Rhizobium radiobacter is an uncommon agent of infection and has been associated with indwelling intravascular devices such as catheter in immunocompromised patients. Here, we report a case of R. radiobacter recovered from blood cultures in stem cell transplantation in a pediatric patient and present an extensive characterization of its antimicrobial susceptibility profile. The isolate presented low MICs to many antimicrobial agents, but high MICs to ceftazidime, piperacillin-tazobactam, aztreonam, and fosfomycin

Bruna Steiner

Fabiane Jamono Vieira

Leandro Reus Rodrigues Perez

Marcelle Duarte Alves

Clinical & Biomedical Research

Directory of Open Access Journals

Rhizobium radiobacter recovered from blood of a pediatric patient with stem cell transplantation: a case report and characterization of antimicrobial susceptibility profile

Rhizobium radiobacter is an uncommon agent of infection and has been associated with indwelling intravascular devices such as catheter in immunocompromised patients. Here, we report a case of R. radiobacter recovered from blood cultures in stem cell transplantation in a pediatric patient and present an extensive characterization of its antimicrobial susceptibility profile. The isolate presented low MICs to many antimicrobial agents, but high MICs to ceftazidime, piperacillintazobactam, aztreonam, and fosfomycin

Steiner, Bruna

Vieira, Fabiane Jamono

Alves, Marcelle Duarte

Perez, Leandro Reus Rodrigues

Universidade Federal do Rio Grande do Sul

Rhizobium radiobacter recovered from blood of a pediatric patient with stem cell transplantation : a case report and characterization of antimicrobial susceptibility profile

Archives of the Faculty of Veterinary Medicine UFRGS

318 Clin Biomed Res 2014;34(3) http://seer.ufrgs.br/hcpaRhizobium RadiobacteR RecoveRed fRom blood of a pediatRic patient with stem cell tRansplantation: a case RepoRt and chaRacteRization of antimicRobial susceptibility pRofileBruna Steiner1, Fabiane J. Vieira2, Marcelle Duarte Alves1,  Leandro R. R. Perez31 Serviço de Infectologia, Hospital de Clínicas de Porto Alegre. Porto Alegre, RS, Brazil.2 Graduação em Farmácia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS).Porto Alegre, RS, Brazil.3 Programa de Pós-Graduação em Ciências Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS).Porto Alegre, RS, Brazil.Corresponding author: Leandro Reus Rodrigues PerezE-mail: leandro.reus@gmail.comLaboratório de Pesquisa em Resistência Bacteriana (LABRESIS)Hospital de Clínicas de Porto Alegre - Serviço de Patologia Clínica Rua Ramiro Barcelos 2350.90035-903, Porto Alegre, RS, Brazil, AbstrActRhizobium radiobacter is an uncommon agent of infection and has been associated with indwelling intravascular devices such as catheter in immunocompromised patients. Here, we report a case of R. radiobacter recovered from blood cultures in stem cell transplantation in a pediatric patient and present an extensive characterization of its antimicrobial susceptibility profile. The isolate presented low MICs to many antimicrobial agents, but high MICs to ceftazidime, piperacillin-tazobactam, aztreonam, and fosfomycin.Keywords: Transplantation; antimicrobial agentsSpecies of Rhizobium (formerly named Agrobacterium, which was reclassified based on 16S rDNA analysis) are aerobic, non-spore forming, oxidase- and catalase-positive, gram-negative microorganisms, affecting a wide variety of plants, making it an important concern for agriculture industry. Among the Rhizobium species, R. radiobacter is the most common agent of infection in humans1,2. Cases of bacteremia, prosthetic valve endocarditis, urinary tract infection, peritonitis, and pneumonia have been reported1,2. Immunocompromised hosts, especially patients with hematological malignancy, bacteremia, and catheter-related bloodstream infection are the most prevalence cases2. Bacteremia due to R. radiobacter is frequently associated with the presence of an indwelling device such as a central venous catheter, probably due to its ability for slime production on the surfaces3,4. The outcome of device-associated infection due to R. radiobacter is generally favorable compared with other pathogens, such as Staphylococcus aureus and S. epidermidis5. Here, we report a case of bacteremia due to R. radiobacter in a stem cell transplantation patient and we discuss the identification and antimicrobial susceptibility profile of the isolate. CaseA 7-year-old male patient, diagnosed with hepatosplenic lymphoma, underwent chemotherapy and autologous bone marrow transplantation. Accomplished pre-transplant conditioning with carmustine, etoposide, cytarabine, and melphalan, he developed severe neutropenia. According to the protocol of febrile neutropenia, we introduced cefepime (administrated during a week), piperacillin/tazobactam (for 2 days), meropenem, and vancomycin. As an Clin Biomed Res. 2014;34(3):318-321Case Reporthttp://seer.ufrgs.br/hcpa 319Clin Biomed Res 2014;34(3)Rhizobium radiobacter bacteremiaantifungal agent, amphotericin B was subsequently replaced by micafungin due to toxicity. The patient evolved with improved thermal curve, microbial cultures without growth of microorganisms, completing 14 days of antimicrobial treatment. After 2 days of stopping the treatment, the patient had fever again, and therefore the antimicrobial treatment was restarted with meropenem and vancomycin. From a couple of blood samples (one from peripheral blood and another from catheter) it was verified the presence of rod-shaped, gram-negative bacteria, presenting oxidase-positive reaction and growth on MacConkey’s and blood agar after 24 h of incubation at 35ºC. This microorganism was submitted to VITEK 2 (bioMérieux, France) and MALDI-TOF (Becton Dickinson, USA) automated systems, being identified as Rhizobium radiobacter by both methods.According to the results of antimicrobial susceptibility profile performed by Etest (bioMérieux, France), this isolate presented low minimal inhibitory concentrations (MICs) to ampicillin/sulbactam, ciprofloxacin, ceftriaxone, and carbapenems (table). It is of note that a possible catheter-related infection was evidenced, according to the time of positivity between peripheral blood and blood collected via catheter. The catheter was removed and the treatment was completed in 14 days with 10 mg\Kg meropenem. The patient evolved with improved clinical parameters, such as decreased inflammatory markers (procalcitonin and C-reactive protein), and immune (normal leukocyte blood count) reconstitution. A new couple of blood cultures were collected and did not show bacterial growth, verifying the clearance of the Rhizobium infection.Antimicrobial agents MIc  (µg/mL)Ampicillin/Sulbactam ≤ 0.16Ciprofloxacin 0.25Gentamicin 3Amikacin 8Cefuroxime 8Ceftriaxone 0.75Ceftazidime 16Cefepime 2Piperacillin/Tazobactam 32Meropenem 2Ertapenem ≤0.5Doripenem 0.094Imipenem ≤0.5Polymyxin B <0.125Colistin 0.25Aztreonam 64Tigecycline 0.5Fosfomycin >1024Chloramphenicol 2Table: MICs for the different antimicrobial agents tested for the R. radiobacter isolate.320Clin Biomed Res 2014;34(3)http://seer.ufrgs.br/hcpaDIscussIonRhizobium radiobacter has been implicated in infections involving prosthetic valve, central venous catheter, and other types of medical devices. On the other hand, a few studies have pointed R. radiobacter as a “true” agent of infection. In fact, this microorganism should be included in the list of pathogens that cause infection, mainly cases of bacteremia, when immunocompromised patients are affected, especially in the presence of an intravenous catheter.Additionally, other two situations should be considered in cases involving R. radiobacter: 1) given the very small number of clinical isolates of R. radiobacter encountered in clinical laboratories, there are limited data on which to judge how well the manual and automated bacterial identification systems identify it; and 2) there is no susceptibility breakpoints defined for these organisms so far, and there are few studies in which R. radiobacter has a full characterization of its antimicrobial susceptibility by the determination of the MIC3,5-8. In fact, most isolates are susceptible to broad-spectrum cephalosporins, carbapenems, tetracyclines, and gentamicin but not tobramycin8,9.Testing of individual isolates is recommended for clinically significant cases once that it is unknown the intrinsic mechanisms of resistance for the rhizobia species.Some studies have pointed that R. radiobacter presents low MICs (inferior to 1 µg/mL in most of cases) to the third generation cephalosporins, cephamycins, carbapenems, fluoroquinolones, tetracycline, nitrofurantoin, and aminoglycosides, but high MIC (superior to 8 µg/mL have been reported) to penicillins, penicillin/enzyme inhibitors, beta-lactam, aztreonam, and  fosfomycin3,6,7. In this report, the isolate showed low MICs for many antibiotics and presented a high MICs for others, mainly aztreonam and fosfomycin (table). For therapeutic approaches, cephalosporins (mainly cefepime) and ciprofloxacin have been used successfully to treat Rhizobium infections6,7,9. Lai et al.2 reported in their study a very lower MICs for carbapenem agents in comparison to our isolate, mainly for meropenem (2 μg/mL for our isolate against a range from 0.03 to 0.06 μg/mL for 18 isolates tested in Lai’s study). For imipenem, a similar MIC value was obtained in comparison with the findings of Lai et al.2 It is of note that, based on a few reports to date, antimicrobial susceptibilities for R. radiobacter is variable. There is no consensus for type or length of treatment or optimum therapy, owing to the small number of cases described to date, and these may logically be dictated by the clinical response, degree of underlying illness, status of the host immune system, and whether microbiologic eradication can be documented. Also, it is not uncommon to recover R. radiobacter from sites of body without obvious pathologic effects and thus it may be present simultaneously with other bacterial species in mixed flora. It is important to note that R. radiobacter should be added to the list of pathogens that induce infections conditions in patients with malignancy, but mainly in pediatric patients. For an empirical and definitive antibiotic therapy, it has been considered the use of cefepime 2 g intravenously every 8 hours for a total of 8-10 days9. In conclusion, we present an unusual case of R. radiobacter bacteremia in a stem cell transplant patient. The isolate presented low MICs to many antimicrobial agents, but high MICs to ceftazidime, piperacillin-tazobactam, aztreonam, and fosfomycin. Further studies are required to characterize the antimicrobial susceptibility profile and the underlying resistance mechanisms of this pathogen.references1. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. London: Elsevier; 2010.2. Lai CC, Teng LJ, Hsueh PR, Yuan A, Tsai KC, Tang JL, et al. Clinical andmicrobiological characteristics of Rhizobium radiobacter infections. Clin Infect Dis. 2004;38:149-53.3. Hulse M, Johnson S, Ferrieri P. Agrobacterium infections in humans: experience at one hospital and review. Clin Infect Dis. 1993;16:112-7.4. Chen CY, Hansen KS, Hansen LK. Rhizobium radiobacter as an opportunistic pathogen in central venous catheter-associated bloodstream infection: case report and review. J Hosp Infect. 2008;68:203-7.5. Mastroianni A, Coronado O, Nanetti A, Manfredi R, Chiodo F. Agrobacterium radiobacter pneumonia in a patient with HIV Steiner et alhttp://seer.ufrgs.br/hcpa 321Clin Biomed Res 2014;34(3)infection. Eur J Clin Microbiol Infect Dis. 1996;15:960-3.6. Paphitou NI, Rolston KV. Catheter-related bacteraemia caused by Agrobacterium radiobacter in a cancer patient: case report and literature review. Infection. 2003;31:421-4.7. Amaya RA, Edwards MS. Agrobacterium radiobacter bacteraemia in pediatric patients: case report and review. Pediatr Infect Dis J. 2003;22:183-6.8. Erol Cipe F, Doğu F, Sucuoğlu D, Aysev D, Ikincioğulları A. Asymptomatic catheter related Rhizobium radiobacter infection in a haploidentical hemapoietic stem cell recipient. J Infect Dev Ctries. 2010;4:530-2.9. Ponnapula S, Swanson JM, Wood GC, Boucher BA, Wells DL, Croce MA, et al. Treatment of Rhizobium radiobacter bacteremia in a critically ill trauma patient. Ann Pharmacother. 2013;47:1584-7.Received: 04/08/2014Accepted: 16/09/2014Rhizobium radiobacter bacteremia

English

Lume 5.8

Portuguese

318 Clin Biomed Res 2014;34(3) http://seer.ufrgs.br/hcpa
Rhizobium RadiobacteR RecoveRed fRom blood of a 
pediatRic patient with stem cell tRansplantation: a 
case RepoRt and chaRacteRization of antimicRobial 
susceptibility pRofile
Bruna Steiner1, Fabiane J. Vieira2, Marcelle Duarte Alves1,  
Leandro R. R. Perez3
1 Serviço de Infectologia, Hospital de 
Clínicas de Porto Alegre. Porto Alegre, 
RS, Brazil.
2 Graduação em Farmácia, Faculdade 
de Farmácia, Universidade Federal do 
Rio Grande do Sul (UFRGS).
Porto Alegre, RS, Brazil.
3 Programa de Pós-Graduação em 
Ciências Farmacêutica, Faculdade de 
Farmácia, Universidade Federal do 
Rio Grande do Sul (UFRGS).
Porto Alegre, RS, Brazil.
Corresponding author: 
Leandro Reus Rodrigues Perez
E-mail: leandro.reus@gmail.com
Laboratório de Pesquisa em 
Resistência Bacteriana (LABRESIS)
Hospital de Clínicas de Porto Alegre - 
Serviço de Patologia Clínica 
Rua Ramiro Barcelos 2350.
90035-903, Porto Alegre, RS, Brazil, 
AbstrAct
Rhizobium radiobacter is an uncommon agent of infection and has been associated 
with indwelling intravascular devices such as catheter in immunocompromised 
patients. Here, we report a case of R. radiobacter recovered from blood cultures 
in stem cell transplantation in a pediatric patient and present an extensive 
characterization of its antimicrobial susceptibility profile. The isolate presented 
low MICs to many antimicrobial agents, but high MICs to ceftazidime, piperacillin-
tazobactam, aztreonam, and fosfomycin.
Keywords: Transplantation; antimicrobial agents
Species of Rhizobium (formerly named Agrobacterium, which was 
reclassified based on 16S rDNA analysis) are aerobic, non-spore forming, 
oxidase- and catalase-positive, gram-negative microorganisms, affecting 
a wide variety of plants, making it an important concern for agriculture 
industry. Among the Rhizobium species, R. radiobacter is the most 
common agent of infection in humans1,2. Cases of bacteremia, prosthetic 
valve endocarditis, urinary tract infection, peritonitis, and pneumonia have 
been reported1,2. Immunocompromised hosts, especially patients with 
hematological malignancy, bacteremia, and catheter-related bloodstream 
infection are the most prevalence cases2. Bacteremia due to R. radiobacter 
is frequently associated with the presence of an indwelling device such as 
a central venous catheter, probably due to its ability for slime production 
on the surfaces3,4. The outcome of device-associated infection due to R. 
radiobacter is generally favorable compared with other pathogens, such as 
Staphylococcus aureus and S. epidermidis5. 
Here, we report a case of bacteremia due to R. radiobacter in a stem cell 
transplantation patient and we discuss the identification and antimicrobial 
susceptibility profile of the isolate. 
Case
A 7-year-old male patient, diagnosed with hepatosplenic lymphoma, 
underwent chemotherapy and autologous bone marrow transplantation. 
Accomplished pre-transplant conditioning with carmustine, etoposide, cytarabine, 
and melphalan, he developed severe neutropenia. According to the protocol 
of febrile neutropenia, we introduced cefepime (administrated during a week), 
piperacillin/tazobactam (for 2 days), meropenem, and vancomycin. As an 
Clin Biomed Res. 2014;34(3):318-321
Case Report
http://seer.ufrgs.br/hcpa 319Clin Biomed Res 2014;34(3)
Rhizobium radiobacter bacteremia
antifungal agent, amphotericin B was subsequently 
replaced by micafungin due to toxicity. The patient 
evolved with improved thermal curve, microbial 
cultures without growth of microorganisms, 
completing 14 days of antimicrobial treatment. 
After 2 days of stopping the treatment, the patient 
had fever again, and therefore the antimicrobial 
treatment was restarted with meropenem and 
vancomycin. From a couple of blood samples (one 
from peripheral blood and another from catheter) 
it was verified the presence of rod-shaped, gram-
negative bacteria, presenting oxidase-positive 
reaction and growth on MacConkey’s and blood agar 
after 24 h of incubation at 35ºC. This microorganism 
was submitted to VITEK 2 (bioMérieux, France) and 
MALDI-TOF (Becton Dickinson, USA) automated 
systems, being identified as Rhizobium radiobacter 
by both methods.
According to the results of antimicrobial 
susceptibility profile performed by Etest 
(bioMérieux, France), this isolate presented 
low minimal inhibitory concentrations (MICs) to 
ampicillin/sulbactam, ciprofloxacin, ceftriaxone, 
and carbapenems (table). It is of note that a possible 
catheter-related infection was evidenced, according 
to the time of positivity between peripheral blood 
and blood collected via catheter. The catheter 
was removed and the treatment was completed in 
14 days with 10 mg\Kg meropenem. The patient 
evolved with improved clinical parameters, such as 
decreased inflammatory markers (procalcitonin and 
C-reactive protein), and immune (normal leukocyte 
blood count) reconstitution. A new couple of blood 
cultures were collected and did not show bacterial 
growth, verifying the clearance of the Rhizobium 
infection.
Antimicrobial agents MIc  (µg/mL)
Ampicillin/Sulbactam ≤ 0.16
Ciprofloxacin 0.25
Gentamicin 3
Amikacin 8
Cefuroxime 8
Ceftriaxone 0.75
Ceftazidime 16
Cefepime 2
Piperacillin/Tazobactam 32
Meropenem 2
Ertapenem ≤0.5
Doripenem 0.094
Imipenem ≤0.5
Polymyxin B <0.125
Colistin 0.25
Aztreonam 64
Tigecycline 0.5
Fosfomycin >1024
Chloramphenicol 2
Table: MICs for the different antimicrobial agents tested for the R. radiobacter isolate.
320
Clin Biomed Res 2014;34(3)
http://seer.ufrgs.br/hcpa
DIscussIon
Rhizobium radiobacter has been implicated in 
infections involving prosthetic valve, central venous 
catheter, and other types of medical devices. On 
the other hand, a few studies have pointed R. 
radiobacter as a “true” agent of infection. In fact, 
this microorganism should be included in the list 
of pathogens that cause infection, mainly cases of 
bacteremia, when immunocompromised patients 
are affected, especially in the presence of an 
intravenous catheter.
Additionally, other two situations should be 
considered in cases involving R. radiobacter: 1) 
given the very small number of clinical isolates of 
R. radiobacter encountered in clinical laboratories, 
there are limited data on which to judge how well 
the manual and automated bacterial identification 
systems identify it; and 2) there is no susceptibility 
breakpoints defined for these organisms so far, and 
there are few studies in which R. radiobacter has a 
full characterization of its antimicrobial susceptibility 
by the determination of the MIC3,5-8. In fact, 
most isolates are susceptible to broad-spectrum 
cephalosporins, carbapenems, tetracyclines, 
and gentamicin but not tobramycin8,9.Testing of 
individual isolates is recommended for clinically 
significant cases once that it is unknown the 
intrinsic mechanisms of resistance for the rhizobia 
species.
Some studies have pointed that R. radiobacter 
presents low MICs (inferior to 1 µg/mL in most of 
cases) to the third generation cephalosporins, 
cephamycins, carbapenems, fluoroquinolones, 
tetracycline, nitrofurantoin, and aminoglycosides, 
but high MIC (superior to 8 µg/mL have been 
reported) to penicillins, penicillin/enzyme inhibitors, 
beta-lactam, aztreonam, and  fosfomycin3,6,7. In 
this report, the isolate showed low MICs for many 
antibiotics and presented a high MICs for others, 
mainly aztreonam and fosfomycin (table). For 
therapeutic approaches, cephalosporins (mainly 
cefepime) and ciprofloxacin have been used 
successfully to treat Rhizobium infections6,7,9. Lai 
et al.2 reported in their study a very lower MICs for 
carbapenem agents in comparison to our isolate, 
mainly for meropenem (2 μg/mL for our isolate 
against a range from 0.03 to 0.06 μg/mL for 18 
isolates tested in Lai’s study). For imipenem, a 
similar MIC value was obtained in comparison with 
the findings of Lai et al.2 It is of note that, based on a 
few reports to date, antimicrobial susceptibilities for 
R. radiobacter is variable. There is no consensus 
for type or length of treatment or optimum therapy, 
owing to the small number of cases described to 
date, and these may logically be dictated by the 
clinical response, degree of underlying illness, 
status of the host immune system, and whether 
microbiologic eradication can be documented. 
Also, it is not uncommon to recover R. radiobacter 
from sites of body without obvious pathologic 
effects and thus it may be present simultaneously 
with other bacterial species in mixed flora. It is 
important to note that R. radiobacter should be 
added to the list of pathogens that induce infections 
conditions in patients with malignancy, but mainly 
in pediatric patients. For an empirical and definitive 
antibiotic therapy, it has been considered the use of 
cefepime 2 g intravenously every 8 hours for a total 
of 8-10 days9. In conclusion, we present an unusual 
case of R. radiobacter bacteremia in a stem cell 
transplant patient. The isolate presented low MICs 
to many antimicrobial agents, but high MICs to 
ceftazidime, piperacillin-tazobactam, aztreonam, 
and fosfomycin. Further studies are required to 
characterize the antimicrobial susceptibility profile 
and the underlying resistance mechanisms of this 
pathogen.
references
1. Mandell, Douglas, and Bennett's 
Principles and Practice of Infectious 
Diseases. 7th ed. London: Elsevier; 
2010.
2. Lai CC, Teng LJ, Hsueh PR, Yuan 
A, Tsai KC, Tang JL, et al. Clinical 
andmicrobiological characteristics of 
Rhizobium radiobacter infections. Clin 
Infect Dis. 2004;38:149-53.
3. Hulse M, Johnson S, Ferrieri P. 
Agrobacterium infections in humans: 
experience at one hospital and 
review. Clin Infect Dis. 1993;16:112-7.
4. Chen CY, Hansen KS, Hansen 
LK. Rhizobium radiobacter as an 
opportunistic pathogen in central 
venous catheter-associated 
bloodstream infection: case 
report and review. J Hosp Infect. 
2008;68:203-7.
5. Mastroianni A, Coronado O, 
Nanetti A, Manfredi R, Chiodo 
F. Agrobacterium radiobacter 
pneumonia in a patient with HIV 
Steiner et al
http://seer.ufrgs.br/hcpa 321Clin Biomed Res 2014;34(3)
infection. Eur J Clin Microbiol Infect 
Dis. 1996;15:960-3.
6. Paphitou NI, Rolston KV. Catheter-
related bacteraemia caused by 
Agrobacterium radiobacter in 
a cancer patient: case report 
and literature review. Infection. 
2003;31:421-4.
7. Amaya RA, Edwards MS. 
Agrobacterium radiobacter 
bacteraemia in pediatric patients: 
case report and review. Pediatr Infect 
Dis J. 2003;22:183-6.
8. Erol Cipe F, Doğu F, Sucuoğlu 
D, Aysev D, Ikincioğulları A. 
Asymptomatic catheter related 
Rhizobium radiobacter infection in 
a haploidentical hemapoietic stem 
cell recipient. J Infect Dev Ctries. 
2010;4:530-2.
9. Ponnapula S, Swanson JM, Wood 
GC, Boucher BA, Wells DL, Croce 
MA, et al. Treatment of Rhizobium 
radiobacter bacteremia in a critically 
ill trauma patient. Ann Pharmacother. 
2013;47:1584-7.
Received: 04/08/2014
Accepted: 16/09/2014
Rhizobium radiobacter bacteremia


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Rhizobium radiobacter recovered from blood of a pediatric patient with stem cell transplantation: a case report and characterization of antimicrobial susceptibility profile

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