The Risk Factors and Mechanisms of Azole Resistance of Candida tropicalis Blood Isolates in Thailand : A Retrospective Cohort Study

Funding Information: The study was supported by the Siriraj Research Fund, Grant Number R016333035, Faculty of Medicine Siriraj Hospital, Mahidol University. Acknowledgments We gratefully acknowledge the Mycobacteriology and Mycology laboratory at the Department of Microbiology, the Faculty of Medicine Siriraj Hospital, Mahidol University for providing strains and preliminary identification results.Peer reviewedPublisher PD

Clinical characteristics and diagnosis of intestinal tuberculosis in clinical practice at Thailand’s largest national tertiary referral center: An 11-year retrospective review

Background Diagnosing intestinal tuberculosis (ITB) is challenging due to the low diagnostic sensitivity of current methods. This study aimed to assess the clinical characteristics and diagnosis of ITB at our tertiary referral center, and to explore improved methods of ITB diagnosis. Methods This retrospective study included 177 patients diagnosed with ITB at Siriraj Hospital (Bangkok, Thailand) during 2009–2020. Results The mean age was 49 years, 55.4% were male, and 42.9% were immunocompromised. Most diagnoses (108/177) were made via colonoscopy; 12 patients required more than one colonoscopy. Among those, the sensitivity of tissue acid-fast bacilli (AFB), presence of caseous necrosis, polymerase chain reaction (PCR), and culture was 40.7%, 13.9%, 25.7%, and 53.4%, respectively. Among patients with negative tissue histopathology, 4 (3.7%) and 13 (12.0%) were ITB positive on tissue PCR and culture, respectively. The overall sensitivity when all diagnostic methods were used was 63%. Seventy-six patients had stool tests for mycobacteria. The overall sensitivity of stool tests was 75.0%. However, when analyzing the 31 patients who underwent both endoscopy and stool testing, the sensitivity of stool testing when using tissue biopsy as a reference was 45.8%. Combining stool testing and tissue biopsy did not significantly increase the sensitivity compared to tissue biopsy alone (83.9% vs. 77.4%, respectively). Conclusion Despite the availability of PCR and culture for TB, the overall diagnostic sensitivity was found to be low. The sensitivity increased when the tests were used in combination. Repeated colonoscopy may be beneficial. Adding stool mycobacteria tests did not significantly increase the diagnostic yield if endoscopy was performed, but it could be beneficial if endoscopy is unfeasible

Assessment of Biofilm Formation by <i>Candida albicans</i> Strains Isolated from Hemocultures and Their Role in Pathogenesis in the Zebrafish Model

Candida albicans, an opportunistic pathogen, has the ability to form biofilms in the host or within medical devices in the body. Biofilms have been associated with disseminated/invasive disease with increased severity of infection by disrupting the host immune response and prolonging antifungal treatment. In this study, the in vivo virulence of three strains with different biofilm formation strengths, that is, non-, weak-, and strong biofilm formers, was evaluated using the zebrafish model. The survival assay and fungal tissue burden were measured. Biofilm-related gene expressions were also investigated. The survival of zebrafish, inoculated with strong biofilms forming C. albicans,, was significantly shorter than strains without biofilms forming C. albicans. However, there were no statistical differences in the burden of viable colonogenic cell number between the groups of the three strains tested. We observed that the stronger the biofilm formation, the higher up-regulation of biofilm-associated genes. The biofilm-forming strain (140 and 57), injected into zebrafish larvae, possessed a higher level of expression of genes associated with adhesion, attachment, filamentation, and cell proliferation, including eap1, als3, hwp1, bcr1, and mkc1 at 8 h. The results suggested that, despite the difference in genetic background, biofilm formation is an important virulence factor for the pathogenesis of C. albicans. However, the association between biofilm formation strength and in vivo virulence is controversial and needs to be further studied

Diagnostic methods of intestinal tuberculosis of patients.

Diagnostic methods of intestinal tuberculosis of patients.</p

Fig 1 -

Endoscopic (A and B), computed tomography (C), and pathological findings (D) from the patient with intestinal tuberculosis. A and B showed a large ulcer involving the IC valve. C was an axial contrast-enhanced CT scan showing moderate segmental wall thickening with increased mucosal and mural enhancement at the terminal ileum with associated increasing IC valve thickness. D showed ulcerated ileal mucosa with dense chronic inflammatory cell infiltration and aggregates of epithelioid histiocytes (granuloma) with central necrosis (arrow).</p

Diagnostic methods in 108 patients undergoing colonoscopy.

Diagnostic methods in 108 patients undergoing colonoscopy.</p

Baseline demographic and clinical characteristics, clinical presentations, laboratory findings, colonoscopy findings, computed tomography findings, and histopathology findings in patients diagnosed with intestinal tuberculosis.

Baseline demographic and clinical characteristics, clinical presentations, laboratory findings, colonoscopy findings, computed tomography findings, and histopathology findings in patients diagnosed with intestinal tuberculosis.</p

The sensitivity of each diagnostic modality used to evaluate tissue biopsies obtained by colonoscopy and stool specimens for mycobacteria.

The sensitivity of each diagnostic modality used to evaluate tissue biopsies obtained by colonoscopy and stool specimens for mycobacteria.</p

S1 Data -

BackgroundDiagnosing intestinal tuberculosis (ITB) is challenging due to the low diagnostic sensitivity of current methods. This study aimed to assess the clinical characteristics and diagnosis of ITB at our tertiary referral center, and to explore improved methods of ITB diagnosis.MethodsThis retrospective study included 177 patients diagnosed with ITB at Siriraj Hospital (Bangkok, Thailand) during 2009–2020.ResultsThe mean age was 49 years, 55.4% were male, and 42.9% were immunocompromised. Most diagnoses (108/177) were made via colonoscopy; 12 patients required more than one colonoscopy. Among those, the sensitivity of tissue acid-fast bacilli (AFB), presence of caseous necrosis, polymerase chain reaction (PCR), and culture was 40.7%, 13.9%, 25.7%, and 53.4%, respectively. Among patients with negative tissue histopathology, 4 (3.7%) and 13 (12.0%) were ITB positive on tissue PCR and culture, respectively. The overall sensitivity when all diagnostic methods were used was 63%. Seventy-six patients had stool tests for mycobacteria. The overall sensitivity of stool tests was 75.0%. However, when analyzing the 31 patients who underwent both endoscopy and stool testing, the sensitivity of stool testing when using tissue biopsy as a reference was 45.8%. Combining stool testing and tissue biopsy did not significantly increase the sensitivity compared to tissue biopsy alone (83.9% vs. 77.4%, respectively).ConclusionDespite the availability of PCR and culture for TB, the overall diagnostic sensitivity was found to be low. The sensitivity increased when the tests were used in combination. Repeated colonoscopy may be beneficial. Adding stool mycobacteria tests did not significantly increase the diagnostic yield if endoscopy was performed, but it could be beneficial if endoscopy is unfeasible.</div

Stool test results compared to tissue biopsy results in patients who underwent both stool testing for mycobacteria and evaluation of tissue biopsies obtained during colonoscopy to diagnose intestinal tuberculosis (N = 31).

Stool test results compared to tissue biopsy results in patients who underwent both stool testing for mycobacteria and evaluation of tissue biopsies obtained during colonoscopy to diagnose intestinal tuberculosis (N = 31).</p