Korean J Lab Med.  2007 Aug;27(4):292-297. 10.3343/kjlm.2007.27.4.292.

In Vitro Activity of Arbekacin Against Clinical Isolates of Staphylococcus species and Gram-negative Bacilli

• Lee J
• Kim CK
• Roh KH
• Lee H
• Yum JH
• Yong D
• Lee K
• Chong Y

• KMID: 1781499
• DOI: http://doi.org/10.3343/kjlm.2007.27.4.292

Abstract

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and some gram-negative bacilli are very prevalent nosocomial pathogens, commonly causing mixed infections, and are often resistant to multiple drugs. Arbekacin is an aminoglycoside used for the treatment of MRSA infections, but is also active against some gram-negative bacilli. The aim of this study was to determine in vitro activity of arbekacin against recent clinical isolates of staphylococci and gram-negative bacilli. Materials and METHODS: The strains were isolated from clinical specimens of patients at Severance Hospital in 2003. Antimicrobial susceptibility was tested by the Clinical and Laboratory Standards Institute agar dilution method. The following arbekacin breakpoints were used: susceptible, < or =4 microgram/mL; and resistant, > or =16 microgram/mL . RESULTS: All isolates of staphylococci tested were inhibited by < or =4 microgram/mL of arbekacin, regardless of their methicillin susceptibility. The MIC90s of arbekacin, 1-4 microgram/mL, were 8->32-fold and >32-128-fold lower than those of amikacin and gentamicin, respectively. The resistance rates of MRSA, methicillin-susceptible S. aureus, methicillin-resistant coagulase-negative staphylococci (CNS) and methicillin-susceptible CNS were 0% to arbekacin, 0-54% to amikacin, and 24-79% to gentamicin. The MIC90s of arbekacin for Escherichia coli and Citrobacter freundii, 1 microgram/mL and 16 microgram/mL, were 2-4-fold and 8-16-fold lower than those of amikacin and gentamicin, respectively. However, The MIC90s of arbekacin for other species of gram-negative bacilli, 64->128 microgram/mL, were similar to those of other aminoglycosides. CONCLUSIONS: Arbekacin may be a useful alternative to glycopeptides for the treatment of monomicrobial methicillin-resistant staphylococcal infections, as well as mixed infections with gram-negative bacilli, as most isolates of E. coli, C. freundii and some other gram-negative bacilli were also susceptible to arbekacin.

Keyword

Arbekacin; MRSA; Gram-negative bacilli; In vitro activity

MeSH Terms

Anti-Bacterial Agents/*pharmacology
Dibekacin/*analogs & derivatives/pharmacology
Gram-Negative Bacteria/*drug effects/isolation & purification
Gram-Negative Bacterial Infections/microbiology
Humans
Methicillin Resistance
Microbial Sensitivity Tests
Staphylococcal Infections/microbiology
Staphylococcus aureus/*drug effects/isolation & purification

Reference

References

1. Chambers HF. Methicillin-resistant staphylococci. Clin Microbiol Rev. 1988; 1:173–86.

2. Menichetti F. Current and emerging serious Gram-positive infections. Clin Microbiol Infect. 2005; 11(S):):S22–8.

3. Cunha BA. Methicillin-resistant Staphylococcus aureus: clinical manifestations and antimicrobial therapy. Clin Microbiol Infect. 2005; 11:33–42.

4. Wie SH, Kang JH, Huh DH, Lee DG, Kim SI, Kim YR, et al. Antimicrobial activities of arbekacin against clinical isolates of Staphylococcus aureus and coagulase-negative Staphylococcus species. Korean J Infect Dis. 2001; 33:254–60.

5. Drinka P, Faulks JT, Gauerke C, Goodman B, Stemper M, Reed K. Adverse events associated with methicillin-resistant Staphylococcus aureus in a nursing home. Arch Intern Med. 2001; 161:2371–7.

6. Shankar EM, Mohan V, Premalatha G, Srinivasan RS, Usha AR. Bacterial etiology of diabetic foot infections in South India. Eur J Intern Med. 2005; 16:567–70.

7. Zahar JR, Clec'h C, Tafflet M, Garrouste-Orgeas M, Jamali S, Mourvillier B, et al. Is methicillin resistance associated with a worse prognosis in Staphylococcus aureus ventilator-associated pneumonia? Clin Infect Dis. 2005; 41:1224–31.

8. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; Seventeenth informational supplement. M100-S17. Wayne, PA: Clinical and Laboratory Standards Institute;2007.

9. Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM. Aminoglycosides: activity and resistance. Antimicrob Agents Chemother. 1999; 43:727–37.

10. Azucena E, Mobashery S. Aminoglycoside-modifying enzymes: mechanisms of catalytic processes and inhibition. Drug Resist Updat. 2001; 4:106–17.

11. Ferretti JJ, Gilmore KS, Courvalin P. Nucleotide sequence analysis of the gene specifying the bifunctional 6′-aminoglycoside acetyl-transferase 2″-aminoglycoside phosphotransferase enzyme in Streptococcus faecalis and identification and cloning of gene regions specifying the two activities. J Bacteriol. 1986; 167:631–8.

12. Shaw KJ, Rather PN, Hare RS, Miller GH. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev. 1993; 57:138–63.

13. Schmitz FJ, Fluit AC, Gondolf M, Beyrau R, Lindenlauf E, Verhoef J, et al. The prevalence of aminoglycoside resistance and corresponding resistance genes in clinical isolates of staphylococci from 19 European hospitals. J Antimicrob Chemother. 1999; 43:253–9.

14. Ida T, Okamoto R, Shimauchi C, Okubo T, Kuga A, Inoue M. Identification of aminoglycoside-modifying enzymes by susceptibility testing: epidemiology of methicillin-resistant Staphylococcus aureus in Japan. J Clin Microbiol. 2001; 39:3115–21.

15. Obayashi Y, Fujita J, Ichiyama S, Hojo S, Negayama K, Takashima C, et al. Investigation of nosocomial infection caused by arbekacin-resistant, methicillin-resistant Staphylococcus aureus. Diagn Microbiol Infect Dis. 1997; 28:53–9.

16. Ishino K, Ishikawa J, Ikeda Y, Hotta K. Characterization of a bifunctional aminoglycoside-modifying enzyme with novel substrate specificity and its gene from a clinical isolate of methicillin-resistant Staphylococcus aureus with high arbekacin resistance. J Antibiot (Tokyo). 2004; 57:679–86.

17. Cordeiro JC, Reis AO, Miranda EA, Sader HS. In vitro antimicrobial activity of the aminoglycoside arbekacin tested against oxacillinresistant Staphylococcus aureus isolated in Brazilian hospitals. Braz J Infect Dis. 2001; 5:130–5.

18. Matsuo H, Kobayashi M, Kumagai T, Kuwabara M, Sugiyama M. Molecular mechanism for the enhancement of arbekacin resistance in a methicillin-resistant Staphylococcus aureus. FEBS Lett. 2003; 546:401–6.

19. Chong Y, Lee K, Shin JW, Shin HB, Lim JB. Activities of arbekacin against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Korean J Chemother. 1997; 15:319–28.

20. Lee SM, Song EJ, Yang EK, Bae IK, Jeong SH, Kim JM, et al. Antimicrobial activities of arbekacin against recent isolates of Staphylococcus aureus in Korean hospitals. Korean J Clin Microbiol. 2006; 9:13–7.

21. Lee JY, Oh WS, Ko KS, Heo ST, Moon CS, Ki HK, et al. Synergy of arbekacin-based combinations against vancomycin hetero-intermediate Staphylococcus aureus. J Korean Med Sci. 2006; 21:188–92.

22. Kim TH, Choo EJ, Lee MS, Kim NJ, Woo JH, Ryu JS, et al. Clinical efficacy and safety with arbekacin for methicillin-resistant Staphylococcus aureus (MRSA) infections. Korean J Med. 2003; 65:239–44.

23. Deguchi K, Suzuki Y, Ishihara R, Ishii Y, Nakazawa A, Matsumoto Y, et al. Antimicrobial activities of arbekacin against methicillin-resistant Staphylococcus aureus. Jpn J Antibiot. 1997; 50:1–11.

24. Ishino K, Ishikawa J, Ikeda Y, Hotta K. Characterization of a bifunctional aminoglycoside-modifying enzyme with novel substrate specificity and its gene from a clinical isolate of methicillin-resistant Staphylococcus aureus with high arbekacin resistance. J Antibiot (Tokyo). 2004; 57:679–86.

25. Choi SM, Kim SH, Kim HJ, Lee DG, Choi JH, Yoo JH, et al. Multiplex PCR for the detection of genes encoding aminoglycoside modifying enzymes and methicillin resistance among Staphylococcus species. J Korean Med Sci. 2003; 18:631–6.

26. Miller GH, Sabatelli FJ, Hare RS, Glupczynski Y, Mackey P, Shlaes D, et al. The most frequent aminoglycoside resistance mechanisms-changes with time and geographic area: a reflection of aminoglycoside usage patterns? Aminoglycoside Resistance Study Groups. Clin Infect Dis. 1997; 24:46–62.

27. Park YJ, Lee S, Yu JK, Woo GJ, Lee K, Arakawa Y. Co-production of 16S rRNA methylases and extended-spectrum beta-lactamases in AmpC-producing Enterobacter cloacae, Citrobacter freundii and Serratia marcescens in Korea. J Antimicrob Chemother. 2006; 58:907–8.