Review
Klebsiella pneumoniae liver abscess: a new invasive syndrome

https://doi.org/10.1016/S1473-3099(12)70205-0Get rights and content

Summary

Klebsiella pneumoniae is a well known human nosocomial pathogen. Most community-acquired K pneumoniae infections cause pneumonia or urinary tract infections. During the past two decades, however, a distinct invasive syndrome that causes liver abscesses has been increasingly reported in Asia, and this syndrome is emerging as a global disease. In this Review, we summarise the clinical presentation and management as well the microbiological aspects of this invasive disease. Diabetes mellitus and two specific capsular types in the bacterium predispose a patient to the development of liver abscesses and the following metastatic complications: bacteraemia, meningitis, endophthalmitis, and necrotising fasciitis. For patients with this invasive syndrome, appropriate antimicrobial treatment combined with percutaneous drainage of liver abscesses increases their chances of survival. Rapid detection of the hypervirulent strain that causes this syndrome allows earlier diagnosis and treatment, thus minimising the occurrence of sequelae and improving clinical outcomes.

Introduction

Klebsiella pneumoniae is a well known human pathogen. However, a distinct invasive syndrome has been detected in southeast Asia in the past two decades.1, 2 Liver abscesses in patients infected with K pneumoniae were first described in the 1980s in anecdotal reports and case series from Taiwan.2, 3 Extrahepatic complications resulting from bacteraemic dissemination, including endophthalmitis,3 meningitis,4 necrotising fasciitis,5 and other illnesses,6 have also been recorded. The invasive syndrome was subsequently reported in many southeast Asian countries, including Singapore,7, 8 Hong Kong,9, 10 Korea,11, 12 and Vietnam.13, 14 Few cases were reported from China.15 Findings from a meta-analysis showed that the prevalence of K pneumoniae infection has been increasing since the late 1980s, and that it is now the main cause of liver abscess in Hong Kong,10 Singapore,8 South Korea,11 and Taiwan.2

The reasons for the predominance of this syndrome in Asian people are unclear. In 2002, Ko and colleagues16 showed that the major factor was the microbe itself. K pneumoniae isolated from Asian patients with the invasive syndrome had distinct phenotypic and genotypic featuresā€”eg, when assessed in mouse models, it was much more virulent than were strains isolated from patients from outside Asia.16 Moreover, a genotype strongly associated with this highly invasive disease is widespread worldwide.17, 18, 19

In the past two decades, this syndrome has been described in anecdotal reports from North America.20, 21 Most patients from outside Asia with this invasive syndrome were of Asian descent. However, in the past decade, cases in patients of non-Asian descent are now being reported in North America and South America, and the isolated strains of K pneumoniae have been classified as serotypes K1 and K2.17, 19 In this Review, we describe the epidemiology, clinical manifestations, diagnosis, and treatment of liver abscesses caused by K pneumoniae.

Section snippets

Definition of the invasive syndrome

First, we propose a case definition for this newly described invasive liver abscess syndrome, to allow clear identification of cases. As knowledge about this distinct aspect of infection with K pneumoniae accumulates, this definition can be modified (panel).

The invasive nature of some K pneumoniae strains includes a hypermucoviscous phenotype associated with serotypes K1 and K2 and the regulator of mucoid phenotype A gene (rmpA). A loss or reduction of capsule synthesis will decrease a strain's

Epidemiology and risk factors

In the past decade, 38 patients were diagnosed as having a liver abscess caused by K pneumoniae in two case series in the USA.21, 24 South Korea has the second highest prevalence of K pneumoniae liver abscesses (Taiwan has the highest prevalence), with 321 patients identified in two national studies.11, 12 We reviewed the demographic and clinical characters of 512 patients from four large-scale studies in Taiwan (table 1).25, 26, 27, 28 Nearly all patients had community-acquired infections.

Virulence factors

Several virulence factors have been described for K pneumoniae, and include the presence of the capsular serotype, mucoviscosity-associated gene A (magA), rmpA, and aerobactin (table 2).43 K pneumoniae strains expressing capsular type K1 or K2 antigen are especially virulent. These serotypes have a high prevalence of resistance to phagocytosis and intracellular killing by neutrophils and bactericidal complements in a patient's serum. Mutant strains without a capsule are highly susceptible to

Clinical manifestations and diagnosis

The most common clinical manifestations in patients with K pneumoniae liver abscesses are fever, chills, and abdominal pain.25, 26, 27, 28 Nausea and vomiting occur in about a quarter of patients.25, 26, 27, 28 However, these symptoms are not characteristic for the K pneumoniae invasive syndrome. Leucocytosis, thrombocytopenia, increased concentrations of C-reactive protein and glucose in blood, and abnormal results of liver function tests were common.27

In terms of clinical diagnosis, in

Management

Because of the potential for metastatic infection, clinicians should assess patients for such complications when clinical response is poor. Strict glycaemic control can prevent the development of metastatic complications.35

The selection of antimicrobial treatment should be based on in-vitro susceptibilities and clinical response. Cephalosporins are the antibiotic mainstay of treatment in Asia for K pneumoniae abscesses (table 3).11, 12, 25, 28 Patients in the USA were treated successfully with

Conclusions

This invasive syndrome seems to be spreading to countries outside Asia. Presentation of liver abscess with bacteraemia in patients infected with K pneumoniae strains that have a positive string test result (figure) can be the first clinical clue. Rapid diagnosis followed by appropriate treatment should improve a patient's outcome and prevent metastatic complications, which are severe. Further research should aim to find out why Asian populations (particularly Taiwanese people) are especially

Search strategy and selection criteria

We searched PubMed for papers published between Jan 01, 1970, and June 30, 2012, by using combinations of the following keywords: ā€œKlebsiella pneumoniaeā€, ā€œliver abscessā€, ā€œendophthalmitisā€, and ā€œmeningitisā€. We selected articles published in English or Chinese. We selected reports of large case series for inclusion in this Review in favour of anecdotal reports, of which we identified many. Data surveyed included ethnic origin, underlying diseases, clinical manifestations, treatments, and

References (78)

  • HF Hsieh et al.

    Aggressive hepatic resection for patients with pyogenic liver abscess and APACHE II score > or =15

    Am J Surg

    (2008)
  • FZ el Baba et al.

    Intravitreal penetration of oral ciprofloxacin in humans

    Ophthalmology

    (1992)
  • FY Chang et al.

    A clinical study of Klebsiella liver abscess

    Taiwan Yi Xue Hui Za Zhi

    (1988)
  • FY Chang et al.

    Comparison of pyogenic liver abscesses caused by Klebsiella pneumoniae and non-K pneumoniae pathogens

    J Formos Med Assoc

    (1995)
  • YC Liu et al.

    Klebsiella pneumoniae liver abscess associated with septic endophthalmitis

    Arch Intern Med

    (1986)
  • M Saccente

    Klebsiella pneumoniae liver abscess, endophthalmitis, and meningitis in a man with newly recognized diabetes mellitus

    Clin Infect Dis

    (1999)
  • BS Hu et al.

    Necrotizing fasciitis associated with Klebsiella pneumoniae liver abscess

    Clin Infect Dis

    (1999)
  • HP Cheng et al.

    Extended-spectrum cephalosporin compared to cefazolin for treatment of Klebsiella pneumoniae-caused liver abscess

    Antimicrob Agents Chemother

    (2003)
  • KM Yeh et al.

    Capsular serotype K1 or K2, rather than magA and rmpA, is a major virulence determinant for Klebsiella pneumoniae liver abscess in Singapore and Taiwan

    J Clin Microbiol

    (2007)
  • KG Yeoh et al.

    Tropical liver abscess

    Postgrad Med J

    (1997)
  • WM Wong et al.

    Pyogenic liver abscess: retrospective analysis of 80 cases over a 10-year period

    J Gastroenterol Hepatol

    (2002)
  • KH Lok et al.

    Pyogenic liver abscess: clinical profile, microbiological characteristics, and management in a Hong Kong hospital

    J Microbiol Immunol Infect

    (2008)
  • SB Kim et al.

    Computed tomographic differences of pyogenic liver abscesses caused by Klebsiella pneumoniae and non-Klebsiella pneumoniae

    J Comput Assist Tomogr

    (2007)
  • NG Chau et al.

    Pylephlebitis and pyogenic liver abscesses: a complication of hemorrhoidal banding

    Can J Gastroenterol

    (2007)
  • SK Sobirk et al.

    Primary Klebsiella pneumoniae Liver Abscess with Metastatic Spread to Lung and Eye, a North-European Case Report of an Emerging Syndrome

    Open Microbiol J

    (2010)
  • J Li et al.

    Early diagnosis and therapeutic choice of Klebsiella pneumoniae liver abscess

    Front Med China

    (2010)
  • WC Ko et al.

    Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns

    Emerg Infect Dis

    (2002)
  • JF Turton et al.

    Genetically similar isolates of Klebsiella pneumoniae serotype K1 causing liver abscesses in three continents

    J Med Microbiol

    (2007)
  • LK Siu et al.

    Molecular typing and virulence analysis of serotype K1 Klebsiella pneumoniae strains isolated from liver abscess patients and stool samples from noninfectious subjects in Hong Kong, Singapore, and Taiwan

    J Clin Microbiol

    (2011)
  • A Vila et al.

    Appearance of Klebsiella pneumoniae liver abscess syndrome in Argentina: case report and review of molecular mechanisms of pathogenesis

    Open Microbiol J

    (2011)
  • J Rahimian et al.

    Pyogenic liver abscess: recent trends in etiology and mortality

    Clin Infect Dis

    (2004)
  • KM Yeh et al.

    Revisiting the importance of virulence determinant magA and its surrounding genes in Klebsiella pneumoniae causing pyogenic liver abscesses: exact role in serotype K1 capsule formation

    J Infect Dis

    (2010)
  • ER Lederman et al.

    Pyogenic liver abscess with a focus on Klebsiella pneumoniae as a primary pathogen: an emerging disease with unique clinical characteristics

    Am J Gastroenterol

    (2005)
  • KS Chan et al.

    Pyogenic liver abscess caused by Klebsiella pneumoniae: analysis of the clinical characteristics and outcomes of 84 patients

    Chin Med J (Engl)

    (2007)
  • SS Lee et al.

    Predictors of septic metastatic infection and mortality among patients with Klebsiella pneumoniae liver abscess

    Clin Infect Dis

    (2008)
  • CC Yang et al.

    Comparison of pyogenic liver abscess caused by non-Klebsiella pneumoniae and Klebsiella pneumoniae

    J Microbiol Immunol Infect

    (2004)
  • CP Fung et al.

    A global emerging disease of Klebsiella pneumoniae liver abscess: is serotype K1 an important factor for complicated endophthalmitis?

    Gut

    (2002)
  • CP Fung et al.

    Virulence of Klebsiella pneumoniae serotype K2 should not be underestimated in K pneumoniae liver abscess

    Clin Infect Dis

    (2007)
  • JC Lin et al.

    Nosocomial liver abscess caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae

    J Clin Microbiol

    (2007)
  • Cited by (613)

    View all citing articles on Scopus
    View full text