Antimicrobial susceptibilities of Campylobacter fetus: report from a reference laboratory.

Campylobacter fetus is known to cause human disease, particularly in elderly and immunocompromised hosts. There are limited published data for antimicrobial susceptibility patterns with this organism, and no interpretive criteria are available. We reviewed antimicrobial susceptibilities of C. fetus isolates tested at a tertiary care center and reference laboratory over an 11-year period. C. fetus isolates from patients treated at Mayo Clinic and those sent as referrals for identification and susceptibility were included. Antimicrobial susceptibility testing was performed using agar dilution for ciprofloxacin, doxycycline, erythromycin, gentamicin, meropenem, and tetracycline. Geographic distribution, culture source, organism minimal inhibitory concentration (MIC) distributions, and MIC50 and MIC90 were examined. Excluding duplicates, 105 unique isolates were identified from 110 positive cultures. Blood cultures represented the most common source, followed by body fluids, skin and soft tissue, and central nervous system. Gentamicin and meropenem had favorable MIC50 and MIC90 of 1 µg/mL. Ciprofloxacin demonstrated an MIC50 of 1 µg/mL; however, the MIC90 was >2 µg/mL. Erythromycin demonstrated MIC50 and MIC90 of 2 µg/mL. Tetracycline and doxycycline were tested on a limited number of isolates and showed a wide range of MICs. Gentamicin and meropenem demonstrated favorable MICs in C. fetus isolates. These may represent therapeutic options for consideration in serious C. fetus infections, pending susceptibility results. Ciprofloxacin, which showed variable results, may be more appropriate for use only after susceptibility testing. C. fetus interpretive criteria are needed to aid clinicians in selection of both empiric and definitive therapies. IMPORTANCE: Our findings contribute to the scant literature on Campylobacter fetus antimicrobial susceptibility test results. We used a reference test method of agar dilution and provide MICs for a large number of organisms and antimicrobial agents.

Biochemical and molecular characterization of Campylobacter fetus isolates from bulls subjected to bovine genital campylobacteriosis diagnosis in Spain.

BACKGROUND: Bovine genital campylobacteriosis (BGC) is caused by Campylobacter fetus subsp. venerealis (Cfv) including its biovar intermedius (Cfvi). This sexually transmitted disease induces early reproductive failure causing considerable economic losses in the cattle industry. Using a collection of well-characterized isolates (n = 13), C. fetus field isolates (n = 64) and saprophytic isolates resembling Campylobacter (n = 75) obtained from smegma samples of breeding bulls, this study evaluated the concordance of the most used phenotypic (H2S production in cysteine medium and 1% glycine tolerance) and molecular (PCR) methods for the diagnosis of BGC and assessed possible cross-reactions in the molecular diagnostic methods. RESULTS: Characterization at the subspecies level (fetus vs. venerealis) of C. fetus isolated from bull preputial samples using phenotypic and molecular (PCR targeting nahE and ISCfe1) methods showed moderate concordance (κ = 0.462; CI: 0.256-0.669). No cross-reactions were observed with other saprophytic microaerophilic species or with other Campylobacter species that can be present in preputial samples. Whole genome sequencing (WGS) of discrepant isolates showed 100% agreement with PCR identification. For the differentiation of Cfv biovars, comparison of the H2S test (at 72 h and 5 days of incubation) and a PCR targeting the L-cysteine transporter genes showed higher concordance when H2S production was assessed after 5 days (72 h; κ = 0.553, 0.329-0.778 CI vs. 5 days; κ = 0.881, 0.631-1 CI), evidencing the efficacy of a longer incubation time. CONCLUSIONS: This study confirmed the limitations of biochemical tests to correctly identify C. fetus subspecies and biovars. However, in the case of biovars, when extended incubation times for the H2S test (5 days) were used, phenotypic identification results were significantly improved, although PCR-based methods produced more accurate results. Perfect agreement of WGS with the PCR results and absence of cross-reactions with non-C. fetus saprophytic bacteria from the smegma demonstrated the usefulness of these methods. Nevertheless, the identification of new C. fetus subspecies-specific genes would help to improve BGC diagnosis.

Campylobacter fetus Invasive Infections and Risks for Death, France, 2000-2021.

Campylobacter fetus accounts for 1% of Campylobacter spp. infections, but prevalence of bacteremia and risk for death are high. To determine clinical features of C. fetus infections and risks for death, we conducted a retrospective observational study of all adult inpatients with a confirmed C. fetus infection in Nord Franche-Comté Hospital, Trevenans, France, during January 2000-December 2021. Among 991 patients with isolated Campylobacter spp. strains, we identified 39 (4%) with culture-positive C. fetus infections, of which 33 had complete records and underwent further analysis; 21 had documented bacteremia and 12 did not. Secondary localizations were reported for 7 (33%) patients with C. fetus bacteremia, of which 5 exhibited a predilection for vascular infections (including 3 with mycotic aneurysm). Another 7 (33%) patients with C. fetus bacteremia died within 30 days. Significant risk factors associated with death within 30 days were dyspnea, quick sequential organ failure assessment score >2 at admission, and septic shock.

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.

Campylobacter fetus seeding of a cavernous malformation resulting in brain abscess: case report and literature review.

Microbial seeding of a cerebral cavernous malformation is an extremely rare occurrence with only 3 cases reported in the literature thus far. Campylobacter fetus is an opportunistic pathogen that rarely causes neurological infection with only 3 cases of C. fetus cerebral abscesses and 38 cases of C. fetus meningitis reported in the literature. There have been no cases of cerebral cavernous malformation seeding by C. fetus reported to date. We report the first case of cerebral cavernous malformation seeding by C. fetus, a case occurring in a previously healthy 16-year-old female who presented with suspected left cerebellar cavernous malformation with subacute hemorrhage. She underwent a suboccipital craniectomy for the resection of the cavernous malformation with additional intraoperative findings suggestive of cerebral abscess. Following positive blood and CSF cultures and surgical pathology results, the patient was diagnosed with C. fetus meningoencephalitis with co-infected left cerebellar cavernous malformation. This is the fourth reported case of microbial seeding of a cerebral cavernous malformation, and to our knowledge, the first case of a C. fetus-infected cavernous malformation. Compared to previous reports, the clinical events of this case strongly support the presence of a preexisting lesion that was secondarily seeded versus de novo formation as a result of prior infection.

Genome analysis of clinical isolate of Campylobacter fetus subspecies fetus MMM01 from India reveals genetic determinants of pathogenesis and adaptation.

In this study we report the whole genome sequencing (WGS) based analysis of blood-borne Campylobacter fetus subsp. fetus MMM01 isolated from a diabetic patient to obtain deeper insights in to the virulence and host adaptability. The sequenced genome of C. fetus subsp. fetus MMM01 along with reference genomes retrieved from NCBI was subjected to various in-silico analysis including JSpecies, MLST server, PATRIC server, VFanalyzer, CARD, PHASTER to understand their phylogenetic relation, virulence and antimicrobial resistance profile. The genome had a size of 1,788,790 bp, with a GC content of 33.09%, nearly identical to the reference strain C. fetus subsp. fetus 82-40. The MLST based phylogenetic tree constructed revealed the polyphyletic branching and MMM01 (ST25) was found to be closely related to ST11, both belong to the sap-A serotype which are more common in human infections. VFanalyzer identified 88 protein-coding genes coding for several virulence factors including Campylobacter adhesion to fibronectin, flagellar apparatus, cytolethal distending toxin operons and Campylobacter invasion antigen proteins which enhance the virulence of bacteria along with resistance genes against antibiotics including fluoroquinolone, chloramphenicol, tetracycline, and aminoglycoside in MMM01, which points to enhanced survival and pathogenicity of this zoonotic pathogen. It was interesting to find that MMM01 lacked FGI-II island found in most of the clinical isolates, which encoded CRISPR Cas and prophage II regions. More details about the complexity and evolution of this zoonotic pathogen could be learned from future studies that concentrate on comparative genome analysis using larger genome datasets.

Campylobacter fetus releases S-layered and immunoreactive outer membrane vesicles.

The study of outer membrane vesicles (OMVs) became relevant because of their probable important role in the transfer of virulence factors to host cells. Campylobacter fetus is mainly a mammal pathogen whose virulence characterization is still limited. The aim of this study was to evaluate and to characterize the secretion of OMVs in this bacterium. By transmission electron microscopy, we confirmed the production of OMVs in all the strains assayed. Purified OMVs showed a spherical shape and variable size, although comparable to those of other gram-negative bacteria. We also confirmed the presence of the S-layer on the surface of the OMVs of all the strains assayed with the exception of those derived from the NTCC reference strain. In addition, we demonstrated their immunoreactivity by the dot-blot assay. Hence, C. fetus OMVs could contribute to the modulation of the host response and constitute a candidate to be evaluated as an adjuvant of current vaccines used in the veterinary field. This work represents a platform to drive future studies towards the role of these subcellular structures in C. fetus-host interaction.

Placentitis and abortion caused by a multidrug resistant strain of Campylobacter fetus subspecies fetus in a sheep in Uruguay.

Campylobacter fetusfetus (Cff) is a major infectious cause of abortion in sheep worldwide, and an opportunistic human pathogen. Information on Cff as an ovine abortifacient in South America is limited. We describe a case of abortion caused by a multidrug resistant strain of Cff in a sheep in Uruguay. In August 2017, 3/57 pregnant ewes (5.3%) aborted whithin one week. Histopathologic examination of the placenta of an aborted ewe revealed severe neutrophilic and fibrinonecrotizing placentitis with vasculitis and thrombosis of the chorionic arterioles. Cff was isolated on microaerobic culture in Skirrow agar, and further confirmed by 16S rDNA PCR amplification and sequencing, and endpoint and real time PCR assays. Antimicrobial sensitivity testing revealed resistance to tetracyclines, nalidixic acid, telithromycin and clindamycin. Other abortifacients were not detected. Further studies are necessary to determine the geographic distribution, ecology, epidemiology, economic impact, and antimicrobial resistance of Cff in sheep flocks in Uruguay.

Campylobacter fetus subspecies venerealis meningitis associated with a companion dog in a young adult: a case report.

BACKGROUND: Campylobacter spp., common commensals in the gastrointestinal tract of animals, especially poultry, can cause acute gastrointestinal illness in humans through animal-to-human transmission. Although Campylobacter fetus, especially subspecies fetus, rarely leads to systemic infections such as bacteremia in immunocompromised patients, it is unclear whether Campylobacter fetus subspecies venerealis (Cfv) causes infectious diseases in humans. CASE PRESENTATION: A 28-year-old man with a history of chronic alcoholism visited the emergency department with weakness of the left extremities. The patient was clinically diagnosed with community-acquired bacterial meningitis. The organism from the blood culture was subsequently identified as Campylobacter fetus. On phylogenetic analysis, the 16S rRNA sequence showed 99.93% similarity with other Cfv 16S rRNA sequences. The patient had no exposure to identifiable sources except for close contact with a companion dog, which could have been a possible source of transmission. CONCLUSIONS: This case suggests that Cfv could lead to human systemic infections such as meningitis and that companion animals, in addition to well-known animal hosts, could be sources of transmission.

Campylobacter fetus bacteremia and meningitis in an acute lymphoblastic leukemia patient undergoing maintenance therapy: a case report.

BACKGROUND: Campylobacter fetus is an uncommon Campylobacter species, and its infections mainly cause infective endocarditis, aortic aneurysm, and meningitis rather than enteritis. It is more likely to be detected in blood than Campylobacter jejuni or Campylobacter coli, specifically reported in 53% of patients. In our case, C. fetus was detected in both blood and cerebrospinal fluid (CSF) cultures. CASE PRESENTATION: A 33-year-old woman, who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL), presented to our clinic with chief complaints of severe headache and nausea. Blood and CSF cultures revealed C. fetus. We administrated meropenem 2 g intravenously (IV) every 8 h for 3 weeks, and she was discharged without neurological sequelae. CONCLUSION: We encountered a case of C. fetus meningitis without gastrointestinal symptoms, neck stiffness or jolt accentuation in a patient with ALL. Undercooked beef was considered the source of C. fetus infection in this case, suggesting that the need for a neutropenic diet and safe food handling be considered.

Endovascularly Treated Superficial Femoral Artery Aneurysm Rupture Secondary to Campylobacter fetus Bacteremia: A Case Report.

Degenerative aneurysms of the superficial femoral artery (SFA) are relatively rare and often recognized when they become symptomatic such as rupture. Infected SFA aneurysms are much rarer, especially those caused by Campylobacter fetus bacteremia. We report a case of a 67-year-old woman referred to our hospital owing to the presence of a painful reddish swelling on her left thigh. A huge SFA aneurysm rupture was diagnosed, and endovascular treatment with a covered stent was performed. C. fetus was detected in the blood culture thereafter, and antibacterial therapy was successfully performed without any additional surgical interventions. She remained well without any evidence of indolent infection 19 months after the endovascular treatment. The endovascular approach with appropriate prolonged antibacterial therapy would be a feasible alternative for managing selected infected aneurysm cases.

Sequential breast implant infections due to Campylobacter fetus subsp. fetus.

Campylobacter jejuni and Campylobacter coli are the leading causes of bacterial intestinal infections worldwide, while Campylobacter fetus subsp. fetus (C. fetus) has been reported to cause extraintestinal infections, including medical device implant infections. However, breast implant infections have rarely been reported. We describe the case of a 64-year-old woman with breast implant infection and vertebral osteomyelitis due to C. fetus. The patient recovered by surgical removal of the infected left implant and was treated with antibiotics for 6 weeks. However, two weeks after the completion of antibiotics, she experienced an infection in the right implant due to C. fetus, which had developed quinolone resistance with a G91T mutation during the treatment course. This case showed that C. fetus can cause breast implant infections, and although the infection may appear to be unilateral initially, the possibility of sequential contralateral infection should be considered.

Performance of bovine genital campylobacteriosis diagnostic tests in bulls from Uruguay: a Bayesian latent class model approach.

The sensitivity (Se) and specificity (Sp) of three diagnostic tests for the detection of Campylobacter fetus venerealis (Cfv) using field samples were estimated using a Bayesian latent class model (BLCM), accounting for the absence of a gold standard. The tests included in this study were direct immunofluorescence antibody test (IFAT), polymerase chain reaction (PCR), and real-time PCR (RT-PCR). Twelve farms from two different populations were selected and bull prepuce samples were collected. The IFAT was performed according to the OIE Manual. The conventional PCR was performed as multiplex, targeting the gene nahE for C. fetus species identification and insertion element ISCfe1 for Cfv identification. The RT-PCR was performed as uniplex: one targeting the gene nahE for C. fetus and the other targeting the insertion ISCfe1 (ISC2) for Cfv. Results from the BLCM showed a median Se of 11.7% (Bayesian credibility interval (BCI): 1.93-29.79%), 53.7% (BCI: 23.1-95.0%), and 36.1% (BCI: 14.5-71.7%) for IFAT, PCR, and RT-PCR respectively. The Sp were 94.5% (BCI: 90.1-97.9%), 97.0% (BCI: 92.9-99.3%), and 98.4% (BCI: 95.3-99.7%) for IFAT, PCR, and RT-PCR respectively. The correlation between PCR and RT-PCR was positive and low in samples from both sampled population (0.63% vs 8.47%). These results suggest that diagnostic sensitivity of the studied tests is lower using field samples than using pure Cfv strains.

[Invasive Campylobacter infections]. / Infections invasives à Campylobacter.

Campylobacter genus encompasses many species, among which C. jejuni, C. coli and C. fetus are the main human pathogens. C. jejuni/coli frequently cause self-limited enteritis in immunocompetent hosts and are seldomly associated with bacteriemia. C. fetus is less common as a human pathogen. It is rarely identified in fecal samples but can sometimes be isolated in blood samples from patients with comorbidities or immunosuppression. Campylobacter fetus bacteriemia is remarkable since it is associated with endovascular and deep-seated infections.

Le genre Campylobacter comprend plusieurs espèces pathogènes pour l'homme, en particulier C. jejuni, C. coli et C. fetus. C. jejuni et C. coli sont responsables d'entérites généralement spontanément résolutives chez l'individu sain, et peu fréquemment associées à des bactériémies. C. fetus est un pathogène méconnu, rarement identifié dans les échantillons fécaux mais parfois retrouvé dans des hémocultures, en particulier chez des patients présentant des comorbidités ou immunosupprimés. La bactériémie à C. fetus se distingue par son association avec des infections endovasculaires et des foyers infectieux profonds sans symptomatologie digestive.

Polyclonal Campylobacter fetus Infections Among Unrelated Patients, Montevideo, Uruguay, 2013-2018.

In Montevideo (2013-2018), 8 Campylobacter fetus extraintestinal infections were reported. The polyclonal nature of strains revealed by whole-genome sequencing and the apparent lack of epidemiological links was incompatible with a single contamination source, supporting alternative routes of transmission.

Effects of Campylobacter fetus on bull sperm quality.

Campylobacter fetus is a gram-negative, motile, spiral or S-shaped bacterium, which induces campylobacteriosis. This disease causes decrease productivity of cattle. Although considerable research has been done on the role of C. fetus on female fertility, little is known about the effect on bulls. The aim of this work was to evaluate the effect of C. fetus subsp. fetus (Cff) and C. fetus subsp. venerealis (Cfv) on bull sperm quality. Samples of frozen semen (n = 29 straws) were each distributed into three groups: two of them incubated with the microorganism (Cff, Cfv) and a control group. The proportions of live spermatozoa, with functional membrane and true acrosomal reaction in control group were significantly (P < 0.01) greater than those observed in Cff and Cfv groups. However, no significant differences (P > 0.05) were found in sperm chromatin structure among treatments. In adhesion assay, proportions of spermatozoa with adhered Campylobacter were similar for both subspecies. Results confirm that Cff and Cfv have the same ability to bind in an irreversible way to bull spermatozoa and to affect sperm quality. It is proposed that adherence could be considered as the main cause of sperm alterations, and also an important step of pathogenesis and venereal transmission.

Genotyping and antibiotic resistance patterns of Campylobacter fetus subsp.venerealis from cattle farms in India.

Bovine genital campylobacteriosis caused by Campylobacter fetus subsp. venerealis (Cfv) is of considerable economic importance to the cattle industry worldwide. Cfv causes syndrome of temporary infertility in female cattle, early embryonic mortality, aberrant oestrus cycles, delayed conception, abortions and poor calving rates. In the present study, a total of 200 samples obtained from vaginal swabs, cervicovaginal mucous (CVM), preputial washes and semen straws were investigated that were obtained from organized cattle farm of MLRI, Manasbal and unorganized sectors. Out of a total of 200 samples, 49 (47·57%) vaginal swabs, 1 (3·33%) preputial wash and 8 (25%) carried out CVM samples were positive for Cfv, whereas none of the semen straws were positive for Cfv. A total of eleven isolates of Cfv were recovered. PFGE (Pulse field gel electrophoresis) analysis revealed four different pulsotypes (I-IV) circulating in the screened farms. A common pulsotype circulating among farms could not be established. Insertion element (ISCfe1), a 233 bp amplicon of Cfv, was sequenced and the sequence was deposited in GenBank (accession no: MK475662).

Isolation of Campylobacter fetus subspecies fetus from an abdominal abscess in an adult mare.

A 12-year-old Warmblood mare was referred for evaluation of behavioral changes not explained by general physical examination or lameness evaluation. Transrectal ultrasound examination was performed to determine if the behavioral changes were related to ovarian abnormalities, and a large abscess was found near the base of the cecum. Laparoscopic-guided aspiration and lavage of the abscess cavity followed by injection of benzyl penicillin G was carried out. Culture of the lavage sample yielded Campylobacter fetus subspecies fetus, an organism not previously reported as an etiological agent in abdominal abscesses in horses. The mare was treated after surgery with an extended course of antibiotics (minocycline per os q12h for 10 days followed by enrofloxacin per os q24h for 42 days). The mare resumed work in competitive eventing 10 months after surgery, and the behavioral complaints had resolved according to the owner. Key clinical message: We describe the diagnosis and treatment of a mare with an abdominal abscess from which Campylobacter fetus subspecies fetus was cultured. This organism has not previously been reported as an etiological agent in abdominal abscesses in horses.

Isolement de Campylobacter fetus sous-espèce fetus d'un abcès abdominal chez une jument adulte. Une jument Warmblood âgée de 12 ans fut référée pour évaluation de changements de comportement non-expliqués par un examen physique général ou une évaluation de boiterie. Un examen échographique transrectal fut effectué afin de déterminer si les changements de comportement étaient reliées à des anomales ovariennes et un large abcès fut trouvé près de la base du caecum. Une aspiration guidée par laparoscopie et un lavage de la cavité de l'abcès suivis d'une injection de benzyle pénicilline G furent effectués. Une culture de l'échantillon de lavage permis d'identifier Campylobacter fetus sous-espèce fetus, un organisme n'ayant pas été rapporté antérieurement comme agent étiologique dans les abcès abdominaux chez les chevaux. La jument fut traitée après la chirurgie avec un régime prolongé d'antibiotiques (minocycline per os q12h pour 10 jours suivi d'enrofloxacine per os q24h pour 42 jours). La jument recommença à travailler dans des compétitions 10 mois après la chirurgie et les plaintes concernant le comportement étaient résolues selon le propriétaire.Message clinique clé:Nous décrivons le diagnostic et le traitement d'une jument avec un abcès abdominal à partir duquel on isola C. fetus sous-espèce fetus. Cet organisme n'a pas été rapporté antérieurement comme agent étiologique dans les abcès abdominaux chez les chevaux.(Traduit par Dr Serge Messier).

The Campylobacter fetus S layer provides resistance to photoactivated zinc oxide nanoparticles.

The antimicrobial activity of metal-based compounds, including metal oxides, has resulted in numerous agricultural, industrial, and medical applications. Zinc oxide nanoparticles are toxic to Gram-positive and Gram-negative bacteria as well as to some fungi. In this study we assess the sensitivity of Campylobacter fetus, a Gram-negative bacterial pathogen of humans and animals, to ZnO nanoparticles and determine whether the S layer protects C. fetus from the antibacterial action of these nanoparticles. Broth and agar dilution assays revealed that ZnO nanoparticles at 100 µg/mL were bacteriocidal for C. fetus. Resazurin reduction assays confirmed the absence of metabolic activity, indicating that C. fetus cells had not entered into a viable but nonculturable state. Photoactivation of ZnO nanoparticles greatly enhanced their antibacterial activity, as evidenced by minimum bacteriocidal concentration (MBC) values decreasing to 16-62.5 µg/mL as a function of strain. MBC assays completed in the presence and absence of catalase revealed that H2O2, a product of ZnO nanoparticle photoactivation, contributed to C. fetus but not to C. jejuni cell death. S-layer-expressing C. fetus strains were more resistant to H2O2-mediated cell killing than were isogenic S-layer-deficient strains. These data indicate that C. fetus is sensitive to the antibacterial activity of ZnO nanoparticles and that the C. fetus S layer imparts protection against photoactivated nanoparticles.