Journal of Antimicrobial Chemotherapy (2002) 49, 173-176
© 2002 The British Society for Antimicrobial Chemotherapy
Brief report |
Fluoroquinolone resistance among clinical isolates of Streptococcus pneumoniae belonging to international multiresistant clones
a Pneumococcal Diseases Research Unit of the Medical Research Council, The South African Institute for Medical Research and the University of the Witwatersrand, Johannesburg, South Africa; b Northern Ireland Public Health Laboratory, Belfast City Hospital, Belfast, UK; c Department of International Health, The Rollins School of Public Health, Emory University, Atlanta, GA, USA
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Abstract |
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Twenty-nine fluoroquinolone (FQ)-resistant clinical isolates of Streptococcus pneumoniae from a collection of isolates from the Alexander Project (1992–1997) and a study from Northern Ireland were identified on the basis of ofloxacin MICs
4 mg/L. DNA fingerprint analyses using BOX-fingerprinting and pulsed-field gel electrophoresis revealed serotype 9V and 23F high-level FQ-resistant strains indistinguishable from the pandemic Spain23F-1 and Spain9V-3 clones, the type strains of which are low-level resistant or susceptible to the fluoroquinolones. |
Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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Streptococcus pneumoniae continues to be a significant cause of morbidity and mortality. It is the leading cause of bacterial pneumonia, sinusitis and otitis media, and is an important cause of meningitis. Over the past two decades, the emergence of pneumococci with decreased susceptibility to ß-lactam and non-ß-lactam antibiotics has emphasized the need for new therapeutic agents and has focused attention on the fluoroquinolones (FQs). FQ resistance in wild-type strains of S. pneumoniae has recently been shown to have emerged in Canada.1 These strains do not appear to have had a common clonal origin.
Motivated by the emergence of antimicrobial resistance and the spread of resistant organisms worldwide, subtyping methods to differentiate S. pneumoniae strains of the same serogroup/type have been developed and applied. Extensive molecular typing studies from various regions in the world have identified a number of clones of highly penicillin-resistant pneumococci, some of which have spread globally. Predominant among these are the well-characterized Spanish multidrug-resistant serotype 23F and 6B clones and the major penicillin-resistant serotype 9V clone.2–4
We therefore sought to determine the clonality of FQ resistance of wild-type isolates of S. pneumoniae from different geographical locations in an attempt to provide further insight into the epidemiology of FQ resistance in this important pathogen. A collection of strains was obtained from a study in Northern Ireland and from the Alexander Project, which was established in 1992 to monitor the susceptibility of major lower respiratory tract bacterial pathogens to a variety of antimicrobials and to identify trends in the development of resistance over time.5,6
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Materials and methods |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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Twenty-nine FQ-resistant (ofloxacin MIC
4 mg/L) isolates of S. pneumoniae were selected from a collection of clinical isolates from the Alexander Project (1992–1997) and a collection of strains from 1997 from Northern Ireland (Belfast City Hospital). To assess genetic relatedness of strains we compared these strains with 11 well-characterized international pneumococcal clones: Spain23F-1 (ATCC 700669), Spain6B-2 (ATCC 700670), Spain9V-3 (ATCC 700671), Tennessee23F-4 (ATCC 51916), Spain14-5 (ATCC 700672), Hungary19A-6 (ATCC 700673), S. Africa19A-7 (ATCC 700674), S. Africa6B-8 (ATCC 700675), England14-9 (ATCC700676), CSR14-10 (ATCC 700677) and CSR19A-11 (ATCC 700678).7 MICs of the following antibiotics were determined using broth microdilution methods according to NCCLS guidelines:8 penicillin, chloramphenicol, tetracycline, erythromycin, clindamycin, trimethoprim–sulfamethoxazole, rifampicin, cefotaxime, ciprofloxacin, ofloxacin and levofloxacin. MICs of ciprofloxacin, ofloxacin and levofloxacin were confirmed using Etests (AB Biodisk, Solna, Sweden) according to manufacturer's instructions. The term ‘resistance’ includes intermediate and high-level MICs.
Serotyping of strains was carried out by the Quellung reaction with antisera from the Statens Serum Institut, Copenhagen, Denmark. PCR-based BOX-fingerprinting was carried out on chromosomal DNA by a method adapted from Ertugrul et al.9 Macrorestricted (using SmaI) chromosomal DNA prepared using the method described by Lefevre et al.10 was separated by pulsed-field gel electrophoresis (PFGE) with a Pulsaphor system (Pharmacia, Uppsala, Sweden). Fingerprint patterns were compared with those of 11 international clones.
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Results |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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Of the 29 FQ-resistant strains, eight (28%) belonged to serotype 23F, eight (28%) to serotype 9V and five (17%) to serogroup 6. Serotypes 35, 22, 34, 14 and 20 accounted for the remaining eight isolates. Penicillin resistance (MICs
0.12 mg/L) was found in 65.5% of strains. Twenty-three (70%) strains were multidrug resistant, with resistance to the FQs and at least two other classes of antibiotic. MICs of the FQs were comparable by broth microdilution and Etest. DNA typing of strains using BOX-fingerprinting and PFGE revealed a basically heterogeneous population with 16 types identified by BOX–PCR and PFGE for the 29 strains tested (Table
). A number of the FQ-resistant strains were identified as belonging to the Spain23F-1 and Spain9V-3 international clones (Table). The remaining isolates appeared to be unrelated to the other nine international pneumococcal clones.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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The past decade has seen a dramatic increase in the incidence of pneumococcal strains that are resistant to ß-lactam and non-ß-lactam antimicrobials. The problem has been exacerbated by the spread of a limited number of pneumococcal clones from country to country and from continent to continent. Seven serotype 9V ofloxacinresistant strains (six from Northern Ireland and one from France) were identified as being indistinguishable from the Spain9V-3 clone present in Spain2 and France.4 This clone has become widely disseminated throughout the world and has been identified in parts of Europe, the USA, South America and the Far East.
Four FQ-resistant isolates (three from France and one from Spain) were identical or closely related (fewer than three band differences) to the well-documented Spain23F-1 clone (Table
). This clone has been reported in numerous countries in Europe,2 the USA, South Africa, South America and some regions in the Far East. A recent study in Asia, Europe and North America revealed that 32% of all highly penicillin-resistant isolates belonged to the Spain23F-1 clone.11
These data indicate that FQ resistance may be emerging in pandemic clones of multi-resistant pneumococci, necessitating the need for expanded surveillance for FQ resistance.
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Acknowledgements |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionAcknowledgementsReferences |
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We thank the Alexander Project for the use of S. pneumoniae strains from their 1992 and 1997 collection and SmithKline Beecham for financial support of the study.
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Notes |
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* Correspondence address. Department of Clinical Microbiology and Infectious Diseases, SAIMR, PO Box 1038, Johannesburg 2000, South Africa. Tel: +27-11-4899335; Fax: +27-11-4899332; E-mail: lesmcgee{at}hotmail.com
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References |
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1 . Chen, D. K., McGeer, A., De Azavedo, J. C. & Low, D. E. (1999). Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. New England Journal of Medicine 341, 233–9.
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4 . Lefevre, J. C., Bertrand, M. A. & Faucon, G. (1995). Molecular analysis by pulse-field gel electrophoresis of penicillin-resistant Streptococcus pneumoniae from Toulouse, France. European Journal of Clinical Microbiology and Infectious Diseases 14, 491–7. [Web of Science][Medline]
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8 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Fifth Edition: Approved Standard M7-A5. NCCLS, Villanova, PA.
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Received 18 June 2001; returned 11 August 2001; revised 18 September 2001; accepted 25 September 2001
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