Scandinavian Journal of Infectious Diseases

ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19

Predominant association of Raoultella bacteremia with diseases of the biliary tract Eefje de Jong, Sandra Erkens-Hulshof, Lieven B. J. van der Velden, Andreas Voss, Ron Bosboom, Caspar J. Hodiamont, Peter C. Wever, Rob J. Rentenaar & Patrick D. Sturm To cite this article: Eefje de Jong, Sandra Erkens-Hulshof, Lieven B. J. van der Velden, Andreas Voss, Ron Bosboom, Caspar J. Hodiamont, Peter C. Wever, Rob J. Rentenaar & Patrick D. Sturm (2014) Predominant association of Raoultella bacteremia with diseases of the biliary tract, Scandinavian Journal of Infectious Diseases, 46:2, 141-143 To link to this article: http://dx.doi.org/10.3109/00365548.2013.857044

Published online: 11 Dec 2013.

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Scandinavian Journal of Infectious Diseases, 2014; 46: 141–143

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Predominant association of Raoultella bacteremia with diseases of the biliary tract

EEFJE DE JONG1,2, SANDRA ERKENS-HULSHOF3, LIEVEN B. J. VAN DER VELDEN1,4, ANDREAS VOSS1,4, RON BOSBOOM2, CASPAR J. HODIAMONT5, PETER C. WEVER6, ROB J. RENTENAAR7 & PATRICK D. STURM3 From the 1Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, 2Department of Medical Microbiology and Medical Immunology, Rijnstate Hospital, Arnhem, 3Department of Medical Microbiology, Laboratory for Pathology and Medical Microbiology (PAMM), Veldhoven, 4Department of Medical Microbiology, Canisius Wilhelmina Hospital, Nijmegen, 5Department of Medical Microbiology, Academic Medical Center, Amsterdam, 6Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, ’s-Hertogenbosch, and 7Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands

Abstract A case series of 14 patients with Raoultella bacteremia was compared with 28 Klebsiella oxytoca and 28 Klebsiella pneumoniae bacteremia cases. Forty-three percent of Raoultella bacteremia cases were associated with biliary tract disease, compared to 32% and 22% of patients with K. oxytoca and K. pneumoniae bacteremia, respectively.

Keywords: Raoultella, Klebsiella, disease association, cholangitis

Introduction

Methods

Before the introduction of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), Raoultella spp. and Klebsiella oxytoca were difficult to distinguish in the routine clinical microbiology laboratory using classical and automated biochemical identification methods [1,2]. MALDI-TOF MS allows for more accurate discrimination between Raoultella spp. and K. oxytoca, but Raoultella spp. remain infrequently encountered pathogens in clinical microbiology laboratories [3]. Disease associations of Raoultella ornithinolytica and Raoultella planticola bacteremia are limited to case reports [4–10]. In a previous study, 3 of 5 Raoultella isolates appeared to be from patients with bacteremia related to biliary tract disease; consequently, we hypothesized that Raoultella bacteremia is associated with biliary tract disease [3].

A retrospective chart review was performed in 7 clinical microbiology laboratories serving 11 hospitals (3 academic, 8 non-academic) across the Netherlands. All laboratories used the Bruker MALDI-TOF MS system (MALDI Biotyper, Bruker Daltonics, Bremen, Germany) for routine identification of Gram-negative rods. A case was defined as a patient with a Raoultella bacteremia identified by MALDI-TOF MS with a score value ⱖ 2.000 and a percent differential score value of at least 10% to K. oxytoca, indicating reliable genus level identification [3]. In each laboratory, cases were collected from the introduction of the MALDITOF-MS system for the identification of Gram-negative rods (between 1 December 2009 and 12 June 2012) through January 2013. These cases were compared in a 1 to 2 ratio case–control fashion with K. oxytoca and Klebsiella pneumoniae bacteremia cases, stratified by laboratory.

Correspondence: E. de Jong, University Medical Center Nijmegen, Department of Medical Microbiology, route number 777, PO Box 9101, 6500 HB Nijmegen, Netherlands. Tel: ⫹ 31 (0)24 3614356. Fax: ⫹ 31 (0)24 3540216. E-mail: [email protected] (Received 3 September 2013 ; accepted 15 October 2013) ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2013.857044

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The first 2 patients with K. oxytoca bacteremia as well as the first 2 patients with K. pneumoniae bacteremia following (in time) the identification of a case, were selected as controls. Clinical characteristics of cases and controls were collected from electronic patient files, using a standardized clinical research form. Data collected included sex, age, clinical diagnosis, all culture results related to the current episode of infection, C-reactive protein (CRP) level, white blood cell count (WBC), and liver enzyme blood levels. Cholangitis diagnoses were graded retrospectively as ‘suspected’ or ‘definite’, according to the revised Tokyo Guidelines (TG13) [11]. Results A total of 14 Raoultella bacteremia cases, 28 controls with K. oxytoca bacteremia, and 28 controls with K. pneumoniae bacteremia were investigated (Table I). Each participating laboratory contributed at least 1 case and 4 control patients (5, 3, 2, and 1 cases from 1, 1, 1, and 4 laboratories, respectively). Cases were identified at 9 of the 11 participating hospitals (1–3 patients per hospital). Demographics of the cases and controls are presented in Table I. Three (21%) cases were polymicrobial (co-infecting pathogens: Citrobacter freundii n ⫽ 1, Enterobacter cloacae n ⫽ 2).

Polymicrobial bloodstream infections occurred in 11 (39%) and 5 (18%) of the patients with a K. oxytoca and K. pneumoniae bacteremia, respectively (most common co-infecting pathogens: Escherichia coli (n ⫽ 8) and Enterococcus faecalis (n ⫽ 4)). Eight Raoultella bacteremia cases (57%) were in patients with upper gastrointestinal tract disease (Table I). Six patients had biliary tract abnormalities or disease and 2 patients had duodenal perforation (Table I). Nine of 28 (32%) K. oxytoca bacteremia controls cases and 5 of 28 (18%) K. pneumoniae bacteremia control cases were related to biliary tract diseases (Table I) [11]. One of 28 (4%) K. oxytoca controls had a gastric perforation and 1 of 28 (4%) K. pneumoniae controls had an infected pancreatic necrosis. Bacteremia was associated with urinary tract infection in 1 (7%), 10 (35%), and 6 (21%) patients with Raoultella spp., K. oxytoca, and K. pneumoniae bacteremia, respectively (Table I). Discussion Almost half of the Raoultella spp. bacteremia cases were associated with biliary tract diseases. This association resembles the association of K. oxytoca bacteremia with disease of the biliary tract. Two case series of K. oxytoca bacteremia described biliary

Table I. Patient characteristics.a

Age, y Sex, male/female Differential score Diagnosis Cholecystitis/cholangitis Definite cholangitisb Suspected cholangitisb Cholangitis not scoredc Cholecystitis Duodenal perforation Gastric perforation Infected pancreatic necrosis Obstruction of terminal ileum Abdominal abscess Enteric ischemia Urosepsis Central line-associated bloodstream infection Other (febrile neutropenia, infected intracardial thrombus, wound infection, liver cysts) Pneumonia No focus of infection Polymicrobial infection Cholecystitis/cholangitis aResults

Raoultella spp. (Cases)

Klebsiella oxytoca (Controls)

Klebsiella pneumoniae (Controls)

73 (35–89) (n ⫽ 14) 10/4 (71%/29%) 16 (11–24) (n ⫽ 14)

72 (0–92) (n ⫽ 28) 19/9 (68%/32%) 11 (0–22) (n ⫽ 26)

67 (0–84) (n ⫽ 28) 18/10 (64%/36%) Not determined

6 (43%) 3 (21%) 2 (14%) – 1 (7%) 2 (14%) – – – – – 1 (7%) 1 (7%) – 1 (7%) 3 (21%) 3 1

9 3 3 1 2

(32%) (11%) (11%) (4%) (7%) – (4%) – – (4%) – (35%) (7%) –

5 (18%) 1 (4%) 4 (14%) – – – – 1 (4%) 1 (4%) – 1 (4%) 6 (21%) – 4 (14%)

1 (4%) 4 (14%) 11 7

– 10 (35%) 5 1

1

1 10 2

are given as the median (range) (n), or as n (%). according to revised Tokyo Guidelines (TG13) [11]. cInsufficient revised Tokyo Guidelines (TG13) criteria retrievable by retrospective chart review. A clinical diagnosis of cholangitis was established according to the chart. bGrading

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Raoultella bacteremia and biliary tract disease tract disease as the source of bacteremia in 44% and 58% of cases [12,13]. In contrast, in 2 K. pneumoniae bacteremia studies, the biliary tract was the source of infection in 19% and less than 16% of cases, respectively [14,15]. In the 9 previously described R. ornithinolytica or R. planticola bacteremia cases, only 2 were in patients with biliary tract disease [4,8]. However, in 5 patients the source of bacteremia remained unclear [5–7]. The current study included 14 patients and is the largest case series of Raoultella bacteremia, in a retrospective cohort from multiple laboratories. Thereby, this study allows for a better estimation of the true frequency of diseases associated with Raoultella bacteremia. Nevertheless, the small sample size remains an important limitation of this study, as only 14 patients with Raoultella spp. bacteremia were included during the study period and a focus of bacteremia could not be identified in 3 of these patients. A strength of this study is the participation of diverse hospitals (academic and non-academic) from various parts of the Netherlands, thus limiting the risk of patient selection bias for hospitals with expertise in certain diseases (e.g. upper gastrointestinal tract). MALDI-TOF MS accurately identifies many infrequently cultured organisms that were previously difficult to identify in routine clinical microbiology laboratories. The widespread use of MALDI-TOF MS in clinical microbiology laboratories may result in the description of new pathogen–disease associations [16–18]. In many bacteremic patients, the cause of bacteremia is evident from the patient history, physical examination, and initial laboratory and radiology studies. Sometimes a clear source is not immediately evident. In such cases, the identity of the infecting organism may point clinicians to likely diagnoses or anatomic lesions. For example, bacteremia with Streptococcus gallolyticus urges investigations into colonic cancer or polyps. The disease association of Raoultella bacteremia we describe may guide clinicians to prioritize further investigations in the management of a patient with Raoultella bacteremia without a clear source infection, and may thereby lead to more precise diagnoses and optimal treatments. Declaration of interest: The authors declare that they have no conflict of interest. References [1] 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;60:492–9.

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Predominant association of Raoultella bacteremia with diseases of the biliary tract.

A case series of 14 patients with Raoultella bacteremia was compared with 28 Klebsiella oxytoca and 28 Klebsiella pneumoniae bacteremia cases. Forty-t...
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