Campylobacter occurrence and antimicrobial resistance profile in under five-year-old diarrheal children, backyard farm animals, and companion pets.

Campylobacteriosis disproportionately affects children under five in low-income countries. However, epidemiological and antimicrobial resistance (AMR) information at the children-animal interface is lacking. We hypothesized that Campylobacter is a major cause of enteritis in children in Ethiopia, and contact with animals is a potential source of transmission. The objective of the study was to determine Campylobacter occurrence and its AMR in children under five with diarrhea, backyard farm animals, and companion pets. Stool from 303 children and feces from 711 animals were sampled. Campylobacter was isolated through membrane filtration on modified charcoal cefoperazone deoxycholate agar plates under microaerobic incubation, and the technique showed to be feasible for use in regions lacking organized laboratories. Typical isolates were characterized with MALDI-TOF MS and multiplex PCR. Of 303 children, 20% (n = 59) were infected, with a higher proportion in the 6 to 11-month age group. Campylobacter occurred in 64% (n = 14) of dogs and 44% (n = 112) of poultry. Campylobacter jejuni was present in both a child and animal species in 15% (n = 23) of 149 households positive for Campylobacter. MICs using the gradient strip diffusion test of 128 isolates displayed resistance rates of 20% to ciprofloxacin and 11% to doxycycline. MICs of ciprofloxacin and doxycycline varied between C. coli and C. jejuni, with higher resistance in C. coli and poultry isolates. Campylobacter infection in children and its prevalent excretion from backyard poultry and dogs is a understudied concern. The co-occurrence of C. jejuni in animals and children suggest household-level transmission As resistance to ciprofloxacin and doxycycline was observed, therapy of severe campylobacteriosis should consider susceptibility testing. Findings from this study can support evidence-based diagnosis, antimicrobial treatment, and further investigations on the spread of AMR mechanisms for informed One Health intervention.

Oral curcumin ameliorates acute murine campylobacteriosis.

Introduction: Human infections with the food-borne enteropathogen Campylobacter jejuni are responsible for increasing incidences of acute campylobacteriosis cases worldwide. Since antibiotic treatment is usually not indicated and the severity of the enteritis directly correlates with the risk of developing serious autoimmune disease later-on, novel antibiotics-independent intervention strategies with non-toxic compounds to ameliorate and even prevent campylobacteriosis are utmost wanted. Given its known pleiotropic health-promoting properties, curcumin constitutes such a promising candidate molecule. In our actual preclinical placebo-controlled intervention trial, we tested the anti-microbial and anti-inflammatory effects of oral curcumin pretreatment during acute experimental campylobacteriosis. Methods: Therefore, secondary abiotic IL-10-/- mice were challenged with synthetic curcumin via the drinking water starting a week prior oral C. jejuni infection. To assess anti-pathogenic, clinical, immune-modulatory, and functional effects of curcumin prophylaxis, gastrointestinal C. jejuni bacteria were cultured, clinical signs and colonic histopathological changes quantitated, pro-inflammatory immune cell responses determined by in situ immunohistochemistry and intestinal, extra-intestinal and systemic pro-inflammatory mediator measurements, and finally, intestinal epithelial barrier function tested by electrophysiological resistance analysis of colonic ex vivo biopsies in the Ussing chamber. Results and discussion: Whereas placebo counterparts were suffering from severe enterocolitis characterized by wasting symptoms and bloody diarrhea on day 6 post-infection, curcumin pretreated mice, however, were clinically far less compromised and displayed less severe microscopic inflammatory sequelae such as histopathological changes and epithelial cell apoptosis in the colon. In addition, curcumin pretreatment could mitigate pro-inflammatory innate and adaptive immune responses in the intestinal tract and importantly, rescue colonic epithelial barrier integrity upon C. jejuni infection. Remarkably, the disease-mitigating effects of exogenous curcumin was also observed in organs beyond the infected intestines and strikingly, even systemically given basal hepatic, renal, and serum concentrations of pro-inflammatory mediators measured in curcumin pretreated mice on day 6 post-infection. In conclusion, the anti-Campylobacter and disease-mitigating including anti-inflammatory effects upon oral curcumin application observed here highlight the polyphenolic compound as a promising antibiotics-independent option for the prevention from severe acute campylobacteriosis and its potential post-infectious complications.

Menthol Pretreatment Alleviates Campylobacter jejuni-Induced Enterocolitis in Human Gut Microbiota-Associated IL-10-/- Mice.

Human Campylobacter jejuni infections are of worldwide importance and represent the most commonly reported bacterial enteritis cases in middle- and high-income countries. Since antibiotics are usually not indicated and the severity of campylobacteriosis is directly linked to the risk of developing post-infectious complications, non-toxic antibiotic-independent treatment approaches are highly desirable. Given its health-promoting properties, including anti-microbial and anti-inflammatory activities, we tested the disease-alleviating effects of oral menthol in murine campylobacteriosis. Therefore, human gut microbiota-associated IL-10-/- mice were orally subjected to synthetic menthol starting a week before C. jejuni infection and followed up until day 6 post-infection. Whereas menthol pretreatment did not improve campylobacteriosis symptoms, it resulted in reduced colonic C. jejuni numbers and alleviated both macroscopic and microscopic aspects of C. jejuni infection in pretreated mice vs. controls. Menthol pretreatment dampened the recruitment of macrophages, monocytes, and T lymphocytes to colonic sites of infection, which was accompanied by mitigated intestinal nitric oxide secretion. Furthermore, menthol pretreatment had only marginal effects on the human fecal gut microbiota composition during the C. jejuni infection. In conclusion, the results of this preclinical placebo-controlled intervention study provide evidence that menthol application constitutes a promising way to tackle acute campylobacteriosis, thereby reducing the risk for post-infectious complications.

Positive cases of bovine genital campylobacteriosis and bovine trichomonosis in the eradication program of La Pampa, Argentina: 2008-2021.

Bovine genital campylobacteriosis, caused by the gram-negative bacteria Campylobacter fetus venerealis, and bovine trichomonosis, caused by the parasite protozoan Tritrichomonas foetus, are venereal diseases that occur with long intercalving periods and abortion. The control of both diseases relies on microbiological testing and culling infected bulls. Vaccination and antibiotic treatment may help in controlling campylobacteriosis but are not recommended for trichomonosis control. Several regions of the world have active control programs for trichomonosis, not campylobacteriosis. In Argentina, the state of La Pampa aims to eradicate trichomonosis and campylobacteriosis by imposing annual diagnostic testing of every bull and slaughtering positive animals. Prior studies indicated a declining trend in the prevalence of campylobacteriosis and trichomonosis in La Pampa. It was also proposed that the prevalence of one disease could be estimated from the prevalence of the other. The purpose of this retrospective analysis of data gathered from 2008 to 2021 was to determine the La Pampa program's efficacy. Descriptive statistics were employed to determine the reason behind the correlation between tricomonosis and campylobacteriosis diagnostic results. The outcomes refute the notion that this program of venereal eradication was a success. Furthermore, an excess of false positives in both diagnoses may have contributed to the correlation between the prevalences of campylobactriosis and trichomonosis. The practice of killing animals without verifying positive results hinders the determination of disease prevalence and results in the death of numerous healthy animals.

Acquisition and clearance dynamics of Campylobacter spp. in children in low- and middle-income countries.

The prevalence of Campylobacter infection is generally high among children in low- and middle-income countries (LMIC), but the dynamics of its acquisition and clearance are understudied. We aim to quantify this process among children under two years old in eight LMIC using a statistical modeling approach, leveraging enzyme-immunoassay-based Campylobacter genus data and quantitative-PCR-based Campylobacter jejuni/coli data from the MAL-ED study. We developed a Markov model to compare the dynamics of acquisition and clearance of Campylobacter across countries and to explore the effect of antibiotic usage on Campylobacter clearance. Clearance rates were generally higher than acquisition rates, but their magnitude and temporal pattern varied across countries. For C. jejuni/coli, clearance was faster than acquisition throughout the two years at all sites. For Campylobacter spp., the acquisition rate either exceeded or stayed very close to the clearance rate after the first half year in Bangladesh, Pakistan and Tanzania, leading to high prevalence. Bangladesh had the shortest (28 and 57 days) while Brazil had the longest (328 and 306 days) mean times from last clearance to acquisition for Campylobacter spp. and C. jejuni/coli, respectively. South Africa had the shortest (10 and 8 days) while Tanzania had the longest (53 and 41 days) mean times to clearance for Campylobacter spp. and C. jejuni/col, respectively. The use of Macrolide accelerated clearance of C. jejuni/coli in Bangladesh and Peru and of Campylobacter spp. in Bangladesh and Pakistan. Fluoroquinolone showed statistically meaningful effects only in Bangladesh but for both Campylobacter groups. Higher prevalence of Campylobacter infection was mainly driven by a high acquisition rate that was close to or surpassing the clearance rate. Acquisition rate usually peaked in 11-17 months of age, indicating the importance of targeting the first year of life for effective interventions to reduce exposures.

Prophylactic Oral Application of Activated Charcoal Mitigates Acute Campylobacteriosis in Human Gut Microbiota-Associated IL-10-/- Mice.

The incidence of human Campylobacter jejuni infections is increasing worldwide. It is highly desirable to prevent campylobacteriosis in individuals at risk for severe disease with antibiotics-independent non-toxic compounds. Activated charcoal (AC) has long been used as an anti-diarrheal remedy. Here, we tested the disease-mitigating effects of oral AC versus placebo in human gut microbiota-associated (hma) IL-10-/- mice starting a week prior to C. jejuni infection. On day 6 post-infection, the gastrointestinal C. jejuni loads were comparable in both infected cohorts, whereas campylobacteriosis symptoms such as wasting and bloody diarrhea were mitigated upon AC prophylaxis. Furthermore, AC application resulted in less pronounced C. jejuni-induced colonic epithelial cell apoptosis and in dampened innate and adaptive immune cell responses in the colon that were accompanied by basal concentrations of pro-inflammatory mediators including IL-6, TNF-α, IFN-γ, and nitric oxide measured in colonic explants from AC treated mice on day 6 post-infection. Furthermore, C. jejuni infection resulted in distinct fecal microbiota shift towards higher enterobacterial numbers and lower loads of obligate anaerobic species in hma mice that were AC-independent. In conclusion, our pre-clinical placebo-controlled intervention study provides evidence that prophylactic oral AC application mitigates acute murine campylobacteriosis.

Whole-Genome Sequencing-Based Profiling of Antimicrobial Resistance Genes and Core-Genome Multilocus Sequence Typing of Campylobacter jejuni from Different Sources in Lithuania.

Campylobacter jejuni is known as one of the main causative agents of gastroenteritis in humans worldwide, and the rise of antimicrobial resistance (AMR) in Campylobacter is a growing public health challenge of special concern. Whole-genome sequencing (WGS) was used to characterize genetic determinants of AMR in 53 C. jejuni isolates from dairy cattle, broiler products, wild birds, and humans in Lithuania. The WGS-based study revealed 26 C. jejuni AMR markers that conferred resistance to various antimicrobials. Genetic markers associated with resistance to beta-lactamases, tetracycline, and aminoglycosides were found in 79.3%, 28.3%, and 9.4% of C. jejuni isolates, respectively. Additionally, genetic markers associated with multidrug resistance (MDR) were found in 90.6% of C. jejuni isolates. The WGS data analysis revealed that a common mutation in the quinolone resistance-determining region (QRDR) was R285K (854G > A) at 86.8%, followed by A312T (934G > A) at 83% and T86I (257C > T) at 71.7%. The phenotypic resistance analysis performed with the agar dilution method revealed that ciprofloxacin (CIP) (90.6%), ceftriaxone (CRO) (67.9%), and tetracycline (TET) (45.3%) were the predominant AMR patterns. MDR was detected in 41.5% (22/53) of the isolates tested. Fifty-seven virulence genes were identified in all C. jejuni isolates; most of these genes were associated with motility (n = 28) and chemotaxis (n = 10). Additionally, all C. jejuni isolates harbored virulence genes related to adhesion, invasion, LOS, LPS, CPS, transportation, and CDT. In total, 16 sequence types (STs) and 11 clonal complexes (CC) were identified based on core-genome MLST (cgMLST) analysis. The data analysis revealed distinct diversity depending on phenotypic and genotypic antimicrobial resistance of C. jejuni.

Case Commentary: An espresso, a free puppy, and multidrug-resistant Campylobacter.

Campylobacter species infections in immunocompromised patients have the potential to progress to bacteremia and other extra-intestinal diseases. There is a sparsity of robust data, including antibiotic susceptibility data for contemporary agents, upon which to base treatment decisions. Moreover, intrinsic antimicrobial resistance in Campylobacter spp. further limits treatment options. The current publication by Bonilla-Moreno et al. elaborates on this clinical dilemma through the development, treatment, and molecular investigation of the putative mechanisms of carbapenem resistance in an immunocompromised patient with Campylobacter coli bacteremia.

Anti-infective treatment of gastro-intestinal tract infections in children.

Gastroenteritis is most often viral in origin and Rotavirus and Norovirus most frequently implicated in young children. Stool-based multiplex Polymerase Chain Reaction (PCR) can detect bacteria, viruses or parasites that may or may not be responsible for gastroenteritis (colonization). While the etiological profile of these digestive infections has greatly benefited from PCR, in the absence of underlying pathologies the presence of potential pathogens does not justify anti-infectious treatment. Indeed, very few bacterial causes require antibiotic treatment, apart from shigellosis, severe forms of salmonellosis and a few Campylobacter sp. infections. The development of antibiotic resistance in Salmonella sp., Shigella sp. and Campylobacter sp. is a cause for concern worldwide, limiting therapeutic options. The antibiotics proposed in this guide are in line with the joint recommendations of the European Society of Pediatric Infectious Diseases and the European Society of Pediatric Gastroenterology and Nutrition. Azithromycin is preferentially used to treat infections with Shigella sp. or Campylobacter sp. Ceftriaxone and ciprofloxacin are recommended for salmonellosis requiring antibiotic therapy. Empirical treatments without bacterial identification are not indicated except in cases of severe sepsis or in subjects at risk (e.g., sickle-cell disease). Metronidazole should be prescribed only for acute intestinal amebiasis after microbiological confirmation.

Clinical Features, Immunological Characteristics, and Treatment Outcomes of Campylobacter spp. Infections in Patients With Common Variable Immunodeficiency.

BACKGROUND: Campylobacter infection usually causes a self-limited clinical illness lasting 5 to 7 days, resolving without antimicrobial treatment in immunocompetent subjects. However, an inadequate immune response can lead to a prolonged and severe disease requiring antibiotics and more aggressive therapeutic approaches. OBJECTIVE: To comprehensively describe Campylobacter spp. infections in patients with common variable immunodeficiency (CVID). METHODS: A retrospective cohort of 14 CVID patients with Campylobacter infection and 95 CVID controls attending the immunology clinic at a large tertiary hospital was assessed. Immunological, clinical, and microbiological parameters were measured with median follow-up over 20 years in both cohorts. Patients were treated according to a novel algorithm for Campylobacter in antibody-deficient patients. RESULTS: Campylobacter patients had a higher proportion of CD21lowCD38low and transitional B cells (median 38.0% vs 14.2% and 5.4% vs 3.2%) and lower long-term average CD19+ B cells (median 0.06 vs 0.18 × 109/L) and CD4+ T cells (0.41 vs 0.62 × 109/L) in comparison with the controls. Similarly, Campylobacter patients showed a decline in B cells (median 0.02 vs 0.14 × 109/L), CD4+ T cells (0.33 vs 0.59 × 109/L), CD8+ T cells (0.26 vs 0.62 × 109/L), and natural killer cells (0.08 vs 0.18 × 109/L) over time. Antimicrobial resistance, especially to macrolides and fluoroquinolones, was common. Bacterial clearance with associated clinical improvement was obtained after a median of 20 and 113 days for acute Campylobacter (resolution within 3 mo of onset) and chronic Campylobacter (>3 mo) infections, respectively. Seven received first-line treatment (azithromycin or chloramphenicol), 4 second-line (neomycin), and 3 third-line (combination of tigecycline, chloramphenicol, and ertapenem; 1 received gentamicin owing to resistance to carbapenems). CONCLUSIONS: Our study highlights immunological and clinical characteristics of recurrent Campylobacter infections in patients with CVID. Our treatment algorithm was successful and should be evaluated in a larger cohort.

A scoping review of factors associated with antimicrobial-resistant Campylobacter species infections in humans.

Human infection with antimicrobial-resistant Campylobacter species is an important public health concern due to the potentially increased severity of illness and risk of death. Our objective was to synthesise the knowledge of factors associated with human infections with antimicrobial-resistant strains of Campylobacter. This scoping review followed systematic methods, including a protocol developed a priori. Comprehensive literature searches were developed in consultation with a research librarian and performed in five primary and three grey literature databases. Criteria for inclusion were analytical and English-language publications investigating human infections with an antimicrobial-resistant (macrolides, tetracyclines, fluoroquinolones, and/or quinolones) Campylobacter that reported factors potentially linked with the infection. The primary and secondary screening were completed by two independent reviewers using Distiller SR®. The search identified 8,527 unique articles and included 27 articles in the review. Factors were broadly categorised into animal contact, prior antimicrobial use, participant characteristics, food consumption and handling, travel, underlying health conditions, and water consumption/exposure. Important factors linked to an increased risk of infection with a fluoroquinolone-resistant strain included foreign travel and prior antimicrobial use. Identifying consistent risk factors was challenging due to the heterogeneity of results, inconsistent analysis, and the lack of data in low- and middle-income countries, highlighting the need for future research.

Development of Meropenem Resistance in a Multidrug-Resistant Campylobacter coli Strain Causing Recurrent Bacteremia in a Hematological Malignancy Patient.

Campylobacter bacteremia is an uncommon disease that mainly occurs in immunocompromised patients and is associated with antibiotic resistance, particularly in Campylobacter coli. We report a patient with persistent blood infection because of a multidrug-resistant (MDR) C. coli strain over a 3-month period. Through this period monotherapy with meropenem was associated with the development of resistance to it. Improving immunity status and a combined therapy for intestinal decolonization were useful to control persistent C. coli infection in this patient.

Recurrent Campylobacter jejuni Infections with In Vivo Selection of Resistance to Macrolides and Carbapenems: Molecular Characterization of Resistance Determinants.

We present two independent cases of recurrent multidrug-resistant Campylobacter jejuni infection in immunocompromised hosts and the clinical challenges encountered due to the development of high-level carbapenem resistance. The mechanisms associated with this unusual resistance for Campylobacters were characterized. Initial macrolide and carbapenem-susceptible strains acquired resistance to erythromycin (MIC > 256mg/L), ertapenem (MIC > 32mg/L), and meropenem (MIC > 32mg/L) during treatment. Carbapenem-resistant isolates developed an in-frame insertion resulting in an extra Asp residue in the major outer membrane protein PorA, within the extracellular loop L3 that connects ß-strands 5 and 6 and forms a constriction zone involved in Ca2+ binding. The isolates presenting the highest MIC to ertapenem exhibited an extra nonsynonymous mutation (G167A|Gly56Asp) at PorA's extracellular loop L1. IMPORTANCE Carbapenem susceptibility patterns suggest drug impermeability, related to either insertion and/or single nucleotide polymorphism (SNP) within porA. Similar molecular events occurring in two independent cases support the association of these mechanisms with carbapenem resistance in Campylobacter spp.

Pericarditis due to Campylobacter coli infection: a case report.

Campylobacter spp. is a gram-negative bacillus that causes infectious enteritis and consists of several species, including Campylobacter jejuni, Campylobacter coli, and Campylobacter fetus. Although C. jejuni and C. coli cause infectious enteritis primarily in immunocompetent hosts, C. fetus causes extraintestinal infections such as septicemia, meningitis, and perinatal infections in immunocompromised hosts, as well as myopericarditis in rare cases. Only a few cases of infectious myo(peri)carditis associated with C. coli in immunocompetent hosts have been reported. These studies concentrated on antecedent C. coli enterocolitis and never demonstrated a positive culture in the pericardial fluid.A 72-year-old Japanese man presented with a 2-week fever, cough, and vomiting lasting. He was on hemodialysis for polycystic kidney disease, as well as medication for diabetes and hypertension. A chest computed tomography (CT) scan and a transthoracic echocardiogram revealed bilateral pleural fluid and large pericardial fluid at the time of admission. C. coli was identified from blood culture samples and blood-tinged pericardial fluid. He was successfully treated with antibacterial chemotherapy as well as pericardial fluid drainage and was discharged from the hospital with no complications.In this case, the presence of C. coli in the pericardial fluid confirmed the diagnosis of C. coli pericarditis. C. coli may cause septic pericarditis in immunocompromised hosts, despite typically causing only enteritis.

Antimicrobial use and its association with the isolation of and antimicrobial resistance in Campylobacter spp. recovered from fecal samples from Canadian dairy herds: A cross-sectional study.

Campylobacteriosis is one of the most common zoonotic diseases in North America. As opposed to humans, animal infections caused by Campylobacter spp. are often asymptomatic. In this study, data collected through the Canadian Dairy Network for Antimicrobial Stewardship surveillance system were used to determine the proportion of Campylobacter spp. and antimicrobial resistant isolates recovered from dairy cattle herds. Additionally, the association of antimicrobial use (AMU) with fecal carriage and antimicrobial resistance (AMR) of Campylobacter spp. were investigated. Pooled fecal samples from 5 animals from each production phase (pre-weaned calves, post-weaned heifers, lactating cows), and a manure storage sample were collected from 140 dairy herds across Canada. Samples were cultured using selective media, and Campylobacter isolates were speciated using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined using the minimum inhibitory concentration test, and interpretation was made according to the Clinical and Laboratory Standards Institute. Two multilevel logistic regression models were used to investigate the association between the AMU with the isolation and antimicrobial resistance in Campylobacter spp. Of 560 samples, 63.8% were positive for Campylobacter spp., and 96% of the participating farms had at least one sample source (i.e., calves, heifers, lactating cows, or manure storage) positive for Campylobacter spp. Overall, 54.3% of the Campylobacter spp. isolates were resistant to at least one antimicrobial. Resistance to tetracycline was observed in 49.7% of the Campylobacter spp. isolates, followed by ciprofloxacin (19.9%) and nalidixic acid (19.3%). The proportion of multi-drug resistant (≥3 antimicrobial classes) Campylobacter spp. isolates was low (0.3%); however, 15.6% were resistant to two different classes of antimicrobials. Samples collected from lactating cows, heifers, and manure storage were more likely to be positive for Campylobacter spp. compared to calves. Total AMU was associated with a decreased probability of recovering Campylobacter spp. In addition, AMR to either tetracycline or ciprofloxacin had an interaction with antimicrobial use. The probability of resistance to tetracycline increased for each unit increase in the total AMU (Defined Course Dose/100 animal-years), while the probability of resistance to ciprofloxacin decreased. Campylobacter coli isolates were more likely to be resistant to ciprofloxacin and tetracycline when compared to C. jejuni. Our study demonstrated that Campylobacter spp. is widespread among Canadian dairy farms, and a higher proportion of resistance to tetracycline was identified. The total AMU was associated with increased resistance to tetracycline in Campylobacter spp. isolates; however, for ciprofloxacin the AMU was associated with decreased resistance.

Antimicrobial resistance profiles of Campylobacter jejuni and Salmonella spp. isolated from enteritis patients in Japan.

Understanding the antimicrobial resistance of Campylobacter jejuni and Salmonella spp. isolated from patients with enteritis will aid in therapeutic decision-making. This study aimed to characterize C. jejuni and Salmonella spp. isolates from patients with enteritis. For C. jejuni, the resistance rates against ampicillin, tetracycline, and ciprofloxacin were 17.2%, 23.8%, and 46.4%, respectively. All the C. jejuni isolates were susceptible to erythromycin, which is recommended as a first-choice antimicrobial if Campylobacter enteritis is strongly suspected. C. jejuni was classified into 64 sequence types (STs), and the five major STs were ST22, ST354, ST21, ST918, and ST50. The ciprofloxacin-resistance rate of ST22 was 85.7%. For Salmonella, the resistance rates against ampicillin, cefotaxime, streptomycin, kanamycin, tetracycline, and nalidixic acid were 14.7%, 2.0%, 57.8%, 10.8%, 16.7%, and 11.8%, respectively. All the Salmonella spp. isolates were susceptible to ciprofloxacin. Therefore, fluoroquinolones are the recommended antimicrobials against Salmonella enteritis. S. Thompson, S. Enteritidis, and S. Schwarzengrund were the three most prevalent serotypes. The two cefotaxime-resistant isolates were serotyped as S. Typhimurium and were found to harbor blaCMY-2. The results of this study would help select antimicrobials for treating patients with Campylobacter and Salmonella enteritis.

Molecular Targets in Campylobacter Infections.

Human campylobacteriosis results from foodborne infections with Campylobacter bacteria such as Campylobacter jejuni and Campylobacter coli, and represents a leading cause of bacterial gastroenteritis worldwide. After consumption of contaminated poultry meat, constituting the major source of pathogenic transfer to humans, infected patients develop abdominal pain and diarrhea. Post-infectious disorders following acute enteritis may occur and affect the nervous system, the joints or the intestines. Immunocompromising comorbidities in infected patients favor bacteremia, leading to vascular inflammation and septicemia. Prevention of human infection is achieved by hygiene measures focusing on the reduction of pathogenic food contamination. Molecular targets for the treatment and prevention of campylobacteriosis include bacterial pathogenicity and virulence factors involved in motility, adhesion, invasion, oxygen detoxification, acid resistance and biofilm formation. This repertoire of intervention measures has recently been completed by drugs dampening the pro-inflammatory immune responses induced by the Campylobacter endotoxin lipo-oligosaccharide. Novel pharmaceutical strategies will combine anti-pathogenic and anti-inflammatory effects to reduce the risk of both anti-microbial resistance and post-infectious sequelae of acute enteritis. Novel strategies and actual trends in the combat of Campylobacter infections are presented in this review, alongside molecular targets applied for prevention and treatment strategies.

Therapeutic Oral Application of Carvacrol Alleviates Acute Campylobacteriosis in Mice Harboring a Human Gut Microbiota.

Human Campylobacter jejuni infections are rising globally. Since antibiotics are usually not indicated in acute campylobacteriosis, antibiotic-independent intervention measures are desirable. The phenolic compound carvacrol constitutes a promising candidate molecule given its antimicrobial and immune-modulatory features. To test the disease-alleviating effects of oral carvacrol treatment in acute murine campylobacteriosis, IL-10-/- mice harboring a human gut microbiota were perorally infected with C. jejuni and treated with carvacrol via the drinking water. Whereas C. jejuni stably established in the gastrointestinal tract of mice from the placebo cohort, carvacrol treatment resulted in lower pathogen loads in the small intestines on day 6 post infection. When compared to placebo, carvacrol ameliorated pathogen-induced symptoms including bloody diarrhea that was accompanied by less distinct histopathological and apoptotic cell responses in the colon. Furthermore, innate and adaptive immune cell numbers were lower in the colon of carvacrol- versus placebo-treated mice. Notably, carvacrol application dampened C. jejuni-induced secretion of pro-inflammatory mediators in intestinal, extra-intestinal and systemic organs to naive levels and furthermore, resulted in distinct shifts in the fecal microbiota composition. In conclusion, our preclinical placebo-controlled intervention study provides evidence that therapeutic carvacrol application constitutes a promising option to alleviate campylobacteriosis in the infected vertebrate host.