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[Aminoglycosides resistance of methicillin-resistant Staphylococcus aureus]
Abstract:
In the last decade, there has been a dramatic increase in the isolation frequency of methicillin-resistant Staphylococcus aureus (MRSA) in Japan. Especially, a high incidence of multiple resistant MRSA strains has been reported. These strains are resistant not only to beta-lactams but to aminoglycosides and macrolides. About 90% of MRSA strains were resistant to gentamicin (GM) and/or tobramycin (TOB), producing an aminoglycoside modifying enzyme, mainly, APH (2")/AAC (6) and/or AAD (4',4"). Based on these modifying enzymes produced, MRSA strains were classified into three groups; group 1 produced APH (2")/AAC (6), belonging to phage group I and coagulase IV, group 2 produced AAD (4',4"), belonging to phage group III and coagulase II, and group 3 produced APH (2")/AAC (6) and AAD (4',4"), belonging to phage group III and coagulase II. The epidemiological results suggest that MRSA strains changed from group 1 to group 2, and then to group 3. Recently, arbekacin (ABK), a new anti-MRSA aminoglycoside, has been introduced into clinical practice. ABK shows a potent activity to GM-resistant strains, due to poorly modification by APH (2")/AAC (6'). However, there were few ABK- and GM-resistant strains in clinical isolates. These strains produced a higher amount of the enzyme than ABK-susceptible and GM-resistant strains. This observation suggests that ABK-resistant strains might be derived from GM-resistant strains by mutation of the gene coding APH (2")/AAC (6').
Insights
Methicillin-resistant Staphylococcus aureus (MRSA) strains in Japan show increasing resistance to multiple antibiotics, including gentamicin and tobramycin. New aminoglycoside arbekacin remains effective against most strains, though some resistance mechanisms are emerging.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Context:
- Methicillin-resistant Staphylococcus aureus (MRSA) infections pose a significant global health threat.
- Japan has observed a marked increase in MRSA isolation frequency and multidrug-resistant strains.
- Aminoglycoside resistance is a growing concern in MRSA, mediated by specific modifying enzymes.
Purpose:
- To classify MRSA strains based on aminoglycoside resistance mechanisms.
- To evaluate the efficacy of arbekacin (ABK) against gentamicin (GM)-resistant MRSA.
- To investigate the emergence of arbekacin-resistant MRSA strains.
Summary:
- MRSA strains in Japan are increasingly resistant to beta-lactams, aminoglycosides (gentamicin, tobramycin), and macrolides.
- Aminoglycoside resistance is primarily due to enzymes like APH(2”)/AAC(6’) and AAD(4’,4”), classifying strains into three groups.
- Arbekacin demonstrates potent activity against GM-resistant MRSA due to limited modification by APH(2”)/AAC(6’), but emerging resistance suggests potential mutational pathways.
Impact:
- Understanding MRSA resistance patterns is crucial for effective treatment strategies.
- The classification of MRSA strains aids in epidemiological tracking and understanding resistance evolution.
- The emergence of arbekacin resistance highlights the need for ongoing surveillance and development of new antimicrobial agents.