The frequency and associated factors of typhoid carriage in patients undergoing cholecystectomy for gallbladder disease in Pakistan: A cross-sectional study.

BACKGROUND: Enteric fever is caused by Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi A, B, and C. It continues to be a significant cause of morbidity and mortality worldwide. In highly endemic areas, children are disproportionately affected, and antimicrobial resistance reduces therapeutic options. It is estimated that 2-5% of enteric fever patients develop chronic asymptomatic infection. These carriers may act as reservoirs of infection; therefore, the prospective identification and treatment of carriers are critical for long-term disease control. We aimed to find the frequency of Salmonella Typhi carriers in patients undergoing cholecystectomy. We also compared the detection limit of culturing versus qPCR in detecting S. Typhi, performed a geospatial analysis of the carriers identified using this study, and evaluated the accuracy of anti-Vi and anti-YncE in identifying chronic typhoid carriage. METHODS: We performed a cross-sectional study in two centers in Pakistan. Gallbladder specimens were subjected to quantitative PCR (qPCR) and serum samples were analyzed for IgG against YncE and Vi by ELISA. We also mapped the residential location of those with a positive qPCR result. FINDINGS: Out of 988 participants, 3.4% had qPCR-positive gallbladder samples (23 S. Typhi and 11 S. Paratyphi). Gallstones were more likely to be qPCR positive than bile and gallbladder tissue. Anti-Vi and YncE were significantly correlated (r = 0.78 p<0.0001) and elevated among carriers as compared to qPCR negative controls, except for anti-Vi response in Paratyphi A. But the discriminatory values of these antigens in identifying carriers from qPCR negative controls were low. CONCLUSION: The high prevalence of typhoid carriers observed in this study suggests that further studies are required to gain information that will help in controlling future typhoid outbreaks in a superior manner than they are currently being managed.

Association of Microbial Dysbiosis with Gallbladder Diseases Identified by Bile Microbiome Profiling.

BACKGROUND: Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully. We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. METHODS: We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. RESULTS: No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. CONCLUSION: We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.

Disseminated Tuberculosis with Cholecystitis in a Patient after Cord Blood Transplantation.

The incidence of an active tuberculosis infection after allogeneic hematopoietic cell transplantation is high. We herein report the case of a patient with acute myeloid leukemia after cord blood transplantation (CBT). On day 36 after CBT, the patient developed fever, and a computed tomography scan on day 36 showed mild thickening of the wall of the gallbladder. Subsequently, a sputum specimen and a blood culture returned positive for the growth of Mycobacterium tuberculosis. After 2 months of administering combination therapy, both the symptoms and gallbladder findings improved. We therefore describe a case of disseminated tuberculosis with the gallbladder mimicking acute cholecystitis in a CBT recipient.

Intraepithelial neutrophils in mammary, urinary and gall bladder infections.

Neutrophil mobilization is a crucial response to protect the host against invading microorganisms. Neutrophil recruitment and removal have to be tightly regulated to prevent uncontrolled inflammation and excessive release of their toxic content causing tissue damage and subsequent organ dysfunctions. We show here the presence of live and apoptotic neutrophils in the cytoplasm of inflamed mammary, urinary and gall bladder epithelial cells following infection with E. coli and Salmonella bacteria. The entry process commenced with adherence of transmigrated neutrophils to the apical membrane of inflamed epithelial cells. Next, nuclear rearrangement and elongation associated with extensive actin polymerization enabled neutrophils to crawl and invaginate the apical membrane into cytoplasmic double membrane compartments. Scission of the invaginated cell membrane from the entry point and loss of these surrounding membranes released intracellular neutrophils into the cytoplasm where they undergone apoptotic death. The co-occurrence of this observation with bacterial invasion and formation of intracellular bacterial communities (IBCs) might link entry of infected neutrophils to the formation of IBCs and chronic carriage in E. coli mastitis and cystitis and Salmonella cholecystitis.

Mutational and non mutational adaptation of Salmonella enterica to the gall bladder.

During systemic infection of susceptible hosts, Salmonella enterica colonizes the gall bladder, which contains lethal concentrations of bile salts. Recovery of Salmonella cells from the gall bladder of infected mice yields two types of isolates: (i) bile-resistant mutants; (ii) isolates that survive lethal selection without mutation. Bile-resistant mutants are recovered at frequencies high enough to suggest that increased mutation rates may occur in the gall bladder, thus providing a tentative example of stress-induced mutation in a natural environment. However, most bile-resistant mutants characterized in this study show defects in traits that are relevant for Salmonella colonization of the animal host. Mutation may thus permit short-term adaptation to the gall bladder at the expense of losing fitness for transmission to new hosts. In contrast, non mutational adaptation may have evolved as a fitness-preserving strategy. Failure of RpoS- mutants to colonize the gall bladder supports the involvement of the general stress response in non mutational adaptation.

An uncommon case of gall bladder mass: gall bladder tuberculosis.

Gall bladder tuberculosis (TB) is a rare entity and differentiation of gall bladder TB from gall bladder malignancy is difficult. We hereby present an unusual case of incidental diagnosis of gall bladder TB during the evaluation of a gall bladder with suspicion of gall bladder cancer in a 49-year-old woman. The diagnosis of gall bladder TB was made with fine needle aspiration cytology (FNAC) from the gall bladder mass as the disease was found unresectable after cross-sectional imaging. Even with the advancement of cross-sectional imaging, the differentiation of gall bladder TB from gall bladder malignancy is not possible without tissue diagnosis.

Prospective evaluation of abdominal ultrasonographic findings in 35 dogs with leptospirosis.

Despite the emergence of new serovars, a detailed and current abdominal ultrasonographic description of dogs with leptospirosis is lacking. The purpose of this prospective, observational, single cohort study was to illustrate abdominal ultrasonographic findings in 35 dogs with confirmed leptospirosis. At least one ultrasonographic abnormality was seen in all of the dogs. Ultrasound renal abnormalities were found in all the dogs and included increased renal cortical echogenicity (100%), increased medullary echogenicity (86%), reduced corticomedullary definition (80%), cortical thickening (74%), renomegaly (60%), pelvic dilation (31%), and medullary band (14%). Hepatic changes were identified in 83% of the dogs, with diffuse hypoechoic parenchyma (71%) and hepatomegaly (60%). Biliary gallbladder abnormalities were found in 60% of the dogs, with biliary sludge (46%), wall thickening (29%), mucocele (26%), and hyperechoic wall (20%). The other most frequently observed abdominal abnormalities were perirenal (60%) and peritoneal (46%) effusions, small intestinal wall thickening (49%), and lymphadenopathy (38%). Two dogs (6%) presented with a small intestinal intussusception. No association was found between serogroups and the presence of ultrasonographic findings. This study is the first to prospectively and exhaustively describe abdominal ultrasonographic findings in dogs with leptospirosis. Our results should prompt clinicians to systematically perform abdominal ultrasounds on dogs with suspected leptospirosis even in the absence of abnormal physical signs. The presence of a gallbladder mucocele could be a warning sign of leptospirosis in dogs.

A case of a chronic salmonella infection following Roux-en-Y gastric bypass surgery, treated successfully by a laparoscopic cholecystectomy.

We report a case of chronic infection caused by Salmonella and cured by a laparoscopic cholecystectomy after Roux-en-Y gastric bypass (RYGB) surgery for obesity. This patient presented with a 2-year history of chronic abdominal pain, loose stools and excessive weight loss. Her stool and urine cultures were positive for Salmonella Despite multiple courses of antibiotics, she remained positive.After undergoing a laparoscopic cholecystectomy, the patient became asymptomatic and stools remained negative. In chronic carriers for Salmonella, the gall bladder is the common reservoir for the bacteria and removing it is usually curative.The possibility that the source of the may be in the biliary limb of her bariatric procedure and not in the gall bladder remained a concern.In patients who have had a RYGB, cholecystectomy is an effective treatment.All patients presenting with abdominal symptoms following RYGB should have stool and urine cultures taken as part of their work up.

Human Bile Reduces Antimicrobial Activity of Selected Antibiotics against Enterococcus faecalis and Escherichia coli In Vitro.

It has been known from previous studies that body fluids, such as cerebrospinal fluid, lung surfactant, and urine, have a strong impact on the bacterial killing of many anti-infective agents. However, the influence of human bile on the antimicrobial activity of antibiotics is widely unknown. Human bile was obtained and pooled from 11 patients undergoing cholecystectomy. After sterilization of the bile fluid by gamma irradiation, its effect on bacterial killing was investigated for linezolid (LZD) and tigecycline (TGC) against Enterococcus faecalis ATCC 29212. Further, ciprofloxacin (CIP), meropenem (MEM), and TGC were tested against Escherichia coli ATCC 25922. Time-kill curves were performed in pooled human bile and Mueller-Hinton broth (MHB) over 24 h. Bacterial counts (in CFU per milliliter after 24 h) of bile growth controls were approximately equal to MHB growth controls for E. coli and approximately 2-fold greater for E. faecalis, indicating a promotion of bacterial growth by bile for the latter strain. Bile reduced the antimicrobial activity of CIP, MEM, and TGC against E. coli as well as the activity of LZD and TGC against E. faecalis This effect was strongest for TGC against the two strains. Degradation of TGC in bile was identified as the most likely explanation. These findings may have important implications for the treatment of bacterial infections of the gallbladder and biliary tract and should be explored in more detail.

Retrospective analysis of canine gallbladder contents in biliary sludge and gallbladder mucoceles.

The pathophysiology of canine gallbladder diseases, including biliary sludge, gallbladder mucoceles and gallstones, is poorly understood. This study aimed to evaluate the component of gallbladder contents and bacterial infection of the gallbladder in order to elucidate the pathophysiology of biliary sludge and gallbladder mucoceles. A total of 43 samples of canine gallbladder contents (biliary sludge, 21 and gallbladder mucoceles, 22) were subjected to component analysis by infrared spectroscopy, and the resultant infrared spectra were compared with that of swine mucin. Of the 43 samples, 41 were also evaluated by aerobic and anaerobic bacterial culture. The contents of 20 (95.2%) biliary sludge and 22 (100%) gallbladder mucocele samples exhibited similar infrared spectra as swine mucin. Although biliary sludge and gallbladder mucocele contents exhibited similar infrared spectra, one sample of biliary sludge (4.8%) was determined to be composed of proteins. The rate of bacterial infection of the gallbladder was 10.0% for biliary sludge and 14.3% for gallbladder mucoceles. Almost all of the identified bacterial species were intestinal flora. These results indicate that the principal components of gallbladder contents in both gallbladder mucoceles and biliary sludge are mucins and that both pathophysiologies exhibit low rates of bacterial infection of the gallbladder. Therefore, it is possible that gallbladder mucoceles and biliary sludge have the same pathophysiology, and, rather than being independent diseases, they could possibly represent a continuous disease. Thus, biliary sludge could be considered as the stage preceding the appearance of gallbladder mucoceles.

Listeria monocytogenes-associated biliary tract infections: a study of 12 consecutive cases and review.

At present, little is known regarding Listeria monocytogenes-associated biliary tract infection, a rare form of listeriosis.In this article, we will study 12 culture-proven cases reported to the French National Reference Center for Listeria from 1996 to 2013 and review the 8 previously published cases.Twenty cases were studied: 17 cholecystitis, 2 cholangitis, and 1 biliary cyst infection. Half were men with a median age of 69 years (32-85). Comorbidities were present in 80%, including cirrhosis, rheumatoid arthritis, and diabetes. Five patients received immunosuppressive therapy, including corticosteroids and anti-tumor necrosis factor biotherapies. Half were afebrile. Blood cultures were positive in 60% (3/5). Gallbladder histological lesions were analyzed in 3 patients and evidenced acute, chronic, or necrotic exacerbation of chronic infection. Genoserogroup of the 12 available strains were IVb (n=6), IIb (n=5), and IIa (n=1). Their survival in the bile was not enhanced when compared with isolates from other listeriosis cases. Adverse outcome was reported in 33% (5/15): 3 deaths, 1 recurrence; 75% of the patients with adverse outcome received inadequate antimicrobial therapy (P=0.033).Biliary tract listeriosis is a severe infection associated with high mortality in patients not treated with appropriate therapy. This study provides medical relevance to in vitro and animal studies that had shown Listeria monocytogenes ability to survive in bile and induce overt biliary infections.

Tuberculosis of gallbladder neck: a cause of cholecystitis with cholelithiasis.

Tuberculosis of gallbladder neck is not a very common problem reported in the literature. Here, we report a case of gallbladder neck tuberculosis complicated with chronic cholecystitis with cholelithiasis in a 55-year-old woman. Diagnosis was made postoperatively on surgical biopsy.

Primitive gallbladder tuberculosis: a case report with review of the literature.

Gallbladder tuberculosis is an exceedingly rare disease. A correct preoperative diagnosis of Gallbladder tuberculosis is difficult, and it may be confused with different gallbladder diseases. We present a new case of a patient who underwent surgery with the preoperative diagnosis of cholelithiasis. Diagnosis of gallbladder tuberculosis was obtained with the histological examination of the frozen section.

Antimicrobial susceptibility profiles of Gram-negative bacilli isolated from patients with hepatobiliary infections in Taiwan: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2006-2010.

We investigated the trends in antimicrobial resistance among species of Gram-negative bacilli isolated from patients with hepatobiliary tract infections in Taiwan during the period 2006-2010 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, 1032 isolates of Gram-negative bacilli that had been collected from patients with hepatobiliary infections were tested for susceptibility to 12 antimicrobial agents in accordance with the Clinical and Laboratory Standards Institute guidelines. Enterobacteriaceae accounted for the majority (n = 874, 84.7%) of isolates and Escherichia coli was the most common pathogen (n = 323, 31.3%). There were significantly more E. coli (P = 0.001) and Proteus mirabilis (P = 0.031) isolates collected from patients who had been hospitalized for less than 48 h and significantly more Serratia marcescens (P = 0.035) and Pseudomonas aeruginosa (P = 0.008) isolates collected from patients who had been hospitalized for 48 h or longer. The prevalence of extended-spectrum ß-lactamase (ESBL)-producing pathogens was low. The decline in susceptibility rates with time was remarkable for ceftazidime (P = 0.036), ciprofloxacin (P = 0.029), and levofloxacin (P = 0.018). The most effective antibiotics, i.e., those that were active against more than 90% of Enterobacteriaceae, were amikacin, cefepime, imipenem, ertapenem, and piperacillin-tazobactam. Susceptibility of P. aeruginosa to anti-pseudomonal agents was greater than 80%. In this study, we found an overall increase in resistance to antimicrobial agents among Gram-negative bacilli isolated from patients with hepatobiliary tract infections in Taiwan. Surveillance of antimicrobial susceptibility and updates of treatment guidelines are recommended to help achieve optimal therapy for patients with hepatobiliary infections.

Candida tropicalis infection in a term neonate with gall bladder masses and infective endocarditis.

Candida endocarditis is extremely rare in term neonates, and gall bladder involvement due to candidemia has never been reported amongst neonates and infants. A term, appropriate for gestational age neonate developed Candida tropicalis blood stream infection in second week of life. He was started on conventional amphotericin B. However, he failed to show any clinical improvement, and candidemia keep on persisting. Repeat sanctuary sites screening revealed multiple echogenic masses in heart (vegetations) and gall bladder. On changing the treatment to liposomal amphotericin B and fluconazole, he recovered clinically, echogenic masses in gall bladder disappeared, and intracardiac vegetations decreased in size.

Helicobacter pylori in gallbladder mucosa in patients with gallbladder disease.

BACKGROUND: Helicobacter species have been found to be associated with biliary tract diseases. This prospective study was done to determine the prevalence of H. pylori in the biliary tract of patients suffering from gallbladder disease. METHODS: Forty-nine patients undergoing laparoscopic/open cholecystectomy for benign biliary tract diseases were investigated with urea breath test for H. pylori infection of gastric antrum. Bile and gallbladder tissues were studied for presence of H. pylori by rapid urease test, histopathological examination, culture and PCR analysis. Gallbladder specimens from two patients who underwent Whipple's operation and from 10 cadavers were studied as controls. RESULTS: The mean (SD) age of patients was 42.4 (11.1) years. Urea breath test was positive in 17 (34.6%) cases. Rapid urease test was negative in all the cases. There was no evidence of H. pylori infection of gallbladder on histopathological examination using H&E, Giemsa and Warthin Starry stains. H. pylori DNA were detected in 16 patients (32.6%) and none of the 12 controls by PCR analysis (p = 0.025). The presence of H. pylori DNA in bile and/or gallbladder was associated with positive urea breath test, (p < 0.0001). Other factors like age, gender, jaundice and cholestasis were not associated with H. pylori infection of bile and gallbladder. CONCLUSIONS: Nearly three quarters of patients with positive urea breath test have detectable H. pylori DNA in gallbladder tissue. The significance of these findings needs to be further evaluated.

Helicobacter pylori: association with gall bladder disorders in Pakistan.

Helicobacter species colonise the biliary tract and therefore this study explores the relationship between of Helicobacter pylori and cholecystitis. Bile and gall bladder tissue samples were obtained from 144 patients who underwent cholecystectomy. Of these, 89 had chronic cholecystitis with cholelithiasis, 44 had gall bladder carcinoma and 11 had gall bladder polyps. Histopathology examination included special staining and immunohistochemistry (IHC), while Helicobacter species (H. pylori, H. bilis and H. hepaticus) were detected by the polymerase chain reaction (PCR). Sequencing and BLAST query of PCR products was undertaken and samples were considered to contain H. pylori if both PCR and IHC were positive. Immunohistochemistry for H. pylori was positive in 22 (25%) cases compared to five (9%) in the control group (P=0.02). Testing (PCR) for 16S rDNA was positive in 23 (26%) cases compared to six (11%) controls (P=0.03). Negative PCR results were obtained for H. bilis and H. hepaticus. Twenty-four (89%) were positive by both 16S rDNA PCR and IHC for H. pylori (P<0.001). Both PCR for 16S rDNA and IHC were positive in 21 (24%) cases compared to five (9%) controls (P=0.03). Sequencing of 16S rRNA and glmM PCR products were consistent with H. pylori. In conclusion, H. pylori DNA was demonstrated in cases of chronic cholecystitis and gall bladder carcinoma associated with cholelithiasis, but this association requires further study.