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BRIEF REPORT
Clinical and Microbiological
Characteristics of Rhizobium radiobacter
Infections
Chih-Cheng Lai,1 Lee-Jene Teng,2,3 Po-Ren Hsueh,1,2 Ang Yuan,1 KuangChau Tsai,1 Jih-Luh Tang,1 and Hwei-Fang Tien1
Departments of 1Internal Medicine and 2Laboratory Medicine, National Taiwan
University Hospital, and 3School of Medical Technology, National Taiwan
University College of Medicine, Taipei, Taiwan
Data obtained from 1996 to 2002 on 13 patients with Rhizobium radiobacter infections were analyzed. Ten patients
(76%) had underlying hematological malignancy or solidorgan cancer. Six patients (46%) had febrile neutropenia during the course of R. radiobacter infection. The majority (54%)
of infections were catheter-related bacteremia, and 92% of
infections were hospital acquired. All the patients survived.
Eighteen isolates were recovered from the 13 patients, and
each isolate was susceptible to cefepime, piperacillin-tazobactam, carbapenems, and ciprofloxacin. The pulsed-field gel
electrophoresis profiles differed among the isolates recovered
from different patients, indicating the absence of nosocomial
spread of the organism.
Strains of the Rhizobium species (formerly Agrobacterium,
which was reclassified based on 16S rDNA analyses) are aerobic,
motile, oxidase-positive, and non–spore-forming gram-negative bacilli [1–4]. Among the species of Rhizobium (i.e., R.
radiobacter, R. rhizogenes, R. rubi, R. undicola, and R. vitis), R.
radiobacter is the species that most commonly causes disease
in humans [3, 4]. Since the first case of human infection with
R. radiobacter, in a patient with prosthetic aortic valve endocarditis, was reported in 1980 [5], R. radiobacter has been recognized as an opportunistic human pathogen [1, 6, 7]. Most
of patients with R. radiobacter infection have debilitating underlying diseases [1, 6–20]. The clinical presentations associated
with R. radiobacter infection are protean, and bacteremia caused
Received 25 July 2003; accepted 21 August 2003; electronically published 4 December
2003.
Reprints or correspondence: Dr. Po-Ren Hsueh, Depts. of Laboratory Medicine and Internal
Medicine, National Taiwan University, No. 7, Chung-Shan South Rd., Taipei, Taiwan (hsporen
@ha.mc.ntu.edu.tw).
Clinical Infectious Diseases 2004; 38:149–53
2004 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2004/3801-0023$15.00
by this organism is usually secondary to the use of intravenous
catheters (5, 8, 14, 16, 17). The majority of patients with R.
radiobacter infection have appeared to respond well to antibiotic
therapy. In addition, a significant aspect of therapy is the removal of foreign material, because patients who have persistent
infection or who initially respond to therapy risk experiencing
relapse until the foreign body is removed. The outcome of
infection with R. radiobacter is favorable [1, 7].
In this report, we describe the clinical features of 13 patients
with R. radiobacter infections who were treated at the National
Taiwan University Hospital (NTUH) during the period 1996–
2002. Microbiological characteristics were also investigated, including antimicrobial susceptibilities and molecular types of
the 18 isolates recovered from the 13 patients.
Patients and methods. From 1 January 1996 through 31
December 2002, 13 patients with R. radiobacter infections who
were hospitalized in the National Taiwan University Hospital
were identified (table 1). Relevant information on the clinical
presentation of these patients was collected. These data included
the underlying diseases, associated medical condition (e.g., the
use of an indwelling catheter or receipt of chemotherapy), clinical syndromes, hospital day on which a culture result positive
for R. radiobacter was obtained, antibiotic regimens received,
and outcome.
Eighteen isolates of R. radiobacter were recovered from the
13 patients with infection. These were initially identified on the
basis of colonial morphotypes, gram staining characteristics,
oxidase reaction, and growth on triple-sugar agar. These isolates
were also identified as R. radiobacter by their biochemical
profiles, obtained with the Vitek GNI and API 20NE system
(bioMérieux).
The MICs of 13 antimicrobial agents (table 2) for the 18
isolates of R. radiobacter were determined by means of the agar
dilution method according to guidelines established by the
NCCLS [21, 22]. Genotypes of the 18 isolates of R. radiobacter
were determined by PFGE. DNA extraction and purification
were also performed, as described elsewhere [23]. The DNA
was digested by the restriction enzyme PmeI, and the restriction
fragments were separated in a CHEF-DRIII unit (Bio-Rad) [23].
Interpretation of the PFGE profiles followed the description by
Tenover et al. [24].
Patients with intravascular device–associated infections
caused by R. radiobacter were defined as those with a body
temperature of 138.3C and malaise, chills, or tachypnea with
no obvious identifiable source of infection except for the exit
site or tunnel infection, as well as cultures of ⭓2 blood samples
BRIEF REPORT • CID 2004:38 (1 January) • 149
M
M
M
F
F
9
10
11
12
13
37
2
59
53
74
46
21
50
61
30
81
82
66
Celiac sprue
ALL
NHL
Cutaneous lymphoma
Esophageal cancer
AML
NHL
Breast cancer
Breast cancer
Pregnancy
Rhabdosarcoma
Laryngeal cancer
CAD
Underlying
condition
No
Yes
Yes
No
Yes
Yes
Yes
Yes
No
No
No
No
No
Neutropenia
9/24/2002
9/21/2002
8/2/2002; 8/2/2002;
10/03/2002
10/19/2001
4/6/2000
5/3/1997
3/7/1997
1/23/1997
12/5/1996
11/22/1996
9/30/1996
Date of isolation,
month/day/year
Blood (PAC and PB);
Blood (PAC); Blood
(PAC)
11/15/2002; 11/19/2002;
12/2/2002
Blood (PAC); Blood (PAC) 11/7/2002; 11/11/2002
Blood (PAC and PB)
Blood (PAC and PB)
Blood (PAC); Blood (PB);
Blood (PAC and PB)
Blood (CVC)
Blood (PAC)
Sputum
Pleural effusion
Blood
Blood
Pleural effusion
Blood
Site of isolation
Treatment
CRB
CRB
CRB
CRB
CRB
CRB
Cefepime
Ampicillin-sulbactam
and gentamicin
Cefatazidime,
tobramycin
Cefpirome
Piperacillin-tazobactam
Imipenem
Ciprofloxacin
Pneumonia Ceftazidime
Pneumonia Cefoperazone
drainage
Bacteremia Cefmetazone
Bacteremia Ceftriaxone
Pneumonia Antibiotics drainage
Bacteremia Amoxicillin-clavulanate
Type of
infection
M1; M2; M3 CRB
L1; L2
K
J
I1; I2; I3
H
G
F
E
D
C
B
A
Isolate
a
designation
Yes
No
No
No
Yes
Yes
Yes
No
No
No
No
No
No
Survival
Survival
Survival
Survival
Survival
Survival
Survival
Survival
Survival
Survival
Survival
Survival
Survival
Catheter
removal Outcome
a
Isolate designations used in this study; see figure 1.
NOTE. Infections were nosocomial in all patients, with the exception of patient 5, whose infection was community-acquired. ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; CAD, coronary
arterial disease; CRB, catheter-related bacteremia; CVC, central venous catheter; NHL, Non-Hodgkin lymphoma, PAC, Port-a-Cath; PB, peripheral blood.
M
8
F
5
F
F
4
M
M
3
6
M
2
7
M
1
Age,
Patient no. Sex years
Table 1. Demographic and clinical characteristics of 13 patients with cultures positive for Rhizobium radiobacter who were treated at the National Taiwan University Hospital,
1996–2002.
Table 2. In vitro susceptibilities of 18 isolates of Rhizobium
radiobacter from 13 patients who were treated at the National
Taiwan University Hospital, 1996–2002.
MIC, mg/mL
Antimicrobial agent
Range
MIC50
MIC90
No. (%) of
susceptible
a
isolates
Ampicillin-sulbactam
1–16
8
16
11 (61)
Ceftazidime
2–32
8
16
13 (72)
Cefotaxime
1–16
2
16
14 (78)
Piperacillin-tazobactam
⭐0.03–8
0.5
8
18 (100)
Cefepime
0.12–8
1
4
18 (100)
Aztreonam
2–32
4
16
14 (78)
Imipenem
⭐0.03–0.06
0.06
0.06
18 (100)
Meropenem
⭐0.03–0.06
⭐0.03
0.06
18 (100)
Ciprofloxacin
⭐0.03–0.5
⭐0.03
0.25
18 (100)
Moxifloxacin
⭐0.03–0.25
⭐0.03
0.25
…b
Trovafloxacin
⭐0.03–0.5
0.06
0.5
…
b
Garenoxacin
⭐0.03–1
0.12
1
…
b
Amikacin
4–32
8
16
17 (94)
a
Susceptibility results were interpreted according to the MIC interpretative
standards established by the NCCLS for Pseudomonas aeruginosa and organisms other than Enterobacteriaceae [22].
b
Interpretative criteria for defining susceptibility to moxifloxacin, trovafloxacin, and garenoxacin were not provided by the NCCLS [22].
(obtained through the central catheter or from a peripheral
source) positive for R. radiobacter. Episodes of infection that
developed ⭓48 h after admission were regarded as nosocomial,
while episodes of infection identified by positive cultures earlier
than 48 h after admission were considered communityacquired. Neutropenia was defined as a neutrophil count of
!1.0 ⫻ 10 9 cells/L. Antibiotic therapy was considered appropriate if the chosen drug proved to be active against the isolate
on the basis of the results of susceptibility testing. Antibiotypes
were considered identical if the MICs of all antimicrobial agents
tested were identical or had a discrepancy of !1 dilution. Isolates were defined as being the same strain or originating from
a single clone if they had identical antibiotypes and PFGE
profiles.
Results. The clinical characteristics of the 13 patients with
infections are provided in table 1. All 13 patients received their
diagnosis after 1996, and 5 patients (38%) were identified in
2002. The mean age of the patients was 51 years (range, 2–82
years). Ten patients (76%) had underlying hematological malignancies or solid-organ cancer, and 1 patient (7%) had a celiac
sprue. Six patients (46%) had febrile neutropenia during R.
radiobacter infection. Clinical infections included bacteremia
associated with a central venous catheter or Port-A-Cath
(Smiths Industries Medical Systems, Deltec) in 7 patients, primary bacteremia in 3 patients, and pneumonia in 3 patients.
Twelve of the 13 patients acquired R. radiobacter infections
during hospital stays or via chemotherapy-related indwelling
catheters. All but 3 patients wee treated with appropriate antibiotics after blood cultures were reported to be positive for
R. radiobacter. Of the 7 patients with catheter-related bacteremia, 4 patients had their catheters removed, and 3 recovered
without removal of the catheter. All patients survived.
All the isolates were gram-negative bacilli, oxidase-positive,
indole-negative, and glucose-nonfermenters. Colonies that
grew on trypticase soy agar supplemented with 5% sheep’s
blood were mucoid and slightly pink. The reaction profiles
generated by Vitek GNI and API 20NE system were identical.
The following characteristics suggest our isolates were R. radiobacter: positive reactions for urease, phenylalanine deaminase, esculin hydrolysis, and acids from maltose, sucrose, mannitol, and xylose.
All isolates were susceptible to cefepime, piperacillin-tazobactam, imipenem, meropenem, and ciprofloxacin (table 2).
Susceptibilities to ampicillin-sulbactam, ceftazidime, cefotaxime, aztreonam, and amikacin varied. Moxifloxacin, trovafloxacin, and garenoxacin had good in vitro activities against these
isolates, with MIC90 values of ⭐1 mg/mL.
Among the 18 isolates recovered from the 13 patients, a total
of 13 PFGE profiles (figure 1) were identified. PFGE profiles
differed among the isolates recovered from different patients.
Both antibiotypes and genotypes were identical for 2 isolates
from each of 2 patients (isolates I1 and I3 from patient 9 and
isolates M1 and M3 from patient 13) who experienced 2 episodes of Port-A-Cath–related bacteremia at intervals of 2
months and 17 days, respectively.
Discussion. In the present report, the majority of the patients had hematological malignancies or solid-organ cancer,
and most of them had received chemotherapy. Furthermore,
there were 3 patients that did not have any cancer and had
never received immunosuppressive agents. Our findings are
consistent with those of other investigators [1, 7, 10, 13, 14,
18, 20]. We emphasize that R. radiobacter should be included
in the list of pathogens that cause bacteremia even in immunocompentent patients, especially in the presence of an intravenous catheter.
PFGE analysis has been extensively applied for epidemiological typing and the taxonomic study of clinical isolates [23,
24, 25]. No previous reports have described the use of this
technique to type clinical isolates of R. radiobacter. In the present study, 5 of the 13 patients became infected during a 5month interval toward the end of 2002, and all 5 of these
patients had Port-A-Cath–related bacteremia. This raised the
possibility of an outbreak (of bacteremia or pseudobacteremia).
However, the PFGE profiles of the isolates recovered from the
5 patients seen in 2002 and those recovered from different
patients within the 6-year time period of the study differed,
indicating that the isolates were clonally unrelated. The identical
PFGE profiles of the 3 isolates from patient 9 and another 3
BRIEF REPORT • CID 2004:38 (1 January) • 151
Figure 1. Representative PFGE profiles digested with PmeI of 13 clones from 18 isolates of Rhizobium radiobacter recovered from 13 patients
treated at the National Taiwan University Hospital, 1996–2002. Lane M, molecular size markers. Lanes 1–13, pulsotypes of I to XIII, respectively. See
table 2 for designations of isolates.
isolates from patient 13 lead to the conclusion that the 2 episodes of bacteremia were caused by the same strain and were
not due to reinfection with different clones of R. radiobacter.
The infections were strongly related to the presence of foreign
plastic materials (e.g., an intravascular catheter, nephrostomy
tube, or prosthetic valve) [1]. In the present report, 10 patients
presented with bacteremia, and 7 of them had intravascular
catheters. Five out of 10 patients were reported to be neutropenic. All 10 patients received intravenous antibiotics, but 3 of
the patients were not treated with the removal of the catheter.
It appears that antimicrobial therapy is usually successful, and
catheter removal should be considered only if bacteremia continues despite appropriate antimicrobial therapy or if the patient becomes unstable, as was the case with patient 9 and
patient 13. In addition to bacteremia, respiratory tract infection
was also present in 3 patients. This suggests that R. radiobacter
should be added to the list of pathogens that induce pneumonia, especially in patients with malignancy.
In this report, none of the cultures of various clinical specimens performed at the microbiological laboratories of the
NTUH yielded Rhizobium until September 1996. After that
time, increasing numbers of positive cultures—particularly
from blood specimens—that yielded Rhizobium isolates were
noted. Furthermore, all but 1 of the infections were nosocomial,
unlike in a previous study [7]. The reason for this may be the
152 • CID 2004:38 (1 January) • BRIEF REPORT
small number of cases, but these results may imply that R.
radiobacter should be considered a possible pathogen in cases
of hospital-acquired infection. Surveillance studies to determine
the reservoirs in the hospital setting for nosocomial transmission of this organism should be conducted.
An analysis of the antimicrobial susceptibility test results
provides several insights. First, previous findings suggested that
clinical isolates of Rhizobium species that were resistant to aztreonam were common because monobactams could be produced by some soil strains of Rhizobium [4]. However, according to the NCCLS breakpoints for organisms other than
Enterobacteriaceae, only 4 of 19 isolates were not susceptible to
aztreonam (MICs, ⭓16 mg/mL). Second, the susceptibility patterns of the isolates to third-generation cephalosporins were
variable. Testing of antimicrobial susceptibility to these agents
using the standard dilution method should be performed for
every R. radiobacter isolate of clinical significance. Third, cefepime, piperacillin-tazobactam, carbapenems, and fluoroquinolones seemed to be promising agents for treating infections
caused by R. radiobacter, according to the susceptibility test
results. Additional studies (on animals or humans) should be
performed to elucidate the correlation between in vitro susceptibility testing and clinical efficacy. Fourth, the antimicrobial susceptibilities of the isolates at different intervals, ranging
from weeks (in the case of patient 13) to months (in the case
of patient 9), remained nearly identical, despite intervening
therapy.
In conclusion, R. radiobacter should be considered a potential community-acquired or hospital-acquired pathogen in the
presence of foreign plastic materials, especially in immunocompromised patients. In addition, removal of the foreign material may be necessary if there is a poor response to the appropriate antimicrobials.
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