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Antimicrobial Agents and Chemotherapy, January 2001, p. 88-95, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.88-95.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Complexity and Diversity of Klebsiella pneumoniae Strains with Extended-Spectrum beta -Lactamases Isolated in 1994 and 1996 at a Teaching Hospital in Durban, South Africa

Sabiha Y. Essack,1 Lucinda M. C. Hall,2 Devadas G. Pillay,3 Margaret Lynn McFadyen,1 and David M. Livermore4,*

Department of Pharmacy and Pharmacology, University of Durban-Westville, Durban, 4000,1 and Department of Medical Microbiology, University of Natal, Congella, 4013,3 South Africa, and Department of Medical Microbiology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London E1 2AD,2 and Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, London NW9 5HT,4 United Kingdom

Received 10 January 2000/Returned for modification 25 April 2000/Accepted 10 October 2000

beta -Lactamase production was investigated in cultures of 25 Klebsiella pneumoniae isolates isolated at a hospital in Durban, South Africa, in 1994 and 1996. Twenty of these isolates gave ceftazidime MIC/ceftazidime plus clavulanate MIC ratios of >= 8, implying production of extended-spectrum beta -lactamases (ESBLs), and DNA sequencing identified an ESBL gene (blaTEM-53) in a further two isolates. Pulsed-field gel electrophoresis (PFGE) defined 4 distinct strains among the 12 isolates collected in 1994 and 9 distinct strains among the 13 isolates collected in 1996. In three cases, multiple isolates from single patients varied in their PFGE profiles and antibiograms, implying mixed colonization or infection. Isoelectric focusing and DNA hybridization found both TEM and SHV enzymes and their genes in all 25 isolates. Many isolates had multiple identical or different beta -lactamase gene variants, with at least 84 blaSHV and blaTEM gene copies among the 25 organisms. Sequencing identified the genes for the SHV-1, -2, and -5 enzymes and for four new SHV types (SHV-19, -20, -21, and -22). These new SHV variants had novel mutations remote from sites known to affect catalytic activity. Sequencing also found the genes for TEM-1, TEM-53, and one novel type, TEM-63. All the isolates had multiple and diverse plasmids. These complex and diverse patterns of ESBL production and strain epidemiology are far removed from the concept of an ESBL outbreak and suggest a situation in which ESBL production has become endemic and in which evolution is generating a wide range of enzyme combinations. This complexity and diversity complicates patient management and the design of antibiotic use policies.

* Corresponding author. Mailing address: Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, 61 Colindale Ave., London NW9 5HT, United Kingdom. Phone: 0208-200-4400. Fax: 0208-200-7449. E-mail: DLivermore{at}phls.nhs.uk.

Antimicrobial Agents and Chemotherapy, January 2001, p. 88-95, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.88-95.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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