In vitro efficacy of combinations of antibiotics used in clinical practice on clinical isolates of Helicobacter pylori.

BACKGROUND: The main antibiotics used against Helicobacter pylori have been chosen empirically over time, with few preclinical studies to provide support. The rise in resistance to some of these antibiotics is prompting a reassessment of their use. This work aimed to evaluate the in vitro efficacy of 2 × 2 combinations of the most widely used antibiotics against H. pylori. MATERIALS AND METHODS: J99 reference strains and 19 clinical isolates of H. pylori with various antibiotic resistance phenotypes were used. Minimum inhibitory concentrations were carried out using the microdilution method in 96-well plates. The activity of 15 possible combinations of two antibiotics including amoxicillin, clarithromycin (CLA), levofloxacin, rifampicin, tetracycline, and metronidazole was determined for all strains by the checkerboard method. A mean fractional inhibitory concentration index (FICmean) was calculated for each combination and strain and the type of pharmacodynamic interaction was considered as synergic if FICmean ≤ 0.5, additive if 0.5 < FICmean ≤ 1, indifferent if 1 < FICmean < 4 or antagonistic if FICmean ≥ 4. RESULTS: Most of the 285 pharmacodynamic interactions tested with clinical strains were close to additivity (average FICmean = 0.89 [0.38-1.28]). No interaction was found to be antagonistic. When two antibiotics to which a strain was resistant were combined, the concentrations required to inhibit bacterial growth were higher than their respective breakpoints. CONCLUSION: The present results have shown that in vitro, the different antibiotics used in therapeutics have additive effects. The addition of the effects of two antibiotics to which a strain was resistant was not sufficient to inhibit bacterial growth. In probabilistic treatment, the choice of antibiotics to combine should therefore be based on the local epidemiology of resistance, and on susceptibility testing in the case of CLA therapy, so that at least one antibiotic to which the strain is susceptible is used.

Bacteremia due to Lachnoanaerobaculum umeaense in a patient with acute myeloid leukemia during chemotherapy: A case report, and a review of the literature.

The present case reports a bacteremia due to Lachnoanaerobaculum umeaense (a Gram-positive, filamentous, rod-shaped, anaerobic, spore-forming bacillus present in the human oral microbiota) in a patient treated for acute myeloid leukemia. After failed identification by MALDI-TOF, identification was done by sequencing of 16s rRNA. The patient was successfully treated with Amoxicillin-clavulanic acid and ciprofloxacin for seven days. Comparison of V1-V3 regions of the bacterial 16S rRNA gene gene with published sequences failed to classify the strain as pathogenic or non-pathogenic based on this phylogenetic classification alone. Although Lachnoanaerobaculum gingivalis are known to be associated with bacteremia in patients with acute myeloid leukemia, this clinical case of infection by L. umeaense argues for further studies that will lead to more efficient classification of the infection by these microorganisms.

The First Lethal Infection by Oligella ureolytica: A Case Report and Review of the Literature.

Oligella ureolytica is a Gram-negative bacillus, a member of the Alcaligenaceae family, that had never previously been reported as lethal. Herein, a case of fatal infection caused by Oligella ureolytica in an elderly woman with suspected bladder cancer is reported. The species identification was confirmed through Sanger sequencing of the bacterial 16S rRNA sequence and compared to published sequences for phylogenetic analysis. Initial antibiotic therapy with ceftriaxone and oxacillin was initiated but had to be switched due to resistance. Cefepime in combination with metronidazole was administered, unfortunately failing to prevent the patient's death. Further studies are needed to explore additional factors influencing clinical outcomes in Oligella ureolytica infections.

Mice prenatally exposed to valproic acid do not show autism-related disorders when fed with polyunsaturated fatty acid-enriched diets.

Dietary supplementations with n-3 polyunsaturated fatty acid (PUFA) have been explored in autism spectrum disorder (ASD) but their efficiency and potential in ameliorating cardinal symptoms of the disease remain elusive. Here, we compared a n-3 long-chain (LC) PUFA dietary supplementation (n-3 supp) obtained from fatty fish with a n-3 PUFA precursor diet (n-3 bal) obtained from plant oils in the valproic acid (VPA, 450 mg/kg at E12.5) ASD mouse model starting from embryonic life, throughout lactation and until adulthood. Maternal and offspring behaviors were investigated as well as several VPA-induced ASD biological features: cerebellar Purkinje cell (PC) number, inflammatory markers, gut microbiota, and peripheral and brain PUFA composition. Developmental milestones were delayed in the n-3 supp group compared to the n-3 bal group in both sexes. Whatever the diet, VPA-exposed offspring did not show ASD characteristic alterations in social behavior, stereotypies, PC number, or gut microbiota dysbiosis while global activity, gait, peripheral and brain PUFA levels as well as cerebellar TNF-alpha levels were differentially altered by diet and treatment according to sex. The current study provides evidence of beneficial effects of n-3 PUFA based diets, including one without LCPUFAs, on preventing several behavioral and cellular symptoms related to ASD.

French national epidemiology of bacterial superinfections in ventilator-associated pneumonia in patients infected with COVID-19: the COVAP study.

BACKGROUND: Description and comparison of bacterial characteristics of ventilator-associated pneumonia (VAP) between critically ill intensive care unit (ICU) patients with COVID-19-positive, COVID + ; and non-COVID-19, COVID-. METHODS: Retrospective, observational, multicenter study that focused on French patients during the first wave of the pandemic (March-April 2020). RESULTS: 935 patients with identification of at least one bacteriologically proven VAP were included (including 802 COVID +). Among Gram-positive bacteria, S. aureus accounted for more than two-thirds of the bacteria involved, followed by Streptococcaceae and enterococci without difference between clinical groups regarding antibiotic resistance. Among Gram-negative bacteria, Klebsiella spp. was the most frequently observed bacterial genus in both groups, with K. oxytoca overrepresented in the COVID- group (14.3% vs. 5.3%; p < 0.05). Cotrimoxazole-resistant bacteria were over-observed in the COVID + group (18.5% vs. 6.1%; p <0.05), and after stratification for K. pneumoniae (39.6% vs. 0%; p <0.05). In contrast, overrepresentation of aminoglycoside-resistant strains was observed in the COVID- group (20% vs. 13.9%; p < 0.01). Pseudomonas sp. was more frequently isolated from COVID + VAPs (23.9% vs. 16.7%; p <0.01) but in COVID- showed more carbapenem resistance (11.1% vs. 0.8%; p <0.05) and greater resistance to at least two aminoglycosides (11.8% vs. 1.4%; p < 0.05) and to quinolones (53.6% vs. 7.0%; p <0.05). These patients were more frequently infected with multidrug-resistant bacteria than COVID + (40.1% vs. 13.8%; p < 0.01). CONCLUSIONS: The present study demonstrated that the bacterial epidemiology and antibiotic resistance of VAP in COVID + is different from that of COVID- patients. These features call for further study to tailor antibiotic therapies in VAP patients.

First Bacteremia Due to Corynebacterium gottingense in an Immunocompromised Child: A Case Report, 16S rDNA-Based Phylogenetic Analyses and Review of the Literature.

Corynebacterium gottingense is a Gram-positive bacillus that has not been reported as pathogenic in pediatric patients. Herein, a case of catheter-associated bloodstream infection by C. gottingense in a 13-year-old immunocompromised child with febrile neutropenia induced for osteosarcoma is reported. The species was identified by Sanger sequencing of the 16s rRNA sequence of the bacterial strain and was compared phylogenetically with published sequences. As suggested in the literature, the presented strain was multi-susceptible, particularly to amoxicillin. The patient was treated with piperacillin/tazobactam for seven days in the context of a urinary co-infection, resulting in resolution of fever within 48 h and then relaunched with oral amoxicillin for 3 days (for a total of 10 days of antibiotic therapy). Phylogenetic analyses based on 16S rDNA demonstrated the complexity of the genus Corynebacterium spp. but failed to demonstrate a direct benefit in predicting clinical outcome based on this single information.

Diagnostic and Therapeutic Management of Helicobacter pylori Infection in Primary Care: Perspective of Application in France and Narrative Review of the Literature.

BACKGROUND: Helicobacter pylori (Hp) infection affects 30% to 40% of people in industrialized countries. AIM: This study aimed to synthesize knowledge on the diagnostic and therapeutic management of Hp infection in general practice in people under 40 years of age. METHOD: A narrative review of the literature with an inductive content analysis of the articles was performed. RESULTS: The extracted data (22 articles out of 106 included after screening of 965 articles) determined three areas of analysis: indications for screening, methods of screening and diagnosis by non-invasive tests, and treatment modalities. DISCUSSION: Targeted, easily performed screening with noninvasive tests is recommended for patients younger than 45 years of age with no family history of gastric cancer and symptoms of dyspepsia without warning signs. Given their proximity to the general population and their coverage of the territory, general practitioners are ideally positioned. Treatment modalities are well-codified and feasible in primary care. Simplifying the recommendations available to them would optimize the identification of patients at risk and the management of Hp infection. Informing, educating, involving, supporting, and promoting the control of Hp infection in primary care will be future goals. Further research is needed in primary care to evaluate the impact of new procedures on Hp control.

IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin.

Introduction: Although the presence of pathogens in skin wounds is known to delay the wound healing process, the mechanisms underlying this delay remain poorly understood. In the present study, we have investigated the regulatory role of proinflammatory cytokines on the healing kinetics of infected wounds. Methods: We have developed a mouse model of cutaneous wound healing, with or without wound inoculation with Staphylococcus aureus and Pseudomonas aeruginosa, two major pathogens involved in cutaneous wound bacterial infections. Results: Aseptic excision in C57BL/6 mouse skin induced early expression of IL-1ß, TNFα and Oncostatin M (OSM), without detectable expression of IL-22 and IL-17A/F. S. aureus and P. aeruginosa wound inoculation not only increased the expression of IL-1ß and OSM, but also induced a strong cutaneous expression of IL-22, IL-17A and IL-17F, along with an increased number of infiltrating IL-17A and/or IL-22-producing γδ T cells. The same cytokine expression pattern was observed in infected human skin wounds. When compared to uninfected wounds, mouse skin infection delayed the wound healing process. Injection of IL-1α, TNFα, OSM, IL-22 and IL-17 together in the wound edges induced delayed wound healing similar to that induced by the bacterial infection. Wound healing experiments in infected Rag2KO mice (deficient in lymphocytes) showed a wound healing kinetic similar to uninfected Rag2KO mice or WT mice. Rag2KO infected-skin lesions expressed lower levels of IL-17 and IL-22 than WT, suggesting that the expression of these cytokines is mainly dependent on γδ T cells in this model. Wound healing was not delayed in infected IL-17R/IL-22KO, comparable to uninfected control mice. Injection of recombinant IL-22 and IL-17 in infected wound edges of Rag2KO mice re-establish the delayed kinetic of wound healing, as in infected WT mice. Conclusion: These results demonstrate the synergistic and specific effects of IL-22 and IL-17 induced by bacterial infection delay the wound healing process, regardless of the presence of bacteria per se. Therefore, these cytokines play an unexpected role in delayed skin wound healing.

How Did We End Up Using a Quadruple Guided Therapy Combining At Least Two Antibiotics with a PPI to Eradicate Helicobacter pylori?

Since the discovery of Helicobacter pylori, and even if the species is frequently susceptible to many antibiotics in vitro, only six of them (amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin) and bismuth salts could be considered as effective in vivo to eliminate H pylori and have been used in recommended eradication treatments [...].

Impact of Skin Disinfection on Cutaneous Microbiota, before and after Peripheral Venous Catheter Insertion.

Introduction. Patients with invasive medical devices are at high risk for infection. Skin colonization is the initial stage of these infections, leading to the recommendation of practices requiring disinfection using antiseptics. Microbial communities playing a major role in skin health could be impacted by antiseptic procedures. Aim. To characterize and compare the bacterial communities of skin samples from patients before an antisepsis procedure, and after removal of the medical device itself, according to the nature of the antiseptic molecule (povidone iodine or chlorhexidine). Methods. The study focused on alterations in bacterial communities depending on the nature of the antiseptic procedure and type of intravascular device. After amplification of 16S rDNA, libraries (n = 498 samples) were sequenced using MiSeq platform. Results. Using an in-house pipeline (QIIME2 modules), while no alteration in skin microbiota diversity was associated with antiseptic procedure or PVC type, according to culture results (p < 0.05), alterations were at times associated with restricted diversity and higher dissimilarity (p < 0.05). Antiseptic procedures and PVC types were associated with the modification of specific bacterial representations with modulation of the Bacillota/Bacteroidota (Firmicutes/Bacteroidetes) ratio (modulation of C. acnes, Prevotella, Lagierella, and Actinomyces spp.) (p < 0.05). At baseline, the microbiota shows certain bacteria that are significantly associated with future PVC colonization and/or bacteremia (p < 0.05). All of these modulations were associated with altered expression of metabolic pathways (p < 0.05). Discussion. Finally, this work highlights the need to optimize the management of patients requiring intravascular devices, possibly by modulating the skin microbiota.

Mutations Associated to Antibiotic-Resistant Helicobacter pylori: It Is Time to Validate Sequencing Observations.

H. pylori, a Gram-negative microaerophilic microorganism, is the only bacterial pathogen classified as a Class I carcinogen [...].

Guided Treatment of Helicobacter pylori Infections with Non-Invasive PCR Tests-The Glory Days of Primary Care?

In the original article [...].

Efficacy of Three Povidone Iodine Formulations against Cutibacterium acnes Assessed through In Vitro Studies: A Preliminary Study.

Cutibacterium acnes (C. acnes, formerly known as Propionibacterium acnes) is the major causative agent of prosthetic joint infections (PJI). Treatment of PJI with antibiotics is difficult due to antibiotic resistance and adverse side effects on patients' health. Proper disinfection of the surgical site using a variety of povidone iodine formulations could prevent C. acnes infection. In the current study, the efficacy of the three povidone iodine (PVP-I) formulations, viz: PVP-I 10% dermic solution, PVP-I 5% alcoholic solution and PVP-I 4% scrub, was tested against C. acnes, in vitro, in the presence of interfering substances mimicking soiling conditions. C. acnes strain ATCC 6919 was used to test the bactericidal activity of the povidone iodine formulations according to the modified dilution-neutralization method described in French Norm EN standard 13727. A 3-log reduction in the bacterial cell count in 60 s was considered to be significant. The results showed that under experimental conditions, the three PVP-I formulations displayed bactericidal activity against the micro-organism, Cutibacterium acnes, and that the lowest concentration of povidone-iodine active against C. acnes was 0.4%. These results are encouraging as PVP-I offers a low-cost and efficient method of disinfection.

New Strategy for the Detection and Treatment of Helicobacter pylori Infections in Primary Care Guided by a Non-Invasive PCR in Stool: Protocol of the French HepyPrim Study.

Helicobacter pylori (Hp) infects half of the world population and is responsible for gastric, duodenal ulcers and gastric cancer. The eradication of Hp cures ulcers and prevents ulcer recurrences and gastric cancer. Antibiotic resistance of Hp, and particularly clarithromycin resistance, is the primary cause of treatment failure and is a major concern identified by the WHO as a high priority requiring research into new strategies. Treatments guided by the detection of antibiotic resistance have proven their medical and economical superiority. However, this strategy is severely hampered by the invasive nature of the fibroscopy, since antibiotic resistance detection requires gastric biopsies. The eradication of Hp involves primary care physicians. The objective of this study will be to evaluate the feasibility of a strategy for the management of Hp infection in primary care by a recently developed non-invasive procedure and its non-inferiority in eradication rates compared with the strategy recommended by the French National Authority of Health. The non-invasive procedure is a PCR on stool to detect Hp infection and mutations conferring resistance to clarithromycin allowing a treatment guided by the results of the PCR. We present the protocol of a prospective, multicenter, randomized, controlled interventional study in two arms.

Spermatic Microbiome Characteristics in Infertile Patients: Impact on Sperm Count, Mobility, and Morphology.

Through sperm alteration, semen microbiota tend to be recognized as a cause of infertility, but due to the limited number of studies focusing on this ecological niche, this hypothesis remains controversial. This study aimed to characterize and compare the bacterial communities of sperm samples from patients undergoing couple infertility treatment at the time of diagnosis. The study was prospective (September 2019 to March 2020), monocentric, and focused on alterations of spermatic parameters: count, motility, and morphology. After the amplification of the 16S rDNA (V1 to V3), libraries (n = 91, including 53 patients with abnormalities) were sequenced using the MiSeq platform (Illumina). After quality control processing using a homemade pipeline (QIIME2 modules), the main genera were: Prevotella, Finegoldia, Pseudomonas, Peptinophilus, Streptococcus, Anaerococcus and Corynebacterium. Restricted diversity was observed in samples from patients with abnormal sperm morphology (α-diversity, p < 0.05), whereas diversity increased in patients with an abnormal sperm count (ß-diversity, p < 0.05). The enrichment of the genus Prevotella and Haemophilus was observed in negative sperm culture samples and samples with abnormal counts, respectively (p < 0.05). Microbiota differed in their composition according to sperm parameters. Finally, this work highlights the need for the optimization of the management of couples undergoing infertility treatment, possibly by modulating the genital microbiome.

Ulceroglandular Infection and Bacteremia Caused by Francisella salimarina in Immunocompromised Patient, France.

Although Francisella tularensis is a well-known, highly virulent bacterium that causes tularemia in humans, other Francisella species have been associated with sporadic human infections. We describe a human cutaneous infection with bacteremia caused by F. salimarina, a Francisella species recently identified from seawater and fishes, in an immunocompromised patient in France.

Listeria monocytogenes faecal carriage is common and depends on the gut microbiota.

Listeria genus comprises two pathogenic species, L. monocytogenes (Lm) and L. ivanovii, and non-pathogenic species. All can thrive as saprophytes, whereas only pathogenic species cause systemic infections. Identifying Listeria species' respective biotopes is critical to understand the ecological contribution of Listeria virulence. In order to investigate the prevalence and abundance of Listeria species in various sources, we retrieved and analyzed 16S rRNA datasets from MG-RAST metagenomic database. 26% of datasets contain Listeria sensu stricto sequences, and Lm is the most prevalent species, most abundant in soil and host-associated environments, including 5% of human stools. Lm is also detected in 10% of human stool samples from an independent cohort of 900 healthy asymptomatic donors. A specific microbiota signature is associated with Lm faecal carriage, both in humans and experimentally inoculated mice, in which it precedes Lm faecal carriage. These results indicate that Lm faecal carriage is common and depends on the gut microbiota, and suggest that Lm faecal carriage is a crucial yet overlooked consequence of its virulence.

K1 Antigen Is Associated with Different AST Profile in Escherichia coli: A One-Month-Long Pilot Study.

Escherichia coli is responsible for diseases of varying severity. The "K" antigen designates the capsular polysaccharides on the bacterial surface, which are mostly similar to those of highly pathogenic bacteria. The K1 antigen is often found in pathogenic E. coli. Aim: While the published studies on the AST profile of K1-positive E. coli have focused on pregnant women or newborns, this study aimed to characterize the AST profile of K1-positive E. coli independently of the clinical sample of isolation. Over a 4-week-long period, all patients hospitalized/consulting at the Poitiers University Hospital presenting a determined AST on E. coli were prospectively included to define their K1-status (Pastorex Meningitis) and to collect the clinical (age/sex) or biological metadata (AST/MIC). Among the 296 included samples, no differential representation was observed between K1 results regarding sample nature. K1-negative results were associated with multiple antibiotic-resistance (12.3% vs. 33.0%; p < 0.01). AST phenotypes differed between these groups, with a higher proportion of K1-negativity among resistant strains, especially on ß-lactams (ureidopenicillin, 25.8% vs. 14.9%; and ampicillin/inhibitor, 50.0% vs. 26.8%; p < 0.05) or quinolone (19.8% vs. 7.0%) and sulfamethoxazole-trimethoprim (30.2% vs. 12.3%) (p < 0.01). This study analyzed E. coli ASTs in clinical samples of all types, regarding their K1-antigen status.

Helicobacter pylori Infection in Tripoli, North Lebanon: Assessment and Risk Factors.

Helicobacter pylori (H. pylori) infection occurs among half of the general population worldwide, with high geographic variability. Even though H. pylori is the leading cause of several gastric diseases, ranging from gastritis and peptic ulcers to gastric malignancies, such as gastric cancer and mucosa-associated lymphoid tissue lymphoma, most of the infections remain asymptomatic. Early detection and eradication of H. pylori can definitely prevent severe long-term gastric diseases associated with H. pylori. In Lebanon, the prevalence of H. pylori is not well documented, especially in healthy subjects. The aim of this study is to assess H. pylori infections and the associated risk factors in Tripoli, North Lebanon. A cross-sectional study was conducted on 300 healthy Lebanese volunteers, including both children and adults. The H. pylori stool antigens were detected using the Premier Platinum HpSA test. The socio-demographic data, lifestyle characteristics, and gastrointestinal characteristics of all participants were analyzed. Out of the 300 tested volunteer subjects, 31% were found to be positive for H. pylori. A multivariate binary logistic regression analysis for factors associated with H. pylori infection revealed a significant association between H. pylori infection and gastrointestinal disturbances, the crowding index, and occupation. A significant statistical correlation was found between sheesha smoking (p = 0.001) and H. pylori infection. These findings highlight the need for the development of preventive approaches and strategic indications for the appropriate treatment of H. pylori infections in Tripoli, North Lebanon.

Phylogeny of Catabacter hongkongensis Strains Responsible for Bacteremia Is Not Associated with Clinical Outcomes or Therapeutic Efficacy.

Catabacter hongkongensis is a Gram-positive rod, isolated in 2007 in blood culture. Fewer than 15 infections have been reported. Herein, we present a lethal case of bacteremia due to C. hongkongensis identified through phylogenetic analyses. A woman was found unconscious in a context of chronic diarrhea. An abdominal abscess with a hydroaeric level was discovered, associated with sigmoid adenocarcinoma and peritoneal carcinomatosis. Despite hospitalization in an ICU and the adaptation of antibiotic therapy, the patient died. Blood cultures were positive in the final stage of the disease (>60 h). Identification of C. hongkongensis was performed using 16S rDNA sequencing. Phylogenetic analyses did not enable classification of these strains according to clinical outcome or the antibiotic sensitivity to treatment. In this case, bacteria were difficult to isolate and MALDI-TOF remained non-contributive. As strains are resistant to probabilistic treatments, addition of metronidazole or vancomycin could optimize clinical management, highlighting the benefit of rapid molecular identification by sequencing.