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Antimicrobial Agents and Chemotherapy, May 2005, p. 2002-2007, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.2002-2007.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Altered PBP 2A and Its Role in the Development of Penicillin, Cefotaxime, and Ceftriaxone Resistance in a Clinical Isolate of Streptococcus pneumoniae

Anthony M. Smith,^1* Charles Feldman,² Orietta Massidda,³ Kerrigan McCarthy,¹ Dalu Ndiweni,⁴ and Keith P. Klugman^1,5

MRC/NICD/WITS Respiratory and Meningeal Pathogens Research Unit, National Institute for Communicable Diseases, and University of the Witwatersrand, Johannesburg, South Africa,¹ Division of Pulmonology, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa,² Dipartimento di Scienze e Tecnologie Biomediche, Sez. Microbiologia Medica, Università di Cagliari, Cagliari, Italy,³ Department of Paediatrics, Johannesburg Hospital, and University of the Witwatersrand, Johannesburg, South Africa,⁴ Departments of International Health and Infectious Diseases, Emory University, Atlanta, Georgia⁵

Received 7 October 2004/ Returned for modification 30 November 2004/ Accepted 22 January 2005

We report the unusual involvement of altered PBP 2A in the development of ß-lactam resistance in Streptococcus pneumoniae. This was investigated amid three identical serotype 14 isolates (designated isolates 1, 2, and 3, respectively) of pneumococci cultured successfully from the blood of a human immunodeficiency virus-seropositive child with recurrent pneumonia. The passage of this strain through its human host induced several changes in the bacterium, which is typical of the adaptive and evolving nature of the pneumococcus. An efflux resistance mechanism, which conferred increased ciprofloxacin resistance, was induced in isolates 2 and 3. In addition, faster growth rates and larger capsules were also observed for these isolates, with respect to isolate 1. Notably, compared to isolates 1 and 2, isolate 3 showed a decrease in penicillin, cefotaxime, and ceftriaxone resistance. This change was associated with the replacement of an altered PBP 2A for an unaltered PBP 2A. In all likelihood, these events produced a strain which evolved into a fitter and more virulent type, isolate 3, that resulted in an aggravated pneumococcal infection and ultimately in the patient's death.

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* Corresponding author. Mailing address: Respiratory and Meningeal Pathogens Research Unit, National Institute for Communicable Diseases, P.O. Box 1038, Johannesburg 2000, South Africa. Phone: 27-11-4899335. Fax: 27-11-4899332. E-mail: anthony.smith{at}nhls.ac.za.

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Antimicrobial Agents and Chemotherapy, May 2005, p. 2002-2007, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.2002-2007.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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