Genetic and structural basis of colistin resistance in Klebsiella pneumoniae: Unravelling the molecular mechanisms.

OBJECTIVE: Antimicrobial resistance (AMR), together with multidrug resistance (MDR), mainly among Gram-negative bacteria, has been on the rise. Colistin (polymyxin E) remains one of the primary available last resorts to treat infections caused by MDR bacteria during the rapid emergence of global resistance. As the exact mechanism of bacterial resistance to colistin remains undetermined, this study warranted elucidation of the underlying mechanisms of colistin resistance and heteroresistance among carbapenem-resistant Klebsiella pneumoniae isolates. METHODS: Molecular analysis was carried out on the resistant isolates using a genome-wide characterisation approach, as well as MALDI-TOF mass spectrometry, to identify lipid A. RESULTS: Among the 32 carbapenem-resistant K. pneumoniae isolates, several isolates showed resistance and intermediate resistance to colistin. The seven isolates with intermediate resistance exhibited the "skip-well" phenomenon, attributed to the presence of resistant subpopulations. The three isolates with full resistance to colistin showed ions using MALDI-TOF mass spectrometry at m/z of 1840 and 1824 representing bisphosphorylated and hexa-acylated lipid A, respectively, with or without hydroxylation at position C'-2 of the fatty acyl chain. Studying the genetic environment of mgrB locus revealed the presence of two insertion sequences that disrupted the mgrB locus in the three colistin-resistant isolates: IS1R and IS903B. CONCLUSIONS: Our findings show that colistin resistance/heteroresistance was inducible with mutations in chromosomal regulatory networks controlling the lipid A moiety and insertion sequences disrupting the mgrB gene, leading to elevated minimum inhibitory concentration values and treatment failure. Different treatment strategies should be employed to avoid colistin heteroresistance-linked treatment failures, mainly through combination therapy using colistin with carbapenems, aminoglycosides, or tigecycline.

Laparoscopic resection of a gastric lipoma following massive upper gastrointestinal bleeding: A case report.

IMPORTANCE AND BACKGROUND: Gastric lipomas are rare submucosal tumours that account for less than 1 % of all stomach tumours. Despite their benign nature, they can lead to significant clinical manifestations such as gastric outlet obstruction and massive gastrointestinal haemorrhage. CASE PRESENTATION: We report the case of a 50-year-old woman with no prior comorbidities, presenting with severe upper gastrointestinal bleeding. Diagnostic imaging and endoscopy identified a submucosal mass in the prepyloric area, later confirmed to be a gastric lipoma. The surgical intervention involved laparoscopic resection of the mass. DISCUSSION: This case underscores the importance of considering gastric lipomas in differential diagnoses of gastrointestinal bleeding. While often asymptomatic, their potential to cause acute complications necessitates awareness among clinicians. The management strategies range from observational approaches in asymptomatic cases to surgical excision in symptomatic cases. CONCLUSIONS: Gastric lipomas, though rare and often benign, can present with life-threatening complications. Accurate diagnosis using a combination of endoscopy and imaging, particularly CT scans, is critical for effective management. Surgical removal remains the definitive treatment for symptomatic lipomas, highlighting the need for a tailored approach based on the tumour's characteristics and location.

Primary Intracranial Hemorrhage: Characteristics, Distribution, Risk Factors, and Outcomes-A Comparative Study between Jewish and Arab Ethnic Groups in Northern Israel.

Background and purpose: This study aimed to investigate the differences in intracerebral hemorrhage (ICH) between Jews and Arabs residing in northern Israel, focusing on risk factors, hemorrhage volume, and functional outcome. Methods: A retrospective analysis was conducted utilizing a population-based registry to investigate intracerebral hemorrhage (ICH) characteristics, risk factors, and outcomes. The registry consisted of inpatients diagnosed with hemorrhagic stroke. Due to the wide variation in data on ICH characteristics and the limited availability of population-based data on predictors of ICH survival and functional outcomes, we collected retrospective data on all adult patients admitted to the Galilee Medical Center with a diagnosis of ICH. Data were obtained from the registry covering the period from 2013 to 2019. Ethnic differences and risk factors associated with intracranial hemorrhage (ICH) were examined within a diverse population of 241 patients, comprising 52.70% Jews (n = 127) and 47.30% Arabs (n = 114). Results: The results of this study revealed significant differences in age, obesity rates, and intracerebral hemorrhage (ICH) location between the two ethnic groups. Hypertension emerged as the most prevalent condition among ICH patients in both ethnic groups (76.70%), followed primarily by anticoagulant use (63.60%), dyslipidemia (60.70%), diabetes (44.60%), obesity (30.60%), smoking (24.60%), and a history of cardiovascular disease (21.80%). Furthermore, 20.90% of the patients had a history of previous cerebrovascular accidents (CVA). Arab patients with ICH were generally younger (62.90 ± 16.00 years) and exhibited higher rates of obesity (38.70%) compared to Jewish patients with ICH (70.17 ± 15.24 years, 23% obesity; p = 0.001, p = 0.013, respectively). Hemorrhage volume was identified as a crucial determinant of patient outcomes, with larger volumes associated with poorer Modified Rankin Scale (mRS) scores at discharge and higher mortality rates. Interestingly, patients without hypertension had higher hemorrhage volumes compared to those with hypertension. The extent of hemorrhage into the ventricles did not significantly correlate with mRS at discharge in our dataset. Conclusions: This study highlights significant differences in the characteristics and outcomes of intracranial hemorrhage (ICH) between Jews and Arabs in northern Israel. The findings reveal variations in age, obesity rates, and ICH location between the two groups. While hypertension was the most prevalent risk factor for both populations, other risk factors differed. Notably, hemorrhage volume emerged as a crucial prognostic factor, aligning with previously published data. These findings underscore the necessity for tailored approaches that consider ethnic-specific factors in the risk assessment, prevention, and management of ICH. Further research is warranted to elucidate the underlying mechanisms and develop interventions aimed at improving outcomes and enhancing healthcare practices in ICH management.

Post-traumatic lateral abdominal wall hernia: a case report.

Traumatic abdominal wall hernia (TAWH) also known as blunt abdominal TAWH is uncommon. The clinical diagnosis is difficult. The authors present a case report of posthigh-energy abdominal blunt trauma causing a TAWH. Case presentation: A 36-year-women, with unremarkable past medical history, was presented to the Emergency Department after a stuck in high-speed two automobiles. She was hemodynamic, respiratory, and neurologically stable. The BMI was 36 kg/m². The abdomen was not distended with an ecchymotic lesion on the right flank. The thoracic abdominal and pelvic computed tomography (CT) scan revealed a rupture in the lateral abdominal wall muscles with a TAWH in the location of the skin ecchymoses. There was no visceral lesion or intraperitoneal fluid. A conservative treatment was indicated. The follow-up was uneventful, with hematoma resorption and no cellulitis or abscess. The patient was discharged after 1 week. An abdominal repair will be planned using a mesh. Clinical discussion: TAWH is a rare entity. The best imaging modality for diagnosis is the CT scan allowing classification of the hernia and a screen for other injuries. The presence of an isolated TAWH must lower the threshold to closely monitor or to operatively explore, given the high rate of false-negative findings at imaging features. Conclusion: TAWH should be suspected behind any blunt abdominal trauma with high energy. CT scan and ultrasound were helpful for diagnosis and the only curative treatment is surgery to avoid complications.

Gastrointestinal stromal tumor of the ampulla of Vater: A case report and literature review.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) usually develop in the stomach and small intestine and only rarely occur in the ampulla of Vater (AV). CASE PRESENTATION: We report a case of a GIST of the AV. A 21-year-old, previously healthy woman presented with a three-month history of epigastric pain, jaundice and weight loss. The diagnosis of a tumor in the second part of the duodenum was made by the computed tomography. The patient underwent pancreatoduodenectomy, the operative specimen revealed an intermediate risk group of GIST and thus, the patient didn't take adjuvant therapy. DISCUSSION: GIST rarely develops in the duodenal ampulla region and it has no specific symptomatology. Radiological investigations play an important role in the diagnosis of Stromal Tumor of the Ampulla of Vater (STAV) mainly computed tomography because STAV has a large size in the majority of cases contrary to adenocarcinoma. CONCLUSION: The aim of this study is to report a new case of STAV combined with a systematic review of reported cases published in peer-reviewed journals.

Acute pancreatitis secondary to spontaneous intramural duodenal hematoma: A case report and a review of the literature.

INTRODUCTION: Intramural duodenal hematoma is a rare entity, often secondary to traumatic origin, but more rarely spontaneous due to blood flow disorders, especially in the context of anticoagulant therapy. CASE PRESENTATION: We report the case of a 66-year-old woman under anticoagulant treatment for atrial fibrillation, who was diagnosed with acute pancreatitis secondary to a spontaneous duodenal hematoma. The evolution was favorable under medical treatment. DISCUSSION: Intramural duodenal hematoma is frequently associated with abdominal pain and hematemesis, more rarely, it can be responsible for an acute pancreatitis, which is considerate as an unusual complication. We report here a case of duodenal hematoma revealed by acute pancreatitis along with a review of the literature since 2011. CONCLUSION: Monitoring of patients on oral anticoagulants helps prevent the occurrence of IDH and avoid its complications, which can be fatal.

Emergence of multi-drug-resistant Mycobacterium tuberculosis in Niger: A snapshot based on whole-genome sequencing.

BACKGROUND: Among other West African countries experiencing the high endemicity of deadly tuberculosis, the situation in Niger is poorly evidenced by microbiological investigations. METHODOLOGY/PRINCIPAL FINDINGS: The study of 42 isolates of Mycobacterium tuberculosis from Niger by whole genome sequencing using Illumina iSeq technology yielded four M. tuberculosis lineages: Indo-Oceanic L1 (n = 1) (2.3%), East-Asian (n = 1) (2.3%), East-African Indian L3 (n = 2) (4.7%) and Euro-American L4 (n = 38) (90.4%). The sub-lineage L4.1.3 comprising 18 isolates (47.3%) was predominant, followed by the L4.6.2.2 sub-lineage (Cameroon genotype, n = 13 isolates) (34.2%). Investigating drug resistance profile for 12 antibiotics found 8/42 (19%) pan-susceptible isolates and 34/42 (81%) resistant isolates; with 40/42 (95.2%) isolates being susceptible to clofazimine-bedaquiline. CONCLUSIONS/SIGNIFICANCE: These unprecedented data from Niger highlight the dynamics of tuberculosis transmission and drug resistance in Niger and may assist tuberculosis control in this country which continues to support a high burden of tuberculosis.

Rapid Identification of Mycobacterium tuberculosis Complex Using Mass Spectrometry: A Proof of Concept.

Mycobacteria that form the Mycobacterium tuberculosis complex are responsible for deadly tuberculosis in animals and patients. Identification of these pathogens at the species level is of primary importance for treatment and source tracing and currently relies on DNA analysis, including whole genome sequencing (WGS), which requires a whole day. In this study, we report the unprecedented discrimination of M. tuberculosis complex species using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), with WGS as the comparative reference standard. In the first step, optimized peptide extraction applied to 36 isolates otherwise identified in five of the 11 M. tuberculosis complex variants by WGS yielded 139 MALDI-TOF spectra, which were used to identify biomarkers of interest that facilitate differentiation between variants. In a second step, 70/80 (88%) other isolates were correctly classified by an algorithm based on specific peaks. This study is the first to report a MALDI-TOF-MS method for discriminating M. tuberculosis complex mycobacteria that is easily implemented in clinical microbiology laboratories.

Whole Genome Sequence Analysis of Mycobacterium bovis Cattle Isolates, Algeria.

Mycobacterium bovis (M. bovis), a Mycobacterium tuberculosis complex species responsible for tuberculosis in cattle and zoonotic tuberculosis in humans, is present in Algeria. In Algeria however, the M. bovis population structure is unknown, limiting understanding of the sources and transmission of bovine tuberculosis. In this study, we identified the whole genome sequence (WGS) of 13 M. bovis strains isolated from animals exhibiting lesions compatible with tuberculosis, which were slaughtered and inspected in five slaughterhouses in Algeria. We found that six isolates were grouped together with reference clinical strains of M. bovis genotype-Unknown2. One isolate was related to M. bovis genotype-Unknown7, one isolate was related to M. bovis genotype-Unknown4, three isolates belonged to M. bovis genotype-Europe 2 and there was one new clone for two M. bovis isolates. Two isolates from Blida exhibited no pairwise differences in single nucleotide polymorphisms. None of these 13 isolates were closely related to four zoonotic M. bovis isolates previously characterized in Algeria. In Algeria, the epidemiology of bovine tuberculosis in cattle is partly driven by cross border movements of animals and animal products.

Case Report: A New Mycobacterium ulcerans Genotype Causing Buruli Ulcer in Côte d'Ivoire.

Mycobacterium ulcerans, the opportunistic pathogen causing Buruli ulcer, is reported to affect rural populations in 36 tropical countries. We report one case of Buruli ulcer in a peri-urban area in Côte d'Ivoire, confirmed by whole genome sequencing which indicated a M. ulcerans genotype previously unreported in Côte d'Ivoire.

Beyond phenotype: The genomic heterogeneity of co-infecting Mycobacterium abscessus smooth and rough colony variants in cystic fibrosis patients.

Two unrelated cystic fibrosis patients were co-infected with Mycobacterium abscessus smooth and rough phenotypes. Smooth M. abscessus is proposed as the infecting form, and the subsequent loss of glycopeptidolipids in the host leads to a rough phenotype. Whole-genome sequencing (WGS) diagnosed two different M. abscessus strains in patient N°1 but only one strain in patient N°2. In patient N°1, rough isolate had novel mutations potentially involved in smooth-to-rough morphology changes. In patient N°2, four genes were present in only the smooth isolate. In addition, we obtained different susceptibility profiles in the four clinical isolates. We revealed a new paradigm describing a cystic fibrosis patient infected with two different clones, including a rough isolate, and identifying a rough M. abscessus clone that did not lose glycopeptidolipids. We propose WGS for the identification of heterogenic isolates and genetic determinants of antimicrobial resistance, which we believe will positively influence treatment prognosis.

Mycobacterium bovis Pulmonary Tuberculosis, Algeria.

We analyzed 98 Mycobacterium tuberculosis complex isolates collected in 2 regions of Algeria in 2015-2018 from 93 cases of pulmonary tuberculosis. We identified 93/98 isolates as M. tuberculosis lineage 4 and 1 isolate as M. tuberculosis lineage 2 (Beijing). We confirmed 4 isolates as M. bovis by whole-genome sequencing.

Mycobacterium bovis Pulmonary Tuberculosis after Ritual Sheep Sacrifice in Tunisia.

A woman in France was diagnosed with pulmonary tuberculosis caused by Mycobacterium bovis after a ritual sheep sacrifice in her home country of Tunisia. This investigation sheds light on ritual sacrifice of sheep as a circumstance in which religious tradition and practices can expose millions of Muslims worldwide to this disease.

Tracing Mycobacterium ulcerans along an alimentary chain in Côte d'Ivoire: A one health perspective.

BACKGROUND: Mycobacterium ulcerans is an environmental mycobacterium responsible for an opportunistic, noncontagious tropical infection named Buruli ulcer that necrotizes the skin and the subcutaneous tissues. M. ulcerans is thought to penetrate through breached skin after contact with contaminated wetland environments, yet the exact biotopes where M. ulcerans occurs remain elusive, hence obscuring the epidemiological chain of transmission of this opportunistic pathogen. METHODOLOGY/PRINCIPAL FINDINGS: Polymerase chain reaction investigations detected M. ulcerans in 39/46 (84.7%) rhizosphere specimens collected in 13 Buruli ulcer-endemic areas in Côte d'Ivoire and 3/20 (15%) specimens collected in a nonendemic area (P = 5.73.E-7); only 3/63 (4.7%) sediment specimens from sediment surrounding the rhizospheres were positive in endemic area (P = 6.51.E-12). High-throughput sequencing further detected three PCR-positive plants, Croton hirtus, Corton kongensis and Oriza sativa var. japonica (rice), in the rectal content of two M. ulcerans-positive wild Thryonomys swinderianus grasscutters that were hunted in Buruli ulcer-endemic areas, while no PCR-positive plants were detected in the rectal content of two negative control animals that were farmed in a nonendemic area. CONCLUSIONS/SIGNIFICANCE: Our data suggest an alimentary chain of transmission of M. ulcerans from plants to T. swinderianus grasscutters and people that utilize T. swinderianus as bush meat in Buruli ulcer-endemic areas in Côte d'Ivoire. Guidance to adopt protective measures and avoid any direct contact with potentially contaminated rhizospheres and with grasscutter intestinal content when preparing the animals for cooking should be established for at-risk populations.

Shell-vial Assay in Diagnosis of Disseminated BCG Infection in an Immunodeficient Child.

We are reporting a case of Bacillus Calmette-Guérin vaccine-disseminated infection in a 19-month-old HIV-negative girl diagnosed with severe combined immunodeficiency. While standard culture protocols failed to isolate and culture the Mycobacterium bovis Bacillus Calmette-Guérin strain, it was isolated from skin and mesenteric lymph node biopsies using the shell-vial assay, allowing whole-genome sequencing and in silico drug susceptibility testing.

Translocation of Mycobacterium tuberculosis after experimental ingestion.

Human tuberculosis is a life-threatening infection following the inhalation of Mycobacterium tuberculosis, while the closely related bacteria Mycobacterium bovis and Mycobacterium canettii are thought to be transmitted by ingestion. To explore whether M. tuberculosis could also infect individuals by ingestion, male BALBc mice were fed 2 x 106 CFUs of M. tuberculosis Beijing or phosphate-buffered saline as a negative control, over a 28-day experiment. While eight negative control mice remained disease-free, M. tuberculosis was identified in the lymph nodes and lungs of 8/14 mice and in the spleens of 4/14 mice by microscopy, PCR-based detection and culture. Whole-genome sequencing confirmed the identity of the inoculum and the tissue isolates. In these genetically identical mice, the dissemination of M. tuberculosis correlated with the results of the culture detection of four intestinal bacteria. These observations indicate that ingested M. tuberculosis mycobacteria can translocate, notably provoking lymphatic tuberculosis.

Genome Sequence of Enorma sp. Strain Marseille-P9525T, a Member of a Human Gut Microbiome.

Strain Marseille-P9525T was isolated from the gut microbiota of a 28-year-old woman and exhibits a 2.23-Mb (G+C content, 66.8%) draft genome sequence containing 1,902 protein-coding genes, 49 tRNAs, and 3 rRNAs. The 16S rRNA sequencing and in silico DNA-DNA hybridization indicated that strain Marseille-P9525T represents a new species to be described.

Routine Culture-Resistant Mycobacterium tuberculosis Rescue and Shell-Vial Assay, France.

We used shell-vial assay with a medium that buffered rifampin to isolate routine culture-resistant Mycobacterium tuberculosis bacteria from cerebrospinal fluid and rifampin-containing intervertebral disc and vertebral corpus of a patient in treatment for Pott's disease and disseminated tuberculosis. Whole-genome sequencing confirmed M. tuberculosis lineage 4 (Euro-American) strain.

Whole-Genome Sequencing of Mycobacterium tilburgii Strain MEPHI.

Mycobacterium tilburgii is a fastidious mycobacterium which has previously been reported to cause severe disseminated infections. Genome sequencing of the M. tilburgii MEPHI clinical isolate yielded 3.14 Mb, with 66.3% GC content, and confirmed phylogenetic placement within the Mycobacterium simiae complex.