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Published on: September 8, 2021
Inhibition of Erythromycin and Erythromycin-Induced Resistance among Staphylococcus aureus Clinical Isolates
Aya A Mahfouz1,2, Heba S Said1, Sherin M Elfeky3
1Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Abstract:
The increasing incidence of erythromycin and erythromycin-induced resistance to clindamycin among Staphylococcus aureus (S. aureus) is a serious problem. Patients infected with inducible resistance phenotypes may fail to respond to clindamycin. This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance.
Insights
Antibiotic resistance in Staphylococcus aureus is rising. This study found that doxorubicin, neomycin, and omeprazole can reduce erythromycin resistance, while other compounds may reverse clindamycin resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Increasing incidence of erythromycin resistance and erythromycin-induced clindamycin resistance in Staphylococcus aureus poses a significant clinical challenge.
- Patients with inducible resistance phenotypes may experience treatment failure with clindamycin therapy.
Purpose of the Study:
- To determine the prevalence of erythromycin resistance and erythromycin-induced clindamycin resistance in Staphylococcus aureus isolates.
- To identify potential therapeutic agents that can inhibit or reverse these resistance mechanisms.
Main Methods:
- Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB) resistance using D-test.
- Identification of MLSB-resistance genes via PCR.
- Screening of various compounds for their inhibitory effects on erythromycin and inducible clindamycin resistance using broth microdilution and checkerboard assays, followed by docking analysis.
Main Results:
- Out of 99 clinical isolates, 91 were identified as Staphylococcus aureus.
- Prevalence rates were: constitutive MLSB (39.6%), inducible MLSB (14.3%), and macrolide-streptogramin (MS) (2.2%).
- Specific resistance genes (ermC, ermA, ermB, msrA, msrB, lnuA, mphC) were detected at varying frequencies. Doxorubicin, neomycin, and omeprazole significantly reduced erythromycin resistance. Quinine, ketoprofen, and fosfomycin reversed erythromycin/clindamycin-induced resistance.
Conclusions:
- The study underscores the importance of managing antibiotic resistance and addressing clindamycin treatment failures.
- Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin show potential as inhibitors against erythromycin and inducible clindamycin resistance in Staphylococcus aureus.
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