Introduction

According to the latest clinical practice guidelines, the empirical antimicrobial therapy used for managmente of patients with acute cholangitis should be established according to its level of severity. However, this recommendation have been highly questioned in those settings where the prevalence of broad spectrum beta-lactamase (ESBL) producing E.coli or Klebsiella exceeds 10-20%, and some experts recommend starting with a broader coverage in a systematic way.

Aims & Methods

To evaluate the prevalence of multidrug-resistant cholangitis in our hospital setting, identify possible predictors and antibiotic adequacy.
We made a retrospective analysis of 331 patients diagnosed with acute cholangitis (gathering demographic, clinical, analytical and microbiological data) admitted to the Hospital del Mar during the period from 2018 to 2021.

Results

After assessing the baseline characteristics of theses sample, we obtained a mean age of 78 years, and 53% male. Blood cultures were extracted in 92% of the patients, of which 49% were positive (149 patients) and of these, 12% had multiresistant germs (19 patients, with 17 cases positive for BLEE). The most frequent empirical regimens were amoxicillin-clavulanic acid (112 cases) and cephalosporins with metronidazole (120 cases) with 94.8% and 96.1% of therapeutic adequacy, respectively. The bacteria identified were mainly: E.coli (88%), Enterobacter spp (16%) and Klebsiella spp (21%). Previous colonization by multidrug-resistant germs (3.9%) and institutionalized patients (5.14%) were the only variables related to the presence of cholangitis due to multidrug-resistant germs, but in the multivariate analysis only colonization was a predictor factor (OR 6.69, CI 1.16-38.35). No analytical or hemodynamic variables were found to be associated to bacteremia due to multidrug-resistant germs. Otherwise, bacteremia due to multidrug-resistant germs didn't correlate with a higher mortality.

Conclusion

The prevalence of multidrug-resistant cholangitis in our setting is considerable. However, high antibiotic adequacy is achieved with amoxicillin-clavulanic acid or third generation cephalosporins in most cases. In patients with history of infection or previous colonization by conflicting germs, a broad-spectrum antibiotic coverage including multidrug-resistant germs should be considered empirically.

Introduction

Nowadays one of the biggest healthcare burdens is the diseases of the gastrointestinal tract (GIT). Taking into consideration, that the human gut harbors more than 10¹⁴ CFU of bacteria, through the years scientists have linked those diseases to bacteria species like: Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli, and Helicobacter pylori. Nevertheless, according to World Health Organisation (WHO), Klebsiella pneumoniae is the priority pathogen with the main bacterial pool in the gastrointestinal tract and is easily transmitted between patients, leading to nosocomial outbreaks. Therefore, scientific research with dependable murine models of Klebsiella pneumoniae infection in GIT is highly required.

Aims & Methods

Within the frames of this study, we aimed to develop a dependable mice model for gastrointestinal tract infection of K. pneumoniae as a method for testing novel antimicrobial therapies. Three different study design settings, overall, six experimental groups, and two bacterial strains (ATCC12657, ATCC43816) were used to test the most effective approach for Klebsiella pneumoniae infection: Control groups (10⁸ CFU: G1 - K. pneumoniae ATCC12657; G4 - K. pneumoniae ATCC43816); antibiotics (penicillin 2000 U/ml, streptomycin 2 mg/ml) pre-treated groups with ampicillin therapy (125 mg/l) (10⁸ CFU: G2 - K. pneumoniae ATCC12657; G3, G5, G6 - K. pneumoniae ATCC43816). Real-time PCR for khe (specific K. pneumoniae gene) and 16S rRNA gene sequencing was performed on DNA extracted from faecal samples of the study animals.

Results

The gastrointestinal K. pneumoniae colonization was detected in the antibiotic pre-treated mice group followed by the introduction of K. pneumoniae in all study groups. The control groups of just K. pneumoniae inoculation for three continuous days resulted in (G1) 2,1 x 10⁸ CFU/50mg and (G4) 6.39 x 10⁸ CFU/50mg (p=0,008). To disrupt the host microbiota, the antibiotic pre-treatment in drinking water (streptomycin and penicillin) for three continuous days and low dose ampicillin afterward, were used in two study groups (G2) 6,67 x 10⁸ CFU/50 mg; (G3) 8,24 x 10⁸ CFU/50 mg (p=0,03). Because of sufficient colonization results using three days of antibiotic pre-treatment, one study group was tested with a singular dose of streptomycin and penicillin before bacterial inoculation ((G5) 6,24 x 10⁸ CFU/50 mg) and another one with additional ampicillin therapy ((G6) 9,01 x 10⁸CFU/50 mg) (p=0,31). Analysis of the gastrointestinal tract colonization with K. pneumoniae proved effective with or without antibiotic pre-treatment. The effectiveness and differences in microbiota using two bacterial species were also confirmed by 16S rRNA gene sequencing. All above-mentioned results are statistically significant considering p<0.05 with ±95% confidence intervals.

Conclusion

Our study demonstrates that colonization of mice intestinal tract by K. pneumoniae can be achieved with or without eradicating resident gut microbiota. Nevertheless, any of the six murine models can be used in further studies of GIT diseases.

References

1. Kaur, Christina Parvinder, et al. “Impact of Klebsiella Pneumoniaein Lower Gastrointestinal Tract Diseases.” Journal of Digestive Diseases, vol. 19, no. 5, 2018, pp.262–271., https://doi.org/10.1111/1751-2980.12595.
2. Zhou, Bolun, et al. “Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract.” Frontiers in Immunology, vol. 11, 2020, https://doi.org/10.3389/fimmu.2020.00575.

Clinical Case Summary

We collected clinical, laboratory, radiological, cholangiographic, endoscopic and pathological findings from a 58 years old male, obese, with type 2 diabetes and with cardiovascular comorbidity. During 2020-2021, he was admitted several times at the Emergency Department for abdominal and thoracic pain, nausea and cold sweating, with night onset. Radiological, including abdominal Computed Tomography (CT) and laboratoristic findings were persistently negative. In 2022 he was hospitalized for acute mild biliopancreatitis. Abdominal Ultrasound (US) resulted negative for bile duct dilatation. During hospitalization, symptomatology improved, but he developed jaundice. Abdominal CT with contrast medium was performed, confirming mild pancreatitis (CT Severity Index 2), thickening and hyperemia of the common bile duct wall. Magnetic Resonance Cholangiopancreatography (MRCP) showed cholelithiasis, choledocolithiasis with multiple chained filling defects, without bile ducts dilatation. Endoscopic Retrograde CholangioPancreatography (ERCP) was then performed, demonstrating a 2 cm filling defect, with extraction of mucus and sludge, mixed with intraluminal tissue. Histopathology described a Bile Duct Intraductal Papillary Mucinous Neoplasm (IPMN-B) with low grade (and focally high grade) dysplasia. Clinical onset and imaging were misleading and ERCP findings were unexpected. IPMN-B is a rare premalignant disease, presenting as an intraluminal papillary mass, sometimes secreting mucus, and leading to abdominal pain, obstructive jaundice and cholangitis. Associated lithiasis is not rare and can be confusing. Pathological and radiological classification have been proposed. Here we focus on clinical presentation and radiological appearance aiming to raise the awareness about this rare entity.

References

1. Endoscopic image showing mucus and sludge, mixed with friable tissue, draining from papilla maior
2. Magnetic Resonance Cholangiopancreatography demonstrating focal lack of signal in common bile duct
3. Retrograde Cholangiogram showing a “peculiar” filling defect in a fusiform dilated choledocus

Introduction

Gastroesophageal reflux disease (GERD) and its long-term complications are a common condition that affects the quality of life of patients. Reflux can reach the oral cavity and affect the teeth and oral mucosa. Dental erosions represent the main oral risk of GERD.
Our research aimed to evaluate the prevalence and severity of oral manifestations in patients with GERD.

Aims & Methods

It was a prospective, descriptive and analytical study, over 4 years (January 2019 to January 2023). We enrolled 40 subjects with GERD and 40 healthy patients (control group). All patients were assessed for oral status by using a survey on oral hygiene habits and a meticulous clinical investigation (assessment of dental erosion, mucosal lesions and measurement of salivary pH). P < 0.05 was considered significant.
All clinical data were collected and analyzed by SPSS20 software.

Results

The results showed that the mean age of our patients was 39.5 ± 14.2 years. The sex ratio M/F was 0.5. There was a significant association between the presence of GERD and the presence of oral mucosal lesions (p=0.02) as well as the presence of dental erosions (p<0.001 for the upper right and lower sectors and p<0.01 for the upper left sector).
The presence of dental erosions in the lower sectors was significantly associated with the presence of mucosal lesions (p=0.05).
Patients with GERD had on average a more acidic salivary pH than the control group (6.53 vs 7.17; p=0.03) and patients with dental erosions had a more acidic salivary pH than those without erosions (6.61 vs 7.15; p=0.01).

Conclusion

GERD is the cause of oral manifestations, of which dental erosion is considered to be the most important. We emphasize the importance of collaboration between gastroenterologists and dentists in the management of the complications associated with this condition.