Immune Activation and Microbial Translocation as Prognostic Biomarkers for AIDS-Related Non-Hodgkin Lymphoma in the AMC-034 Study.

PURPOSE: AIDS-related non-Hodgkin lymphoma (ARL) is the most common cancer in HIV-infected individuals in the United States and other countries in which HIV-positive persons have access to effective combination antiretroviral therapy (cART). Our prior work showed that pretreatment/postdiagnosis plasma levels of some cytokines, such as IL6, IL10, and CXCL13, have the potential to serve as indicators of clinical response to treatment and survival in ARL. The aims of this study were to identify novel prognostic biomarkers for response to treatment and/or survival in persons with ARL, including biomarkers of microbial translocation and inflammation. EXPERIMENTAL DESIGN: We quantified plasma levels of several biomarkers (sCD14, LBP, FABP2, EndoCab IgM, IL18, CCL2/MCP-1, sCD163, IP-10/CXCL10, TARC/CCL17, TNFα, BAFF/BLyS, sTNFRII, sCD44, and sIL2Rα/sCD25) by multiplexed immunometric assays (Luminex) or ELISA in plasma specimens obtained from ARL patients enrolled in the AMC-034 trial, which compared infusional combination chemotherapy (EPOCH: etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) with concurrent or sequential rituximab. Plasma was collected prior to the initiation of therapy (n = 57) and after treatment initiation (n = 55). RESULTS: We found that several biomarkers decreased significantly after treatment, including TNFα, sCD25, LBP, and TARC (CCL17). Moreover, pretreatment plasma levels of BAFF, sCD14, sTNFRII, and CCL2/MCP-1 were univariately associated with overall survival, and pretreatment levels of BAFF, sTNFRII, and CCL2/MCP-1 were also associated with progression-free survival. CONCLUSIONS: Our results suggest that patients with ARL who responded to therapy had lower pretreatment levels of inflammation and microbial translocation as compared with those who did not respond optimally.

Healthcare-associated blood stream infections in hematological patients in Finland during the years 2006-2016.

OBJECTIVES: The aim was to identify the clinical characteristics, outcome, and antimicrobial susceptibility of healthcare-associated bloodstream infections (BSIs) in hematological patients. METHODS: This retrospectively collected laboratory-based surveillance data include 3404 healthcare-associated BSIs in 2296 patients with a hematological malignancy in hospitals participating in the Finnish Hospital Infection Program from January 1, 2006, to December 31, 2016. RESULTS: The most common underlying diseases were acute myelogenous leukemia (35%) and non-Hodgkin lymphoma (22%). Gram-positive organisms accounted for 60%-46% and gram-negative organisms for 24%-36% of BSIs in 2006-2016. The most common causative organism was coagulase-negative staphylococci (CoNS) (n = 731). The 7- and 28-day case fatality rates were 5.2% and 11.4%, respectively, and was highest in BSIs caused by Candida species (10.8% and 30.8%). The median age of patients increased from 59 years in 2006-2008 to 62 years in 2015-2016 (P < .01). Five percent of S aureus isolates were resistant to methicillin and five percent of Pseudomonas aeruginosa isolates were multidrug-resistant. Four percent of Klebsiella and seven percent of E coli isolates were resistant to ceftazidime. CONCLUSIONS: The proportion of gram-positive bacteria decreased and gram-negative bacteria increased over time. The case fatality rate was low and the median age of patients increased during the study.

Empiric Versus Clarithromycin Resistance-Guided Therapy for Helicobacter pylori Based on Polymerase Chain Reaction Results in Patients With Gastric Neoplasms or Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Randomized Controlled Trial.

INTRODUCTION: We investigated to compare the effect of empirical therapy vs clarithromycin resistance-guided tailored therapy (tailored therapy) for eradication of Helicobacter pylori. METHODS: In this prospective, single center, open-label randomized controlled trial, we enrolled 72 patients with H. pylori infection from January 2019 through June 2019 in Korea. The patients were randomly assigned to both groups received empirical (n = 36) or tailored therapy (n = 36). Empirical therapy was defined as triple therapy with esomeprazole, amoxicillin, and clarithromycin for 10 days irrespective of clarithromycin resistance. Tailored therapy was triple or quadruple therapy with esomeprazole, metronidazole, tetracycline, and bismuth for 10 days based on genotype markers of resistance determined by gastric biopsy. Resistance-associated mutations in 23S rRNA were confirmed by multiplex polymerase chain reaction. Eradication status was assessed by C-urea breath test, and the primary outcome was eradication rates. RESULTS: H. pylori was eradicated in 27 patients (75.0%), given empirical therapy and 32 patients (88.9%) treated with tailored therapy (P = 0.136) in intention-to-treat analysis. In per protocol analysis, the eradication rate was 97.0% and 81.8% in tailoredvs empirical groups (P = 0.046). Although clarithromycin-resistant H. pylori was eradicated in 3/9 (33.3%) with empirical therapy, it was treated in 11/12 (91.7%) with tailored therapy (P = 0.009). There was no difference in compliance between 2 groups. The rate of adverse events of the tailored group was higher than that of the empirical group (P = 0.036) because quadruple therapy had more side effects than those of triple therapy (P = 0.001). DISCUSSION: Tailored therapy based on polymerase chain reaction is a good alternative to increase eradication rates in a region of high prevalence of clarithromycin resistance (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A342).

Bacterial infection and non-Hodgkin's lymphoma.

One quarter of all cancers are linked to infectious diseases. The link between viral infection and cancer has been widely studied, but few reports have focused on the carcinogenic role of bacterial infection. Nonetheless, Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni are bacteria that can be associated with non-Hodgkin's lymphoma (NHL), the most common haematologic malignancy. Here, we review the evidence in favour of a link between these bacterial infections and NHL. Sero-epidemiological observation makes it possible to identify a link between H. pylori, C. burnetii, B. burgdorferi infection and NHL. Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni could be identified in NHL tissue samples at the site of chronic inflammation, where B and T lymphocytes are attracted to participate in follicle formation. Lymphoma remissions have been observed under antimicrobial therapies supporting the carcinogenic contribution of bacteria. If the theory of causality is characterized by the lack of universal criteria for establishing a causal link between two diseases, infection and lymphoma, epidemiological, clinical, and histological evidences reported here, should lead clinicians to pay attention to these infectious agents, to detect early lymphoma transformation.

The Role of Microbial Translocation and Immune Activation in AIDS-Associated Non-Hodgkin Lymphoma Pathogenesis: What Have We Learned?

Human immunodeficiency virus (HIV) infection is associated with greatly increased risk for development of non-Hodgkin lymphoma (NHL). Nearly all acquired immunodeficiency syndrome (AIDS)-associated NHL (AIDS-NHL) is of B-cell origin. Two major mechanisms are believed to contribute to the genesis of AIDS-NHL: (1) loss of immunoregulation of Epstein-Barr virus (EBV)+ B cells, resulting from impaired T-cell function late in the course of HIV disease and (2) chronic B-cell activation, leading to DNA-modifying events that contribute to oncogene mutations/ translocations. HIV infection has long been known to be associated with chronic inflammation and polyclonal B-cell activation, and more recently, microbial translocation. Microbial translocation is bacterial product leakage from gut lumen into the peripheral circulation, resulting in high levels of lipopolysaccharide (LPS) in the peripheral circulation, leading to chronic immune activation and inflammation. We review recent literature linking microbial translocation to lymphom-agenesis. This includes epidemiological studies of biomarkers of microbial translocation with risk of AIDS-NHL and emerging data on the mechanisms by which microbial translocation may lead to AIDS-NHL development.

New ST623 of Cryptococcus neoformans isolated from a patient with non-Hodgkin's lymphoma in the Brazilian Amazon.

BACKGROUND: Cryptococcosis is a disease of wide geographic distribution. It is most critical when it affects immunocompromised patients, with AIDS, tuberculosis or other diseases that require prolonged hospitalization. METHODS: This study described a case report, molecular epidemiology, the phylogenetic relationship, along with antifungal susceptibility test of a new ST 623 of C. neoformans isolated in a patient with non-Hodgkin's Lymphoma, from Manaus, Brazil. RESULTS: The new C. neoformans was susceptible to all antifungal drugs tested. Our results showed that ST623 new clone has no evident evolutionary proximity to any other ST of the VNI subtype group identified in Brazil. CONCLUSIONS: In the context of phylogenetic analysis, this new genotype belongs to VNI subtype, and subsequencing complete genome studies are necessary to better understand the phylogenetic relationships amongst STs in this group.

Ibrutinib-associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: An observational study.

BACKGROUND: Invasive fungal diseases (IFD) are life-threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. OBJECTIVES: Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. METHODS: Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non-Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. RESULT: Thirty-five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1-540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. CONCLUSIONS: The prevalence of IFD among chronic lymphocytic leukaemia/non-Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib-associated IFD.

Helicobacter pylori (HP) infection alone, but not HP-induced atrophic gastritis, increases the risk of gastric lymphoma: a case-control study in Japan.

Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H. pylori infection induces lymphomagenesis. Although this chronic mucosal inflammation also results in atrophic gastritis, evidence supporting the possible significance of atrophic gastritis in gastric lymphomagenesis is scarce. Here, to evaluate the association between gastric mucosal atrophy and the risk of gastric lymphoma, we conducted a matched case-control study at Aichi Cancer Center focusing on the attribution of H. pylori infection status and pepsinogen (PG) serum levels. In total, 86 patients with gastric lymphoma (including 49 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and 24 cases of diffuse large B cell lymphoma (DLBCL)) and 1720 non-cancer controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. The adjusted ORs of positive atrophic gastritis relative to negative for overall gastric lymphoma, MALT lymphoma, DLBCL, and other lymphomas were 0.77 (95% CI 0.45-1.33), 0.65 (0.30-1.39), 1.03 (0.38-2.79), and 0.84 (0.22-3.29), respectively. In contrast, a positive association between overall gastric lymphoma and H. pylori infection was observed (OR = 2.14, 95% CI 1.30-3.54). A consistent association was observed for MALT lymphoma, DLBCL, and other lymphomas with ORs of 1.96 (1.00-3.86), 1.92 (0.74-4.95), and 5.80 (1.12-30.12), respectively. These findings suggest that H. pylori infection triggers gastric lymphoma but that epithelial changes due to atrophic gastritis do not inherently affect the development of gastric lymphoma.

A transcriptional signature associated with non-Hodgkin lymphoma in the blood of patients with Q fever.

Coxiella burnetii, the agent causing Q fever, has been associated with B-cell non-Hodgkin lymphoma (NHL). To better clarify this link, we analysed the genetic transcriptomic profile of peripheral blood leukocytes from patients with C. burnetii infection to identify possible links to lymphoma. Microarray analyses revealed that 1189 genes were expressed differently (p <.001 and fold change ≥4) in whole blood of patients with C. burnetii infection compared to controls. In addition, 95 genes expressed in patients with non-Hodgkin lymphoma (NHL) and in patients with C. burnetii persistent infection have allowed us to establish the 'C. burnetii-associated NHL signature'. Among these, 33 genes previously found modulated in C. burnetii-associated -NHL by the microarray analysis were selected and their mRNA expression levels were measured in distinct C. burnetii-induced pathologies, namely, acute Q fever, focalized persistent infection, lymphadenitis and C.burnetii-associated NHL. Specific genes involved in anti-apoptotic process were found highly expressed in leukocytes from patients with C. burnetii associated-NHL: MIR17HG, REL and SP100. This signature differed from that found for NHL-control group. Patients with C. burnetii lymphadenitis presented significant elevated levels of BCL2 and ETS1 mRNAs. Altogether, we identified a specific transcriptionnal signature for NHL during C. burnetii infection reflecting the up-regulation of anti-apoptotic processes and the fact that lymphadenitis might constitute a critical step towards lymphomagenesis.

Exposure to Coxiella burnetii and risk of non-Hodgkin lymphoma: a retrospective population-based analysis in the Netherlands.

BACKGROUND: An association between Coxiella burnetii and non-Hodgkin lymphoma has been suggested. After a large Q fever epidemic in the Netherlands (2007-10), we postulated that the incidence of non-Hodgkin lymphoma would be increased during and after the epidemic in areas with a high endemicity of Q fever compared with those with low endemicity. METHODS: We did a retrospective population-based analysis and calculated relative risks (RRs) of non-Hodgkin lymphoma during 1-year periods before, during, and after the Q fever epidemic, for areas with intermediate and high endemicity of Q fever compared with low endemic areas. We also calculated the RR of non-Hodgkin lymphoma in people with chronic Q fever compared with the general population. FINDINGS: Between Jan 1, 2002, and Dec 31, 2013, 48 760 cases of non-Hodgkin lymphoma were diagnosed. The incidence of non-Hodgkin lymphoma ranged from 21·4 per 100 000 per year in 2002 to 26·7 per 100 000 per year in 2010. A significant association with non-Hodgkin lymphoma was noted in 2009 for areas with a high endemicity of Q fever compared with low endemic areas (RR 1·16, 95% CI 1·02-1·33; p=0·029); no further associations were noted in any other year or for areas with intermediate Q fever endemicity. Among 439 individuals with chronic Q fever, five developed non-Hodgkin lymphoma, yielding a crude absolute risk of 301·0 cases per 100 000 per year (RR 4·99, 95% CI 2·07-11·98; p=0·0003) compared with the general population in the Netherlands. INTERPRETATION: These findings do not support the hypothesis that Q fever has a relevant causal role in the development of non-Hodgkin lymphoma. Several limitations, inherent to the design of this study, might lead to both underestimation and overestimation of the studied association. FUNDING: Foundation Q-support and Institut Mérieux.

Anti-Helicobacter pylori therapy in localized gastric mucosa-associated lymphoid tissue lymphoma: A prospective, nationwide, multicenter study in Japan.

BACKGROUND: Helicobacter pylori eradication therapy was approved in Japan for the first-line, standard treatment of H. pylori-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although several retrospective studies or small-scale single-center studies have been reported, a prospective, large-scale, nationwide, multicenter study has not been reported from Japan. MATERIALS AND METHODS: We conducted a prospective, nationwide, multicenter study to evaluate the clinical efficacy of rabeprazole-based triple H. pylori eradication therapy for patients with localized gastric MALT lymphoma in practice-based clinical trial. A total of 108 H. pylori-positive patients with stage I/II1 gastric MALT lymphoma underwent H. pylori eradication therapy. The primary endpoints were complete remission (CR) rate and the rate of transfer to secondary treatment. The secondary endpoints were CR maintenance duration and overall survival (OS). RESULTS: CR of lymphoma was achieved in 84 of 97 patients (86.6%), during the period 2.0-44.7 months (median, 5.3 months) after starting H. pylori eradication treatment. CR was maintained in 77 of 81 patients (95.1%) for 0.4-53.2 months (median, 33.1 months). Secondary treatments (radiotherapy, rituximab, or gastrectomy) for gastric MALT lymphoma were needed in 10 of the 97 patients (10.31%). During follow-up, OS rate was 96.9% (94/97) and the causes of 3 deaths were not related to lymphoma. CONCLUSIONS: Rabeprazole-based H. pylori eradication therapy demonstrated a high CR rate, long CR maintenance, and a good OS for patients with localized gastric MALT lymphoma in this prospective, practice-based, multicenter study.

Case report: Coxiella burnetii vascular infection and lymphoma in the Netherlands.

OBJECTIVES AND DESIGN: Non-Hodgkin lymphoma has been linked to infection with Coxiella burnetii, potentially through overproduction of IL-10 during infection with C. burnetii. MATERIALS AND METHODS: Description of a case report. RESULTS: We describe a patient with retroperitoneal non-Hodgkin lymphoma and vascular infection with C. burnetii. Immunofluorescence staining and fluorescence in situ hybridization targeting specific C. burnetii 16S rRNA were performed on the retroperitoneal lymphoma tissue sample obtained at diagnosis of NHL. Both were strongly positive for the presence of C. burnetii. CONCLUSIONS: This case provokes questions regarding a potential association between C. burnetii and NHL, and underlines the importance of further exploration of this association.

A New Animal Model of Gastric Lymphomagenesis: APRIL Transgenic Mice Infected by Helicobacter Species.

APRIL is a member of the tumor necrosis factor cytokine family involved in the regulation of B-cell immunity. We present a study of the infection by Helicobacter species of transgenic (Tg) C57BL6 mice, ectopically expressing the human form of APRIL. Wild-type (WT) and APRIL Tg mice were infected with Helicobacter felis and Helicobacter pylori and compared with noninfected animals. Mice were euthanized 18 months after infection, and inflammatory responses and histologic alterations were analyzed. Flow cytometry results revealed that WT-infected mice had less leukocyte infiltration than APRIL Tg-infected mice. In WT-infected mice, infiltrates in gastric tissues were predominantly composed of T cells, mainly CD4+ for H. pylori and CD8+ for H. felis. In APRIL Tg-infected mice, leukocyte infiltrates were composed of B cells with few CD4+ T cells for both species. B cells expressed B surface markers compatible with a marginal zone origin. These results were confirmed by immunohistochemistry. B cells in particular were involved in lymphoepithelial lesions, a hallmark of gastric MALT lymphoma. Monoclonality was observed in a few infiltrates in the presence of lymphoepithelial lesions. These results confirm the importance of APRIL in the development of gastric lymphoid infiltrates induced by Helicobacter species in vivo. We believe that APRIL Tg mice infected by Helicobacter species may represent a novel animal model of gastric lymphomagenesis.

Distribution of gastric carcinoma in an area with a high prevalence of Helicobacter pylori.

BACKGROUND/AIMS: South Asia is an enigma for gastric cancer (GC) because it is a low risk region with a high prevalence of Helicobacter pylori (H. pylori) infections. We evaluated the trend of GC clinical presentation and risk factors in patients with dyspeptic symptoms. MATERIALS AND METHODS: The medical records of patients, coded by the international classification of diseases (ICD-10-CM, 2015, Diagnosis Code C16.9) for malignancies of stomach diagnosed by esophagogastroduodenoscopy (EGD) and histopathology, were studied. RESULTS: 394 GC cases with a mean age of 54±15 years, range of 18 to 88, were analyzed. 256 (65%) were male. Distal non-cardiac and cardiac tumors were 302 (77%) and 92 (23%) cases, respectively. The WHO classification of GC defined 222 (56%) cases as intestinal type adenocarcinoma, 68 (17%) cases as signet ring cell carcinoma (SRC), 62 (16%) cases as diffuse type and 42 (11%) cases as B cell non-Hodgkin lymphoma. The co-morbid conditions associated with GC were H. pylori infection (positive in 246 (62%) cases), diabetes mellitus type 2 (in 90 (23%) cases), and cigarette smoking (in 94 (24%) cases). Of the male patients, 88 (34%) (p<0.001) were smokers. Body mass index was abnormal in all age groups and in both sexes. Cardiac regions for GC were more common in the 46- to 60-year old age range and in males. Diffuse GC was seen in all age groups but there were significantly more common in the 18- to 45-year old age range. Gastric non-Hodgkin's lymphoma was seen at an early age of 18-45 years in 14(12%) and a later of 61-88 years in 20 (15%). CONCLUSION: Intestinal type GC is common at all ages but SRC and diffuse GC are more common in patients less than 50 years old. SRC and diffuse GC were not specific to the elderly in our study population.

Helicobacter pylori and Gastric Cancer: Timing and Impact of Preventive Measures.

Helicobacter pylori (H. pylori) is a Gram negative spiraliform bacterium that is commonly found in the stomach. H. pylori infection is still one of the world's most frequent infections, present in the stomachs of approximately one-half of the world's people. H. pylori infection is etiologically linked to histologic chronic active gastritis, peptic ulcer disease, and primary B-cell gastric lymphoma (gastric MALT lymphoma) and represents the major risk factor for the development of sporadic non-cardia gastric cancer (GC) of both intestinal and diffuse type. Studies that have examined the impact of GC prevention through H. pylori eradication have shown mixed results, but recent data suggest that prevention is only efficacious in patients without intestinal metaplasia or dysplasia. This indicates that, like in Barrett's esophagus, we need better clinical risk markers to indicate which patients are at greatest risk of developing cancer to guide clinical strategies. Furthermore, recent epidemiological data have suggested a possible contribution of H. pylori in modifying the risk of developing other gastrointestinal malignancies (including esophageal, pancreatic, hepatocellular, and colorectal cancer), although mechanistically these associations remain unexplained. We review clinically relevant aspects of H. pylori infection in the context of GC development as well as studies that have examined the impact of eradication on GC development and, lastly, discuss these recent epidemiological studies connecting H. pylori infection to extragastric gastrointestinal malignancies.

Epidemiology, clinical impacts and current clinical management of Helicobacter pylori infection.

Helicobacter pylori infection is a major cause of morbidity and mortality worldwide. More than 50% of the global population is estimated to be infected. Differences in prevalence exist within and between countries, with higher prevalence seen among people with lower socio-economic status. Most transmission of infection occurs early in life, predominantly from person to person in the family setting. H. pylori is the cause of most peptic ulcer disease, gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and causes symptoms in a subset of patients with functional dyspepsia. Choice of diagnostic test depends on the clinical context; urea breath tests and endoscopy with biopsy are the major diagnostic tools. Evidence-based indications for eradication of H. pylori infection are well documented. The most widely used and recommended eradication therapy in Australia is triple therapy comprising a proton pump inhibitor, amoxycillin and clarithromycin, usually for 1 week. Effective alternative regimens are available for patients with proven allergy to penicillin. Antimicrobial resistance is the major determinant of the outcome of eradication therapy. Trends in antibiotic resistance need to be monitored locally, but individual patient susceptibility testing is not usually necessary as it rarely guides the choice of therapy. The outcome of treatment should be assessed not less than 4 weeks after therapy. This is usually done with a urea breath test if follow-up endoscopy is not required. When first-line therapy fails, several proven second-line therapies may be used. Repeat first-line therapy and ad hoc regimens should be avoided. Overall cumulative eradication rates should approach 99%.

In the Aftermath of Helicobacter pylori: Other Helicobacters Rising Up to Become the Next Gastric Epidemic?

Non-Helicobacter pylori-Helicobacters including H. suis, H. heilmanniisensu stricto and H. felis comprise a group of bacteria that may inhabit the stomach of humans and animals. Human gastric infection has been associated with gastritis, ulcer, MALT lymphoma and cancer. Although the fastidious nature of these organisms has hampered their research, recent advancements in in vitro cultivation and recent reports on in vivo models and prevalence studies in humans suggest this group of bacteria to be of more clinical significance than earlier believed. The present review discusses their history, microbiology and relevance to human health.

Campylobacter jejuni Fatal Sepsis in a Patient with Non-Hodgkin's Lymphoma: Case Report and Literature Review of a Difficult Diagnosis.

Campylobacter jejuni (C. jejuni) bacteremia is difficult to diagnose in individuals with hematological disorders undergoing chemotherapy. The cause can be attributed to the rarity of this infection, to the variable clinical presentation, and to the partial overlapping symptoms underlying the disease. Here, we report a case of a fatal sepsis caused by C. jejuni in a 76-year-old Caucasian man with non-Hodgkin's lymphoma. After chemotherapeutic treatment, the patient experienced fever associated with severe neutropenia and thrombocytopenia without hemodynamic instability, abdominal pain, and diarrhea. The slow growth of C. jejuni in the blood culture systems and the difficulty in identifying it with conventional biochemical phenotyping methods contributed to the delay of administering a targeted antimicrobial treatment, leading to a fatal outcome. Early recognition and timely intervention are critical for the successful management of C. jejuni infection. Symptoms may be difficult to recognize in immunocompromised patients undergoing chemotherapy. Thus, it is important to increase physician awareness regarding the clinical manifestations of C. jejuni to improve therapeutic efficacy. Moreover, the use of more aggressive empirical antimicrobial treatments with aminoglycosides and/or carbapenems should be considered in immunosuppressed patients, in comparison to those currently indicated in the guidelines for cancer-related infections supporting the use of cephalosporins as monotherapy.