Journal of Antimicrobial Chemotherapy (2000) 46, 909-915
© 2000 The British Society for Antimicrobial Chemotherapy
In vitro development of resistance to ceftriaxone, cefprozil and azithromycin in Streptococcus pneumoniae
a Departments of Pathology (Clinical Microbiology), Hershey Medical Center, 500 University Drive, Hershey, PA 170331, USA; b Case Western Reserve University, Cleveland, OH 441062, USA
Approval of ceftriaxone for the treatment of otitis media has led to fear of selection of resistant mutants owing to widespread use. To test this, we examined the ability of sequential subcultures in sub-MICs of ceftriaxone, cefprozil and azithromycin to select resistant mutants in 12 pneumococci. Daily subculturing was performed 50 times or until mutants with raised ceftriaxone, cefprozil or azithromycin MICs were selected. Of eight ceftriaxone-susceptible parents, ceftriaxone did not select for any resistant mutants, while cefprozil selected for four mutants (MICs 2–4 mg/L after 21–50 subcultures). Among four ceftriaxone-resistant parents, subculturing in ceftriaxone selected for one stable mutant with raised ceftriaxone MIC (>16 mg/L after 21 subcultures) and subculturing in cefprozil selected for one mutant with raised cefprozil MIC (64 mg/L after 44 subcultures). Mutations were observed in pbp2x and pbp1a. Among six azithromycin-susceptible parents, subculturing in azithromycin selected for five resistant mutants (MIC 0.5–32 mg/L after 10–42 passages) and among six azithromycin-resistant strains, subculturing selected for mutants with raised azithromycin MICs in all six strains (MIC 16–32 mg/L after 4–18 passages). All azithromycin-resistant mutants derived from azithromycinsusceptible parents had mutations in domain V of 23S rRNA while all azithromycin-resistant parents and derived mutants had mefE. Single-step mutation rates among the 12 strains at the MIC ranged from 1.5 x 10–6 to <6.2 x 10–10 for ceftriaxone, >1.3 x 10–5 to 8.9 x 10–8 for cefprozil and >1.1 x 10–6 to 6.7 x 10–10 for azithromycin. Multi-step and single-step testing showed that ceftriaxone selected for resistant mutants less often than cefprozil and azithromycin.
* Corresponding author. Tel: +1-717-531-5113; Fax: +1-717-531-7953; E-mail: pappelbaum{at}psu.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Nagai, T. A. Davies, M. R. Jacobs, and P. C. Appelbaum Effects of Amino Acid Alterations in Penicillin-Binding Proteins (PBPs) 1a, 2b, and 2x on PBP Affinities of Penicillin, Ampicillin, Amoxicillin, Cefditoren, Cefuroxime, Cefprozil, and Cefaclor in 18 Clinical Isolates of Penicillin-Susceptible, -Intermediate, and -Resistant Pneumococci Antimicrob. Agents Chemother., May 1, 2002; 46(5): 1273 - 1280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. de Neeling, B. P. Overbeek, A. M. Horrevorts, E. E. J. Ligtvoet, and W. G. Goettsch Antibiotic use and resistance of Streptococcus pneumoniae in The Netherlands during the period 1994-1999 J. Antimicrob. Chemother., September 1, 2001; 48(3): 441 - 444. [Abstract] [Full Text] [PDF]
|
|