Introduction

Raoultella planticola is an aerobic, non-motile, encapsulated, Gram-negative bacterium within the Enterobacteriaceae family [1]. It was initially classified as a member of the Klebsiella genus as Klebsiella planticola or as Klebsiella trevisanii. The current taxonomy was established based on comparative analysis of the 16S rRNA and rpoB genes, resulting in the creation of the new genus Raoultella. There have been sporadic case reports suggesting that R. planticola is a pathogen, with recent reports describing its role in urinary tract infections [2] and in bacteremia following gastroenteritis [3]. Although it may be a well-established potential pathogen, its virulence and susceptibility to antimicrobial agents have yet to be thoroughly investigated. We performed a 4 year retrospective review of R. planticola bacteremia isolates to demonstrate its clinical characteristics as a pathogen.

Methods

We retrospectively reviewed the clinical microbiology reports from our institute for the period spanning October 2008 to September 2012.

All blood isolates that were reported as R. planticola were selected and the medical records of these patients were reviewed. The clinical features of these infections were reviewed, and cases with symptoms indicative of bacteremia were included in the study. The medical record investigation included the patient’s gender and age, any underlying disease, symptoms indicating infection, the number of blood culture sets that yielded R. planticola, the antimicrobial regimen administered for the infection, any microbes other than R. planticola that were isolated, and the outcome of the infection.

All blood culture sets issued contained a secondary and/or a tertiary blood culture at different venous site. When all blood vials yielded positive results on a single blood culture set, and when the isolates from each vial showed identical bacteriologic characteristics, identification and antimicrobial susceptibility testing was done on the first specimen.

Isolation of microbes from blood culture samples was performed using the BacT/ALERT Culture Media system (bioMérieux, Marcy l’Étoile, France). Microbe identification and antibiotic susceptibility tests were performed using the automated VITEK 2 system (bioMérieux, Marcy l’Étoile, France) accompanied by routine bacteriologic methods. Version of the VITEK 2 system was 5.01 prior to 2009, and 5.02 after that. All isolates were identified with a probability score exceeding 96 %. Antimicrobial susceptibility testing was conducted according to the standards established by the Clinical and Laboratory Standards Institute [4].

Results

Overall, 20 inpatients were identified with R. planticola bacteremia during the 4 year period of the study. Over the same period, a total of 26,208 patients were evaluated with blood cultures, and 13,764 tests showed positive blood culture results, while R. planticola was isolated 41 times. Consequently, R. planticola bacteremia occurred in less than 0.3 % of positive blood culture test results. The number of R. planticola bacteremia cases ranged from 2 to 6 cases per year, with an average of five cases annually. The majority of patients (17/20, 85 %) survived the infection. In the three cases in which the patient did not survive, blood cultures revealed evidence of polymicrobial infection.

The gender distribution of the patients was 11 males and 9 females. Patient ages ranged from 18 to 81 years, with a mean of 65 years. The major underlying disease was found to be malignancy (17 patients). Among these patients, nine were diagnosed with solid tumors within or with metastasis to the gallbladder or bile duct. Of these nine cases, seven had adenocarcinoma involving the gallbladder or bile duct. Six cases had hematologic malignancies with pancytopenia after having received allogeneic or autologous hematologic stem cell transplants. In 14 cases, R. planticola was the sole microbial isolate, while in 6 cases, additional microbes were also isolated. All cases are described in chronological order in Table 1.

Table 1 Patient characteristics of the 20 cases with Raoultell aplanticola bacteremia
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Antimicrobial susceptibility testing revealed a universal resistance to both ampicillin and piperacillin, while all strains were susceptible to these antibiotics when combined with β-lactamases inhibitors. Most strains showed susceptibility to cephalosporins; however, occasional resistance to cephalothin (6 %) or intermediate susceptibility to cefoxitin (10 %) was observed. Isolated stains were also susceptible to all third generation cephalosporins, as well as to carbapenems. No resistance to fluoroquinolone agents was observed (Table 2).A total of seven cases (case nos. 1, 4, 9, 12, 18, and 20) were patients with pancytopenia following hematopoietic stem cell transplantation. In ten patients (case nos. 2, 3, 6, 7, 10, 13, 14, 15, 16, and 19) cytotoxic anti-neoplastic agents had been administered, resulting in some degree of myelosuppression. With the exception of case no. 10, all patients recovered with the use of various antimicrobial agents ranging from ciprofloxacin to the combination of vancomycin and cefepime. Case no. 10 was a patient with polymicrobial infection whose blood culture results showed growth of both Pseudomonas aeruginosa and R. planticola. Despite the administration of meropenem, the last blood culture obtained revealed the presence of both pathogens, and the patient died. Case no. 8 was a patient with hepatocellular carcinoma with multiple metastases who refused all forms of treatment.

Table 2 Antibiotic susceptibility of the isolates and cases reported as Raoultell aplanticola
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Among the three cases without underlying malignant diseases, case nos. 11 and 17 had positive outcomes. Case no. 5 was a patient who experienced cardiac arrest with the return of spontaneous circulation after cardiopulmonary resuscitation. Despite the use of cutaneous cardiopulmonary support and vigorous administration of norepinephrine, the patient failed to maintain a mean blood pressure of 60 mmHg. We were unable to determine whether the low blood pressure was of cardiogenic origin or sepsis-related; nonetheless the patient’s blood culture results showed growth of both Morganella morganii and R. planticola.

Discussion

Raoultella sp. is known to be a Gram-negative aerobic bacillus that is a member of the Enterobacteriaceae family. First described by Ferragut et al. [5], it was subsequently reported by Freney et al. to be a cause of sepsis in three patients [6, 7]. Additional reports of R. planticola as a pathogen include cases with acute pancreatitis and retroperitoneal abscess [8], cellulitis [9], cholangitis [10], cholecystitis [11], necrotizing fasciitis [12], and cystitis [2]. All described cases were resolved with fair clinical outcomes. Our current observations, in conjunction with these findings, demonstrate that patients with R. planticola infections generally have a good clinical outcome when first line empirical antimicrobial agents are administered. The majority of the patients in our study had underlying malignancies resulting in low blood neutrophil counts, making bacteremia an imminent issue.

The narrow characteristics of the underlying disorders seen in our 20 patients are of note. Despite the fact that malignancies involving the gallbladder or bile duct are of low prevalence in Korea [13], seven patients in our study had gallbladder adenocarcinoma or cholangiocarcinoma as an underlying disease. In addition, all six cases with hematologic malignancies were in the post-transplantation phase of hematopoietic stem cell transplantation, a condition well known to be prone to infection [14].

Despite the immunosuppressive state of many of our patients, the clinical outcome was fair when proper therapy was administered and R. planticola was the only microbe isolated. In our study, no patients with R. planticola as the sole microbial isolate died. However, in cases with polymicrobial infection, the outcomes differed. Our data revealed that in the six cases with polymicrobial infection, half failed to recover. On the other hand, all of the 14 patients with R. planticola as the sole isolate recovered.

The susceptibility of R. planticola to antimicrobial agents has yet to be fully investigated. In our data, we found that, while all isolates were resistant to ampicillin and piperacillin, the addition of β-lactamases inhibitors overcame this resistance. The isolates were susceptible to most cephalosporins, and a single isolate that was resistant to cephalothin. No resistance to third generation cephalosporins or carbapenems was observed. However, there have been case reports of R. planticola bacteremia that resulted in poor outcomes [15]. R. planticola isolates in these cases were resistant to carbapenem and harbored the blaKPC gene. This was not the case in our study as the R. planticola isolated from the three patients that died showed no resistance to imipenem or meropenem. However, considering the similarities between Raoultella and Klebsiella species, resistance to carbapenem may pose a potential treat.

Suggestions have been made regarding this species as virulent as other Klebsiella species [16]. Serotyping of the capsular antigen, patterns in serum resistance, or the type of pili expressed on the cellular surface showed that R. planticola and Klebsiella pneumoniae share similar traits, and among these traits are some that have been proven to be factors in the microbe’s virulence. In a retrospective analysis of 640 cases of K. pneumoniae bacteremia, it showed to be prevalent in elderly patients in a nosocomial environment, with risk factors as solid organ transplantation, chronic liver disease, dialysis dependence, and malignancies. Primary sites of infection were the biliary and urinary tract. Overall mortality was around 20 %, yet patients with bacteremia from non-biliary or non-genitourinary sources, and patients with comorbid conditions showed worse outcome [17]. However, contrary to K. pneumoniae bacteremia, the virulence of R. planticola bacteremia has not been well demonstrated in the literature. We do notice some similarities with K. pneumoniae and R. planticola bacteremia; biliary tract was thought to be the portal of entry in a large portion of cases, and was prevalent in elderly patients with malignancies. However, excluding the three cases with polymicrobial infection that resulted in poor outcome, R. planticola bacteremia as a sole pathogen did not share similar outcome compared to K. pneumoniae bacteremia.

According to our data, R. planticola as a sole pathogen is of low virulence in bacteremia. Although the small number of patients recruited in our study may not be very representative, R. planticola does not seem to be resistant to most cephalosporins and carbapenems. Polymicrobial infection does seem to pose a threat, despite the generally low virulence of R. planticola as a pathogen on its own. Accrual of sufficient data would be helpful in obtaining a more complete understanding of the significance of R. planticola infections.