Neutrophil-to-lymphocyte ratio as a feasible prognostic marker for pyogenic liver abscess in the emergency department.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is an effective predictor of mortality in patients with for various conditions. To date, there are no previous studies on NLR as a prognostic marker for pyogenic liver abscess (PLA), especially on admission to the emergency department (ED). METHODS: From January 2013 to December 2015, 102 patients diagnosed with PLA in the ED were included. Clinico-radiological and laboratory results, including NLR, were evaluated as variables. NLR was calculated as absolute neutrophil count/absolute lymphocyte count. To evaluate the prognosis of PLA, data on hospital mortality, intensive care unit (ICU) admission, and development of septic shock were obtained. Multivariate logistic regression analyses and receiver-operating characteristic (ROC) curve analysis were performed. RESULTS: Among 102 patients, 10 (9.8%) died, 14 (13.7%) were admitted to the ICU, and 15 (14.7%) developed septic shock during hospitalization. Multivariate logistic regression analysis revealed NLR as an independent factor in predicting death [odds ratio (OR), 1.4; p = 0.020], ICU admission (OR, 1.4; p = 0.021), and development of septic shock (OR, 1.6; p = 0.041). NLR showed an excellent predictive performance for death (areas under the ROC curves [AUC], 0.941; cut-off value, 19.7; p < 0.001), ICU admission (AUC, 0.946; cut-off value, 16.9; p < 0.001), and development of septic shock (AUC, 0.927; cut-off value, 16.9; p < 0.001). CONCLUSION: NLR was positively associated with poor prognosis of PLA; elevated NLR could predictor of high risk of death, ICU admission, and development of septic shock. Emergency physicians should consider NLR for the prognosis of PLA and early aggressive treatment, especially in patients with NLR > 16.9.

Comparison of Diabetic and Non-diabetic Human Leukocytic Responses to Different Capsule Types of Klebsiella pneumoniae Responsible for Causing Pyogenic Liver Abscess.

The major risk factor for Klebsiella liver abscess (KLA) is type 2 diabetes mellitus (DM), but the immunological mechanisms involved in the increased susceptibility are poorly defined. We investigated the responses of neutrophils and peripheral blood mononuclear cells (PBMCs) to hypervirulent Klebsiella pneumoniae (hvKP), the causative agent of KLA. DNA and myeloperoxidase levels were elevated in the plasma of KLA patients compared to uninfected individuals indicating neutrophil activation, but diabetic status had no effect on these neutrophil extracellular trap (NET) biomarkers in both subject groups. Clinical hvKP isolates universally stimulated KLA patient neutrophils to produce NETs ex vivo, regardless of host diabetic status. Ability of representative capsule types (K1, K2, and non-K1/K2 strains) to survive intra- and extra-cellular killing by type 2 DM and healthy neutrophils was subsequently examined. Key findings were: (1) type 2 DM and healthy neutrophils exhibited comparable total, phagocytic, and NETs killing against hvKP, (2) phagocytic and NETs killing were equally effective against hvKP, and (3) hypermucoviscous K1 and K2 strains were more resistant to total, phagocytic, and NETs killing compared to the non-mucoviscous, non-K1/K2 strain. The cytokine response and intracellular killing ability of type 2 DM as well as healthy PBMCs upon encounter with the different capsule types was also examined. Notably, the IL-12-IFNγ axis and its downstream chemokines MIG, IP-10, and RANTES were produced at slightly lower levels by type 2 DM PBMCs than healthy PBMCs in response to representative K1 and non-K1/K2 strains. Furthermore, type 2 DM PBMCs have a mild defect in its ability to control hvKP replication relative to healthy PBMCs. In summary, our work demonstrates that type 2 DM does not overtly impact neutrophil intra- and extra-cellular killing of hvKP, but may influence cytokine/chemokine production and intracellular killing by PBMCs.

Identification of a capsular variant and characterization of capsular acetylation in Klebsiella pneumoniae PLA-associated type K57.

Klebsiella pneumoniae can cause community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) is important for its virulence. Among 79 capsular (K) types discovered thus far, K57 is often associated with PLA. Here, we report the identification of a K57 variant. Cps gene locus sequencing revealed differences between the K57 reference strain 4425/51 (Ref-K57) and a variant, the PLA isolate A1142. While Ref-K57 cps contained orf13 encoding a putative acetyltransferase, the insertion of a putative transposase-encoding gene at this position was detected in A1142. This variation was detected in other K57 clinical strains. Biochemical analyses indicated that A1142 was deficient in CPS acetylation. Genetic replacement and complementation verified that orf13 was responsible for CPS acetylation. Acetylation increased CPS immunoreactivity to antiserum and enhanced K. pneumoniae induction of pro-inflammatory cytokines through JNK and MAPK signaling. While acetylation diminished the serum resistance of bacteria, it promoted adhesion to intestinal epithelial cells possibly via increasing production of type I fimbriae. In conclusion, acetylation-mediated capsular variation in K57 was observed. Capsular acetylation contributed to the variety and antigenic diversity of CPS, influenced its biological activities, and was involved in K. pneumoniae-host interactions. These findings have implications for vaccine design and pathogenicity of K. pneumoniae.

Pyogenic liver abscess caused by Fusobacterium in a 21-year-old immunocompetent male.

A 21-year-old male with no significant past medical history, presented with right upper quadrant (RUQ) abdominal pain along with fevers and chills. Lab work revealed leukocytosis, anemia, and slightly elevated alkaline phosphatase. Viral serology for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative and he was immunocompetent. Computed tomography imaging revealed hepatic abscesses, the largest measuring 9.5 cm. Empiric antibiotics were started and percutaneous drains were placed in the abscesses. Anaerobic cultures from the abscesses grew Fusobacterium nucleatum. This is a gram negative anaerobic bacteria; a normal flora of the oral cavity. Fusobacterium is most commonly seen in Lemiere's disease, which is translocation of oral bacteria to the internal jugular vein causing a thrombophlebitis and subsequent spread of abscesses. Our patient did not have Lemiere's, and is the first case described of fusobacterium pyogenic liver abscess in a young immunocompetent male with good oral hygiene. This case was complicated by sepsis, empyema, and subsequent abscesses located outside the liver. These abscesses' have the propensity to flare abruptly and can be fatal. This case not only illustrates fusobacterium as a rare entity for pyogenic liver abscess, but also the need for urgent diagnosis and treatment. It is incumbent on physicians to diagnose and drain any suspicious hepatic lesions. While uncommon, such infections may develop without any overt source and can progress rapidly. Prompt drainage with antibiotic therapy remains the cornerstone of therapy.

Identification of an immuno-dominant protein from Klebsiella pneumoniae strains causing pyogenic liver abscess: implication in serodiagnosis.

BACKGROUND: Klebsiella pneumoniae has emerged worldwide as a cause of pyogenic liver abscess (PLA) often complicated by meningitis and endophthalmitis. Early detection of this infectious disease will improve its clinical outcome. Therefore, we tried to isolate immunodominant proteins secreted by K. pneumoniae strains causing PLA. RESULTS: The secreted proteins of the NTUH-K2044 strain were separated by two-dimensional electrophoresis and then immunoblotted using convalescent sera from patients with K. pneumoniae PLA. A ~30-kDa immunodominant protein was then identified. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed an open reading frame (KP1_p307) located on the pK2044 plasmid and bioinformatic analysis identified this protein as a signal peptide of unknown function. The KP1_p307 gene was more prevalent in PLA strains and capsular type K1/K2 strains, but disruption of this gene in NTUH-K2044 strain did not decrease virulence in mice. Ten of fourteen (71%) sera from patients with K. pneumoniae PLA were immunoreactive with the recombinant KP1_p307 protein. Seroconversion demonstrated by a rise in serum titer in serial serum samples confirmed that antibodies against the KP1_p307 protein were elicited after infection. CONCLUSIONS: The KP1_p307 protein could be used as an antigen for early serodiagnosis of K. pneumoniae PLA, particularly in K1/K2 PLA strains.

Role of C-reactive protein in response-guided therapy of pyogenic liver abscess.

BACKGROUND: Protocols for antibiotic treatment of pyogenic liver abscess (PLA) are usually based on clinicians' own experience without any validation. Our study was to evaluate the clinical implication of C-reactive protein (CRP) in predicting treatment outcome and adequacy of antibiotic therapy of PLA. PATIENTS AND METHODS: Patients with PLA in whom white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and CRP were checked regularly during the clinical course were included. The prolife of CRP during the clinical course was compared with that of ESR and WBC. The usefulness of CRP in predicting the chance of recovery and adequacy of antibiotic therapy was examined. RESULTS: From 2000 to 2011, 109 patients with PLA underwent regular monitoring of WBC, ESR, and CRP. Except for ESR, both WBC and CRP showed an initial rapid reduction in first 3 weeks, followed by a relatively slow decrease. From week 3 to week 6, the CRP ratio (relative to CRP at week 1) of patients with and without adverse events (i.e. including mortality) was compared; a significant difference was found at week 3 (P=0.001), week 4 (P=0.004), week 5 (P=0.011), and week 6 (P=0.018), whereas no statistically significant difference was found in the WBC ratio over the same period. By week 3, a CRP ratio of 0.423 or less was a marker of good outcome (sensitivity 0.846; specificity 0.667) and was also a marker of adequacy of antibiotic therapy of 5 weeks or less (sensitivity 0.786; specificity 0.714) if the ratio was 0.278 or less. CONCLUSION: Weekly CRP measurement was useful in the identification of patients with PLA with good outcome and adequacy of antibiotic therapy of 5 weeks or less.

Evaluation of antigen detection and polymerase chain reaction for diagnosis of amoebic liver abscess in patients on anti-amoebic treatment.

BACKGROUND: Diagnosis of amoebic liver abscess (ALA) in patients on anti-amoebic drugs is difficult. There is scanty data on this issue using Entamoeba histolytica (E. histolytica) lectin antigen and polymerase chain reaction (PCR). We studied utility of lectin antigen, PCR, and IgG antibody in diagnosis of liver abscess in patients on anti-amoebic treatment. Liver aspirate of 200 patients, of which 170 had anti-amoebic drug prior to drainage, was tested for E. histolytica lectin antigen by (ELISA), PCR, bacterial culture, and serum IgG antibody by (ELISA). Classification of abscesses was based on result of anti-amoebic IgG antibody and bacterial culture, E. histolytica PCR and bacterial culture, and E. histolytica lectin antigen and bacterial culture. FINDINGS: Using anti-amoebic IgG antibody and bacterial culture, 136/200 (68.0%) were classified as ALA, 12/200 (6.0%) as pyogenic liver abscess (PLA), 29/200 (14.5%) as mixed infection, and 23/200 (11.5%) remained unclassified. Using amoebic PCR and bacterial culture 151/200 (75.5%) were classified as ALA, 25/200 (12.5%) as PLA, 16/200 (8.0%) as mixed infection, and 8/200 (4.0%) remained unclassified. With E. histolytica lectin antigen and bacterial culture, 22/200 (11.0%) patients were classified as ALA, 39/200 (19.5%) as PLA, 2/200 (1.0%) as mixed infection, and 137/200 (68.5%) remained unclassified. CONCLUSIONS: E. histolytica lectin antigen was not suitable for classification of ALA patients who had prior anti-amoebic treatment. However, PCR may be used as alternative test to anti-amoebic antibody in diagnosis of ALA.

Lipopolysaccharide O1 antigen contributes to the virulence in Klebsiella pneumoniae causing pyogenic liver abscess.

Klebsiella pneumoniae is the common cause of a global emerging infectious disease, community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) and lipopolysaccharide (LPS) are critical for this microorganism's ability to spread through the blood and to cause sepsis. While CPS type K1 is an important virulence factor in K. pneumoniae causing PLA, the role of LPS in PLA is not clear. Here, we characterize the role of LPS O antigen in the pathogenesis of K. pneumoniae causing PLA. NTUH-K2044 is a LPS O1 clinical strain; the presence of the O antigen was shown via the presence of 1,3-galactan in the LPS, and of sequences that align with the wb gene cluster, known to produce O-antigen. Serologic analysis of K. pneumoniae clinical isolates demonstrated that the O1 serotype was more prevalent in PLA strains than that in non-tissue-invasive strains (38/42 vs. 9/32, P<0.0001). O1 serotype isolates had a higher frequency of serum resistance, and mutation of the O1 antigen changed serum resistance in K. pneumoniae. A PLA-causing strain of CPS capsular type K2 and LPS serotype O1 (i.e., O1:K2 PLA strain) deleted for the O1 synthesizing genes was profoundly attenuated in virulence, as demonstrated in separate mouse models of septicemia and liver abscess. Immunization of mice with the K2044 magA-mutant (K(1) (-) O(1)) against LPS O1 provided protection against infection with an O1:K2 PLA strain, but not against infection with an O1:K1 PLA strain. Our findings indicate that the O1 antigen of PLA-associated K. pneumoniae contributes to virulence by conveying resistance to serum killing, promoting bacterial dissemination to and colonization of internal organs after the onset of bacteremia, and could be a useful vaccine candidate against infection by an O1:K2 PLA strain.

Role of T lymphocytes in liver abscess formation by Bacteroides fragilis in mice.

The underlying mechanisms of liver abscess formation have not been fully elucidated with regard to the interaction between bacterial virulence factors and the immune response. The objective of this study was to determine the role of the host T cells in liver abscess formation caused by Bacteroides fragilis. We developed a liver abscess mouse model with inoculation of B. fragilis through the hepatic portal vein and examined the role of T cells by studying T cell-deficient mice, as well as conducting adoptive T cell transfer experiments. No microabscess was formed in the αß T cell receptor-positive (αßTCR(+)) T cell-depleted mice, in contrast to the results for the control mice. In addition, the αßTCR knockout (KO) mice showed significantly lower numbers of microabscesses, and the abscesses were smaller in size than those in the wild-type mice. Adoptive transfer of T cells purified from the wild-type mice into the αßTCR KO mice resulted in liver abscess formation in those mice. These findings suggest that T cells play an essential role in liver abscess formation caused by B. fragilis in mice.

Pyogenic liver abscess with Prevotella species and Fusobacterium necrophorum as causative pathogens in an immunocompetent patient.

Pyogenic liver abscess of odontogenic origin in an immunocompetent patient is extremely rare. We report an immunocompetent 25-year-old male hepatitis B carrier with severe dental disease that led to the development of liver abscess. A periapical abscess in the upper left molar area was seen on his dental X-ray. Two sets of blood cultures grew Prevotella species, bacteria that are commonly found inside the oral cavity. Bacterial culture of the liver abscess drainage sample grew both Prevotella and Fusobacterium necrophorum. This led to our diagnosis of pyogenic liver abscess of dental origin, since we found no other source of infection in our patient except for his dental disease. After antibiotic therapy with drainage, abdominal sonography showed resolution of the abscess. The diseased teeth were also extracted. During 1 year of follow-up, there was no sign of abscess recurrence. A diagnosis of pyogenic liver abscess necessitates a complete evaluation to rule out possible biliary, colonic or other associated diseases. However, when a liver abscess is thought to be cryptogenic, we also recommend a careful dental examination to help identify the source of infection.