Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial.

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2-3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

Clinical characteristics, diagnosis, treatment, and outcome of patients with liver abscess due to Aspergillus spp: a systematic review of published cases.

BACKGROUND: Aspergillus spp liver abscess is a relatively rare entity and thus far no systematic review has been performed examining patients' demographics, clinical manifestations, diagnosis, management, and outcome. METHODS: We performed a systematic review of the literature using MEDLINE and LILACS databases. We searched for articles published in the period from January 1990 to December 24, 2022, to identify patients who developed liver abscesses due to Aspergillus spp. RESULTS: Our search yielded 21 patients all of whom had invasive aspergillosis confirmed on liver biopsy. Of these patients 81% were adults, and 60% were males. The majority (86%) of patients were immunocompromised and 95% had symptomatic disease at the time of diagnosis. The most common symptoms were fever (79%), abdominal pain (47%), and constitutional symptoms (weight loss, chills, night sweats, fatigue) (38%). Liver enzymes were elevated in 50%, serum galactomannan was positive in 57%, and fungal blood cultures were positive in only 11%. Co-infection with other pathogens preceded development of apsergillosis in one-third of patients, and the majority of the abscesses (43%) were cryptogenic. In the remaining patients with known source, 28% of patients developed liver abscess through dissemination from the lungs, 19% through the portal vein system, and in 10% liver abscess developed through contiguous spread. The most common imaging modality was abdominal computerized tomography done in 86% of patients. Solitary abscess was present in 52% of patients while 48% had multiple abscesses. Inadequate initial empiric therapy was prescribed in 60% of patients and in 44% of patients definite treatment included combination therapy with two or more antifungal agents. Percutaneous drainage of the abscesses was done in 40% of patients, while 20% required liver resection for the treatment of the abscess. Overall mortality was very high at 38%. CONCLUSION: Further studies are urgently needed for a better understanding of pathophysiology of liver aspergillosis and for developement of newer blood markers in order to expedite diagnosis and decrease mortality.

Evaluating the liver abscess microbiota of beef cattle during a reduction in tylosin supplementation shows differences according to abscess size and fraction.

Liver abscesses (LA) resulting from bacterial infection in cattle pose a significant global challenge to the beef and dairy industries. Economic losses from liver discounts at slaughter and reduced animal performance drive the need for effective mitigation strategies. Tylosin phosphate supplementation is widely used to reduce LA occurrence, but concerns over antimicrobial overuse emphasize the urgency to explore alternative approaches. Understanding the microbial ecology of LA is crucial to this, and we hypothesized that a reduced timeframe of tylosin delivery would alter LA microbiomes. We conducted 16S rRNA sequencing to assess severe liver abscess bacteriomes in beef cattle supplemented with in-feed tylosin. Our findings revealed that shortening tylosin supplementation did not notably alter microbial communities. Additionally, our findings highlighted the significance of sample processing methods, showing differing communities in bulk purulent material and the capsule-adhered material. Fusobacterium or Bacteroides ASVs dominated LA, alongside probable opportunistic gut pathogens and other microbes. Moreover, we suggest that liver abscess size correlates with microbial community composition. These insights contribute to our understanding of factors impacting liver abscess microbial ecology and will be valuable in identifying antibiotic alternatives. They underscore the importance of exploring varied approaches to address LA while reducing reliance on in-feed antibiotics.

Case report: A case of high virulence and multidrug resistant Klebsiella pneumoniae liver abscess in Ningxia, China.

RATIONALE: Highly virulent multidrug-resistant Klebsiella pneumoniae (KP) is becoming more and more common in clinical practice, especially the rise of carbapenem-resistant KP in clinical practice, resulting in the emergence of KP liver abscess in Ningxia, China. For the prognosis of liver abscess patients, it is particularly important to identify the types of pathogens and identify antibiotics that are sensitive to the pathogens. PATIENT CONCERNS: A 73-year-old man from China presents to our hospital with abdominal pain, jaundice and fever. Patients have no obvious cause of abdominal pain, abdominal distension, and abdominal pain is persistent. Abdominal examination showed hepatomegaly, no tenderness 2 cm from the right costal margin, abdominal distension and other general examinations did not have obvious abnormalities. He had no history of hypertension and diabetes, ERCP was performed for cholangiocarcinoma 1 year before the current visit, and no significant complications occurred. DIAGNOSES: His initial diagnosis was obstructive cholangitis, and computed tomographic images and liver drainage fluid bacterial culture and genetic polymerase chain reaction tests later determined that the patient had KP liver abscess. INTERVENTIONS: Drainage by liver catheter and antibiotic treatment for 7 weeks. OUTCOMES: The patient liver abscess is basically gone. LESSION: It is particularly important to optimize the diagnosis of liver abscess pathogens for timely and effective treatment of patients.

Effect of continuous in-feed administration of tylosin to feedlot cattle on macrolide and tetracycline resistant enterococci in a randomized field trial.

Liver abscess causes substantial economic loss to the beef cattle industry through liver condemnation, reduced animal performance, and carcass yield. Continuous in-feed use of tylosin is the most effective and a commonly used practice in beef cattle production to prevent liver abscess. However, such mass medication can increase the level of antimicrobial resistant bacteria. We investigated the effect of continuous in-feed use of tylosin in feedlot cattle on (i) concentrations and prevalence of erythromycin-resistant (ERYr) and tetracycline-resistant (TETr) enterococci; (ii) associated antimicrobial resistance genes (ARGs) for resistance; (iii) species distribution; iv) macrolide and tetracycline resistance gene concentrations; and (v) tylosin concentration. A cohort of weaned calves were randomized to receive tylosin-medicated feed (Tylosin; n = 10) or nonmedicated feed (Control; n = 10) for a full feedlot cycle. Feces, feed and pen-surface samples were collected and processed by culture, droplet digital PCR, and liquid chromatography/mass spectroscopy for bacterial enumeration, detection and characterization, ARG quantification, and tylosin concentration, respectively. Data were analyzed by mixed effects linear- or binary-regression models depending on the outcomes. Tylosin administration significantly increased fecal concentration (P < 0.001) and prevalence (P = 0.021) of ERYr enterococci and erm(B) gene concentration (P < 0.001), compared to the control group. Interestingly, tylosin administration significantly reduced (P = 0.037) fecal TETr enterococci concentration compared to the control group, with no significant effect (P = 0.758) on fecal tet(M) concentration. In both treatment groups, enterococci concentrations increased over time, peaking on 174 days in feed before returning to the baseline. ERYr enterococci concentration was significantly (P = 0.012) higher in tylosin medicated feeds, with no significant effect (P = 0.321) on TETr enterococci concentration. Pen-surface concentration of ermB was significantly (P = 0.024) higher in the tylosin group, with no significant effect (P > 0.05) on bacterial concentrations. Increased diversity and a shift in the composition of enterococcal species and ARGs were observed over time, although tylosin use did not significantly affect (P > 0.05) their prevalence. Tylosin concentration was significantly higher in the feces of tylosin administered cattle (P < 0.001) and medicated feed (P = 0.027), with numerically higher pen-surface concentration (P = 0.065) in the tylosin group. In conclusion, continuous in-feed use of tylosin in feedlot cattle increases macrolide resistant enterococci and its fecal excretion, while decreasing tetracycline resistance. Two medically important species, E. faecium and E. faecalis, were predominant regardless of resistance status or sample source. Risk-based approaches including label changes to limit tylosin use such as withdrawal period, and development of effective manure treatments are potential areas of research to reduce environmental and public health impacts.

Unexpected finding of Fusobacterium varium as the dominant Fusobacterium species in cattle rumen: potential implications for liver abscess etiology and interventions.

Fusobacterium varium has been generally overlooked in cattle rumen microbiome studies relative to the presumably more abundant liver abscess-causing Fusobacterium necrophorum. However, F. varium was found to be more abundant in the rumen fluid of cattle and under culture conditions tailored to enrich F. necrophorum. Using near-full length 16S ribosomal ribonucleic acid sequencing, we demonstrate that F. varium grows under restrictive conditions commonly used to enumerate F. necrophorum, suggesting that previous F. necrophorum abundance assessment may have been inaccurate and that F. varium may be an underestimated member of the ruminal bacterial community. Fusobacterium varium were not as susceptible as F. necrophorum to in-feed antibiotics conventionally used in feedlots. Exposure to tylosin, the current gold standard for liver abscess reduction strategies in cattle, consistently hindered growth of the F. necrophorum strains tested by over 67% (P < 0.05) relative to the unexposed control. In contrast, F. varium strains were totally or highly resistant (0%-13% reduction in maximum yield, P < 0.05). Monensin, an ionophore antibiotic, had greater inhibitory activity against F. necrophorum than F. varium. Finally, preliminary genomic analysis of two F. varium isolates from the rumen revealed the presence of virulence genes related to those of pathogenic human F. varium isolates associated with active invasion of mammalian cells. The data presented here encourage further investigation into the ecological role of F. varium within the bovine rumen and potential role in liver abscess development, and proactive interventions.

The conventional method of liver abscess prevention in feedlot cattle is in-feed use of tylosin to target Fusobacterium necrophorum, which has been presumed to be the most common Fusobacterium species within the ruminal compartment. Our investigation into ruminal Fusobacterium, however, revealed a different species, Fusobacterium varium, to be abundant and ubiquitous in ruminal content samples. Furthermore, growth conditions tailored to enrich F. necrophorum consistently promoted growth of F. varium, and the bovine isolates tested had much lower susceptibilities to the commonly fed antibiotics tylosin and monensin compared to F. necrophorum. Fusobacterium varium is an emerging pathogen in humans and preliminary genome sequencing of two ruminal F. varium isolates revealed genes linked to pathogenicity. While the ecological role of F. varium in the rumen is still not fully understood, our findings draw attention to this pathogen and its potential implication in liver abscesses.

First Italian report of a liver abscess and metastatic endogenous endophthalmitis caused by ST-23 hypervirulent Klebsiella pneumoniae in an immunocompetent individual.

BACKGROUND: Klebsiella pneumoniae is a common species in the gut of mammals and is widely distributed in the environment. However, the environmental source of hvKp that precedes gut colonization is unclear, but once that it reaches the gut there is a possible generalized spread y fecal-oral transmission especially in endemic areas. Liver abscess might develop when the bacteria, using its virulence factors, cross the intestinal barrier and invade the liver by the portal circulation. This syndrome, prevalent mostly in Asian countries, is increasingly reported in Western Countries and leaves open questions about the source of infection. CASE: Here we describe for the first time in Italy, a case of pyogenic liver abscess caused by a hypervirulent Klebsiella pneumoniae (HvKp) complicated by endophthalmitis and other metastatic infections in lung and prostate in an immunocompetent Chinese healthy individual with no recent travel in Asia. CONCLUSION: This case underlines the need for increased awareness of hypervirulent K. pneumoniae, even in settings where it occurs infrequently and where there are not evident epidemiological links.

Comparison of clinical and microbiological characteristics of community-acquired hypervirulent Klebsiella pneumoniae liver abscess in diabetic and non-diabetic patients.

Invasive infection caused by hypervirulent Klebsiella pneumoniae (HvKP) has been reported worldwide. Most of the patients are community population, related to diabetes mellitus (DM), chronic liver disease and other basic diseases, which prone to systemic migratory infection. In this study, we collected 377 patients with community acquired Klebsiella pneumoniae liver abscess in our hospital from January 2013 to December 2018, 65.8% of whom were male, and 49.6% had DM. Patients with DM are prone to eye and central nervous system (CNS) infection, which need continuous local abscess drainage during treatment. Among them, patients with poor blood glucose control have a higher rate of blood stream infections (BSI). 219 strains of HvKP were obtained, with K1/K2 Serotype accounted for 81.7%. The incidence of BSI in K2 patients was higher than that in K1 patients. The PCR results indicate that the carrying rate of virulence genes (rmpA、areo、kfu、allS、iroN、magA、uge、wcaG) in K1/K2 type strains is significantly higher than that in non K1/K2 type strains. ST23 and ST65 are the most common multilocus sequence typing (MLST), which belong to K1 and K2 Serotype respectively. All of HvKP strains showed high sensitivity to commonly used clinical antibiotics other than ampicillin, with 54.3% of the strains exhibiting high viscosity characteristics. Meanwhile, 35 classic Klebsiella pneumoniae (cKP) strains were collected, and their serum typing is mainly non K1/K2. The carrying rate of virulence genes and viscosity degree in HvKP are significantly higher than those in cKP. Primary liver abscess caused by HvKP is prone to multiple tissue and organ infections, but it shows higher sensitivity to most commonly used antibiotics in clinical practice except for ampicillin. After effective treatment, the overall prognosis of patients is better. This study analyzes the pathogenic characteristics of HvKP and elaborates on the clinical characteristics of patients, which can provide reference for clinical and scientific research work.

Pathogenesis of Liver Abscesses in Cattle.

Liver abscesses are a bacterial infection, which occurs because of entry, via portal vein, of pyogenic bacteria into the hepatic parenchyma. Liver abscesses are a polymicrobial infection; however, Fusobacterium necrophorum, a ruminal bacterium, is the primary etiologic agent. Ruminal acidosis disrupts the protective barrier function of the ruminal epithelium and facilitates entry and colonization of F. necrophorum in the ruminal wall and subsequent entry into the portal circulation. Virulence factors of F. necrophorum contribute to the evasion of host defense mechanisms and cause tissue damage to set up an infection in the liver. The potential role of the hindgut in pathogenesis remains to be investigated.

Metagenome Analysis of the Bacterial Characteristics in Invasive Klebsiella Pneumoniae Liver Abscesses.

Background: Klebsiella pneumoniae liver abscess (KPLA) combined with extrahepatic migratory infection (EMI) is defined as invasive KPLA (IKPLA) and is associated with a poor prognosis. The mechanism of IKPLA formation is yet to be elucidated. In this study, metagenomic sequencing was used to compare the bacterial characteristics between IKPLA and KPLA to explore the underlying mechanism of invasiveness. Methods: Clinical details, imaging, and microbial features were retrospectively evaluated by medical record review. Metagenomic sequencing was performed on the pus samples of liver abscesses whose culture results were indicative of monomicrobial Klebsiella pneumoniae (K. pneumoniae). Bacterial diversity and composition in IKPLA and KPLA were comparatively analyzed, and the key pathways and genes that may affect invasiveness were further explored. Results: Sixteen patients were included in this study. Five patients with EMI were included in the IKPLA group, and the other eleven patients without EMI were assigned to the KPLA group. There was no statistical difference in the hypermucoviscous phenotype and serotype of K. pneumoniae between the two groups. The bacterial diversity of IKPLA was lower than that of KPLA. The abundant taxa in the IKPLA group were primarily species of unclassified Enterobacteriaceae and K. pneumoniae. The KPLA group had a high abundance of the genera Tetrasphaera and Leuconostoc. Metabolic pathway genes represented most of the enriched genes in IKPLA. Fourteen pathogenic genes with significant differences in abundance were identified between the two groups, including ybtS, fepC, phoQ, acrB, fimK, magA, entC, arnT, iucA, fepG, oqxB, entA, tonB, and entF (p < 0.001). Conclusion: The diversity and bacterial composition of IKPLA were significantly different from those of KPLA. Microbiological changes in the abscess, activation of the related metabolic pathways, and the pathogenic gene expression may constitute a novel mechanism that regulates the invasiveness of KPLA.

Liver abscess microbiota of feedlot steers finished in natural and traditional management programs.

Liver abscess etiology in feedlot steers involves the escape of bacteria from the digestive tract to form a polymicrobial abscess within or on the external surface of the liver. However, little is known about the effects of feedlot finishing systems on the microbial composition of the liver abscess purulent material. Liver abscesses were collected at the time of harvest from steers originating from a single feedlot managed in either a traditional program (which included tylosin phosphate supplementation) or a natural program (without tylosin phosphate supplementation). The purulent material of liver abscesses from traditionally managed steers (N = 53 abscesses) and that of naturally managed steers (N = 62 abscesses) was characterized using the V4 region of the 16S rRNA gene. Two phyla and three genera were found in greater than 1% relative abundance across all abscesses. The genus Fusobacterium was identified in all liver abscess samples and accounted for 64% of sequencing reads. Bacteroides and Porphyromonas genera accounted for 33% and 1% of reads, respectively. Trueperella was more likely to be found in the liver abscesses of naturally managed steers than traditionally managed steers (P = 0.022). Over 99% of the genus-level bacterial sequences observed across all liver abscesses belonged to Gram-negative genera. Bacteria known to colonize both the rumen and hindgut were identified within liver abscesses. No differences in alpha diversity or beta diversity were detected between liver abscess communities (between the two management programs or individual pens) when tested as richness, Shannon Diversity Index, or weighted UniFrac distances (P > 0.05). These results were consistent with previous identification of Fusobacterium necrophorum as the primary bacteriologic agent within liver abscesses and emphasized the relationship between the gastrointestinal microbiota and liver abscess formation. Though the microbiota of the liver abscess purulent material was similar between steers fed an antibiotic-free diet and those fed an antibiotic-containing diet from the same feedlot, divergence was detected in liver abscess communities with some being dominated by Fusobacterium and others being dominated by Bacteroides.

As feedlot cattle consume grain, the rumen becomes more acidic. If the lining of the digestive tract is damaged, bacteria that normally remain in the digestive tract can enter the body. Certain bacteria like Fusobacterium necrophorum are involved in the formation of liver abscesses. Feedlot cattle are commonly fed an antibiotic (tylosin phosphate) to reduce the occurrence of liver abscesses, but increasing scrutiny is placed on the antibiotic use. However, the effect of eliminating the antibiotic used to prevent liver abscesses on the bacterial communities involved in liver abscess formation is unknown. This study compared the bacteria found within liver abscesses of cattle fed tylosin phosphate with that of cattle not fed tylosin phosphate. All liver abscesses contained F. necrophorum, and Bacteroides was the second most commonly identified bacterium. Trace amounts of bacteria known to colonize the mouth and digestive tract were observed. Trueperella, a bacteria targeted by tylosin phosphate, was found more frequently in liver abscesses from cattle that received no antibiotic. While the core bacterial composition of the liver abscess was unaffected by antibiotic supplementation to feedlot steers, reduced Trueperella in liver abscesses from cattle-fed tylosin phosphate could be related to a reduction in liver abscess prevalence.

Interaction of Klebsiella pneumoniae with tissue macrophages in a mouse infection model and ex-vivo pig organ perfusions: an exploratory investigation.

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKp) strains of capsule type K1 and K2 cause invasive infections associated with hepatic abscesses, which can be difficult to treat and are frequently associated with relapsing infections. Other K pneumoniae strains (non-hvKp), including lineages that have acquired carbapenem resistance, do not manifest this pathology. In this work we aimed to test the hypothesis that within-macrophage replication is a key mechanism underpinning abscess formation in hvKp infections. METHODS: In this exploratory investigation, to study the pathophysiology of abscess formation, mice were intravenously infected with 106 colony forming units (CFU) of either hvKp isolates (six strains) or non-hvKp isolates (seven strains). Intracellular bacterial replication and neutrophil influx in liver and spleen was quantified by fluorescence microscopy of sliced cryopreserved organs of mice collected 30 min, 6 h, and 24 h after infection with the aim to provide data of bacterial association to Kupffer cells in the liver and to the different tissue macrophages in the spleen. Microbiological and microscopy analysis of an ex-vivo model of pig liver and spleen infection were used to confirm within-macrophage replication. Pig organs were perfused with heparinised, autologous pig's blood and injected with 6·5 × 107 CFU of hvKp K2 sequence type 25 strain GMR151. Blood and tissue biopsies collected before infection and 30 min, 1 h, 2 h, 3 h, 4 h, and 5 h after infection were used to measure bacterial counts and to identify the subcellular localisation of bacteria by immunohistochemistry analysis. FINDINGS: We show that hvKp resisted phagocyte-mediated clearance and replicated in mouse liver macrophages to form clusters 6 h after infection, with a mean of 7·0 bacteria per Kupffer cell (SD 6·2); however, non-hvKp were efficiently cleared (mean 1·5 bacteria per cell [SD 1·1]). HvKp infection promoted neutrophil recruitment to sites of infection, which in the liver resulted in histopathological signs of abscess formation as early as 24 h post-infection. Experiments in pig organs which share a high functional and anatomical resemblance to human organs, provided strong evidence for the propensity of hvKp to replicate within the hepatic macrophages. INTERPRETATION: These findings show subversion of innate immune processes in the liver by K pneumoniae and resistance to Kupffer cell mediated clearance as an explanation for the propensity of hvKp strains to cause hepatic abscesses. FUNDING: University of Oxford and a Royal Society Wolfson grant funded biosafety facility.

Genomic analysis of Burkholderia cenocepacia isolated from a liver abscess in a patient with cystic fibrosis.

Burkholderia cenocepacia complex is associated with high transmissibility, virulence, and poor prognosis in cystic fibrosis (CF) patients. However, extrapulmonary infections are rare. We investigated the genome of a B. cenocepacia IIIA isolated from a liver abscess in a Brazilian CF patient and compared it to strain J2315. The whole genome was sequenced, and contigs were annotated by Rapid Annotation using Subsystem Technology. The Pathosystems Resource Integration Center was used to map antimicrobial and virulence genes. The genomic island (GIs) analysis was performed using two prediction methods, and the presence of putative plasmids and insertion sequences (ISs) was investigated. The isolate was confirmed as B. cenocepacia IIIA to ST-28 (ET12 lineage). A total of 64 genes for antimicrobial resistance and 47 genes related to virulence were identified. Among the virulence factors, there was a predominance of factors related to the invasion mechanism, to the flagellar biosynthesis protein, and to the RNA polymerase sigma factor for flagellar operon (cdpA). Two IS families (IS3 and IS5) and only one plasmid were found. On average 56 GIs were predicted by at least one of the methods applied. Comparative analysis showed resistance mechanisms and virulence factors revealing invasive determinants used by B. cenocepacia IIIA (ET12) in the process of disease spread to other infection sites (extrapulmonary) of highly virulent strains in CF patients.

Fibrohistiocytic Variant of Hepatic Pseudotumor: An Antibiotic Responsive Tumefactive Lesion.

Inflammatory pseudotumor is a term used to designate inflammation-rich tumefactive lesions. Following the exclusion of specific entities such as IgG4-related disease and other neoplastic entities previously included in this entity, the majority of hepatic pseudotumors show a prominent fibrohistiocytic inflammatory reaction and have been previously categorized as fibrohistiocytic variant of hepatic pseudotumor (FHVHPT). The goal of this study was to examine the clinical, radiologic, histologic, and etiologic aspects of this entity. After excluding neoplastic diseases, we identified 30 patients with FHVHPT from 3 institutions between 2009 and 2019. We extracted demographic and clinical data, liver function tests as well as culture results and radiologic information. Hematoxylin and eosin-stained slides were reviewed for pattern of inflammation as well as its cellular composition. Immunohistochemistry for IgG4 and IgG was performed in all cases. The mean age of the 30 lesions characterized as FHVHPT was 56 years (range: 23 to 79 y). Nineteen patients showed solitary lesions; 11 were multiple. The mean size of the lesion was 3.8 cm (range: 1 to 7.5 cm). On imaging, a neoplastic process or metastasis was the leading diagnostic consideration (n=15, 50%). The most common symptom was abdominal pain (n=14/30); 8 patients presented with symptoms compatible with an infectious process, including fever. The inflammatory infiltrate was dominated by lymphocytes and plasma cells, and in most cases, a prominent histiocytic infiltrate (22/30). Neutrophils were identified in 12 cases, with microabscess noted in 8. Storiform pattern of fibrosis was seen in 14/30 cases; obliterative phlebitis was not identified. Culture identified a microorganism in 4 of 9 cases evaluated. The mean IgG4 count was 9.3 per HPF (range: 0 to 51) with 9 of the 26 (35%) biopsies showing >10 IgG4 positive plasma cells per HPF. The mean IgG4 to IgG ratio was 8% (range: 8% to 46%). A hepatectomy was performed in 4 cases. On broad spectrum antibiotics (n=14) the lesions either resolved or decreased in size. Eight patients did not receive specific therapy, nevertheless, the lesion(s) resolved spontaneously in 6 cases, remained stable or decreased in size in 2 cases. Notably, none of these patients showed evidence of a hepatic recurrence. FHVHPT, a tumefactive lesion that mimics hepatic neoplasia, is histologically characterized by a fibrohistiocytic infiltrate. In the majority of patients FHVHPT represents the organizing phase of hepatic abscess and can be successfully managed with antibiotic therapy.

Stool metagenome analysis of patients with Klebsiella pneumoniae liver abscess and their domestic partners.

OBJECTIVES: Hypermucoviscous Klebsiella pneumoniae is an emerging cause of community-acquired liver abscess. The aim of this study was to investigate whether hypermucoviscous strains could be shared among households. METHODS: The clinical K. pneumoniae isolates from a cohort of 24 patients with Klebsiella liver abscess were genotyped, and the stool metagenomes of the index patients and their cohabiting domestic partners were analyzed. RESULTS: K. pneumoniae was identified in 33% of index patient stools, and one index patient's clinical isolate was identified in their domestic partner's stool. CONCLUSIONS: This could represent a transmission event or could represent exposure to a common environmental source.

MicroRNA Interference in Hepatic Host-Pathogen Interactions.

The liver is well recognized as a non-immunological visceral organ that is involved in various metabolic activities, nutrient storage, and detoxification. Recently, many studies have demonstrated that resident immune cells in the liver drive various immunological reactions by means of several molecular modulators. Understanding the mechanistic details of interactions between hepatic host immune cells, including Kupffer cells and lymphocytes, and various hepatic pathogens, especially viruses, bacteria, and parasites, is necessary. MicroRNAs (miRNAs), over 2600 of which have been discovered, are small, endogenous, interfering, noncoding RNAs that are predicted to regulate more than 15,000 genes by degrading specific messenger RNAs. Several recent studies have demonstrated that some miRNAs are associated with the immune response to pathogens in the liver. However, the details of the underlying mechanisms of miRNA interference in hepatic host-pathogen interactions still remain elusive. In this review, we summarize the relationship between the immunological interactions of various pathogens and hepatic resident immune cells, as well as the role of miRNAs in the maintenance of liver immunity against pathogens.

Leukotoxin production by Fusobacterium necrophorum strains in relation to severity of liver abscesses in cattle.

Fusobacterium necrophorum, a Gram-negative anaerobe, is the primary etiologic agent of liver abscesses of beef cattle. The bacterium, a member of the microbial community of the rumen, travels to the liver via portal circulation to cause abscesses. The severity of liver abscesses vary from mild with one or two small abscesses to severe with medium to large multiple abscesses. Leukotoxin, a secreted protein, is the critical virulence factor involved in the infection. Our objective was to compare leukotoxin production between strains of F. necrophorum isolated from mild and severe liver abscesses collected from slaughtered cattle. The quantification of leukotoxin was based on assays to measure cytotoxicity and protein antigen concentration. One-hundred strains, 50 from mild and 50 from severe abscesses, were utilized in the study. Cell-free supernatants were prepared from cultures grown in anaerobic broth at 9 and 24 h incubations. The leukotoxic activity was quantified by measuring cytotoxicity based on the release of lactic dehydrogenase from bovine lymphocyte cells, BL3, treated with the culture supernatant. Leukotoxin protein concentration was quantified by a sandwich ELISA assay with a leukotoxin-specific monoclonal antibody as the capture antibody. The leukotoxin activity and concentration were highly variable among the strains within each severity of liver abscesses. Although the leukotoxic activity was unaffected by incubation time, leukotoxin protein concentration was consistently higher at 24 h compared to 9 h incubation. Strains from severe liver abscesses had significantly higher leukotoxic activity and higher protein concentration compared to strains from mild liver abscesses (P < 0.0001) at both 9 and 24 h culture supernatants. Across all strains, the correlation coefficients between leukotoxic activity and leukotoxin concentration at 9 and 24 h were 0.14 (P = 0.17) and 0.47 (P < 0.0001), respectively. In conclusion, strains isolated from severe liver abscesses had significantly higher leukotoxic activities and leukotoxin protein concentrations compared to strains isolated from mild liver abscesses.