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Scientific Reports Oct 2023Non-tuberculosis mycobacterial (NTM) diseases are steadily increasing in prevalence and mortality worldwide. Mycobacterium avium and M. intracellulare, the two major...
Non-tuberculosis mycobacterial (NTM) diseases are steadily increasing in prevalence and mortality worldwide. Mycobacterium avium and M. intracellulare, the two major pathogens of NTM diseases, are resistant to antibiotics, and chlorine, necessitating their capacity to survive in natural environments (e.g. soil and rivers) and disinfected municipal water. They can also form biofilms on artificial surfaces to provide a protective barrier and habitat for bacilli, which can cause refractory systemic disseminated NTM disease. Therefore, preventing biofilm formation by these pathogens is crucial; however, not many in vivo experimental systems and studies on NTM biofilm infection are available. This study develops a mouse model of catheter-associated systemic disseminated disease caused by M. intracellulare that reproduces the pathophysiology of catheter-associated infections observed in patients undergoing peritoneal dialysis. In addition, the bioluminescence system enabled noninvasive visualization of the amount and distribution of bacilli in vivo and conveniently examine the efficacy of antimicrobials. Furthermore, the cellulose-based biofilms, which were extensively formed in the tissue surrounding the catheter insertion site, reduced drug therapy effectiveness. Overall, this study provides insights into the cause of the drug resistance of NTM and may guide the development of new therapies for NTM diseases.
Topics: Humans; Mice; Animals; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Mice, Inbred Strains; Catheters; Biofilms; Bacillus
PubMed: 37816786
DOI: 10.1038/s41598-023-44403-0 -
Critical Care (London, England) Nov 2023Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments....
BACKGROUND
Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-D-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC.
METHODS
This prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell beta-D-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements.
RESULTS
Between 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54-72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5-1578.0] pg/ml) compared to non-IAC patients (133 [16.0-831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0-9.0] pg/ml) than in non-IAC patients (3 [3.0-3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0-211.0] pg/ml) than in non-IAC patients (50 [23.0-141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%.
CONCLUSION
In critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure.
TRIAL REGISTRATION
The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).
Topics: Humans; Male; Middle Aged; Aged; Female; Prospective Studies; Glucans; Critical Illness; Candidiasis; Antifungal Agents; Intraabdominal Infections; Peritonitis; beta-Glucans; Sensitivity and Specificity
PubMed: 38037130
DOI: 10.1186/s13054-023-04761-7 -
The Indian Journal of Tuberculosis Apr 2024Mycobacterium tuberculosis causes tuberculosis, a fatal infection resulting in widespread illness and death. In 2020, approximately 10 million people were diagnosed with... (Review)
Review
Mycobacterium tuberculosis causes tuberculosis, a fatal infection resulting in widespread illness and death. In 2020, approximately 10 million people were diagnosed with tuberculosis. The top 30 tuberculosis-endemic countries accounted for 86% of all estimated occurrence cases worldwide. In this context, eight of these accounted for two-thirds of the global total, with India having a prevalence of 26%. Aside from lung inflammation, the risk factors for tuberculosis in women include extra-pulmonary infection, particularly genital tuberculosis, tuberculous mastitis, and tuberculous in the peritoneum, intestine, and spine. Depending on the epidemiologic context and screening methods, different tuberculosis symptoms and disease diagnoses are more or less common among expectant mothers. The disease is almost certainly going to have a global impact. The social stigma and anxiety associated with tuberculosis may have a much more significant negative impact on women's health behaviors than men. Notably, the abdominal sites of miliary tuberculosis could mimic tumor likely, carcinoma and lymphoma. Also, the results of the diagnostic accuracy tests for the condition demonstrate that extra-pulmonary tuberculosis can be quickly and accurately diagnosed in various sites using both the T-SPOT assay and the GeneXpert/PCR test. Therefore, this review exemplified the prevalence of extra-pulmonary tuberculosis at various points in women's lives. On the contrary, it also illustrated the symptoms and dangers of TB as they relate to women's health.
Topics: Male; Female; Humans; Mycobacterium tuberculosis; Tuberculosis, Extrapulmonary; Tuberculosis, Miliary; Risk Factors; Women's Health
PubMed: 38589124
DOI: 10.1016/j.ijtb.2023.06.002 -
Clinical and Experimental Nephrology Jul 2024Peritonitis is the leading cause of peritoneal dialysis (PD) discontinuation. However, few data concern risk factors of peritonitis development and catheter removal...
BACKGROUND
Peritonitis is the leading cause of peritoneal dialysis (PD) discontinuation. However, few data concern risk factors of peritonitis development and catheter removal caused by treatment failure in pediatric patients.
METHODS
This single-center, retrospective study analyzed data from pediatric patients who underwent chronic PD between March 2002 and June 2022. The incidence rates of peritonitis by the person-year method were calculated, and they were stratified by patient age groups. Risk factors for peritonitis development and catheter removal were also analyzed by multivariate analysis using logistic regression model.
RESULTS
Ninety patients were enrolled, and 62 peritonitis episodes were observed in 41 (46%) patients. The incidence rate of peritonitis was 0.21 episodes per patient-year, which was the highest in children aged under 2 years old (0.26 episodes per patient-year). Moreover, 44 (71%) cases were successfully cured by antibiotics alone, although 17 (27%) cases required catheter removal, and 4 (6%) cases transitioned to chronic hemodialysis because of peritoneal dysfunction. One patient died. The risk factor for peritonitis development and catheter removal caused by treatment failure was PD insertion at under 2 years old (odds ratio = 2.5; P = 0.04) and Pseudomonas aeruginosa (odds ratio = 11.0; P = 0.04) in the multivariate analysis. P. aeruginosa was also a risk factor for difficulty in re-initiating PD (P = 0.004).
CONCLUSIONS
The incidence rate of peritonitis was the highest in children under 2 years old. P. aeruginosa peritonitis is a risk factor for catheter removal and peritoneal dysfunction.
Topics: Humans; Peritonitis; Peritoneal Dialysis; Male; Female; Child, Preschool; Child; Retrospective Studies; Risk Factors; Infant; Incidence; Prognosis; Adolescent; Device Removal; Anti-Bacterial Agents; Age Factors; Catheter-Related Infections; Pseudomonas Infections; Pseudomonas aeruginosa; Treatment Failure; Kidney Failure, Chronic
PubMed: 38472543
DOI: 10.1007/s10157-024-02482-x -
Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis.Stem Cell Research & Therapy Dec 2023The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it...
BACKGROUND
The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis.
METHODS
We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 10 cells/kg or 4 × 10 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity.
RESULTS
One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-β in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity.
CONCLUSIONS
Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.
Topics: Humans; Animals; Swine; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Mesenchymal Stem Cells; Peritonitis; Sepsis; Anti-Bacterial Agents
PubMed: 38087374
DOI: 10.1186/s13287-023-03588-x -
Internal Medicine (Tokyo, Japan) Feb 2024
Topics: Humans; Female; Ascites; Peritoneum; Tuberculosis; Ovarian Neoplasms; Peritonitis, Tuberculous
PubMed: 37344427
DOI: 10.2169/internalmedicine.2013-23 -
Transplantation Sep 2023Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI). Safety concerns around FMT are increased in...
BACKGROUND
Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI). Safety concerns around FMT are increased in immunocompromised populations, such as solid organ transplant (SOT) recipients. Outcomes among adult SOT recipients suggest FMT is efficacious and safe; however, pediatric SOT data are lacking.
METHODS
We describe the efficacy and safety of FMT among pediatric SOT recipients in a single-center retrospective study from March 2016 to December 2019. Successful FMT was defined as no recurrence of CDI within 2 mo of FMT. We identified 6 SOT recipients ages 4-18 y who received FMT a median of 5.3 y post-SOT.
RESULTS
Success after a single FMT was 83.3%. One liver recipient did not achieve cure after 3 FMTs and remains on low-dose vancomycin. One serious adverse event (SAE) occurred; cecal perforation and bacterial peritonitis occurred following colonoscopic FMT coordinated with intestinal biopsy in a kidney transplant recipient. He achieved full recovery and CDI cure. There were no other SAEs. There were no adverse events related to immunosuppression or transplantation status including: bacteremia, cytomegalovirus activation or reactivation, allograft rejection, or allograft loss.
CONCLUSIONS
In this limited series, efficacy of FMT in pediatric SOT is comparable to efficacy in the general pediatric recurrent CDI population. There may be an increased risk of procedure-related SAE in SOT patients and larger cohort studies are needed.
Topics: Male; Adult; Humans; Child; Fecal Microbiota Transplantation; Retrospective Studies; Clostridioides difficile; Treatment Outcome; Clostridium Infections; Transplant Recipients; Organ Transplantation
PubMed: 37211643
DOI: 10.1097/TP.0000000000004656 -
Surgical Infections Dec 2023Intra-abdominal candidiasis (IAC) is associated with substantial morbidity and mortality in hospitalized patients. Identifying high-risk populations may facilitate...
Intra-abdominal candidiasis (IAC) is associated with substantial morbidity and mortality in hospitalized patients. Identifying high-risk populations may facilitate early and selective directed therapy in appropriate patients and avoid unwarranted treatment and any associated adverse effects in those who are low risk. This retrospective, case-control study included patients >18 years of age admitted from July 1, 2010 to July 1, 2021 who had a microbiologically confirmed intra-abdominal infection (gastrointestinal culture positive for either a spp. [cases] or bacterial isolate [controls] collected intra-operatively or from a drain placed within 24 hours). Patients receiving peritoneal dialysis treatment or with a peritoneal dialysis catheter in place or treated at an outside hospital were excluded. Multivariable regression was utilized to identify independent risk factors for the development of IAC. : Five hundred twenty-three patients were screened, and 250 met inclusion criteria (125 per cohort). Multivariable analysis identified exposure to corticosteroids (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.52-13.32; p < 0.0001), upper gastrointestinal tract surgery (OR, 3.51; 95% CI, 1.25-9.87; p = 0.017), and mechanical ventilation (OR, 3.09; 95% CI 1.5-6.37; p = 0.002) were independently associated with IAC. The area under the receiver operating characteristic (AUROC) and goodness of fit were 0.7813 and p = 0.5024, respectively. Exposure to corticosteroids, upper gastrointestinal tract surgery, and mechanical ventilation are independent risk factors for the development of microbiologically confirmed IAC suggesting these factors may help identify high-risk individuals requiring antifungal therapy.
Topics: Humans; Antifungal Agents; Retrospective Studies; Case-Control Studies; Candidiasis; Intraabdominal Infections; Risk Factors; Adrenal Cortex Hormones
PubMed: 38011638
DOI: 10.1089/sur.2023.149 -
Journal of Nephrology Sep 2023Peritoneal dialysis- (PD) related infections continue to be a major cause of morbidity and mortality in patients on renal replacement therapy via PD. However, despite... (Review)
Review
Peritoneal dialysis- (PD) related infections continue to be a major cause of morbidity and mortality in patients on renal replacement therapy via PD. However, despite the great efforts in the prevention of PD-related infectious episodes, approximately one third of technical failures are still caused by peritonitis. Recent studies support the theory that ascribes to exit-site and tunnel infections a direct role in causing peritonitis. Hence, prompt exit site infection/tunnel infection diagnosis would allow the timely start of the most appropriate treatment, thereby decreasing the potential complications and enhancing technique survival. Ultrasound examination is a simple, rapid, non-invasive and widely available procedure for tunnel evaluation in PD catheter-related infections. In case of an exit site infection, ultrasound examination has greater sensitivity in diagnosing simultaneous tunnel infection compared to the physical exam alone. This allows distinguishing the exit site infection, which will likely respond to antibiotic therapy, from infections that are likely to be refractory to medical therapy. In case of a tunnel infection, the ultrasound allows localizing the catheter portion involved in the infectious process, thus providing significant prognostic information. In addition, ultrasound performed after two weeks of antibiotic administration allows monitoring patient response to therapy. However, there is no evidence of the usefulness of ultrasound examination as a screening tool for the early diagnosis of tunnel infections in asymptomatic PD patients.
Topics: Humans; Catheter-Related Infections; Catheters, Indwelling; Peritoneal Dialysis; Anti-Bacterial Agents; Peritonitis
PubMed: 36939999
DOI: 10.1007/s40620-023-01589-w -
Frontiers in Cellular and Infection... 2023Bacterial infections and the concurrent inflammation have been associated with increased long-term cardiovascular (CV) risk. In patients receiving peritoneal dialysis...
Bacterial infections and the concurrent inflammation have been associated with increased long-term cardiovascular (CV) risk. In patients receiving peritoneal dialysis (PD), bacterial peritonitis is a common occurrence, and each episode further increases late CV mortality risk. However, the underlying mechanism(s) remains to be elucidated before safe and efficient anti-inflammatory interventions can be developed. Damage-Associated Molecular Patterns (DAMPs) have been shown to contribute to the acute inflammatory response to infections, but a potential role for DAMPs in mediating long-term vascular inflammation and CV risk following infection resolution in PD, has not been investigated. We found that bacterial peritonitis in mice that resolved within 24h led to CV disease-promoting systemic and vascular immune-mediated inflammatory responses that were maintained up to 28 days. These included higher blood proportions of inflammatory leukocytes displaying increased adhesion molecule expression, higher plasma cytokines levels, and increased aortic inflammatory and atherosclerosis-associated gene expression. These effects were also observed in infected nephropathic mice and amplified in mice routinely exposed to PD fluids. A peritonitis episode resulted in elevated plasma levels of the DAMP Calprotectin, both in PD patients and mice, here the increase was maintained up to 28 days. , the ability of culture supernatants from infected cells to promote key inflammatory and atherosclerosis-associated cellular responses, such as monocyte chemotaxis, and foam cell formation, was Calprotectin-dependent. , Calprotectin blockade robustly inhibited the short and long-term peripheral and vascular consequences of peritonitis, thereby demonstrating that targeting of the DAMP Calprotectin is a promising therapeutic strategy to reduce the long-lasting vascular inflammatory aftermath of an infection, notably PD-associated peritonitis, ultimately lowering CV risk.
Topics: Humans; Mice; Animals; Peritoneal Dialysis; Peritonitis; Inflammation; Bacterial Infections; Atherosclerosis
PubMed: 38094743
DOI: 10.3389/fcimb.2023.1285193