Vol.53 No.1 January 2005

In vitro activity of antibacterial agents against β -lactam antibiotic-induced vancomycin resistant MRSA

Kazunori Maebashi, Makiko Tabata, Mariko Tani, Masaki Shimizu, Yoshihisa Kato and Muneo Hikida

Infectious Disease Research Laboratories, Meiji Seika Kaisha, Ltd.,
760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa, Japan

Abstract

We compared the sensitivity of methicillin-resistant Staphylococcus aureus (MRSA) to drugs such as arbekacin (ABK), vancomycin (VCM) and teicoplanin (TEIC) in β -lactam antibiotic-induced VCM-resistant MRSA (BIVR) and non-BIVR strains. MRSA clinical isolates (121 strains) were classified into 16 strains of BIVR and 105 strains of non-BIVR due to the existence of antagonism between ceftizoxime (CZX) and VCM in an Mu3 medium. There was a slight difference between the susceptibility of BIVR and non-BIVR to ABK. The antibacterial activity of ABK was also not affected in combination with low-concentrations of CZX (0.06 or 1 μ g/mL). On the other hand, the minimum inhibitory concentrations, MIC₅₀ and MIC₉₀, of VCM against BIVR strains were both twice higher than against non-BIVR strains, and were also 4 times higher than against non-BIVR strains in combination with CZX. Although the antibacterial activity of TEIC against BIVR strains did not change in the presence of CZX, the MIC₅₀ and MIC₉₀ of TEIC alone were 8 and 4 times higher than against non-BIVR strains, respectively. Next, the relationship between the MIC of TEIC and detection frequency of BIVR strains was investigated. As a result, the higher the MIC of TEIC, the more frequently BIVR strains were found. Furthermore, BIVR strains were isolated from non-BIVR sub-populations with diminished susceptibility to TEIC.
In conclusion, the antibacterial activity of ABK was not changed by the difference between BIVR and non-BIVR strains. On the other hand, VCM showed antagonistic effects in combination with CZX at low concentrations against BIVR strains. TEIC alone was less effective against BIVR strains, although TEIC did not reveal any antagonistic effect against BIVR strains in combination with CZX.

Key word

MRSA, arbekacin, vancomycin, teicoplanin, β-lactam antibiotic-induced vancomycin resistant MRSA

Received

October 15, 2004

Accepted

November 24, 2004

Jpn. J. Chemother. 53 (1): 5-10, 2005