J Infect Chemother 20 (2014) 589e591
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Note
Clinical characteristics of Raoultella ornithinolytica bacteremia: A case series and literature review Yuto Haruki a, *, Hideharu Hagiya b, Akiko Sakuma a, Tomoko Murase c, Tetsuhiro Sugiyama a, Sachiyo Kondo a a b c
Department of Pharmacy, Tsuyama Chuo Hospital, 1756, Kawasaki, Tsuyama, Okayama 708-0841, Japan Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan Department of Clinical Laboratory, Microbiology Division, Tsuyama Chuo Hospital, Okayama, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 April 2014 Received in revised form 19 May 2014 Accepted 26 May 2014 Available online 8 July 2014
Raoultella ornithinolytica is a rare pathogen in human infection and bacteremic cases had been scarcely reported. For further comprehension of the rare infection, we summarized clinical characteristics of 6 cases that were detected at our medical facility and 5 cases from previous literature. The most common infectious focus was biliary infection and elderly patients with a history of any biliary intervention or malignancy were considered to be at a great risk for the infection. The prognosis of the patients was quite satisfactory. Bacterial identification in this report was performed on the basis of biochemical tests alone, and further investigations by molecular analysis are required to confirm our findings. © 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Bacteremia Biliary infection Histamine reaction Raoultella ornithinolytica
Raoultella ornithinolytica is an encapsulated gram-negative aerobic bacillus belonging to the family Enterobacteriaceae. The organism was once classified as a Klebsiella species, and only recently separated on the basis of new molecular analysis [1]. Although R. ornithinolytica is ubiquitously found in aquatic environments [2], it hardly causes invasive infections in human. So far, there have been only a few clinical reports on R. ornithinolytica bacteremia [2e4] and clinical characteristics of such cases have not been determined. We herein report 6 cases of R. ornithinolytica bacteremia in our facility with a summary of previously reported 5 cases. First, we performed a retrospective review of blood culture records at Tsuyama Chuo Hospital (a 535-bed community hospital in Japan) between 2005 and 2014 (a 10-year period). The present study (No. 193) was approved by the Ethics Committee of Tsuyama Chuo Hospital. A signal blood culture system (Oxoid USA Inc., Columbia, MD, USA) was used prior to 2007, and a BacT/Alert 3D rieux, Tokyo, Japan) was used thereafter. system (Sysmex bioMe Bacterial identification and antibiotic susceptibility testing were performed by the Microscan Walkaway 40 SI system (Siemens Healthcare Diagnostics, Tokyo, Japan). R. ornithinolytica bacteremia was defined as a case that showed positive blood culture for
* Corresponding author. Tel.: þ81 868 21 8111; fax: þ81 868 21 8222. E-mail address: [email protected] (Y. Haruki).
R. ornithinolytica. Medical records were reviewed retrospectively to assess the patient's clinical characteristics. During the study period, we identified 6 patients (3 men and 3 women) with R. ornithinolytica bacteremia at our hospital (Table 1; Cases 1e6). All the isolates in our facility showed positive reactions for ornithine decarboxylase tests. The average age of the patients was 71 years, with a standard deviation of 15.9 years. Five cases were caused by cholangitis, while the remaining case was possibly caused by acute prostatitis. Four patients with cholangitis (Cases 2e4, 6) had a history of hepatic or biliary disease such as malignancy or cholelithiasis. They had received each of bile duct interventions including cholecystectomy, endoscopic retrograde biliary drainage and the placement of a biliary stent. Any of these patients did not reveal systemic rashes that can occur as a result of histamine reactions. Although Case 6 was complicated by septic shock, the patient was successfully treated with antibiotic therapy. A literature review was then performed by searching the PubMed database using the following search terms (without quotes): “Raoultella ornithinolytica bacteremia” and “Klebsiella ornithinolytica bacteremia”. As a result, we identified 3 English reports (including 5 patients) that concerned R. ornithinolytica bacteremia (Table 1) [2e4]. Overall, the cases involved 6 male and 5 female patients. Excluding a case involving an infant, the average patient age was 71.1 years, with a standard deviation of 16.1 years. Of the 11 cases, hepatic
http://dx.doi.org/10.1016/j.jiac.2014.05.005 1341-321X/© 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
590
Y. Haruki et al. / J Infect Chemother 20 (2014) 589e591
Table 1 Summary of Raoultella ornithinolytica bacteremia. Cases 1e6 were reported from our hospital and the other cases were from previous literature. Most patients were relatively elderly with malignant complications. A major focus of the bacteremia was biliary infection. The prognosis of the patients was excellent with antibiotic therapy. Case
Reference
Sex
Age
Underlying diseases
Primary focus
Antibiotics
Duration (days)
Prognosis
1 2 3
Our case, 2005 Our case, 2008 Our case, 2008
F M F
73 75 92
Cholangitis Cholangitis Cholangitis
PIPC / CAZ CFPM þ AMK CPZ/SBT / CPFX
3 4 5
Survived Survived Survived
4
Our case, 2011
M
44
Cholangitis
CPZ/SBT / AMPC/CVA
9
Survived
5 6 7 8
Our case, 2012 Our case, 2014 Morais VP et al, 2009 Mau N et al, 2010
M F F M
65 77 82 0
Acute prostatitis Cholangitis Enterocolitis Cholangitis
CFPM / LVFX PIPC/TAZ / CEZ CPFX / AMPC/CVA CFPM, MNZ, AMK / MEPM, AMK
14 14 20 7
Survived Survived Survived Survived
9 10 11
Hadano Y et al, 2012 Hadano Y et al, 2012 Hadano Y et al, 2012
M F M
92 52 59
Cerebral infarction Cholecystolithiasis Cholangitis, pancreatitis, choledocholithiasis Sigmoid colon cancer, liver metastasis None Cholangiocarcinoma Degenerative arthropathy Visceral heterotaxy, asplenia, congenital cardiac anomaly Cholangiocarcinoma Pancreatic cancer Gastric cancer
Cholangitis Cholangitis Cholangitis
PIPC/TAZ IMP/CS / CMZ PIPC/TAZ / CMZ / AMPC/CVA
14 15 14
Survived Survived Survived
AMK: amikacin; AMPC/CVA: amoxicillin/clavulanate; CAZ: ceftazidime; CEZ: cefazolin; CFPM: cefepime; CMZ: cefmetazole; CPFX: ciprofloxacin; CPZ/SBT: cefoperazone/ sulbactam; IMP/CS: imipenem/cilastatin; LVFX: levofloxacin; MEPM: meropenem; MNZ: metronidazole; PIPC: piperacillin; PIPC/TAZ: peperacillin/tazobactam.
or biliary disease was observed in 7 cases (63.6%), and malignant disease was observed in 5 cases (45.5%). Nine cases (81.8%) were primarily caused by biliary infection. Only 1 patient (9.1%) had red skin flushing related to a histamine reaction (Case 8). Although the treatment periods varied from 3 to 20 days, all 11 patients survived after receiving antibiotics therapy (mainly b-lactams). Table 2 summarizes the microbiological testing. The BacT/Alert system was commonly used as an automated microbial detection system for blood cultures, and the MicroScan Walkaway was the main system for bacterial identification. The isolates were resistant to ampicillin (ABPC), but showed susceptibility to piperacillin (70%, 7/10 cases), cefotaxime (CTX) (100%, 7/7 cases), and levofloxacin (LVFX) (100%, 10/10 cases). Clinical characteristics of R. ornithinolytica bacteremia were summarized in this report. Among the 11 cases, the major focus of the bacteremia was biliary infection. Examination of these cases suggests that elderly patients with a history of any biliary interventions, biliary tract diseases, or malignancy are at elevated risk for R. ornithinolytica bacteremia. The pathogens were susceptible to both third-generation cephalosporin and fluoroquinolone and all the 11 patients were treated effectively with antibiotic therapy. Including the newly reported cases from our hospital, 9 of the 11 cases have been reported in Japan. The organism is universally found in natural environments and it is not expected to have any geographic focal point. Actually, those bacteremia cases were reported from Spain [2], the USA [3] and Japan [4], and nonbacteremia cases have been reported in Turkey [5], India [6], and China [7]. It is not clear whether Japanese or, more generally,
Asian population are especially vulnerable to R. ornithinolytica bacteremia. Patients infected with R. ornithinolytica are assumed to have a poor prognosis because (A) R. ornithinolytica was once considered to belong to the genus Klebsiella, which includes pathogens that are highly virulent in humans and (B) patients with R. ornithinolytica infections tend to be elderly and have a history of malignancy. However, the outcomes of treatment for R. ornithinolytica bacteremia were satisfactory for all cases. Because of the small number of subjects, firm conclusions cannot be reached based only on the present study, and further investigation would be necessary to assess the prognosis of R. ornithinolytica bacteremia definitively. R. ornithinolytica is an encapsulated organism and patients with hyposplenism are assumed to be at risk for the infection. There were, however, no such patients in this study, with the exception of an infant with congenital asplenia [3]. As a result of producing chromosomally-encoded class A betalactamases [8], R. ornithinolytica is reported to be resistant to ABPC [9]. In our study, all isolates were resistant to ABPC; however, the isolates had satisfactory susceptibility to CTX and LVFX. Nonetheless, an emergence of carbapenemase-positive R. ornithinolytica has been reported [6,7] and additional attention may be required for the susceptibility testing of the organism. The method of identifying the organism is a limitation to the present study. Some previous reports noted that the identification of R. ornithinolytica may be insufficient if it is based on commercial biochemical identification systems alone [10e12]. Particularly, the discrimination of R. ornithinolytica from Klebsiella oxytoca has been
Table 2 Summary of the microbiological testing of the cases. The BacT/Alert system was mostly used for blood culture examinations and the MicroScan Walkaway was mostly used for identification. The strains were resistant to ABPC, but susceptible to PIPC, CTX and LVFX. Case
Reference
Blood culture device
Identification
Antibiotics susceptibility ABPC
PIPC
CTX
LVFX
1 2 3 4 5 6 7 8 9 10 11
Our case, 2005 Our case, 2008 Our case, 2008 Our case, 2011 Our case, 2012 Our case, 2014 Morais VP et al, 2009 Mau N et al, 2010 Hadano Y et al, 2012 Hadano Y et al, 2012 Hadano Y et al, 2012
Signal blood culture system BacT/Alert BacT/Alert BacT/Alert BacT/Alert BacT/Alert Wider system unknown BacT/Alert BacT/Alert BacT/Alert
MicroScan MicroScan MicroScan MicroScan MicroScan MicroScan API-20E unknown MicroScan MicroScan MicroScan
R R R R R R R R R R R
R S S S R R n.p. S S S S
S S S S S S n.p. S n.p. n.p. n.p.
S S S S S S n.p. S S S S
Walkaway Walkaway Walkaway Walkaway Walkaway Walkaway
Walkaway Walkaway Walkaway
ABPC: ampicillin; CTX: cefotaxime; LVFX: levofloxacin; PIPC: piperacillin; R: resistant; S: susceptible; n.p.: not provided.
Y. Haruki et al. / J Infect Chemother 20 (2014) 589e591
reported to be difficult [13]. Although the Vitek 2 GN card (biorieux, Marcy-l'Etoile, France) was reported to provide acceptable Me and highly accurate identification of R. ornithinolytica [14], Microrieux, Marcy l'Etoile, France) asScan and API-20E strip (bioMe sessments may require additional examinations to confirm the identification [11]. The bacterial identification of our cases depended only on the biochemical characteristic of the pathogens, mainly by using the MicroScan Walkaway, and misidentification was therefore inevitable. Yet, while R. ornithinolytica was misidentified as K. oxytoca by the biochemical tests in previous reports, misidentification of K. oxytoca as R. ornithinolytica did not occur [12]. Therefore, we insist that the identifications of R. ornithinolytica was reliable. Matrix-assisted laser desorption/ionization time-offlight mass spectrometry has been shown to be a valid means of discriminating R. ornithinolytica [13]. This method or a similar novel technology may be required for accurate identification in future studies. There are various rare pathogens that cause cholangitis, as well as R. ornithinolytica. Edwardsiella tarda, a gram negative anaerobic bacillus, would be a representative of such organisms. E. tarda usually does not inhabit human, but colonization in human intestine can occur through ingestion of raw seafood. Though rare, mortality rate of patients with E. tarda bacteremia were once reported as high as 50% [15]. Thus, an effort for comprehensive understanding of infections by rare pathogens, as performed in this report, would be clinically important. In conclusion, we have summarized the clinical characteristics of R. ornithinolytica bacteremia in this report. A major focus of the bacteremia was biliary infection. It appears that elderly patients with a history of any biliary interventions, biliary tract diseases, or malignancy are at elevated risk for R. ornithinolytica bacteremia. The patients had an excellent prognosis with antibiotic therapy, but further study with additional patients and more reliable identification methods would be required to confirm our findings. Conflict of interest The authors declare that they have no conflict of interest.
591
References [1] Drancourt M, Bollet C, Carta A, Rousselier P. Phylogenetic analyses of Klebsiella species delineate Klebsiella and Raoultella gen. nov., with description of Raoultella ornithinolytica comb. nov., Raoultella terrigena comb. nov. and Raoultella planticola comb. nov. Int J Syst Evol Microbiol 2001;51:925e32. [2] Morais VP, Daporta MT, Bao AF, Campello MG, Andres GQ. Enteric fever-like syndrome caused by Raoultella ornithinolytica (Klebsiella ornithinolytica). J Clin Microbiol 2009;47:868e9. [3] Mau N, Ross LA. Raoultella ornithinolytica bacteremia in an infant with visceral heterotaxy. Pediatr Infect Dis J 2010;29:477e8. [4] Hadano Y, Tsukahara M, Ito K, Suzuki J, Kawamura I, Kurai H. Raoultella ornithinolytica bacteremia in cancer patients: report of three cases. Intern Med 2012;51:3193e5. [5] Solak Y, Gul EE, Atalay H, Genc N, Tonbul HZ. A rare human infection of Raoultella ornithinolytica in a diabetic foot lesion. Ann Saudi Med 2011;31: 93e4. [6] Khajuria A, Praharaj AK, Grover N, Kumar M. First report of blaNDM-1 in Raoultella ornithinolytica. Antimicrob Agents Chemother 2013;57:1092e3. [7] Zhou G, Guo S, Luo Y, Ye L, Song Y, Sun G, et al. NDM-1-producing strains, family Enterobacteriaceae, in hospital, Beijing, China. Emerg Infect Dis 2014;20:340e2. [8] Walckenaer E, Poirel L, Leflon-Guibout V, Nordmann P, Nicolas-Chanoine MH. Genetic and biochemical characterization of the chromosomal class A betalactamases of Raoultella (formerly Klebsiella) planticola and Raoultella ornithinolytica. Antimicrob Agents Chemother 2004;48:305e12. [9] Hostacka A, Klokocnikova. Antibiotic susceptibility, serum response and surface properties of Klebsiella species. Microbios 2001;104:115e24. [10] Granier SA, Leflon-Guibout V, Goldstein FW, Nicolas-Chanoine MH. Enterobacterial repetitive intergenic consensus 1R PCR assay for detection of Raoultella sp. isolates among strains identified as Klebsiella oxytoca in the clinical laboratory. J Clin Microbiol 2003;41:1740e2. [11] Park JS, Hong KH, Lee HJ, Choi SH, Song SH, Song KH, et al. Evaluation of three phenotypic identification systems for clinical isolates of Raoultella ornithinolytica. J Med Microbiol 2011;60:492e9. [12] Richter SS, Sercia L, Branda JA, Burnham CA, Bythrow M, Ferraro MJ, et al. Identification of Enterobacteriaceae by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry using the VITEK MS system. Eur J Clin Microbiol Infect Dis 2013;32:1571e8. [13] de Jong E, de Jong AS, Smidts-van den Berg N, Rentenaar RJ. Differentiation of Raoultella ornithinolytica/planticola and Klebsiella oxytoca clinical isolates by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Diagn Microbiol Infect Dis 2013;75:431e3. [14] Renaud FN, Bergeron E, Tigaud S, Fuhrmann C, Gravagna B, Freney J. Evaluation of the new Vitek 2 GN card for the identification of gram-negative bacilli frequently encountered in clinical laboratories. Eur J Clin Microbiol Infect Dis 2005;24:671e6. [15] Janda JM, Abbott SL. Infections associated with the genus Edwardsiella: the role of Edwardsiella tarda in human disease. Clin Infect Dis 1993;17:742e8.
Contents lists available at ScienceDirect
Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic
Note
Clinical characteristics of Raoultella ornithinolytica bacteremia: A case series and literature review Yuto Haruki a, *, Hideharu Hagiya b, Akiko Sakuma a, Tomoko Murase c, Tetsuhiro Sugiyama a, Sachiyo Kondo a a b c
Department of Pharmacy, Tsuyama Chuo Hospital, 1756, Kawasaki, Tsuyama, Okayama 708-0841, Japan Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan Department of Clinical Laboratory, Microbiology Division, Tsuyama Chuo Hospital, Okayama, Japan
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 April 2014 Received in revised form 19 May 2014 Accepted 26 May 2014 Available online 8 July 2014
Raoultella ornithinolytica is a rare pathogen in human infection and bacteremic cases had been scarcely reported. For further comprehension of the rare infection, we summarized clinical characteristics of 6 cases that were detected at our medical facility and 5 cases from previous literature. The most common infectious focus was biliary infection and elderly patients with a history of any biliary intervention or malignancy were considered to be at a great risk for the infection. The prognosis of the patients was quite satisfactory. Bacterial identification in this report was performed on the basis of biochemical tests alone, and further investigations by molecular analysis are required to confirm our findings. © 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Keywords: Bacteremia Biliary infection Histamine reaction Raoultella ornithinolytica
Raoultella ornithinolytica is an encapsulated gram-negative aerobic bacillus belonging to the family Enterobacteriaceae. The organism was once classified as a Klebsiella species, and only recently separated on the basis of new molecular analysis [1]. Although R. ornithinolytica is ubiquitously found in aquatic environments [2], it hardly causes invasive infections in human. So far, there have been only a few clinical reports on R. ornithinolytica bacteremia [2e4] and clinical characteristics of such cases have not been determined. We herein report 6 cases of R. ornithinolytica bacteremia in our facility with a summary of previously reported 5 cases. First, we performed a retrospective review of blood culture records at Tsuyama Chuo Hospital (a 535-bed community hospital in Japan) between 2005 and 2014 (a 10-year period). The present study (No. 193) was approved by the Ethics Committee of Tsuyama Chuo Hospital. A signal blood culture system (Oxoid USA Inc., Columbia, MD, USA) was used prior to 2007, and a BacT/Alert 3D rieux, Tokyo, Japan) was used thereafter. system (Sysmex bioMe Bacterial identification and antibiotic susceptibility testing were performed by the Microscan Walkaway 40 SI system (Siemens Healthcare Diagnostics, Tokyo, Japan). R. ornithinolytica bacteremia was defined as a case that showed positive blood culture for
* Corresponding author. Tel.: þ81 868 21 8111; fax: þ81 868 21 8222. E-mail address: [email protected] (Y. Haruki).
R. ornithinolytica. Medical records were reviewed retrospectively to assess the patient's clinical characteristics. During the study period, we identified 6 patients (3 men and 3 women) with R. ornithinolytica bacteremia at our hospital (Table 1; Cases 1e6). All the isolates in our facility showed positive reactions for ornithine decarboxylase tests. The average age of the patients was 71 years, with a standard deviation of 15.9 years. Five cases were caused by cholangitis, while the remaining case was possibly caused by acute prostatitis. Four patients with cholangitis (Cases 2e4, 6) had a history of hepatic or biliary disease such as malignancy or cholelithiasis. They had received each of bile duct interventions including cholecystectomy, endoscopic retrograde biliary drainage and the placement of a biliary stent. Any of these patients did not reveal systemic rashes that can occur as a result of histamine reactions. Although Case 6 was complicated by septic shock, the patient was successfully treated with antibiotic therapy. A literature review was then performed by searching the PubMed database using the following search terms (without quotes): “Raoultella ornithinolytica bacteremia” and “Klebsiella ornithinolytica bacteremia”. As a result, we identified 3 English reports (including 5 patients) that concerned R. ornithinolytica bacteremia (Table 1) [2e4]. Overall, the cases involved 6 male and 5 female patients. Excluding a case involving an infant, the average patient age was 71.1 years, with a standard deviation of 16.1 years. Of the 11 cases, hepatic
http://dx.doi.org/10.1016/j.jiac.2014.05.005 1341-321X/© 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
590
Y. Haruki et al. / J Infect Chemother 20 (2014) 589e591
Table 1 Summary of Raoultella ornithinolytica bacteremia. Cases 1e6 were reported from our hospital and the other cases were from previous literature. Most patients were relatively elderly with malignant complications. A major focus of the bacteremia was biliary infection. The prognosis of the patients was excellent with antibiotic therapy. Case
Reference
Sex
Age
Underlying diseases
Primary focus
Antibiotics
Duration (days)
Prognosis
1 2 3
Our case, 2005 Our case, 2008 Our case, 2008
F M F
73 75 92
Cholangitis Cholangitis Cholangitis
PIPC / CAZ CFPM þ AMK CPZ/SBT / CPFX
3 4 5
Survived Survived Survived
4
Our case, 2011
M
44
Cholangitis
CPZ/SBT / AMPC/CVA
9
Survived
5 6 7 8
Our case, 2012 Our case, 2014 Morais VP et al, 2009 Mau N et al, 2010
M F F M
65 77 82 0
Acute prostatitis Cholangitis Enterocolitis Cholangitis
CFPM / LVFX PIPC/TAZ / CEZ CPFX / AMPC/CVA CFPM, MNZ, AMK / MEPM, AMK
14 14 20 7
Survived Survived Survived Survived
9 10 11
Hadano Y et al, 2012 Hadano Y et al, 2012 Hadano Y et al, 2012
M F M
92 52 59
Cerebral infarction Cholecystolithiasis Cholangitis, pancreatitis, choledocholithiasis Sigmoid colon cancer, liver metastasis None Cholangiocarcinoma Degenerative arthropathy Visceral heterotaxy, asplenia, congenital cardiac anomaly Cholangiocarcinoma Pancreatic cancer Gastric cancer
Cholangitis Cholangitis Cholangitis
PIPC/TAZ IMP/CS / CMZ PIPC/TAZ / CMZ / AMPC/CVA
14 15 14
Survived Survived Survived
AMK: amikacin; AMPC/CVA: amoxicillin/clavulanate; CAZ: ceftazidime; CEZ: cefazolin; CFPM: cefepime; CMZ: cefmetazole; CPFX: ciprofloxacin; CPZ/SBT: cefoperazone/ sulbactam; IMP/CS: imipenem/cilastatin; LVFX: levofloxacin; MEPM: meropenem; MNZ: metronidazole; PIPC: piperacillin; PIPC/TAZ: peperacillin/tazobactam.
or biliary disease was observed in 7 cases (63.6%), and malignant disease was observed in 5 cases (45.5%). Nine cases (81.8%) were primarily caused by biliary infection. Only 1 patient (9.1%) had red skin flushing related to a histamine reaction (Case 8). Although the treatment periods varied from 3 to 20 days, all 11 patients survived after receiving antibiotics therapy (mainly b-lactams). Table 2 summarizes the microbiological testing. The BacT/Alert system was commonly used as an automated microbial detection system for blood cultures, and the MicroScan Walkaway was the main system for bacterial identification. The isolates were resistant to ampicillin (ABPC), but showed susceptibility to piperacillin (70%, 7/10 cases), cefotaxime (CTX) (100%, 7/7 cases), and levofloxacin (LVFX) (100%, 10/10 cases). Clinical characteristics of R. ornithinolytica bacteremia were summarized in this report. Among the 11 cases, the major focus of the bacteremia was biliary infection. Examination of these cases suggests that elderly patients with a history of any biliary interventions, biliary tract diseases, or malignancy are at elevated risk for R. ornithinolytica bacteremia. The pathogens were susceptible to both third-generation cephalosporin and fluoroquinolone and all the 11 patients were treated effectively with antibiotic therapy. Including the newly reported cases from our hospital, 9 of the 11 cases have been reported in Japan. The organism is universally found in natural environments and it is not expected to have any geographic focal point. Actually, those bacteremia cases were reported from Spain [2], the USA [3] and Japan [4], and nonbacteremia cases have been reported in Turkey [5], India [6], and China [7]. It is not clear whether Japanese or, more generally,
Asian population are especially vulnerable to R. ornithinolytica bacteremia. Patients infected with R. ornithinolytica are assumed to have a poor prognosis because (A) R. ornithinolytica was once considered to belong to the genus Klebsiella, which includes pathogens that are highly virulent in humans and (B) patients with R. ornithinolytica infections tend to be elderly and have a history of malignancy. However, the outcomes of treatment for R. ornithinolytica bacteremia were satisfactory for all cases. Because of the small number of subjects, firm conclusions cannot be reached based only on the present study, and further investigation would be necessary to assess the prognosis of R. ornithinolytica bacteremia definitively. R. ornithinolytica is an encapsulated organism and patients with hyposplenism are assumed to be at risk for the infection. There were, however, no such patients in this study, with the exception of an infant with congenital asplenia [3]. As a result of producing chromosomally-encoded class A betalactamases [8], R. ornithinolytica is reported to be resistant to ABPC [9]. In our study, all isolates were resistant to ABPC; however, the isolates had satisfactory susceptibility to CTX and LVFX. Nonetheless, an emergence of carbapenemase-positive R. ornithinolytica has been reported [6,7] and additional attention may be required for the susceptibility testing of the organism. The method of identifying the organism is a limitation to the present study. Some previous reports noted that the identification of R. ornithinolytica may be insufficient if it is based on commercial biochemical identification systems alone [10e12]. Particularly, the discrimination of R. ornithinolytica from Klebsiella oxytoca has been
Table 2 Summary of the microbiological testing of the cases. The BacT/Alert system was mostly used for blood culture examinations and the MicroScan Walkaway was mostly used for identification. The strains were resistant to ABPC, but susceptible to PIPC, CTX and LVFX. Case
Reference
Blood culture device
Identification
Antibiotics susceptibility ABPC
PIPC
CTX
LVFX
1 2 3 4 5 6 7 8 9 10 11
Our case, 2005 Our case, 2008 Our case, 2008 Our case, 2011 Our case, 2012 Our case, 2014 Morais VP et al, 2009 Mau N et al, 2010 Hadano Y et al, 2012 Hadano Y et al, 2012 Hadano Y et al, 2012
Signal blood culture system BacT/Alert BacT/Alert BacT/Alert BacT/Alert BacT/Alert Wider system unknown BacT/Alert BacT/Alert BacT/Alert
MicroScan MicroScan MicroScan MicroScan MicroScan MicroScan API-20E unknown MicroScan MicroScan MicroScan
R R R R R R R R R R R
R S S S R R n.p. S S S S
S S S S S S n.p. S n.p. n.p. n.p.
S S S S S S n.p. S S S S
Walkaway Walkaway Walkaway Walkaway Walkaway Walkaway
Walkaway Walkaway Walkaway
ABPC: ampicillin; CTX: cefotaxime; LVFX: levofloxacin; PIPC: piperacillin; R: resistant; S: susceptible; n.p.: not provided.
Y. Haruki et al. / J Infect Chemother 20 (2014) 589e591
reported to be difficult [13]. Although the Vitek 2 GN card (biorieux, Marcy-l'Etoile, France) was reported to provide acceptable Me and highly accurate identification of R. ornithinolytica [14], Microrieux, Marcy l'Etoile, France) asScan and API-20E strip (bioMe sessments may require additional examinations to confirm the identification [11]. The bacterial identification of our cases depended only on the biochemical characteristic of the pathogens, mainly by using the MicroScan Walkaway, and misidentification was therefore inevitable. Yet, while R. ornithinolytica was misidentified as K. oxytoca by the biochemical tests in previous reports, misidentification of K. oxytoca as R. ornithinolytica did not occur [12]. Therefore, we insist that the identifications of R. ornithinolytica was reliable. Matrix-assisted laser desorption/ionization time-offlight mass spectrometry has been shown to be a valid means of discriminating R. ornithinolytica [13]. This method or a similar novel technology may be required for accurate identification in future studies. There are various rare pathogens that cause cholangitis, as well as R. ornithinolytica. Edwardsiella tarda, a gram negative anaerobic bacillus, would be a representative of such organisms. E. tarda usually does not inhabit human, but colonization in human intestine can occur through ingestion of raw seafood. Though rare, mortality rate of patients with E. tarda bacteremia were once reported as high as 50% [15]. Thus, an effort for comprehensive understanding of infections by rare pathogens, as performed in this report, would be clinically important. In conclusion, we have summarized the clinical characteristics of R. ornithinolytica bacteremia in this report. A major focus of the bacteremia was biliary infection. It appears that elderly patients with a history of any biliary interventions, biliary tract diseases, or malignancy are at elevated risk for R. ornithinolytica bacteremia. The patients had an excellent prognosis with antibiotic therapy, but further study with additional patients and more reliable identification methods would be required to confirm our findings. Conflict of interest The authors declare that they have no conflict of interest.
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