Jpn. J. Infect. Dis., 53, 2000

Laboratory and Epidemiology Communications"Cephem‑Induced Vancomycin Resistance" Observed in PhenotypICallyMethicillin‑Sensitive Staphylococcus aureus Isolated froma Patient Treated with Vancomycln and Cephems
Kozue Iwakawal, Junko Kizul･2, Yoshio Hosakal･3 and Kenji Yamamotol,4*JBun tin Hospital of Universi0, of Too,0,Mejirodai 3‑28‑6, BunbJo‑ku, To砂0 112‑8688,

2Kyoritsu College of Pharmacy, Shibakoen I‑5‑30, Minato‑ku, Too,0 1 05‑8512,
3Deparlmenl of Uy10logy, Organized Clinical Research and Education Medical Center
International UniversiO, of Health and Welfwe,Kilakanemaru, Ohtawara‑shi. Tochigi 324‑0011 and4Department ofMedical Ecology and Genomics, ReseayICh Institute,Internationa/ Medical Center ofJapan,
Toyama I‑21‑1, Shinjuku‑ku, Tob70 162‑8655
Communicated by Hiroshi Yoshikura(Accepted August 1 5, 2000)

and MRSA were classified according to their sensitivIty tooxacillin (MPIPC); isolates whose minimum inhibitory
concentration of MPIPC was less than 4 LLg/ml were judged
to be MSSA.

A patient with recu汀ent transitional cell bladder carcinoma

was operated on three times in succession. First, resection of
the recumnt lesion was perf♭med, then radical cystectomy,

and finally debridement of the surglCal wound. The last

"Cephem‑induced vancomycln resistance" in S. aureus

operation was necessitated by an infection by Staphylococ‑

cus. au7u･ Both methicillin‑sensitive (MSSA) and methicillin‑(CIVRSA) was defined previously ( 1 ) and detected as follows.

resIStant Staphylococcus aureus (MRSA) were isolated during
the course of clinical treatment (Fig. 1). In this study MSSA

Fifty microliters ofovemight culture ofS. aweus whose OD578
nm was adjusted to 0.3 were plated evenly on MU3/VAN
agar (Becton Dickinson Co., Paramus, NJ., USA) which'Corresponding author: E‑mail: backen@ri.imcj.go.jp

contained 4 LLg/ml of vancomycin (VCM). Disks dipped in167

JpnJ. Infect. Dis., 53, 2000
December t98

January '99■February '99

匝団

FMOX

昆M

March｡F,N

●99

FMU.X

loDK｡且April‑KM■99

I EM H
DKB

Antibiotics

回[璽現B叩LX巌

DvEEcBMJao

B
VCM

RS.aureus R
#1

#2

SS

RRRR

#3 #4 #5#6#7#8S♯9

R#14

R#16 R削8

R#15

R#17

Operation

ぎぎ言享 享…
コ層戸.
⊂)コ○■◆)

17/12/98

21/12β829/12/98‑5/I/99

10/2/99 15/2/99

18/1/99

良:MRSA S:MSSA

Fig. I. Clinical course of the patient.

Antibiotics administered are shown in the upper part of the figure. Bacterial isolates are shown in the middle (R: MRSA; S:MSSA), and treatments and symptoms at the bottom･ The dates are indicated as date/month/year･ FMOX, noTPoxef; KM,

kanamycln; CFDN, cefdinir; MINO,minocycline; DKB, dibekacin, VCM, vancomycln; TFLX, tosufloxacln; MEPM,meropenem; EM, erythromycln.

2310111516Fig. 2.Assay forCIVR.
The numbers indicate isolate numbers. Four disks on each plate had been dipped in ceftizoxime dissolved at a concentration

ofO.I, 1.0, 10, or 100 FLg/ml (see diagram at theright end of the bottom).

ceftizoxime (CZX) solutions at concentrations of 0. 1 , 1.0,

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.

10, and 100 LL g/ml were placed on the culture. Isolatesgiving
rise to doughnuトshaped growths around the disks were168

Jpn｣. Infect. Dis., 53, 2000
Table. Sensitivlty Of isolates to antibiotics
Isolates

削舵約糾舶鵬那鵬彬削 削 削 削 削≧ ≧ ≧ ≦≧ ≧ ≧ ≧ ≧MPIPC0 12 1 1 01 10 0 80 0ABPC≧ ≧ ≧ ≦ ≧ ≧ ≧ ≧ ≧ ≧ ≧ 1 1 10 1▲ 1 1 1‑ 6 6 6 6 .2 6 6 6 6 6≧ ≧ ≧ ≧ ≦≧ ≧ ≧ ≧ ≧tJ つ Jt つJt J つ o つJt つJ つJt つJ つJCEZCMZ

IPM

GM′0 つJ ∠UtJ tJO 2 つJ つJ 6 ′0 ▲U /L 上U ′L

2 2 2 2 一J 2 2 2 2 2≧≧≧≧ ≧≧≧≧≧

ABKEM

CLDM

MINO

VCM

LVFX

TFLX

≦ ≦ ≦ ≦ 0一1 1 2 0 2 1 0 ‑ 1≧ m n n n n n m ≧ ≧ ≧ ≧ ≧ ≧ 8 L ‑: ‑: ⊥ ‑: ‑: 上 ‑:･J 8 8 88‑lactamase′0 ▲U∠ ′0 /▲U′hV∠U′0 人U′L ‑U′0 lUエリ′0 ′LU

4242 2 2 24 4 4≧ ≧ ≧ ≧ ≧ ≧ ≧ ≧ ≧ 1 1 I1l ▲Il ▲l1 1 1≧ ≧ ≧ ≧ ≧ ≦ ≧ ≧ ≧ ≧ ≧ ≧ ≧ ≧ 1 4 1 10 41 1 1 6 6 6 .2 6 6 6 6≦ ≧ ≧ ≧ ≧ ≧ ≧ ≦ ≧ ≦ ≧ ≦ ≦ ≦ 〇一1 1 0 1 010一10 101 .5 6 6 6 .2 6 .2 6 .5 5

≦ ≧ ≧ ≦ ≦ ≦ 4 1･ 1 一‑ 1 4 1 1 4 4 4≦ ≦ ≧ ≦ ≦ ≦ ≦ ≦ ≦ ≦ 0 0 1 0 0 0 4 0 0 0 0 52. 62 2 2 25 5 5≦ ≦≦≦≦ ≦ ≧ ≦≦≦≦≦≦ 4140 0 0 81 4 4 4≦55 55n≧ ≧ ≧ ≧ ≧ n≧ m礼 礼m礼 t1 1 1 t1 ◆Lt I .′0b ′0b′ 0.′b+山 山 山 山= 山+ +/▲U ∠U ′LU ′0 ′0 ′LU ∠U ′0 /▲U ′0

6 6 6 6 6 .2 6 6 65 555 525 5 5 6* 0 1 2 つJ 4 5 ′b 7 0555555

書

The figures indicate minimum inhibitory concentration (LLg/ml).

MPIPC, oxacillin; ABPC, ampicillin; CEZ, cefazolin; CMZ, cefmetazole; IPM, imlPenem; GM, gentamycin; ABK, arbekacin; EM, erythromycln;
CLDM, clindamycln; MINO, minocycline; LVFX, 1evonoxacin; TFLX, tosunoxacin.
辛"Cephem‑induced vancomycin‑resistant S. aureus" (CIVRSA)The Table shows the antibiotic sensitivityof these isolates.

VCM was administered just befわre isolation of #9 and 井lo

All were sensitive to VCM. Isolate #9 was MSSA (MIC ≦(on February 19 and March 8). The timing of the combined

0.25 LLg/ml), while #10 was MRSA (MIC ≧ 16 LLg/ml).

antibiotic administration may have influenced the generation

Ilowever, a PCR amplification assay revealed that both #9of CIVRSA.

and #10 had a mecA gene. The reason why #9 was pheno‑REFERENCE

typically MSSA remains unknown. It was noted that #9 was

1. Hanaki, H., Inaba, Y., Sasaki, K.and Hiramatsu, K. (1998):
A novel method of detecting Staphylococcus aureus
heterogenouslyrisistant to vancomycin. Jpn. J. Antibiot. ,generally more sensitive to the tested antibiotics than otherisolates.

Isolate #9 was derived from a sample resected on February

22 and #10 from samples resected on March 9. Cefdinir51, 521‑530.

(CFDN) was continuously administered during this period.

169