THE FUTURE OF AMINOGLYCOSIDES
Efforts to keep aminoglycosides as useful weapons in the arsenal against bacterial infectious diseases include development of aminoglycosides that are more unyielding to AMEs, and the development of inhibitors of AMEs.7,9 Antibiotic stewardship is vital to the future of all antibiotic efficacy. Measures include limiting use of antibiotics only when indicated, education for patients about the importance of finishing their prescription, and de-escalation or narrowing antibiotic therapy from an empirical broad spectrum antimicrobial to a pathogen specific narrow spectrum drug when the laboratory susceptibility results are available.
There have been several studies with promising results of in vitro activity of plazomicin, a new generation aminoglycoside (formerly ACHN-490) against multi-drug resistant clinical isolates of K. pneumoniae, E. coli, Enterobacter spp, and even MRSA. 10 ,11 Plazomicin does not appear to be compromised by most clinically relevant AMEs but does appear to be affected by methyltransferases.
We would like to thank Ms. Lorraine Campbell for her contribution to our newsletter.
Ms. Lorraine Campbell is staff at the Microbiology Laboratory, Calgary Laboratory Services, Calgary, AB; and a member of the Clinical Microbiology Proficiency Testing (CMPT) Microbiology Subcommittee.
References
1. Jorgensen JH, et al. 2015. Antibacterial Agents and Susceptibility Test Methods. Manual of Clinical Microbiology. Eleventh ed. ASM Press. Washington, DC. pp 1180-1182.
2. Mandell, Douglas and Bennett. 2015. Aminoglycosides. Principles and Practice of Infectious Diseases. Eighth Edition. Elsevier Saunders Philadelphia, PA. pp 224-233.
3. Mandell, Douglas and Bennett. 2015. Molecular Mechanisms of Antibiotic Resistance in Bacteria. Principles and Practice of Infectious Diseases. Eighth Edition. Elsevier Saunders Philadelphia, PA. pp 235-251.
4. Jorgensen JH, et al. 2015. Mechanisms of Resistance to Antibacterial Agents. Manual of Clinical Microbiology. Eleventh ed. ASM Press. Washington, DC. Pp 1212-1245.
5. Mandell, Douglas and Bennett. 2015. Principles of Anti-infective Therapy. Principles and Practice of Infectious Diseases. Eighth Edition. Elsevier Saunders. Philadelphia, PA. pp 224-234.
6. Webber MA, Piddock LJV. The importance of efflux pumps in bacterial antibiotic resistance. 2003. Journal of Antimicrobial Chemotherapy. 51: 9-11
7. Ramirez MS, Tolmasky ME. 2010. Aminoglycoside Modifying Enzymes. Drug Resist Update. Dec: 13(6): 151-171
8. CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement. CLSI document M100-S25. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.
9. Vakulenko SB, Mobashery S. Versatility of Aminoglycosides and Prospects for Their Future. 2003. Clinical Microbiology Reviews. 61: 430-450.
10. Walkty A, et al. In Vitro Activity of Plazomicin against 5,015 Gram-Negative and Gram-Positive Clinical Isolates Obtained from Patients in Canadian Hospitals as Part of the CANWARD Study, 2011-2012. 2014. Antimicrobial Agents and Chemotherapy. May; 58(5): 2554-2563.
11. Galani I, et al. Activity of Plazomicin (ACHN-490) against MDR clinical isolates of Klebsiella pneumonia, Escherichia coli, and Enterobacter spp. From Athens, Greece. 2012. Journal of Chemotherapy (Florence, Italy). Aug; 24(4): 191-194.
