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Single and multi-step resistance selection study in Streptococcus pneumoniae comparing ceftriaxone with levofloxacin,
Frederick A Browne1, Cathy Clark, Bülent Bozdogan
1Department of Medicine, Hershey Medical Center, 500 University Drive, PA 17033, USA.
Abstract:
Attempts were made to select resistant pneumococcal mutants by sequential subculturing of 12 clinically isolated pneumococci, [four were penicillin sensitive (MIC) 0.03-0.06 mg/l, four penicillin intermediate (MIC 0.25-0.5 mg/l) and four penicillin resistant (MIC 2-4 mg/l)] in sub-inhibitory concentrations of ceftriaxone, levofloxacin, gatifloxacin and moxifloxacin. Subculturing in gatifloxacin, levofloxacin, moxifloxacin and ceftriaxone selected 12 mutants (12/12), 10 mutants (10/12), 10 mutants (10/12) and three mutants (3/12), respectively. DNA sequencing of the quinolone-resistant mutants showed that most strains had mutations in GyrA at E85 or S81. This in vitro mutation study demonstrates a clear distinction between the low frequency of development of resistance with ceftriaxone exposure as opposed to the high frequency with quinolone exposure.
Insights
This study found that exposing pneumococci to quinolones like gatifloxacin and levofloxacin rapidly selects for resistant mutants. Ceftriaxone, however, showed a much lower frequency of resistance development in vitro.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Antibiotic resistance in Streptococcus pneumoniae is a significant global health concern.
- Pneumococci are common causes of bacterial infections, including pneumonia, meningitis, and sepsis.
- The emergence of antibiotic resistance necessitates continuous monitoring and evaluation of antimicrobial agents.
Purpose of the Study:
- To investigate the in vitro development of resistance in clinical pneumococcal isolates exposed to ceftriaxone and three fluoroquinolones (gatifloxacin, levofloxacin, moxifloxacin).
- To compare the frequency of resistance selection between a cephalosporin (ceftriaxone) and fluoroquinolones.
Main Methods:
- Sequential subculturing of 12 clinical pneumococcal isolates (penicillin-sensitive, intermediate, and resistant) in sub-inhibitory concentrations of antibiotics.
- DNA sequencing of quinolone-resistant mutants to identify specific genetic mutations.
Main Results:
- High frequencies of resistant mutants were selected by gatifloxacin (12/12), levofloxacin (10/12), and moxifloxacin (10/12).
- A significantly lower frequency of resistance was observed with ceftriaxone exposure (3/12).
- Mutations in the GyrA gene (E85 or S81) were common in quinolone-resistant strains.
Conclusions:
- Fluoroquinolones, including gatifloxacin, levofloxacin, and moxifloxacin, readily select for resistant pneumococcal mutants in vitro.
- Ceftriaxone demonstrates a lower propensity for resistance development compared to fluoroquinolones.
- Understanding differential resistance selection is crucial for antimicrobial stewardship and treatment guidelines.
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