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Antimicrobial Agents and Chemotherapy, November 1998, p. 2914-2918, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vitro Selection of Resistance to Four beta -Lactams and Azithromycin in Streptococcus pneumoniae

Glenn A. Pankuch,1 Shane A. Jueneman,1 Todd A. Davies,1 Michael R. Jacobs,2 and Peter C. Appelbaum1,*

Department of Pathology (Clinical Microbiology), Hershey Medical Center, Hershey, Pennsylvania 17033,1 and Department of Pathology (Clinical Microbiology), Case Western Reserve University, Cleveland, Ohio 441062

Received 7 April 1998/Returned for modification 23 July 1998/Accepted 17 August 1998

Selection of resistance to amoxicillin (with or without clavulanate), cefaclor, cefuroxime, and azithromycin among six penicillin G- and azithromycin-susceptible pneumococcal strains and among four strains with intermediate penicillin sensitivities (azithromycin MICs, 0.125 to 4 µg/ml) was studied by performing 50 sequential subcultures in medium with sub-MICs of these antimicrobial agents. For only one of the six penicillin-susceptible strains did subculturing in medium with amoxicillin (with or without clavulanate) lead to an increased MIC, with the MIC rising from 0.008 to 0.125 µg/ml. Five of the six penicillin-susceptible strains showed increased azithromycin MICs (0.5 to >256.0 µg/ml) after 17 to 45 subcultures. Subculturing in medium with cefaclor did not affect the cefaclor MICs of three strains but and led to increased cefaclor MICs (from 0.5 to 2.0 to 4.0 µg/ml) for three of the six strains, with MICs of other beta -lactams rising 1 to 3 twofold dilutions. Subculturing in cefuroxime led to increased cefuroxime MICs (from 0.03 to 0.06 µg/ml to 0.125 to 0.5 µg/ml) for all six strains without significantly altering the MICs of other beta -lactams, except for one strain, which developed an increased cefaclor MIC. Subculturing in azithromycin did not affect beta -lactam MICs. Subculturing of the four strains with decreased penicillin susceptibility in amoxicillin (with or without clavulanate) or cefuroxime did not select for beta -lactam resistance. Subculturing of one strain in cefaclor led to an increase in MIC from 0.5 to 2.0 µg/ml after 19 passages. In contrast to strains that were initially azithromycin susceptible, which required >10 subcultures for resistance selection, three of four strains with azithromycin MICs of 0.125 to 4.0 µg/ml showed increased MICs after 7 to 13 passages, with the MICs increasing to 16 to 32 µg/ml. All azithromycin-resistant strains were clarithromycin resistant. With the exception of strains that contained mefE at the onset, no strains that developed resistance to azithromycin contained ermB or mefE, genes that have been found in macrolide-resistant pneumococci obtained from clinic patients.

* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, 500 University Dr., Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelbaum{at}psghs.edu.

Antimicrobial Agents and Chemotherapy, November 1998, p. 2914-2918, Vol. 42, No. 11
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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