrobial agents.

ESBL production did not affect the activities of carbapenems except when imipenem was tested against strain C1-S2 (which produces SHV-2), for which MICs of 4 µg/ml (105 cfu/ml) and 16 µg/ml (107 cfu/ml) were obtained. It has previously been reported that a clinical isolate of K. pneumoniae that produces SHV-2 was resistant to imipenem (MIC, 8 µg/ml) and meropenem (MIC, 16 µg/ml) (18).

The expression of AmpC-type enzymes affected the activities of cefoxitin (which is in contrast to the effects of ESBLs) and ceftazidime, as has been shown for other plasmid-mediated AmpC-type beta -lactamases (10, 16). On the other hand, only moderate increases were observed when cefepime or cefpirome were tested, with cefepime MICs being two to eight times lower than those of cefpirome. The relative better activities of both cefepime and cefpirome in comparison with those of older cephalosporin derivatives relates to their increased stability to chromosomal AmpC enzymes (from which plasmid-mediated AmpC-type enzymes have been shown to be derived) and to their relatively higher level of permeation through the outer membranes of gram-negative bacteria (33). These data suggest that cefepime and cefpirome could represent therapeutic alternatives against AmpC-type producing organisms resistant to multiple antimicrobial agents, as has already been shown for infections caused by ceftazidime-resistant Enterobacter (34). Caution is suggested, however, from the significant increases in the MICs of both cefepime and cefpirome when a high inoculum was used in the susceptibility assay.

The production of AmpC-type enzymes significantly increased the MICs of carbapenems, in agreement with the report by Bradford et al. (3) with the ACT-1 beta -lactamase. BRL 42715 was able to revert the resistance conferred by AmpC-type enzymes, as expected for class C-related beta -lactamases (16). Although BRL 42715 is not available for clinical use, it would be interesting to develop compounds with activity similar to that of BRL 42715 to assess their therapeutic potential. Resistance to carbapenems also depends on the absence of porins, because restoration of OmpK36 significantly reduced the level of resistance. The results obtained after simultaneous inhibition of the AmpC enzyme and expression of OmpK36 in strains C1-AC248 and C2-AC248 suggest that beta -lactamase production is the most important factor for resistance to imipenem, while loss of porins seems more important or as important for resistance to meropenem.

The apparent existence of different mechanisms of resistance to imipenem and meropenem in K. pneumoniae is also supported by the observation that inhibition of the AmpC enzymes of strains C1-AC248 and C2-AC248 with the same amount of BRL 42715 resulted in a larger decrease in the MICs of imipenem for C2-AC248 than for C1-AC248. Similarly, although both strains present similar levels of resistance to meropenem, the decrease in the MIC of this agent in the presence of BRL 42715 was also higher for strain C2-AC248. It is unlikely that this was caused by a poorer inhibition of the enzyme in strain C1-AC248, because an increase in the concentration of BRL 42715 to 16 µg/ml did not result in an additional decrease in the MIC of either imipenem or meropenem (data not shown).

Although the main objective of this study was to evaluate the mechanisms that lead to resistance to carbapenems and cephalosporins in K. pneumoniae, ciprofloxacin was also included as a control for experiments on OmpK36 expression, because its activity is slightly increased when this porin is produced (20) and possible interactions between beta -lactamase expression and fluoroquinolone activity were of interest. Surprisingly, one of the plasmids coding for an AmpC-type enzyme (pMG252) was able to increase the resistance to ciprofloxacin in the two K. pneumoniae strains evaluated. Details about this finding have been published elsewhere (21). It is noteworthy that pMG252 was the only plasmid of those evaluated in the present study that codes for an enzyme that determined resistance to cefoxitin but not to carbapenems. The AmpC-type enzyme encoded by this plasmid belongs to the group of plasmid-mediated AmpC-type beta -lactamases (CMY-1, FOX-1, MOX-1, and others) distantly related to the chromosomal enzyme of P. aeruginosa (unpublished data). More enzymes of this type need to be tested to determine if this is a general and potentially distinguishing property of this class of enzymes.

Plasmid-mediated AmpC-type enzymes have increasingly been recognized in recent years. Data from previous reports and from this work suggest that these bacterial enzymes may represent a new threat against the more recently introduced antimicrobial agents. The spread of strains that lack porins and that express these new plasmid-mediated enzymes may create serious therapeutic problems in the future.


    ACKNOWLEDGMENTS

This study was supported by grants from Consolidation of Research Groups, Consejería de Educación, Junta de Andalucía (to L.M.-M. and A.P.), and from the Comisión Interministerial de Ciencia y Tecnología, Ministerio de Educación (grant PB96-0197) (to V.J.B.). G.A.J. was partially supported by a VA/DoD Mechanisms of Emerging Pathogens award.


    FOOTNOTES

* Corresponding author. Mailing address: Department of Microbiology, School of Medicine, University of Seville, Apdo. 914, 41080 Seville, Spain. Phone: 34-95-4557448. Fax: 34-95-4377413. E-mail: lmartin{at}cica.es.


    REFERENCES
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

1. Albertí, S., F. Rodríguez-Quiñones, T. Schirmer, G. Rummel, J. M. Tomás, J. P. Rosenbusch, and V. J. Benedí. 1995. A porin from Klebsiella pneumoniae: sequence homology, three-dimensional structure, and complement binding. Infect. Immun. 63:903-910[Abstract].
2. Bauernfeind, A., and G. Hörl. 1987. Novel R-factor borne beta -lactamase of Escherichia coli conferring resistance to cephalosporins. Infection 15:257-259[Medline].
3. Bradford, P. A., C. Urban, N. Mariano, S. J. Projan, J. J. Rahal, and K. Bush. 1997. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC beta -lactamase, and the loss of an outer membrane protein. Antimicrob. Agents Chemother. 41:563-569[Abstract].
4. Chanal, C., D. Sirot, M. Chanal, M. Cluzel, J. Sirot, and R. Cluzel. 1989. Comparative in-vitro activity of meropenem against clinical isolates including Enterobacteriaceae with expanded-spectrum beta -lactamases. J. Antimicrob. Chemother. 24(Suppl. A):133-141.
5. Chow, J. W., and D. M. Shlaes. 1991. Imipenem resistance associated with the loss of a 40 kDa outer membrane protein in Enterobacter aerogenes. J. Antimicrob. Chemother. 28:499-504[Abstract/Free Full Text].
6. Cornaglia, G., L. Guang, R. Fontana, and G. Satta. 1992. Diffusion of meropenem and imipenem through the outer membrane of Escherichia coli K-12 and correlation with their antibacterial activities. Antimicrob. Agents Chemother. 36:1902-1908[Abstract/Free Full Text].
7. Cornaglia, G., K. Russel, G. Satta, and R. Fontana. 1995. Relative importance of outer membrane permeability and group 1 beta -lactamase as determinants of meropenem and imipenem activities against Enterobacter cloacae. Antimicrob. Agents Chemother. 39:350-355[Abstract/Free Full Text].
8. Filip, C., G. Fletcher, J. L. Wulf, and C. F. Earhart. 1973. Solubilization of the cytoplasmic membrane of Escherichia coli by the ionic detergent sodium-lauryl sarcosinate. J. Bacteriol. 115:717-722[Abstract/Free Full Text].
9. Hopkins, J. M., and K. J. Towner. 1990. Enhanced resistance to cefotaxime and imipenem associated with outer membrane protein alterations in Enterobacter aerogenes. J. Antimicrob. Chemother. 25:49-55[Abstract/Free Full Text].
10. Jacoby, G. A. 1994. Genetics of extended-spectrum beta-lactamases. Eur. J. Clin. Microbiol. Infect. Dis. 13(Suppl. 1):2-11.
11. Jacoby, G. A., and L. Sutton. 1991. Properties of plasmids responsible for extended-spectrum beta -lactamase production. Antimicrob. Agents Chemother. 35:164-169[Abstract/Free Full Text].
12. Jacoby, G. A., P. Han, M. Alvarez, and F. Tenover. 1995. Survey of extended-spectrum beta -lactamase (ESBL) production in US clinical isolates, abstr. C40, p. 46. In Program and abstracts of the 35th Interscience Conference Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
13. Jarlier, V., M.-H. Nicolas, G. Fournier, and A. Philippon. 1988. Extended broad-spectrum beta -lactamases conferring transferable resistance to newer beta -lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev. Infect. Dis. 10:867-878[Medline].
14. Katsanis, G. P., J. Spargo, M. J. Ferraro, L. Sutton, and G. A. Jacoby. 1994. Detection of Klebsiella pneumoniae and Escherichia coli strains producing extended-spectrum beta -lactamases. Antimicrob. Agents Chemother 32:691-696.
15. Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (London) 277:680-685.
16. Livermore, D. M. 1995. beta -Lactamases in clinical and laboratory resistance. Clin. Microbiol. Rev. 8:557-584[Abstract].
17. Livermore, D. M. 1997. Acquired carbapenemases. J. Antimicrob. Chemother. 39:673-676[Free Full Text].
18. Mackenzie, F. M., K. J. Forbes, T. Dorai-john, S. G. B. Amyes, and I. M. Gould. 1997. Emergence of a carbapenem-resistant Klebsiella pneumoniae. Lancet 350:783[Medline].
19. Mainardi, J.-L., P. Mugnier, A. Coutrot, A. Buu-Hoï, E. Collatz, and L. Gutmann. 1997. Carbapenem resistance in a clinical isolate of Citrobacter freundii. Antimicrob. Agents Chemother. 41:2352-2354[Abstract].
20. Martínez-Martínez, L., S. Hernández-Allés, S. Albertí, J. M. Tomás, V. J. Benedí, and G. A. Jacoby. 1996. In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum cephalosporins. Antimicrob. Agents Chemother. 40:342-348[Abstract].
20a. Martínez-Martínez, L., A. Pascual, S. Hernández-Allés, D. Alvarez-Díaz, V. J. Benedí, and G. A. Jacoby. 1996. Role of extended-spectrum beta-lactamases (ESBLs) and OmpK36 porin in the activity of antimicrobial agents against Klebsiella pneumoniae, abstr. C37, p. 41. In Program and abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
21. Martínez-Martínez, L., A. Pascual, and G. A. Jacoby. 1998. Quinolone resistance from a transferable plasmid. Lancet 351:797-799[Medline].
21a. Martínez-Martínez, L., A. Pascual, A. I. Suárez, S. Hernández-Allés, D. Alvarez-Díaz, and V. J. Benedí. 1997. Resistance to carbapenems in porins-deficient Klebsiella pneumoniae (Kp) mediated by plasma-encoded AmpC beta-lactamases, abstr. C-94, p. 62. In Program and abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
22. Matthew, M., A. M. Harris, M. J. Marshall, and G. W. Ross. 1975. The use of analytical isoelectric focusing for detection and identification of beta -lactamases. J. Gen. Microbiol. 88:169-178[Medline].
23. National Committee for Clinical Laboratory Standards. 1997. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. Approved standard M7-A4. National Committee for Clinical Laboratory Standards, Wayne, Pa.
24. Nicolas, M.-H., V. Jarlier, N. Honore, A. Philippon, and S. T. Cole. 1989. Molecular characterization of the gene encoding SHV-3 beta -lactamase responsible for transferable cefotaxime resistance in clinical isolates of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 33:2096-2100[Abstract/Free Full Text].
25. Osano, E., Y. Arakawa, R. Wacharatuyankun, M. Ohta, T. Horii, H. Ito, F. Yoshimura, and N. Kato. 1994. Molecular characterization of an enterobacterial metallo-beta -lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance. Antimicrob. Agents Chemother. 38:71-78[Abstract/Free Full Text].
26. Papanicolau, G. A., A. A. Medeiros, and G. A. Jacoby. 1990. Novel plasmid-mediated beta -lactamase (MIR-1) conferring resistance to oxyimino- and alpha -methoxy beta -lactams in clinical isolates of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 34:2200-2209[Abstract/Free Full Text].
27. Piddock, L. V. J., and H. L. Turner. 1992. Activity of meropenem against imipenem-resistant bacteria and selection in vitro of carbapenem-resistant Enterobacteriaceae. Eur. J. Clin. Microbiol. Infect. Dis. 11:1186-1191[Medline].
28. Prágai, Z., S. Hernández-Allés, M. C. Conejo, M. D. Alvarez, V. J. Benedí, and L. Martínez-Martínez. 1998. Effect of OmpF/OmpC expression in the activity of cephalosporins and carbapenems against Escherichia coli hyperproducing chromosomal beta-lactamases, abstr. 12009, p. 15. In Program and abstracts of the 8th International Congress of Infectious Diseases. Excerpta Medical Communications, Boston, Mass.
29. Raimondi, A., A. Traverso, and H. Nikaido. 1991. Imipenem- and meropenem-resistant mutants of Enterobacter cloacae and Proteus rettgeri lack porins. Antimicrob. Agents Chemother. 35:1174-1180[Abstract/Free Full Text].
30. Rice, L. B., S. H. Marshall, L. L. Carias, L. Sutton, and G. A. Jacoby. 1993. Sequences of MGH-1, YOU-1, and YOU-2 extended-spectrum beta -lactamase genes. Antimicrob. Agents Chemother. 37:2760-2761[Abstract/Free Full Text].
31. Rice, L. B., S. H. Willey, G. A. Papanicolau, A. A. Medeiros, G. M. Eliopoulos, R. C. Moellering, Jr., and G. A. Jacoby. 1990. Outbreak of ceftazidime resistance caused by extended-spectrum beta -lactamases at a Massachusetts chronic-care facility. Antimicrob. Agents Chemother 34:2193-2199[Abstract/Free Full Text].
32. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
33. Sanders, C. C. 1996. In vitro activity of fourth generation cephalosporins against Enterobacteriaceae producing extended-spectrum beta -lactamases. J. Chemother. 8(Suppl. 2):57-62.
34. Sanders, W. E., J. H. Tenney, and R. E. Kessler. 1996. Efficacy of cefepime in the treatment of infections due to multiply resistant Enterobacter species. Clin. Infect. Dis. 23:454-461[Medline].
35. Tzouvelekis, L. S., E. Tzelepi, E. Prinarakis, M. Gazouli, A. Katrahoura, P. Giakkoupi, O. Paniara, and N. J. Legakis. 1998. Sporadic emergence of Klebsiella pneumoniae strains resistant to cefepime and cefpirome in greek hospitals. J. Clin. Microbiol. 36:266-268[Abstract/Free Full Text].
36. Yang, Y., P. Wu, and D. M. Livermore. 1990. Biochemical characterization of a beta -lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates. Antimicrob. Agents Chemother. 34:755-758[Abstract/Free Full Text].

Antimicrobial Agents and Chemotherapy, July 1999, p. 1669-1673, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Jeong, S. H., Song, W., Kim, J.-S., Kim, H.-S., Lee, K. M. (2009). Broth Microdilution Method To Detect Extended-Spectrum {beta}-Lactamases and AmpC {beta}-Lactamases in Enterobacteriaceae Isolates by Use of Clavulanic Acid and Boronic Acid as Inhibitors. J. Clin. Microbiol. 47: 3409-3412 [Abstract] [Full Text]  
  • Landman, D., Bratu, S., Quale, J. (2009). Contribution of OmpK36 to carbapenem susceptibility in KPC-producing Klebsiella pneumoniae. J Med Microbiol 58: 1303-1308 [Abstract] [Full Text]  
  • Grobner, S., Linke, D., Schutz, W., Fladerer, C., Madlung, J., Autenrieth, I. B., Witte, W., Pfeifer, Y. (2009). Emergence of carbapenem-non-susceptible extended-spectrum {beta}-lactamase-producing Klebsiella pneumoniae isolates at the university hospital of Tubingen, Germany. J Med Microbiol 58: 912-922 [Abstract] [Full Text]  
  • Doumith, M., Ellington, M. J., Livermore, D. M., Woodford, N. (2009). Molecular mechanisms disrupting porin expression in ertapenem-resistant Klebsiella and Enterobacter spp. clinical isolates from the UK. J Antimicrob Chemother 63: 659-667 [Abstract] [Full Text]  
  • Jacoby, G. A. (2009). AmpC {beta}-Lactamases. Clin. Microbiol. Rev. 22: 161-182 [Abstract] [Full Text]  
  • Fu, Y., Guo, L., Xu, Y., Zhang, W., Gu, J., Xu, J., Chen, X., Zhao, Y., Ma, J., Liu, X., Zhang, F. (2008). Alteration of GyrA Amino Acid Required for Ciprofloxacin Resistance in Klebsiella pneumoniae Isolates in China. Antimicrob. Agents Chemother. 52: 2980-2983 [Abstract] [Full Text]  
  • Mammeri, H., Eb, F., Berkani, A., Nordmann, P. (2008). Molecular characterization of AmpC-producing Escherichia coli clinical isolates recovered in a French hospital. J Antimicrob Chemother 61: 498-503 [Abstract] [Full Text]  
  • Vimont, S., Aubert, D., Mazoit, J.-X., Poirel, L., Nordmann, P. (2007). Broad-spectrum {beta}-lactams for treating experimental peritonitis in mice due to Escherichia coli producing plasmid-encoded cephalosporinases. J Antimicrob Chemother 60: 1045-1050 [Abstract] [Full Text]  
  • Rodloff, A. C., Goldstein, E. J. C., Torres, A. (2006). Two decades of imipenem therapy. J Antimicrob Chemother 58: 916-929 [Abstract] [Full Text]  
  • Mena, A., Plasencia, V., Garcia, L., Hidalgo, O., Ayestaran, J. I., Alberti, S., Borrell, N., Perez, J. L., Oliver, A. (2006). Characterization of a Large Outbreak by CTX-M-1-Producing Klebsiella pneumoniae and Mechanisms Leading to In Vivo Carbapenem Resistance Development.. J. Clin. Microbiol. 44: 2831-2837 [Abstract] [Full Text]  
  • Padilla, E., Alonso, D., Domenech-Sanchez, A., Gomez, C., Perez, J. L., Alberti, S., Borrell, N. (2006). Effect of Porins and Plasmid-Mediated AmpC {beta}-Lactamases on the Efficacy of {beta}-Lactams in Rat Pneumonia Caused by Klebsiella pneumoniae.. Antimicrob. Agents Chemother. 50: 2258-2260 [Abstract] [Full Text]  
  • Jacoby, G. A., Walsh, K. E., Walker, V. J. (2006). Identification of Extended-Spectrum, AmpC, and Carbapenem- Hydrolyzing {beta}-Lactamases in Escherichia coli and Klebsiella pneumoniae by Disk Tests.. J. Clin. Microbiol. 44: 1971-1976 [Abstract] [Full Text]  
  • Tomas, M. d. M., Beceiro, A., Perez, A., Velasco, D., Moure, R., Villanueva, R., Martinez-Beltran, J., Bou, G. (2005). Cloning and Functional Analysis of the Gene Encoding the 33- to 36-Kilodalton Outer Membrane Protein Associated with Carbapenem Resistance in Acinetobacter baumannii. Antimicrob. Agents Chemother. 49: 5172-5175 [Abstract] [Full Text]  
  • Alba, J., Ishii, Y., Thomson, K., Moland, E. S., Yamaguchi, K. (2005). Kinetics Study of KPC-3, a Plasmid-Encoded Class A Carbapenem-Hydrolyzing {beta}-Lactamase. Antimicrob. Agents Chemother. 49: 4760-4762 [Abstract] [Full Text]  
  • Paterson, D. L., Bonomo, R. A. (2005). Extended-Spectrum {beta}-Lactamases: a Clinical Update. Clin. Microbiol. Rev. 18: 657-686 [Abstract] [Full Text]  
  • Pichardo, C., Rodriguez-Martinez, J. M., Pachon-Ibanez, M. E., Conejo, C., Ibanez-Martinez, J., Martinez-Martinez, L., Pachon, J., Pascual, A. (2005). Efficacy of Cefepime and Imipenem in Experimental Murine Pneumonia Caused by Porin-Deficient Klebsiella pneumoniae Producing CMY-2 {beta}-Lactamase. Antimicrob. Agents Chemother. 49: 3311-3316 [Abstract] [Full Text]  
  • Bidet, P., Burghoffer, B., Gautier, V., Brahimi, N., Mariani-Kurkdjian, P., El-Ghoneimi, A., Bingen, E., Arlet, G. (2005). In Vivo Transfer of Plasmid-Encoded ACC-1 AmpC from Klebsiella pneumoniae to Escherichia coli in an Infant and Selection of Impermeability to Imipenem in K. pneumoniae. Antimicrob. Agents Chemother. 49: 3562-3565 [Abstract] [Full Text]  
  • Black, J. A., Thomson, K. S., Buynak, J. D., Pitout, J. D. D. (2005). Evaluation of {beta}-Lactamase Inhibitors in Disk Tests for Detection of Plasmid-Mediated AmpC {beta}-Lactamases in Well-Characterized Clinical Strains of Klebsiella spp.. J. Clin. Microbiol. 43: 4168-4171 [Abstract] [Full Text]  
  • Winstanley, T. G., Parsons, H. K., Horstkotte, M. A., Sobottka, I., Sturenburg, E. (2005). Phenotypic detection of {beta}-lactamase-mediated resistance to oxyimino-cephalosporins in Enterobacteriaceae: evaluation of the Mastascan Elite Expert System. J Antimicrob Chemother 56: 292-296 [Abstract] [Full Text]  
  • Bratu, S., Landman, D., Haag, R., Recco, R., Eramo, A., Alam, M., Quale, J. (2005). Rapid Spread of Carbapenem-Resistant Klebsiella pneumoniae in New York City: A New Threat to Our Antibiotic Armamentarium. Arch Intern Med 165: 1430-1435 [Abstract] [Full Text]  
  • Jacoby, G. A., Munoz-Price, L. S. (2005). The New {beta}-Lactamases. NEJM 352: 380-391 [Full Text]  
  • Woodford, N., Tierno, P. M. Jr., Young, K., Tysall, L., Palepou, M.-F. I., Ward, E., Painter, R. E., Suber, D. F., Shungu, D., Silver, L. L., Inglima, K., Kornblum, J., Livermore, D. M. (2004). Outbreak of Klebsiella pneumoniae Producing a New Carbapenem- Hydrolyzing Class A {beta}-Lactamase, KPC-3, in a New York Medical Center. Antimicrob. Agents Chemother. 48: 4793-4799 [Abstract] [Full Text]  
  • Sturenburg, E., Lang, M., Horstkotte, M. A., Laufs, R., Mack, D. (2004). Evaluation of the MicroScan ESBL plus confirmation panel for detection of extended-spectrum {beta}-lactamases in clinical isolates of oxyimino-cephalosporin-resistant Gram-negative bacteria. J Antimicrob Chemother 54: 870-875 [Abstract] [Full Text]  
  • Pai, H., Kang, C.-I., Byeon, J.-H., Lee, K.-D., Park, W. B., Kim, H.-B., Kim, E.-C., Oh, M.-d., Choe, K.-W. (2004). Epidemiology and Clinical Features of Bloodstream Infections Caused by AmpC-Type-{beta}-Lactamase-Producing Klebsiella pneumoniae. Antimicrob. Agents Chemother. 48: 3720-3728 [Abstract] [Full Text]  
  • Jacoby, G. A., Mills, D. M., Chow, N. (2004). Role of {beta}-Lactamases and Porins in Resistance to Ertapenem and Other {beta}-Lactams in Klebsiella pneumoniae. Antimicrob. Agents Chemother. 48: 3203-3206 [Abstract] [Full Text]  
  • Sturenburg, E., Sobottka, I., Noor, D., Laufs, R., Mack, D. (2004). Evaluation of a new cefepime-clavulanate ESBL Etest to detect extended-spectrum {beta}-lactamases in an Enterobacteriaceae strain collection. J Antimicrob Chemother 54: 134-138 [Abstract] [Full Text]  
  • Alvarez, M., Tran, J. H., Chow, N., Jacoby, G. A. (2004). Epidemiology of Conjugative Plasmid-Mediated AmpC {beta}-Lactamases in the United States. Antimicrob. Agents Chemother. 48: 533-537 [Abstract] [Full Text]  
  • Poirel, L., Heritier, C., Tolun, V., Nordmann, P. (2004). Emergence of Oxacillinase-Mediated Resistance to Imipenem in Klebsiella pneumoniae. Antimicrob. Agents Chemother. 48: 15-22 [Abstract] [Full Text]  
  • Nikaido, H. (2003). Molecular Basis of Bacterial Outer Membrane Permeability Revisited. Microbiol. Mol. Biol. Rev. 67: 593-656 [Abstract] [Full Text]  
  • Yigit, H., Queenan, A. M., Rasheed, J. K., Biddle, J. W., Domenech-Sanchez, A., Alberti, S., Bush, K., Tenover, F. C. (2003). Carbapenem-Resistant Strain of Klebsiella oxytoca Harboring Carbapenem-Hydrolyzing {beta}-Lactamase KPC-2. Antimicrob. Agents Chemother. 47: 3881-3889 [Abstract] [Full Text]  
  • Paterson, D. L., Hujer, K. M., Hujer, A. M., Yeiser, B., Bonomo, M. D., Rice, L. B., Bonomo, R. A., the International Klebsiella Study Group,, (2003). Extended-Spectrum {beta}-Lactamases in Klebsiella pneumoniae Bloodstream Isolates from Seven Countries: Dominance and Widespread Prevalence of SHV- and CTX-M-Type {beta}-Lactamases. Antimicrob. Agents Chemother. 47: 3554-3560 [Abstract] [Full Text]  
  • Domenech-Sanchez, A., Martinez-Martinez, L., Hernandez-Alles, S., del Carmen Conejo, M., Pascual, A., Tomas, J. M., Alberti, S., Benedi, V. J. (2003). Role of Klebsiella pneumoniae OmpK35 Porin in Antimicrobial Resistance. Antimicrob. Agents Chemother. 47: 3332-3335 [Abstract] [Full Text]  
  • Schneiders, T., Amyes, S. G. B., Levy, S. B. (2003). Role of AcrR and RamA in Fluoroquinolone Resistance in Clinical Klebsiella pneumoniae Isolates from Singapore. Antimicrob. Agents Chemother. 47: 2831-2837 [Abstract] [Full Text]  
  • Melano, R., Corso, A., Petroni, A., Centron, D., Orman, B., Pereyra, A., Moreno, N., Galas, M. (2003). Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum {beta}-lactamases in a Klebsiella pneumoniae clinical strain isolated in Argentina. J Antimicrob Chemother 52: 36-42 [Abstract] [Full Text]  
  • Fernandez-Cuenca, F., Martinez-Martinez, L., Conejo, M{a} C., Ayala, J. A., Perea, E. J., Pascual, A. (2003). Relationship between {beta}-lactamase production, outer membrane protein and penicillin-binding protein profiles on the activity of carbapenems against clinical isolates of Acinetobacter baumannii. J Antimicrob Chemother 51: 565-574 [Abstract] [Full Text]  
  • Poirel, L., Heritier, C., Podglajen, I., Sougakoff, W., Gutmann, L., Nordmann, P. (2003). Emergence in Klebsiella pneumoniae of a Chromosome-Encoded SHV {beta}-Lactamase That Compromises the Efficacy of Imipenem. Antimicrob. Agents Chemother. 47: 755-758 [Abstract] [Full Text]  
  • Martinez-Martinez, L., Pascual, A., Conejo, M. d. C., Garcia, I., Joyanes, P., Domenech-Sanchez, A., Benedi, V. J. (2002). Energy-Dependent Accumulation of Norfloxacin and Porin Expression in Clinical Isolates of Klebsiella pneumoniae and Relationship to Extended-Spectrum {beta}-Lactamase Production. Antimicrob. Agents Chemother. 46: 3926-3932 [Abstract] [Full Text]  
  • Crowley, B., Benedi, V. J., Domenech-Sanchez, A. (2002). Expression of SHV-2 {beta}-Lactamase and of Reduced Amounts of OmpK36 Porin in Klebsiella pneumoniae Results in Increased Resistance to Cephalosporins and Carbapenems. Antimicrob. Agents Chemother. 46: 3679-3682 [Abstract] [Full Text]  
  • Vakulenko, S. B., Golemi, D., Geryk, B., Suvorov, M., Knox, J. R., Mobashery, S., Lerner, S. A. (2002). Mutational Replacement of Leu-293 in the Class C Enterobacter cloacae P99 {beta}-Lactamase Confers Increased MIC of Cefepime. Antimicrob. Agents Chemother. 46: 1966-1970 [Abstract] [Full Text]  
  • Philippon, A., Arlet, G., Jacoby, G. A. (2002). Plasmid-Determined AmpC-Type {beta}-Lactamases. Antimicrob. Agents Chemother. 46: 1-11 [Full Text]  
  • Spanu, T., Luzzaro, F., Perilli, M., Amicosante, G., Toniolo, A., Fadda, G. (2002). Occurrence of Extended-Spectrum {beta}-Lactamases in Members of the Family Enterobacteriaceae in Italy: Implications for Resistance to {beta}-Lactams and Other Antimicrobial Drugs. Antimicrob. Agents Chemother. 46: 196-202 [Abstract] [Full Text]  
  • Thomson, K. S., Moland, E. S. (2001). Cefepime, Piperacillin-Tazobactam, and the Inoculum Effect in Tests with Extended-Spectrum beta -Lactamase-Producing Enterobacteriaceae. Antimicrob. Agents Chemother. 45: 3548-3554 [Abstract] [Full Text]  
  • Chang, F.-Y., Siu, L. K., Fung, C.-P., Huang, M.-H., Ho, M. (2001). Diversity of SHV and TEM {beta}-Lactamases in Klebsiella pneumoniae: Gene Evolution in Northern Taiwan and Two Novel {beta}-Lactamases, SHV-25 and SHV-26. Antimicrob. Agents Chemother. 45: 2407-2413 [Abstract] [Full Text]  
  • Steward, C. D., Rasheed, J. K., Hubert, S. K., Biddle, J. W., Raney, P. M., Anderson, G. J., Williams, P. P., Brittain, K. L., Oliver, A., McGowan, J. E. Jr., Tenover, F. C. (2001). Characterization of Clinical Isolates of Klebsiella pneumoniae from 19 Laboratories Using the National Committee for Clinical Laboratory Standards Extended-Spectrum {beta}-Lactamase Detection Methods. J. Clin. Microbiol. 39: 2864-2872 [Abstract] [Full Text]  
  • Siu, L. K., Rasheed, J. K., Martínez-Martínez, L., Jacoby, G. A. (2001). Is OmpK35 Specific for Ceftazadime Penetration?. Antimicrob. Agents Chemother. 45: 1601-1602 [Full Text]  
  • Yigit, H., Queenan, A. M., Anderson, G. J., Domenech-Sanchez, A., Biddle, J. W., Steward, C. D., Alberti, S., Bush, K., Tenover, F. C. (2001). Novel Carbapenem-Hydrolyzing {beta}-Lactamase, KPC-1, from a Carbapenem-Resistant Strain of Klebsiella pneumoniae. Antimicrob. Agents Chemother. 45: 1151-1161 [Abstract] [Full Text]  
  • Fung, H. B., Kuczynski, S., Finch, D. A., Ramos, L. (2001). Current Issues in Gram-Negative Resistance: Extended-Spectrum Beta-Lactamases and Inducible Beta-Lactamases. Journal of Pharmacy Practice 14: 6-17 [Abstract]  
  • Cao, V. T. B., Arlet, G., Ericsson, B.-M., Tammelin, A., Courvalin, P., Lambert, T. (2000). Emergence of imipenem resistance in Klebsiella pneumoniae owing to combination of plasmid-mediated CMY-4 and permeability alteration. J Antimicrob Chemother 46: 895-900 [Abstract] [Full Text]  
  • Domenech-Sanchez, A., Pascual, A., Suarez, A. I., Alvarez, D., Benedi, V. J., Martinez-Martinez, L. (2000). Activity of nine antimicrobial agents against clinical isolates of Klebsiella pneumoniae producing extended-spectrum {beta}-lactamases and deficient or not in porins. J Antimicrob Chemother 46: 858-860 [Full Text]  
  • Rasheed, J. K., Anderson, G. J., Yigit, H., Queenan, A. M., Doménech-Sánchez, A., Swenson, J. M., Biddle, J. W., Ferraro, M. J., Jacoby, G. A., Tenover, F. C. (2000). Characterization of the Extended-Spectrum beta -Lactamase Reference Strain, Klebsiella pneumoniae K6 (ATCC 700603), Which Produces the Novel Enzyme SHV-18. Antimicrob. Agents Chemother. 44: 2382-2388 [Abstract] [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] [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 Martínez-Martínez, L.
Right arrow Articles by Jacoby, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martínez-Martínez, L.
Right arrow Articles by Jacoby, G. A.

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