Shinshu Med J, 65⑵：113～116, 2017

Bacteremia Caused by Yokenella regensburgei
in a Patient with Diabetes Mellitus
Hiromasa Fukatsu1）＊, Akihiro Yashio2） and Takayuki Honda3）
1） Department of Clinical Laboratory Investigation, Graduate School of Medicine, Shinshu University2） Department of Emergency and Critical Care Medicine, Shinshu University School of Medicine
3） Department of Laboratory Medicine, Shinshu University Hospital

Yokenella regensburgei rarely causes human infections, and there is no strong evidence to support its
clinical importance. We report the first case in Japan of bacteremia caused by Y. regensburgei in a patient withdiabetic gangrene. A 74-year-old man was admitted to our hospital. He had type 2 diabetes mellitus, andunderwent surgical amputation of both lower limbs due to gangrene. Y. regensburgei was isolated fromswabbing of the wounds on the limbs and the blood samples. The case was successfully treated by intravenous
administration of ampicillin-sulbactam and ceftazidime. Shinshu Med J 65 : 113―116, 2017
(Received for publication October 31, 2016 ; accepted in revised form December 12, 2016)
Key words : Yokenella regensburgei, bacteremia, diabetes mellitus

was admitted to the emergency department with aⅠ Introduction

decreased level of consciousness. On admission, theThe genus Yokenella belongs to the family Entero-patient had gangrene of the lower limbs. On Day 3

bacteriaceae and comprises one species, Yokenella re-after the admission, the patient underwent surgical

gensburgei 1）. Y. regensburgei has been isolated fromamputation of both lower limbs due to the gangrene.

well water, the intestinal tract of insects, reptiles,

The laboratory examination revealed the following

and salad. Only a few cases of human infection with: a hemoglobin A1c count of 9.4 %, a white blood cell

Y. regensburgei have been reported2）-8）; therefore, at(WBC) count of 10,270 cells/µl, a C-reactive proteinpresent, its clinical significance is not well under-(CRP) level of 27.75 mg/dl, a fibrinogen level ofstood. Furthermore, Y. regensburgei shares some

432 mg/dl, a platelet count of 5.3×104 cells/µl, andbiochemical characteristics with Hafnia alvei. Thus,a D-dimer level of 10.7 µg/ml. On Day 6 after theit is difficult to accurately differentiate between Y.

amputation, the patient had a temperature of 38 ℃.

regensburgei and H. alvei by routine identification

Bacteriological examination was performed bytechniques. In this paper, we report the first case ofswabbing the wounds on the limbs. On Day 8 after

bacteremia caused by Y. regensburgei in a patient

the amputation, body temperature was 38.5 ℃,

with diabetic gangrene in Japan, which could be

blood pressure 71/48 mmHg, and respiratory rate 24

identified using 16S rRNA gene sequence analysis.

breaths/min. Laboratory examination revealed aⅡ Case Report
A 74-year-old man with type 2 diabetes mellitus

WBC count of 7,690 cells/µl, a CRP of 18.35 mg/dl,fibrinogen levels of 363 mg/dl, a platelet count of
13.6×104 cells/µl, and D-dimer levels of 7.7 µg/ml.
Two sets of blood samples from peripheral veins＊

Corresponding author : Hiromasa Fukatsu
Department of Clinical Laboratory Investigation, Graduate
School of Medicine, Shinshu University, 3-1-1 Asahi,Matsumoto, Nagano 390-8621, Japan
E-mail : 15mz004k@shinshu-u.ac.jp

No. 2, 2017

were collected for culture in BACTEC Plus Aerobic/F and Plus Anaerobic/F Mediums bottles (Nippon Becton Dickinson Co., Ltd., Tokyo, Japan) using
a BACTEC FX system (Nippon Becton Dickinson
113

Fukatsu・Yashio・Honda
Table 1

Antimicrobial susceptibility results of Y. regensburgei isolate

Antimicrobial agent
Ampicillin
Amikacin
Amoxicillin-clavulanic acid
Aztreonam
Ceftazidime
Cefaclor
Cefazolin
Cefcapene
Cefmetazole
Cefpirome
Cefoperazone-sulbactam
Cefotiam
Cefotaxime
Flomoxef
Fosfomycin
GentamicinImipenem
Levofloxacin
Minocycline
Piperacillin
Sulfamethoxazole-Trimethoprim
aMIC (µg/mL)

Susceptibility a16I

≤4>16/8≤8≤1>16>160.5
32≤8≤16/8>16
≤8>32
≤4
≤12
≤12
≤8
≤2/38

S
R
S
S
R
RSIS
SR
S
RS
S
S
S
S
S
S

S, susceptible ; I, intermediate ; R, resistantCo., Ltd., Tokyo, Japan). A combination of clindamy-cowanii or Y. regensburgei with a score value of 1.729

cin, meropenem, and piperacillin-tazobactam wasand 1.716, respectively. 16S rRNA gene sequence analysis

administered as antibiotic prophylaxis for bacterialof the isolate showed 99.9 % (1433/1434 bp) identity

infection and continued until Day 9 after the ampu-with Y. regensburgei JCM 2403 (GenBank accession

tation. Doripenem (2 g/day) was commenced on Day

no. AB519796). The isolate was identified as Y. re-7 after the amputation and was administered for 6gensburgei. The MicroScan Neg Combo 6.11J showeddays.

the minimum inhibitory concentrations of antimicro-

Two sets of blood samples turned positive, show-

bial agents (Table 1). The Cefinase disk procedureing gram negative rods on Gram staining. Gram-(Nippon Becton Dickinson Co., Ltd., Tokyo, Japan)

negative and rod-shaped bacteria grew on the sheep

demonstrated that the isolate produced ㌼-lactamase.

blood agar (Nippon Becton Dickinson Co., Ltd., Tokyo,

Culture of the wound sample showed a few smoothJapan) after 24 hours at 35 ℃ in aerobic cultivationcolonies, in addition to predominant colonies of Y. re-from the swabbing and the blood samples. Colonies

gensburgei. The smooth colonies were identified aswere whitish-gray in color, with a fishy odor, andCandida glabrata by RapID Yeast Plus (AMCO Co.,measured 2-4 mm in diameter. The isolate was iden-Ltd., Tokyo, Japan). Following antimicrobial suscepti-

tified as Y. regensburgei or H. alvei by MicroScan

bility testing, ampicillin-sulbactam (6 g/day) and cef-

Neg Combo 6.11J panel (Beckman Coulter, Co., Ltd.,tazidime (4 g/day) were commenced on Day 11 until

Tokyo, Japan). MALDI-TOF MS analysis of the iso-Day 20 after the amputation. On Day 16 after thelate was performed with the MALDI Biotyper sys-amputation, laboratory examination revealed the fol-tem (Bruker Daltonics, Yokohama, Japan) using al-lowing : a WBC count of 3,620 cells/µl, a CRP of 7.14

pha-cyano-4-hydroxycinnamic acid matrix (Brukermg/dl, fibrinogen levels of 194 mg/dl, a plateletDaltonics). The isolate was identified as Kosakonia

count of 5.0×104 cells/µl, and D-dimer levels of 35.5

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Bacteremia caused by Yokenella regensburgei
Meropenem(2 g/day)
Clindamycin(1.8 g/day)
Piperacillin-tazobactam(13.5 g/day)Doripenem(2 g/day)

40

393538373625352034153310325310123456789 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Body temperature (℃)

4030

CRP (mg/dl)

WBC (×103 cells/µl)

Ampicillin-sulbactam(6 g/day)Ceftazidime(4 g/day)
4530

Day of hospitalization
CRPFig. 1WBC

Body temperature

Clinical course of the present case

µg/ml. Y. regensburgei was not cultured from thedifficult to differentiate between Y. regensburgei andwounds or from blood samples obtained 7 days afterH. alvei by biochemical characterization using Mi-treatment with ampicillin-sulbactam and ceftazi-croScan Neg Combo 6.11J panel. Moreover, MALDI

dime, and the patient improved (Fig. 1).

Biotyper system could not differentiate between Y.

ⅢDiscussion

regensburgei and Kosakonia cowanii. A logarithmic
score value of identification from 1.700 to 1.999 by

This case is the first report of bacteremia caused

MALDI Biotyper system will be reported as ʻproba-by Y. regensburgei in a patient with diabetic gan-ble genus identificationʼ, indicating that the genus

grene in Japan. Y. regensburgei rarely causes an in-identification is reliable. The MALDI Biotyper sys-fection with clinical symptoms and findings. In thistem may be unable to differentiate between Y. re-case, Y. regensburgei may have infected the woundgensburgei and Kosakonia cowanii because only one

after surgical amputation, causing bacteremia. Therereference spectrum for Y. regensburgei was regis-

are only 8 reports of infection with Y. regensburgei

tered with reference spectra in the MALDI Biotyper

in humans, and these involved patients with diabetes

library (ver.5.0.0.0). The addition of further reference

mellitus, liver disease or renal disease, or patients af-

spectra for Y. regensburgei will enhance the rapid2）
4）
6）
-8）

ter stem cell transplantation. Of note, two cases

involved patients with Y. regensburgei limb wound2）
8）

identification of Y. regensburgei to the genus andspecies level by MALDI Biotyper.

.

Here, the patient was successfully treated with

16S rRNA gene sequencing is useful for the identi-

doripenem, ampicillin-sulbactam, and ceftazidime.

fication of Y. regensburgei. Y. regensburgei was first

Stock et al. 3） demonstrated that Y. regensburgei wererecognized and reported as “atypical Hafnia alvei”.

resistant in vitro to cefazolin, cefaclor, and amoxicillin-

On occasion, members of the genus Hafnia can also

clavulanic acid, by production of AmpC ㌼-lactamases.

be mistaken for Y. regensburgei 9）. In this case, it was

The isolate in our case showed resistance to first-

infection, as in this caseNo. 2, 2017115Fukatsu・Yashio・Honda

and second-generation cephalosporins and had simi-fore, antimicrobial susceptibility tests may be crucial

lar antimicrobial susceptibility, except for cefotiam.

before administrating antibiotics to treat Y. regens-

Previous reports showed that Y. regensburgei infec-

burgei infection.

tion improved with ciprofloxacin, ceftriaxone, levo-

In conclusion, this is the first report of bacteremia

floxacin, or piperacillin-tazobactam treatment 2）4）5）7）8）.

caused by Y. regensburgei in Japan. Although it isHowever, carbapenem or third-generation cephalo-difficult to identify Y. regensburgei by routine identi-sporins may be necessary to treat bacteremia by Y.

fication techniques, 16S rRNA gene sequence analysis

regensburgei producing AmpC ㌼-lactamase. Con-is useful for correctly identifying it. Additional cases

versely, Enterobacteriaceae with plasmid-mediatedmay be necessary to evaluate the clinical pathogenicity

extended-spectrum beta-lactamases or carbapene-of Y. regensburgei and optimal antibiotic treatment.

mase is often detected in clinical practice

10）
11）

. ThereReferences

1） Kosako Y, Sakazaki T, Yoshizaki E : Yokenella regensburgei gen. nov., sp. nov. : a new genus and species in the family Enterobacteriaceae. Jpn J Med Sci Biol 37 : 117-124, 1984
2） Abbott SL, Janda JM : Isolation of Yokenella regensburgei (“Koserella trabulsii”) from a patient with transient bacteremia and from a patient with a septic knee. J Clin Microbiol 32 : 2854-2855, 1994
3） Stock I, Sherwood KJ, Wiedemann B : Antimicrobial susceptibility patterns, ㌼-lactamases, and biochemical identification of Yokenella regensburgei strains. Diagn Microbial Infect Dis 48 : 5-15, 2004
4） Lo YC, Chuang YW, Lin YH : Yokenella regensburgei in an immunocompromised host : a case report and review ofthe literature. Infection 39 : 485-488, 20115） Jain S, Gaind R, Gupta KB, Dawar R, Kumar D, Paul P, Sardana R, Deb M : Yokenella regensburgei infection in India
mimicking enteric fever. J Med Microbiol 62 : 935-939, 2013
6） Bhowmick T, Weinstein MP : A deceptive case of cellulitis caused by a gram-negative pathogen. J Clin Microbiol51 : 1320-1323, 2013
7） Fill MA, Stephens JL : Abdominal abscess and septic shock secondary to Yokenella regensburgei. Int J Infect Dis 9 :1-3, 20098） Lee SM, Kang YJ, Huh HJ, Ki CS, Lee NY : First report of Yokenella regensburgei isolated from the wound exudate
after disarticulation due to diabetic foot infection in Korea. Ann Clin Microbiol 18 : 135-139, 20159） Sakazaki R : Genus XV. Hafnia. Brenner DJ, Krieg NR, Staley JT (eds), In : Bergey’s Manual of Systematic Bacteriology vol. 2, pp 681-685, Springer, New York, 200510） van Duin D, Kaye KS, Neuner EA, Bonomo RA : Carbapenem-resistant Enterobacteriaceae : a review of treatment
and outcomes. Diagn Microbial Infect Dis 75 : 115-120, 201311） Bradford PA : Extended-spectrum ㌼-lactamases in the 21st century : characterization, epidemiology, and detectionof this important resistance threat. Clin Microbiol Rev 14 : 933-951, 2001

（2016. 10. 31 received；2016. 12. 12 accepted）

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