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In vitro development of resistance of Streptococcus pneumoniae to beta-lactam antibiotics
H Carsenti-Etesse1, J Durant, F De Salvador
1Archet Hospital, Nice University, France.
Abstract:
In recent years, increasing numbers of Streptococcus pneumoniae strains displaying relative resistance to penicillin have been reported. Epidemiological studies have shown a correlation between aminopenicillin administration and resistance. We investigated the development of resistance in six strains (four sensitive and two intermediate-resistant to penicillin) by serial daily passages in subinhibitory concentrations of amoxicillin (AMX), amoxicillin + clavulanic acid (AMC), imipenem (IMP), cefixime (CFM), cefatrizine (CTZ), cefadroxil (CDX), and cefuroxime (CXM). MICs were determined by the macrodilution method in brain-heart broth for each daily passage. The number of daily passages needed to increase the MIC by a factor of 8 was achieved with AMX, AMC, and CFM for most of the strains after a mean of 24, 20, and 11 passages, respectively, and for one-third of the strains, with CDX, IMP, and CTZ after 11, 11, and 21 passages, respectively. Decreased susceptibility to breakpoints for intermediate-resistant S. pneumoniae populations was noted for all strains with CFM, AMX, and AMC after a mean of 10, 18, and 21 serial passages, respectively, and for four of five strains with IMP and CTZ after 12 and 13 passages. CTZ-, CDX-, and CXM-passaged variants had increased MIC values only for cephalosporins, while AMX-, AMC-, IMP-, and CFM-passaged variants exhibited increased MICs to all antibiotics tested. These in vitro data appear to be in agreement with epidemiological studies and warrant further exploration with respect to possible clinical implications.
Insights
This study shows that exposing Streptococcus pneumoniae to certain antibiotics like amoxicillin and cefixime can quickly lead to increased resistance. This in vitro resistance development mirrors real-world findings, suggesting potential clinical concerns.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Increasing reports of penicillin-resistant Streptococcus pneumoniae strains.
- Epidemiological links between aminopenicillin use and resistance development.
Purpose of the Study:
- To investigate the in vitro development of antibiotic resistance in Streptococcus pneumoniae.
- To evaluate resistance development against various antibiotics including amoxicillin, amoxicillin + clavulanic acid, imipenem, cefixime, cefatrizine, cefadroxil, and cefuroxime.
Main Methods:
- Serial daily passages of six Streptococcus pneumoniae strains in subinhibitory antibiotic concentrations.
- Determination of Minimum Inhibitory Concentrations (MICs) using the macrodilution method.
- Evaluation of resistance development across different antibiotic classes.
Main Results:
- Rapid development of resistance (MIC increase by 8-fold) observed with amoxicillin, amoxicillin + clavulanic acid, and cefixime within 11-24 passages.
- Decreased susceptibility to intermediate resistance breakpoints noted for cefixime, amoxicillin, and amoxicillin + clavulanic acid.
- Cross-resistance patterns varied; some variants showed resistance only to cephalosporins, while others developed broader resistance to multiple antibiotic classes.
Conclusions:
- In vitro antibiotic pressure can rapidly induce resistance in Streptococcus pneumoniae.
- Observed resistance patterns align with epidemiological data, highlighting potential clinical implications.
- Further research is warranted to understand the clinical impact of these in vitro findings.