Jpn. J. Infect. Dis., 53, 167-169, 2000

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Laboratory and Epidemiology Communications

"Cephem-Induced Vancomycin Resistance" Observed in Phenotypically Methicillin-Sensitive Staphylococcus aureus Isolated from a Patient Treated with Vancomycin and Cephems

Kozue Iwakawa1, Junko Kizu1,2, Yoshio Hosaka1,3 and Kenji Yamamoto1,4*

1Bun'in Hospital of University of Tokyo, Mejirodai 3-28-6, Bunkyo-ku, Tokyo 112-8688, 2Kyoritu College of Pharmacy, Shibakoen 1-5-30, Minato-ku, Tokyo 105-8512, 3Department of Urology, Organized Clinical Research and Education Medical Center, International University of Health and Welfare, Kitakanemaru, Ohtawara-shi, Tochigi 324-0011 and 4Department of Medical Ecology and Genomics, Research Institute, International Medical Center of Japan, Toyama 1-21-1, Shinjuku-ku, Tokyo 162-8655

Communicated by Hiroshi Yoshikura

(Accepted August 15, 2000)

A patient with recurrent transitional cell bladder carcinoma was operated on three times in succession. First, resection of the recurrent lesion was performed, then radical cystectomy, and finally debridement of the surgical wound. The last operation was necessitated by an infection by Staphylococcus aureus. Both methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) were isolated during the course of clinical treatment (Fig. 1). In this study MSSA and MRSA were classified according to their sensitivity to oxacillin (MPIPC); isolates whose minimum inhibitory concentration of MPIPC was less than 4 μg/ml were judged to be MSSA.

"Cephem-induced vancomycin resistance" in S. aureus (CIVRSA) was defined previously (1) and detected as follows. Fifty microliters of overnight culture of S. aureus whose OD578 nm was adjusted to 0.3 were plated evenly on MU3/VAN agar (Becton Dickinson Co., Paramus, N.J., USA) which contained 4 μg/ml of vancomycin (VCM). Disks dipped in ceftizoxime (CZX) solutions at concentrations of 0.1, 1.0, 10 and 100 μg/ml were placed on the culture. Isolates giving rise to doughnut-shaped growths around the disks were defined as CIVRSA. Figure 2 shows the results of these assays. Among 18 isolates, isolate #9 and #10 showed doughnut-shaped growths, i.e., they were CIVRSA.

The Table shows the antibiotic sensitivity of these isolates. All were sensitive to VCM. Isolate #9 was MSSA (MIC ≦ 0.25 μg/ml), while #10 was MRSA (MIC ≧ 16 μg/ml). However, a PCR amplification assay revealed that both #9 and #10 had a mecA gene. The reason why #9 was phenotypically MSSA remains unknown. It was noted that #9 was generally more sensitive to the tested antibiotics than other isolates.

Isolate #9 was derived from a sample resected on February 22 and #10 from samples resected on March 9. Cefdinir (CFDN) was continuously administered during this period. VCM was administered just before isolation of #9 and #10 (on February 19 and March 8). The timing of the combined antibiotic administration may have influenced the generation of CIVRSA.

REFERENCE

  1. Hanaki, H., Inaba, Y., Sasaki, K. and Hiramatsu, K. (1998): A novel method of detecting Staphylococcus aureus heterogenously risistant to vancomycin. Jpn. J. Antibiot. 51, 521-530.

*Corresponding author: E-mail: backen@ri.imcj.go.jp

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