Epidemiology of Campylobacter Species Infection in Kidney Transplant Recipients: A Retrospective Multicentric Case-Control Study in France.

Background: Campylobacteriosis in kidney transplant recipients (KTRs) is the most common identified bacterial cause of diarrhea. Risk factors in KTRs are unknown. Methods: A 10-year multicentric, retrospective 1:1 case-control study was performed in France between 2010 and 2020. The main aim was to identify factors associated with Campylobacter-related infection in KTRs. The KTRs with a functional graft and campylobacteriosis (positive stool culture and/or blood culture and/or positive nucleic amplification test) and their controls matched on transplantation date within the same center were included. Results: We identified 326 patients with campylobacteriosis. The estimated incidence rate of campylobacteriosis was 2.3/1000 patient-years. The infection occurred at a median of 2.4 years posttransplantation. The independent risk factors for campylobacteriosis were use of corticosteroids as maintenance regimen (75.8% vs 66%; P < .001), acute rejection (8.9% vs 4%; P = .048), low lymphocyte count (0.96 vs 1.4 giga/liter (G/L); P < .001), and low basal estimated glomerular filtration rate (eGFR) (44.2 vs 57.5 mL/minute/1.73 m2; P < .001). A fluoroquinolone was initiated in 64 (21.4%) patients, with 51.1% of antimicrobial resistance, whereas almost all strains were erythromycin sensitive. Conclusions: Campylobacteriosis has a higher incidence in the 2 first years of transplantation. The factors independently associated with campylobacteriosis are corticosteroids as maintenance immunosuppressive regimen, low lymphocyte counts, low eGFR, and a history of acute rejection. Due to high antimicrobial resistance with fluoroquinolone, the first line of treatment should be azithromycin.

Continuous Versus Intermittent Vancomycin Infusions for Coagulase-negative Staphylococcus Bacteremia in Neonates: A Propensity-matched Cohort Study.

BACKGROUND: Coagulase-negative staphylococci (CONS) are a major cause of late-onset neonatal sepsis, particularly in preterm infants, with high morbidity and mortality. While vancomycin is the first-line treatment for these infections, the optimal administration in neonates remains uncertain. OBJECTIVE: We aim to compare the outcomes of neonates with CONS bacteremia treated with adjusted continuous infusion (CIV) versus standard intermittent infusion (IIV) of vancomycin. METHODS: This retrospective study included 110 neonates, with 29 in the CIV group and 47 in the IIV group after propensity score matching. The primary outcome was treatment failure defined by the persistence of a positive blood culture for the same organism after at least 48 hours of vancomycin treatment. RESULTS: After matching, the CIV group exhibited significantly lower treatment failure rates [5/29 (17%) vs. 26/47 (44%); P = 0.014] and a higher rate of achieving therapeutic vancomycin levels after 24 hours [20/29 (69%) vs. 26/47 (44%); P = 0.002] compared to the IIV group. No significant differences were observed in terms of acute kidney failure between the 2 groups. CONCLUSION: Adjusted continuous vancomycin infusion in neonates with CONS bacteremia is associated with a lower treatment failure rate without an increase in renal toxicity compared to standard intermittent infusion. However, due to the observational design, larger prospective studies are needed to validate these results.

Effect of Lactobacillus gasseri BIO6369 and Lacticaseibacillus rhamnosus BIO5326 on Gastric Carcinogenesis Induced by Helicobacter pylori Infection.

BACKGROUND: Helicobacter pylori infection-associated gastric adenocarcinoma is influenced by various factors, including the digestive microbiota. Lactic acid bacteria role in digestive carcinogenesis has been discussed, and some Lactobacillaceae family species have been shown to act against H. pylori-induced inflammation and colonization. However, their effects on H. pylori-related carcinogenesis have not yet been studied. Lactobacillaceae family effects on the epithelial-to-mesenchymal transition (EMT), emergence of cells with cancer stem cell (CSC) properties and the pro-inflammatory response of gastric epithelial cells to H. pylori infection were investigated. MATERIALS AND METHODS: A co-culture model of AGS gastric epithelial cells infected with a carcinogenic strain of H. pylori associated with 18 different probiotic strains candidates were used. Different EMT indicators and CSC properties were studied, including quantification of the mesenchymal phenotype, tumorsphere formation, EMT marker expression, and tight junction evaluation with immunofluorescence microscopy. The effect of the strains on the pro-inflammatory response to H. pylori was also evaluated by quantifying interleukin-8 (IL-8) production using ELISA. RESULTS: Among the strains tested, Lactobacillus gasseri BIO6369 and Lacticaseibacillus rhamnosus BIO5326 induced a 30.6% and 38.4% reduction in the mesenchymal phenotype, respectively, caused a significant decrease in Snail and Zeb1 EMT marker expression and prevented the loss of tight junctions induced by H. pylori infection. A separate co-culture with a Boyden chamber maintained the effects induced by the two strains. H. pylori-induced IL-8 production was also significantly reduced in the presence of L. gasseri BIO6369 and L. rhamnosus BIO5326. CONCLUSION: Lactobacillus gasseri BIO6369 and L. rhamnosus BIO5326 strains decreased epithelial-to-mesenchymal transition and inflammation induced by H. pylori infection, suggesting that these species may have a protective effect against H. pylori-induced gastric carcinogenesis.

Targeting metastasis-initiating cancer stem cells in gastric cancer with leukaemia inhibitory factor.

Gastric cancer's (GC) bad prognosis is usually associated with metastatic spread. Invasive cancer stem cells (CSC) are considered to be the seed of GC metastasis and not all CSCs are able to initiate metastasis. Targeting these aggressive metastasis-initiating CSC (MIC) is thus vital. Leukaemia inhibitory factor (LIF) is hereby used to target Hippo pathway oncogenic members, found to be induced in GC and associated with CSC features. LIF-treated GC cell lines, patient-derived xenograft (PDX) cells and/or CSC tumourspheres underwent transcriptomics, laser microdissection-associated proteomics, 2D and 3D invasion assays and in vivo xenograft in mice blood circulation. LIFR expression was analysed on tissue microarrays from GC patients and in silico from public databases. LIF-treated cells, especially CSC, presented decreased epithelial to mesenchymal transition (EMT) phenotype and invasion capacity in vitro, and lower metastasis initiation ability in vivo. These effects involved both the Hippo and Jak/Stat pathways. Finally, GC's high LIFR expression was associated with better clinical outcomes in patients. LIF treatment could thus represent a targeted anti-CSC strategy to fight against metastatic GC, and LIFR detection in primary tumours could constitute a potential new prognosis marker in this disease.

Gastric microbiota in patients with gastric MALT lymphoma according to Helicobacter pylori infection.

BACKGROUND: Gastric Mucosa Associated Lymphoid Tissue lymphoma (GML) development is triggered by Helicobacter pylori (H. pylori) infection. Little is known about the impact of H. pylori infection on gastric microbiota. METHODS: The gastric microbiota was retrospectively investigated using 16S rRNA gene sequencing in 32 patients with untreated GML (10 H. pylori-positive and 22 H. pylori-negative), 23 with remitted and 18 refractory GML and 35 controls. Differences in microbial diversity, bacterial composition and taxonomic repartition were assessed. RESULTS: There was no change in diversity and bacterial composition between GML and control patients taking into account H. pylori status. Differential taxa analysis identified specific changes associated with H. pylori-negative GML: the abundances of Actinobacillus, Lactobacillus and Chryseobacterium were increased while the abundances of Veillonella, Atopobium, Leptotrichia, Catonella, Filifactor and Escherichia_Shigella were increased in control patients. In patients with remitted GML, the genera Haemophilus and Moraxella were significantly more abundant than in refractory patients, while Atopobium and Actinomyces were significantly more abundant in refractory patients. CONCLUSION: Detailed analysis of the gastric microbiota revealed significant changes in the bacterial composition of the gastric mucosa in patients with GML that may have a role in gastric lymphomagenesis but not any new pathobionts.

Description of a Case of Helicobacter pylori Infection with In Vitro Resistance to Tetracycline: An Exceptional Event with No Consequences?

Resistance in Helicobacter pylori to tetracycline is rare. We describe the case of an H. pylori strain with a high level of resistance to tetracycline (minimum inhibitory concentration = 12 mg/L). However, despite tetracycline resistance, bismuth quadritherapy was effective. Analysis of the patient's antibiotic treatment history over the previous 25 years revealed repeated 3-month courses of tetracycline for the treatment of acne, suggesting in vivo selection pressure responsible for the emergence of the triple mutation (AGA→TTC) in 16S rDNA associated with tetracycline resistance. This is a rare event but one worth monitoring, especially in view of the widespread use of bismuth quadritherapy for probabilistic treatment in countries where it is available.

Combined genomic-proteomic approach in the identification of Campylobacter coli amoxicillin-clavulanic acid resistance mechanism in clinical isolates.

Introduction: Aminopenicillins resistance among Campylobacter jejuni and Campylobacter coli strains is associated with a single mutation in the promoting region of a chromosomal beta-lactamase blaOXA61, allowing its expression. Clavulanic acid is used to restore aminopenicillins activity in case of blaOXA61 expression and has also an inherent antimicrobial activity over Campylobacter spp. Resistance to amoxicillin-clavulanic acid is therefore extremely rare among these species: only 0.1% of all Campylobacter spp. analyzed in the French National Reference Center these last years (2017-2022). Material and methods: Whole genome sequencing with bioinformatic resistance identification combined with mass spectrometry (MS) was used to identify amoxicillin-acid clavulanic resistance mechanism in Campylobacters. Results: A G57T mutation in blaOXA61 promoting region was identified in all C. jejuni and C. coli ampicillin resistant isolates and no mutation in ampicillin susceptible isolates. Interestingly, three C. coli resistant to both ampicillin and amoxicillin-clavulanic acid displayed a supplemental deletion in the promoting region of blaOXA61 beta-lactamase, at position A69. Using MS, a significant difference in the expression of BlaOXA61 was observed between these three isolates and amoxicillin-clavulanic acid susceptible C. coli. Conclusion: A combined genomics/proteomics approach allowed here to identify a rare putative resistance mechanism associated with amoxicillin-clavulanic acid resistance for C. coli.

Campylobacter fetus foodborne illness outbreak in the elderly.

In June 2021, a cluster of seven cases of Campylobacter fetus infections occurred in a rehabilitation center and caused significant morbidity in elderly patients including five with bacteremia and two with osteoarticular medical device infections. The genetic identity identified by whole genome sequencing of the different Campylobacter fetus strains confirms a common source. This foodborne illness outbreak may have resulted from the consumption of unpasteurized dairy products, such as a cow's raw milk cheese resulting from a farm-to-fork strategy.

Dynamics of the digestive acquisition of bacterial carriage and integron presence by French preterm newborns according to maternal colonization: The DAIR3N multicentric study.

Objectives: The study aimed to describe the dynamics and risk factors of Gram-negative bacteria (GNB) acquisition in preterm infants. Methods: This prospective multicenter French study included mothers hospitalized for preterm delivery and their newborns, followed until hospital discharge. Maternal feces and vaginal fluids at delivery, and neonatal feces from birth to discharge were tested for cultivable GNB, potential acquired resistance, and integrons. The primary outcome was the acquisition of GNB and integrons in neonatal feces, and their dynamics, evaluated by survival analysis using the actuarial method. Risk factors were analyzed using Cox models. Results: Two hundred thirty-eight evaluable preterm dyads were included by five different centers over 16 months. GNB were isolated in 32.6% of vaginal samples, with 15.4% of strains producing extended-spectrum beta-lactamase (ESBL) or hyperproducing cephalosporinase (HCase), and in 96.2% of maternal feces, with 7.8% ESBL-GNB or HCase-GNB. Integrons were detected in 40.2% of feces and 10.6% of GNB strains. The mean (SD) length of stay of newborns was 39.5 (15.9) days; 4 died in the hospital. At least one infection episode occurred in 36.1% of newborns. The acquisition of GNB and integrons was progressive from birth to discharge. At discharge, half of newborns had ESBL-GNB or HCase-GNB, independently favored by a premature rupture of membranes (Hazard Ratio (HR), 3.41, 95% confidence interval (CI), 1.71; 6.81), and 25.6% had integrons (protective factor: multiple gestation, HR, 0.367, 95% CI, 0.195; 0.693). Conclusion: In preterm newborns, the acquisitions of GNB, including resistant ones, and integrons are progressive from birth to discharge. A premature rupture of membranes favored the colonization by ESBL-GNB or Hcase-GNB.

RIDA®GENE Helicobacter pylori PCR on the ELITe InGenius System.

PCR detection of Helicobacter pylori infection in gastric biopsies allows the detection of this bacterium and the mutations associated with macrolide resistance. The aim of this study was to evaluate the performance of RIDA®GENE H. pylori PCR (r-Biopharm) on the ELITe InGenius System (Elitech). Two hundred gastric biopsies were obtained. These biopsies were ground in nutrient broth. Two hundred microliters of this suspension was treated with proteinase K, and then, 200 µL was transferred to an ELITe InGenius sample tube and tested using RIDA®GENE H. pylori PCR reagents. In-house H. pylori PCR was used as a reference. The sensitivity of RIDA®GENE H. pylori PCR with ELITe InGenius was 100%, the specificity was 98% (95% confidence interval (CI), 95.3-100%), the PPV was 98% (95% CI, 95.3-100%), and the NPV was 100% for the detection of H. pylori. All of these parameters were 100% for the categorization of macrolide resistance. The adaptation of RIDA®GENE H. pylori PCR reagents on the ELITe InGenius System was successful. This PCR is easy to use on this system.

Recurrent Cellulitis Revealing Helicobacter cinaedi in Patient on Ibrutinib Therapy, France.

Helicobacter cinaedi bacteremia caused recurring multifocal cellulitis in a patient in France who had chronic lymphocytic leukemia treated with ibrutinib. Diagnosis required extended blood culture incubation and sequencing of the entire 16S ribosomal RNA gene from single bacterial colonies. Clinicians should consider H. cinaedi infection in cases of recurrent cellulitis.

Spatial heterogeneity for APRIL production by eosinophils in the small intestine.

Eosinophils may reside in the lower intestine to play several homeostatic functions. Regulation of IgA+ plasma-cell (PC) homeostasis is one of these functions. Here, we assessed regulation of expression for a proliferation-inducing ligand (APRIL), a key factor from the TNF superfamily for PC homeostasis, in eosinophils from the lower intestine. We observed a strong heterogeneity, since duodenum eosinophils did not produce APRIL at all, whereas a large majority of eosinophils from the ileum and right colon produced it. This was evidenced both in the human and mouse adult systems. At these places, the human data showed that eosinophils were the only cellular sources of APRIL. The number of IgA+ PCs did not vary along the lower intestine, but ileum and right colon IgA+ PC steady-state numbers significantly diminished in APRIL-deficient mice. Use of blood cells from healthy donors demonstrated that APRIL expression in eosinophils is inducible by bacterial products. Use of germ-free and antibiotics-treated mice confirmed the dependency on bacteria for APRIL production by eosinophils from the lower intestine. Taken together, our study shows that APRIL expression by eosinophils is spatially regulated in the lower intestine with a consequence on the APRIL dependency for IgA+ PC homeostasis.

Multicenter Retrospective Study of Vascular Infections and Endocarditis Caused by Campylobacter spp., France.

The incidence of campylobacteriosis has substantially increased over the past decade, notably in France. Secondary localizations complicating invasive infections are poorly described. We aimed to describe vascular infection or endocarditis caused by Campylobacter spp. We included 57 patients from a nationwide 5-year retrospective study on Campylobacter spp. bacteremia conducted in France; 44 patients had vascular infections, 12 had endocarditis, and 1 had both conditions. Campylobacter fetus was the most frequently involved species (83%). Antibiotic treatment involved a ß-lactam monotherapy (54%) or was combined with a fluoroquinolone or an aminoglycoside (44%). The mortality rate was 25%. Relapse occurred in 8% of cases and was associated with delayed initiation of an efficient antimicrobial therapy after the first symptoms, diabetes, and coexistence of an osteoarticular location. Cardiovascular Campylobacter spp. infections are associated with a high mortality rate. Systematically searching for those localizations in cases of C. fetus bacteremia may be warranted.

Neonatal toxic shock syndrome-like exanthematous disease: A French case series.

Neonatal toxic shock syndrome-like exanthematous disease (NTED) was first described in Japan in the 1990s. It results from the secretion of superantigenic toxins by Staphylococcus aureus. Diagnostic criteria include generalized macular erythema and at least one of the following three features: fever (>38°C), thrombocytopenia (<150,000/mm3 ), low positive C reactive protein (10-50 mg/L) in the absence of another known disease process. We herein describe four cases from France, involving both MSSA and "Geraldine" MRSA. This report aims to bring this underdiagnosed disease to the attention of pediatricians and infectious disease specialists, to improve the management of affected newborns.

CD44v3 is a marker of invasive cancer stem cells driving metastasis in gastric carcinoma.

BACKGROUND: Cancer stem cells (CSCs) are at the origin of tumour initiation and progression in gastric adenocarcinoma (GC). However, markers of metastasis-initiating cells remain unidentified in GC. In this study, we characterized CD44 variants expressed in GC and evaluated the tumorigenic and metastatic properties of CD44v3+ cells and their clinical significance in GC patients. METHODS: Using GC cell lines and patient-derived xenografts, we evaluated CD44+ and CD44v3+ GC cells molecular signature and their tumorigenic, chemoresistance, invasive and metastatic properties, and expression in patients-derived tissues. RESULTS: CD44v3+ cells, which represented a subpopulation of CD44+ cells, were detected in advanced preneoplastic lesions and presented CSCs chemoresistance and tumorigenic properties in vitro and in vivo. Molecular and functional analyses revealed two subpopulations of gastric CSCs: CD44v3+ CSCs with an epithelial-mesenchymal transition (EMT)-like signature, and CD44+/v3- CSCs with an epithelial-like signature; both were tumorigenic but CD44v3+ cells showed higher invasive and metastatic properties in vivo. CD44v3+ cells detected in the primary tumours of GC patients were associated with a worse prognosis. CONCLUSION: CD44v3 is a marker of a subpopulation of CSCs with metastatic properties in GC. The identification of metastasis-initiating cells in GC represents a major advance for further development of anti-metastatic therapeutic strategies.

Genomic Diversity of Campylobacter lari Group Isolates from Europe and Australia in a One Health Context.

Members of the Campylobacter lari group are causative agents of human gastroenteritis and are frequently found in shellfish, marine waters, shorebirds, and marine mammals. Within a One Health context, we used comparative genomics to characterize isolates from a diverse range of sources and geographical locations within Europe and Australia and assess possible transmission of food, animal, and environmental isolates to the human host. A total of 158 C. lari isolates from Australia, Denmark, France, and Germany, which included 82 isolates from human stool and blood, 12 from food, 14 from domestic animal, 19 from waterbirds, and 31 from the environment were analyzed. Genome-wide analysis of the genetic diversity, virulence, and antimicrobial resistance (AMR) traits was carried-out. Most of the isolates belonged to C. lari subsp. lari (Cll; 98, 62.0%), while C. lari subsp. concheus and C. lari urease-positive thermotolerant Campylobacter (UPTC) were represented by 12 (7.6%) and 15 (9.5%) isolates, respectively. Furthermore, 33 (20.9%) isolates were not assigned a subspecies and were thus attributed to distant Campylobacter spp. clades. Whole-genome sequence-derived multilocus sequence typing (MLST) and core-genome MLST (cgMLST) analyses revealed a high genetic diversity with 97 sequence types (STs), including 60 novel STs and 14 cgMLST clusters (≤10 allele differences), respectively. The most prevalent STs were ST-21, ST-70, ST-24, and ST-58 (accounting for 13.3%, 4.4%, 3.8%, and 3.2% of isolates, respectively). A high prevalence of the 125 examined virulence-related loci (from 76.8 to 98.4% per isolate) was observed, especially in Cll isolates, suggesting a probable human pathogenicity of these strains. IMPORTANCE Currently, relatedness between bacterial isolates impacting human health is easily monitored by molecular typing methods. These approaches rely on discrete loci or whole-genome sequence (WGS) analyses. Campylobacter lari is an emergent human pathogen isolated from diverse ecological niches, including fecal material from humans and animals, aquatic environments, and seafood. The presence of C. lari in such diverse sources underlines the importance of adopting an integrated One Health approach in studying C. lari population structure for conducting epidemiological risk assessment. This retrospective study presents a comparative genomics analysis of C. lari isolates retrieved from two different continents (Europe and Australia) and from different sources (human, domestic animals, waterbirds, food, and environment). It was designed to improve knowledge regarding C. lari ecology and pathogenicity, important for developing effective surveillance and disease prevention strategies.

Clinical and Epidemiologic Characteristics and Therapeutic Management of Patients with Vibrio Infections, Bay of Biscay, France, 2001-2019.

Noncholera vibriosis is a rare, opportunistic bacterial infection caused by Vibrio spp. other than V. cholerae O1/O139 and diagnosed mainly during the hot summer months in patients after seaside activities. Detailed knowledge of circulating pathogenic strains and heterogeneities in infection outcomes and disease dynamics may help in patient management. We conducted a multicenter case-series study documenting Vibrio infections in 67 patients from 8 hospitals in the Bay of Biscay, France, over a 19-year period. Infections were mainly caused by V. alginolyticus (34%), V. parahaemolyticus (30%), non-O1/O139 V. cholerae (15%), and V. vulnificus (10%). Drug-susceptibility testing revealed intermediate and resistant strains to penicillins and first-generation cephalosporins. The acute infections (e.g., those involving digestive disorder, cellulitis, osteitis, pneumonia, and endocarditis) led to a life-threatening event (septic shock), amputation, or death in 36% of patients. Physicians may need to add vibriosis to their list of infections to assess in patients with associated risk factors.