Tuğrul Hoşbul
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Tuğrul Hoşbul has a total of 88 co-authors. Here are the top co-authors by number of shared publications:
- Canset Nur Aydogan
Department of Medical Microbiology, Ordu State Hospital, Ordu, Turkey
6 shared publications - Ilgaz Kazaz
Medical Microbiology Laboratory, Beytepe Murat Erdi Eker State Hospital, 06800 Ankara, Turkey
5 shared publications - Ramazan Gümral
Department of Medical Microbiology, Gülhane Training and Research Hospital, Ankara, Turkey
4 shared publications - Bülent Bozdoğan
Recombinant DNA and Recombinant Protein Center (REDPROM), Aydın Adnan Menderes University, Aydın, Turkey
3 shared publications - Cumhur Artuk
Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences, Gulhane Training and Research Hospital, Ankara, Turkey
3 shared publications - Fatih Şahiner
Division of Medical Virology, Department of Medical Microbiology, Gulhane Military Medical Academy, Ankara, Turkey
3 shared publications
Latest Publications
- Open Access
- 30 September 2026
- Published by Journal of Infection in Developing Countries in The Journal of Infection in Developing Countries
- Vol. 20 (09) , 1351-1360
Evaluation of biofilm activity, virulence genes, and antibiotic susceptibility profiles in clinical Proteus mirabilis isolates
Introduction: Proteus mirabilis is a common opportunistic pathogen in wound and urinary tract infections (UTIs), whose clinical significance is driven by biofilm formation. This virulence-mediated process provides a shield against antimicrobials and host immunity, promoting difficult-to-treat infections. This study aimed to elucidate the relationship between biofilm-forming capacity, presence of virulence genes, and antibiotic resistance profiles in P. mirabilis isolates. Methodology: A total of 76 P. mirabilis isolates from urine and wound samples were analyzed. Isolates were identified using MALDI-TOF MS, antimicrobial susceptibility was tested via VITEK®2, biofilm formation was measured using the crystal violet method, and the presence of virulence genes (ureC, ireA, zapA, rsbA, flaA, atfA, ucaA, and hpmA) was analyzed by PCR. Results: Wound isolates showed significantly enhanced biofilm production and higher resistance rates to multiple antibiotics. Moderate-to-strong biofilm production was significantly associated with catheterization, the presence of the zapA, atfA, and ucaA genes, and increased resistance to ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SXT). The presence of the hpmA gene showed a borderline association with TMP-SXT resistance. The presence of the rsbA gene was significantly associated with a reduced likelihood of ertapenem resistance, suggesting a role in modulating porin-mediated antibiotic uptake. Conclusions: Biofilm-mediated resistance is a significant barrier to managing P. mirabilis infections, particularly in wounds and catheter-associated UTIs. The presence of specific genes in moderate-to-strong biofilm producers indicates their products are integral to the structural integrity and the functional capacity of the biofilm. The inverse relationship between rsbA and carbapenem resistance warrants further investigation as a biomarker for susceptibility.
- 30 September 2026
- Published by Journal of Infection in Developing Countries in The Journal of Infection in Developing Countries
- Vol. 20 (09) , 1351-1360
Open AccessEvaluation of biofilm activity, virulence genes, and antibiotic susceptibility profiles in clinical Proteus mirabilis isolates
Introduction: Proteus mirabilis is a common opportunistic pathogen in wound and urinary tract infections (UTIs), whose clinical significance is driven by biofilm formation. This virulence-mediated process provides a shield against antimicrobials and host immunity, promoting difficult-to-treat infections. This study aimed to elucidate the relationship between biofilm-forming capacity, presence of virulence genes, and antibiotic resistance profiles in P. mirabilis isolates. Methodology: A total of 76 P. mirabilis isolates from urine and wound samples were analyzed. Isolates were identified using MALDI-TOF MS, antimicrobial susceptibility was tested via VITEK®2, biofilm formation was measured using the crystal violet method, and the presence of virulence genes (ureC, ireA, zapA, rsbA, flaA, atfA, ucaA, and hpmA) was analyzed by PCR. Results: Wound isolates showed significantly enhanced biofilm production and higher resistance rates to multiple antibiotics. Moderate-to-strong biofilm production was significantly associated with catheterization, the presence of the zapA, atfA, and ucaA genes, and increased resistance to ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SXT). The presence of the hpmA gene showed a borderline association with TMP-SXT resistance. The presence of the rsbA gene was significantly associated with a reduced likelihood of ertapenem resistance, suggesting a role in modulating porin-mediated antibiotic uptake. Conclusions: Biofilm-mediated resistance is a significant barrier to managing P. mirabilis infections, particularly in wounds and catheter-associated UTIs. The presence of specific genes in moderate-to-strong biofilm producers indicates their products are integral to the structural integrity and the functional capacity of the biofilm. The inverse relationship between rsbA and carbapenem resistance warrants further investigation as a biomarker for susceptibility.
- 7 September 2026
- Published by Wiley in Journal of Medical Virology
- Vol. 98 (9) , e71139
Changes in Anti‐HBc Positivity and Antibody Loss in Immunocompromised Patients: An Eight‐Year Hospital‐Based Analysis From a Tertiary Center in Turkey
This study aimed to evaluate the prevalence of anti‐HBc seropositivity and examine the longitudinal changes in anti‐HBc IgG S/CO reactivity, with particular focus on seroreversion (loss of anti‐HBc antibodies) in immunocompromised patients by correlating laboratory data with clinical history. In this retrospective study (January 2017 and June 2024), serum samples from a tertiary care hospital were tested for hepatitis B serological markers, using chemiluminescent microparticle immunoassay (CMIA). Patients with ≥ 3 anti‐HBc IgG measurements were evaluated for longitudinal monitoring of antibody dynamics. Medical records were reviewed for chronic HBV infection, co‐morbidities, and anti‐HBc loss in immunosuppressed patients. A total of 35,017 clinical samples from 27,758 participants were analysed. In this hospital‐based cohort, the anti‐HBc IgG seropositivity rate was 32.0%. Seropositive individuals were older than seronegatives ( p < 0.001). Longitudinal analyses was performed on 1397 patients with ≥ 3 IgG measurements; consistently 434 remained reactive and 963 remained negative. Linear mixed‐effects analysis showed a significant decline over time (F (1,1679) = 33.65; p < 0.001). Among immunosuppressed patients, 94 initially reactive cases were evaluated; permanent loss occurred in 80.9%. Seroreversion rates were 66.7% in rheumatology, 85.2% in hematology, 100% in oncology, and 69.2% in other departments; massive immunosuppressive cohort (hematology/oncology) had a higher likelihood of seroreversion in an unadjusted, exploratory comparison (OR 3.27; p = 0.04). This study demonstrates time‐dependent decline in anti‐HBc IgG S/CO reactivity. Seroreversion is common in immunocompromised patients. As anti‐HBc reflects past exposure rather than active infection, its loss or negativity in immunosuppressed patients—including seronegative occult HBV infection—means serology alone may give false reassurance. Combined HBsAg/anti‐HBc serology with HBV DNA testing is therefore recommended to detect occult infection and assess reactivation risk in this high‐risk group.
- 7 September 2026
- Published by Wiley in Journal of Medical Virology
- Vol. 98 (9) , e71139
Changes in Anti‐HBc Positivity and Antibody Loss in Immunocompromised Patients: An Eight‐Year Hospital‐Based Analysis From a Tertiary Center in Turkey
This study aimed to evaluate the prevalence of anti‐HBc seropositivity and examine the longitudinal changes in anti‐HBc IgG S/CO reactivity, with particular focus on seroreversion (loss of anti‐HBc antibodies) in immunocompromised patients by correlating laboratory data with clinical history. In this retrospective study (January 2017 and June 2024), serum samples from a tertiary care hospital were tested for hepatitis B serological markers, using chemiluminescent microparticle immunoassay (CMIA). Patients with ≥ 3 anti‐HBc IgG measurements were evaluated for longitudinal monitoring of antibody dynamics. Medical records were reviewed for chronic HBV infection, co‐morbidities, and anti‐HBc loss in immunosuppressed patients. A total of 35,017 clinical samples from 27,758 participants were analysed. In this hospital‐based cohort, the anti‐HBc IgG seropositivity rate was 32.0%. Seropositive individuals were older than seronegatives ( p < 0.001). Longitudinal analyses was performed on 1397 patients with ≥ 3 IgG measurements; consistently 434 remained reactive and 963 remained negative. Linear mixed‐effects analysis showed a significant decline over time (F (1,1679) = 33.65; p < 0.001). Among immunosuppressed patients, 94 initially reactive cases were evaluated; permanent loss occurred in 80.9%. Seroreversion rates were 66.7% in rheumatology, 85.2% in hematology, 100% in oncology, and 69.2% in other departments; massive immunosuppressive cohort (hematology/oncology) had a higher likelihood of seroreversion in an unadjusted, exploratory comparison (OR 3.27; p = 0.04). This study demonstrates time‐dependent decline in anti‐HBc IgG S/CO reactivity. Seroreversion is common in immunocompromised patients. As anti‐HBc reflects past exposure rather than active infection, its loss or negativity in immunosuppressed patients—including seronegative occult HBV infection—means serology alone may give false reassurance. Combined HBsAg/anti‐HBc serology with HBV DNA testing is therefore recommended to detect occult infection and assess reactivation risk in this high‐risk group.
- Open Access
- 27 August 2026
- Published by Karya Journal of Health Science in Karya Journal of Health Science
- Vol. 7 (2) , 65-72
ANTIMICROBIAL RESISTANCE AND CLINICAL OUTCOMES OF BLOODSTREAM INFECTIONS IN A CARDIOVASCULAR SURGERY DEPARTMENT
Objective: Bloodstream infections (BSIs) following cardiovascular surgery and cardiovascular interventions are major postoperative complications associated with substantial morbidity and mortality. Although antimicrobial resistance (AMR) has become an increasingly important global public health concern, this study aimed to clarify its impact on clinical outcomes in patients who develop postoperative BSIs.Method: This retrospective study included 139 adult patients who developed BSIs after cardiovascular surgery or cardiovascular interventions at a tertiary referral center. The associations of multidrug resistance (MDR), carbapenem resistance (CR), methicillin resistance, and penicillin resistance with mortality, hospital length of stay (LOS), intensive care unit (ICU) stay, and mechanical ventilation duration were evaluated. Independent predictors of mortality were identified using multivariable logistic regression analysis.Results: The overall mortality rate was 30.9%. Gram-negative pathogens accounted for 56.8% of BSIs and Gram-positive pathogens for 43.2%. Staphylococcus species were the most frequently isolated pathogens (33.8%), comprising other Staphylococcus species (26.6%) and Staphylococcus aureus (7.2%), followed by Klebsiella pneumoniae (21.6%) and Acinetobacter baumannii (12.9%). Neither MDR nor CR was significantly associated with mortality (p>0.05). However, among patients with Gram-negative BSIs, carbapenem-resistant isolates were associated with significantly longer hospital, and ICU stays than carbapenem-susceptible isolates (both p=0.006). Univariable analyses showed significant associations between mortality and Gram-negative BSIs, diabetes mellitus, hypertension, and surgical procedure type. Multivariable analysis identified prolonged cardiopulmonary bypass (CPB) duration (OR=1.015, 95% CI: 1.005–1.025; p=0.003) and Gram-negative BSI (OR=3.938, 95% CI: 1.225–12.659; p=0.021) as independent predictors of mortality.Conclusion: AMR was associated with greater healthcare resource utilization, particularly prolonged hospital and ICU stays, but was not significantly associated with mortality in this cohort. In contrast, Gram-negative BSIs and prolonged CPB duration were independent predictors of mortality.
- 27 August 2026
- Published by Karya Journal of Health Science in Karya Journal of Health Science
- Vol. 7 (2) , 65-72
Open AccessANTIMICROBIAL RESISTANCE AND CLINICAL OUTCOMES OF BLOODSTREAM INFECTIONS IN A CARDIOVASCULAR SURGERY DEPARTMENT
Objective: Bloodstream infections (BSIs) following cardiovascular surgery and cardiovascular interventions are major postoperative complications associated with substantial morbidity and mortality. Although antimicrobial resistance (AMR) has become an increasingly important global public health concern, this study aimed to clarify its impact on clinical outcomes in patients who develop postoperative BSIs.Method: This retrospective study included 139 adult patients who developed BSIs after cardiovascular surgery or cardiovascular interventions at a tertiary referral center. The associations of multidrug resistance (MDR), carbapenem resistance (CR), methicillin resistance, and penicillin resistance with mortality, hospital length of stay (LOS), intensive care unit (ICU) stay, and mechanical ventilation duration were evaluated. Independent predictors of mortality were identified using multivariable logistic regression analysis.Results: The overall mortality rate was 30.9%. Gram-negative pathogens accounted for 56.8% of BSIs and Gram-positive pathogens for 43.2%. Staphylococcus species were the most frequently isolated pathogens (33.8%), comprising other Staphylococcus species (26.6%) and Staphylococcus aureus (7.2%), followed by Klebsiella pneumoniae (21.6%) and Acinetobacter baumannii (12.9%). Neither MDR nor CR was significantly associated with mortality (p>0.05). However, among patients with Gram-negative BSIs, carbapenem-resistant isolates were associated with significantly longer hospital, and ICU stays than carbapenem-susceptible isolates (both p=0.006). Univariable analyses showed significant associations between mortality and Gram-negative BSIs, diabetes mellitus, hypertension, and surgical procedure type. Multivariable analysis identified prolonged cardiopulmonary bypass (CPB) duration (OR=1.015, 95% CI: 1.005–1.025; p=0.003) and Gram-negative BSI (OR=3.938, 95% CI: 1.225–12.659; p=0.021) as independent predictors of mortality.Conclusion: AMR was associated with greater healthcare resource utilization, particularly prolonged hospital and ICU stays, but was not significantly associated with mortality in this cohort. In contrast, Gram-negative BSIs and prolonged CPB duration were independent predictors of mortality.
- Open Access
- 30 July 2026
- Published by Springer Nature in Journal of Medical Case Reports
- Vol. 20 (1)
Spinal infection by Enterobacter hormaechei: an unusual cause of spondylodiscitis: a case report
Introduction: Spondylodiscitis is an infectious condition involving the intervertebral disc and adjacent vertebral bodies. Although Staphylococcus aureus and Mycobacterium tuberculosis are the most common pathogens, cases caused by Gram-negative bacilli are relatively rare. Enterobacter hormaechei is an exceptionally uncommon etiologic agent in this context. Case presentation: A 69-year-old Turkish male with type 2 diabetes mellitus and a history of prostate adenocarcinoma in remission, with no active immunosuppression, presented with lower back pain and elevated inflammatory markers. Initially suspected to have metastatic spinal involvement, spinal MRI revealed spondylodiscitis at the T12–L1 level. Microbiological evaluation of the needle biopsy specimen yielded Enterobacter hormaechei . Species-level identification was established by culture and MALDI-TOF MS, with off-label syndromic PCR testing (BIOFIRE ® Joint Infection Panel) providing supportive concordant results. The patient was successfully managed with surgical intervention and appropriate antimicrobial therapy. Discussion: Spondylodiscitis due to Enterobacter hormaechei remains exceedingly rare. This case highlights the importance of considering atypical Gram-negative organisms in spinal infections and underscores the value of advanced microbiological methods for accurate species-level identification.
- 30 July 2026
- Published by Springer Nature in Journal of Medical Case Reports
- Vol. 20 (1)
Open AccessSpinal infection by Enterobacter hormaechei: an unusual cause of spondylodiscitis: a case report
Introduction: Spondylodiscitis is an infectious condition involving the intervertebral disc and adjacent vertebral bodies. Although Staphylococcus aureus and Mycobacterium tuberculosis are the most common pathogens, cases caused by Gram-negative bacilli are relatively rare. Enterobacter hormaechei is an exceptionally uncommon etiologic agent in this context. Case presentation: A 69-year-old Turkish male with type 2 diabetes mellitus and a history of prostate adenocarcinoma in remission, with no active immunosuppression, presented with lower back pain and elevated inflammatory markers. Initially suspected to have metastatic spinal involvement, spinal MRI revealed spondylodiscitis at the T12–L1 level. Microbiological evaluation of the needle biopsy specimen yielded Enterobacter hormaechei . Species-level identification was established by culture and MALDI-TOF MS, with off-label syndromic PCR testing (BIOFIRE ® Joint Infection Panel) providing supportive concordant results. The patient was successfully managed with surgical intervention and appropriate antimicrobial therapy. Discussion: Spondylodiscitis due to Enterobacter hormaechei remains exceedingly rare. This case highlights the importance of considering atypical Gram-negative organisms in spinal infections and underscores the value of advanced microbiological methods for accurate species-level identification.
- 7 July 2026
- Published by Springer Nature in Journal of Imaging Informatics in Medicine
- p. 1-13
From Gram Stain to Decision Support: Performance of Multimodal Large Language Models in Blood Culture Microscopy
Multimodal large language models (LLMs) offer significant potential for image-based diagnostics, yet their reliability in routine clinical microbiology workflows, specifically Gram stain interpretation, remains insufficiently characterized. In this prospective diagnostic accuracy study, 100 Gram-stained blood culture smear images from routine laboratory workflows were evaluated by three multimodal LLMs (ChatGPT-4o, Gemini 2.5 Flash, and Claude Opus). Models were assessed using standardized zero-shot prompts across two independent runs to evaluate intramodel consistency. Performance was benchmarked against three expert medical microbiologists and automated organism identification (reference standard) across Gram type, major morphology, combined classification, and fine-grained sub-details. Expert microbiologists achieved 100% concordance with the reference standard for the predefined primary categories of Gram type and major morphology. LLM accuracy was high for Gram-type classification (95–98%) but lower for cellular morphology (84–85%), resulting in combined accuracies of 82–84%. No significant inter-model differences were observed in primary tasks. Intramodel consistency was high across runs (Cohen’s κ = 0.73–0.96). However, performance declined for morphological sub-details, where ChatGPT and Gemini significantly outperformed Claude. Organism-level accuracy was high for Gram-positive cocci and Gram-negative bacilli but substantially lower for Gram-positive bacilli and yeast. Multimodal large language models show promising baseline performance in Gram-stained blood culture interpretation, particularly for Gram type and major morphology. However, reduced accuracy in combined interpretation, fine-grained morphology, and less common organism classes highlights current limitations of out-of-the-box models. These findings support the use of multimodal LLMs as expert-supervised decision-support tools rather than standalone systems and emphasize the need for task-specific optimization and multicenter validation before routine clinical implementation.
- 7 July 2026
- Published by Springer Nature in Journal of Imaging Informatics in Medicine
- p. 1-13
From Gram Stain to Decision Support: Performance of Multimodal Large Language Models in Blood Culture Microscopy
Multimodal large language models (LLMs) offer significant potential for image-based diagnostics, yet their reliability in routine clinical microbiology workflows, specifically Gram stain interpretation, remains insufficiently characterized. In this prospective diagnostic accuracy study, 100 Gram-stained blood culture smear images from routine laboratory workflows were evaluated by three multimodal LLMs (ChatGPT-4o, Gemini 2.5 Flash, and Claude Opus). Models were assessed using standardized zero-shot prompts across two independent runs to evaluate intramodel consistency. Performance was benchmarked against three expert medical microbiologists and automated organism identification (reference standard) across Gram type, major morphology, combined classification, and fine-grained sub-details. Expert microbiologists achieved 100% concordance with the reference standard for the predefined primary categories of Gram type and major morphology. LLM accuracy was high for Gram-type classification (95–98%) but lower for cellular morphology (84–85%), resulting in combined accuracies of 82–84%. No significant inter-model differences were observed in primary tasks. Intramodel consistency was high across runs (Cohen’s κ = 0.73–0.96). However, performance declined for morphological sub-details, where ChatGPT and Gemini significantly outperformed Claude. Organism-level accuracy was high for Gram-positive cocci and Gram-negative bacilli but substantially lower for Gram-positive bacilli and yeast. Multimodal large language models show promising baseline performance in Gram-stained blood culture interpretation, particularly for Gram type and major morphology. However, reduced accuracy in combined interpretation, fine-grained morphology, and less common organism classes highlights current limitations of out-of-the-box models. These findings support the use of multimodal LLMs as expert-supervised decision-support tools rather than standalone systems and emphasize the need for task-specific optimization and multicenter validation before routine clinical implementation.
- Open Access
- 25 May 2026
- Published by MDPI AG in Biomedicines
- Vol. 14 (6) , 1191
Serological and Demographic Correlates of HBV DNA Detection Below the Limit of Quantification in Treated Chronic Hepatitis B and HBsAg-Negative Patients
Objectives: This study aimed to evaluate very low HBV DNA viral load below the limit of quantification and to identify correlational factors in different patient groups, including individuals with chronic hepatitis B (CHB), occult HBV infection (OBI), and others. Methods: We retrospectively analyzed 390 patients with very low-level viremia (VLLV). HBV DNA levels were measured in plasma samples using real-time quantitative PCR (qPCR). Serological markers were evaluated in serum samples using chemiluminescence microparticle immunoassay (CMIA). Demographic variables, HBV serological markers (anti-HBs, anti-HBe, anti-HBc), and DNA results were evaluated. Results: The study included 193 CHB patients with maintained virological suppression and 197 patients in the other group; of which, 60 patients had occult hepatitis B infection (HBV DNA positive, HBsAg negative) and 137 had no occult hepatitis B infection. Very low viral load was more common in men (53.3%) and in individuals aged ≥50 years (63.3%). In univariate analysis, OBI was associated with anti-HBe (odds ratio (OR) = 2.874, 95% CI: 1.255–6.579, p = 0.013), and anti-HBc seropositivity (OR = 5.750; 95% CI: 2.626–12.591, p < 0.001). In multivariate analysis, anti-HBe positivity and anti-HBc positivity were independently associated with OBI. Anti-HBs positivity was independently and inversely associated with OBI. Conclusions: In patients with VLLV cohort, anti-HBc and anti-HBe seropositivity were independently associated with detectable but unquantifiable HBV DNA. Although anti-HBe positivity reflects reduced viral replication, it does not indicate complete viral suppression and may be detected at very low viremia levels, especially in occult HBV infection. These findings highlight the complex interplay between viral replication dynamics and host immune responses across the VLLV spectrum, characterize the serological landscape associated with detectable but unquantifiable HBV DNA, and warrant validation in prospective studies.
- 25 May 2026
- Published by MDPI AG in Biomedicines
- Vol. 14 (6) , 1191
Open AccessSerological and Demographic Correlates of HBV DNA Detection Below the Limit of Quantification in Treated Chronic Hepatitis B and HBsAg-Negative Patients
Objectives: This study aimed to evaluate very low HBV DNA viral load below the limit of quantification and to identify correlational factors in different patient groups, including individuals with chronic hepatitis B (CHB), occult HBV infection (OBI), and others. Methods: We retrospectively analyzed 390 patients with very low-level viremia (VLLV). HBV DNA levels were measured in plasma samples using real-time quantitative PCR (qPCR). Serological markers were evaluated in serum samples using chemiluminescence microparticle immunoassay (CMIA). Demographic variables, HBV serological markers (anti-HBs, anti-HBe, anti-HBc), and DNA results were evaluated. Results: The study included 193 CHB patients with maintained virological suppression and 197 patients in the other group; of which, 60 patients had occult hepatitis B infection (HBV DNA positive, HBsAg negative) and 137 had no occult hepatitis B infection. Very low viral load was more common in men (53.3%) and in individuals aged ≥50 years (63.3%). In univariate analysis, OBI was associated with anti-HBe (odds ratio (OR) = 2.874, 95% CI: 1.255–6.579, p = 0.013), and anti-HBc seropositivity (OR = 5.750; 95% CI: 2.626–12.591, p < 0.001). In multivariate analysis, anti-HBe positivity and anti-HBc positivity were independently associated with OBI. Anti-HBs positivity was independently and inversely associated with OBI. Conclusions: In patients with VLLV cohort, anti-HBc and anti-HBe seropositivity were independently associated with detectable but unquantifiable HBV DNA. Although anti-HBe positivity reflects reduced viral replication, it does not indicate complete viral suppression and may be detected at very low viremia levels, especially in occult HBV infection. These findings highlight the complex interplay between viral replication dynamics and host immune responses across the VLLV spectrum, characterize the serological landscape associated with detectable but unquantifiable HBV DNA, and warrant validation in prospective studies.
- Open Access
- 30 April 2026
- Published by MDPI AG in Preprints.org
Clinical Significance of Very Low Level Viremia in HBV DNA Test: Challenges in Interpreting Positive PCR Results Under the Limit of Quantification
Objectives: This study aimed to evaluate very low HBV DNA viral load below the limit of quantification and to identify associated risk factors in different patient groups, including individuals with chronic hepatitis B, occult HBV infection (OBI) and others. Methods: We retrospectively analyzed 390 patients with very low-level viremia (VLLV). HBV DNA levels were measured in plasma samples using real-time RT-qPCR. Serological markers were evaluated in serum samples using chemiluminescence microparticle immunoassay (CMIA). Demographic variables, HBV serological markers (anti-HBs, anti-HBe, anti-HBc), and DNA results were evaluated. Results: The study included 193 patients in the sustained virological response (SVR) group and 197 patients in the other group; 60 of these patients had occult hepatitis B infection (HBV DNA positive, HBsAg negative) and 137 had no occult hepatitis B infection. Very low viral load was more common in men (53.3%) and in individuals aged ≥50 years (63.3%). In univariate analysis, OBI was associated with anti-HBe (odds ratio (OR)=2.874, 95%CI:1.256-6.172, p=0.012), anti-HBc seropositivity (OR=2.368; 95%CI:1.216-4.527, p=0.008), and being ≥50 years age (OR=1.845, 95% CI:0.963-3.473, p=0.077). In multivariate analysis, being ≥50 years of age, anti-HBe positivity, and anti-HBc positivity were independently associated with OBI. Among SVR patients, VLLV was associated with older age and anti-HBc positivity, but no significant association was observed with gender, anti-HBe, or anti-HBs status. Conclusions: In patients with VLLV, anti-HBc and anti-HBe seropositivity, along with older age, were independently associated with lower HBV DNA levels. Although anti-HBe positivity reflects reduced viral replication, it does not indicate complete viral suppression and may be detected at very low viremia levels, particularly in occult HBV infection. These findings highlight the complex interplay between viral replication dynamics and host immune responses across the VLLV spectrum, and emphasize the need for individualized monitoring strategies. Further validation through prospective studies is warranted.
- 30 April 2026
- Published by MDPI AG in Preprints.org
Open AccessClinical Significance of Very Low Level Viremia in HBV DNA Test: Challenges in Interpreting Positive PCR Results Under the Limit of Quantification
Objectives: This study aimed to evaluate very low HBV DNA viral load below the limit of quantification and to identify associated risk factors in different patient groups, including individuals with chronic hepatitis B, occult HBV infection (OBI) and others. Methods: We retrospectively analyzed 390 patients with very low-level viremia (VLLV). HBV DNA levels were measured in plasma samples using real-time RT-qPCR. Serological markers were evaluated in serum samples using chemiluminescence microparticle immunoassay (CMIA). Demographic variables, HBV serological markers (anti-HBs, anti-HBe, anti-HBc), and DNA results were evaluated. Results: The study included 193 patients in the sustained virological response (SVR) group and 197 patients in the other group; 60 of these patients had occult hepatitis B infection (HBV DNA positive, HBsAg negative) and 137 had no occult hepatitis B infection. Very low viral load was more common in men (53.3%) and in individuals aged ≥50 years (63.3%). In univariate analysis, OBI was associated with anti-HBe (odds ratio (OR)=2.874, 95%CI:1.256-6.172, p=0.012), anti-HBc seropositivity (OR=2.368; 95%CI:1.216-4.527, p=0.008), and being ≥50 years age (OR=1.845, 95% CI:0.963-3.473, p=0.077). In multivariate analysis, being ≥50 years of age, anti-HBe positivity, and anti-HBc positivity were independently associated with OBI. Among SVR patients, VLLV was associated with older age and anti-HBc positivity, but no significant association was observed with gender, anti-HBe, or anti-HBs status. Conclusions: In patients with VLLV, anti-HBc and anti-HBe seropositivity, along with older age, were independently associated with lower HBV DNA levels. Although anti-HBe positivity reflects reduced viral replication, it does not indicate complete viral suppression and may be detected at very low viremia levels, particularly in occult HBV infection. These findings highlight the complex interplay between viral replication dynamics and host immune responses across the VLLV spectrum, and emphasize the need for individualized monitoring strategies. Further validation through prospective studies is warranted.
- 23 October 2025
- Published by Bilimsel Tip Publishing House in Mikrobiyoloji Bulteni
- Vol. 59 (4) , 517-524
Farklı Besiyerlerinin Malassezia furfur’un Kompozit Korelasyon İndeksine Dayalı MALDI-TOF MS Analizi Verilerine Etkisi
Matriks destekli lazer desorpsiyon iyonizasyon uçuş süresi kütle spektrometrisi [matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS)] mikrobiyoloji alanında oldukça geniş kullanım alanı bulmuştur. Cihazdan elde edilen spektrumlar ile küçük pik verilerin de analize alındığı kompozit indeks [composite indicator (CI)] analizleri mikrobiyal farklılıkların incelenmesinde önemli bir yöntemdir. Dış faktörlerin hücre kompozisyonu üzerine etkilerinin incelenmesinde birleşik korelasyon indeksi (CCI); spektrum verilerinin grup halinde analizine imkan tanımaktadır. Son yıllarda, klinik örneklerden giderek artan sayıda Malassezia furfur izolasyonu yapılmaktadır. Bu patojenin lipide bağlı üreme özelliği nedeniyle Sabouraud'un dekstroz agarı gibi rutin mikolojide kullanılan besiyerlerinde üremesi olmamaktadır. Gereksinim halinde her laboratuvarın kendine ait uygun besiyerini hazırlayarak kullanması önerilmektedir. Ancak Malassezia mayalarının üretilmesi için tanımlanan besiyerlerinde içerikler ve miktarları çok farklılıklar gösterir. Modifiye Dixon agar (mDA), modifiye Leeming and Notman agar (mLNA) ve FastFung agar (FFA) besiyerleri hem primer kültür ortamı olarak hem de araştırmalarda yaygın olarak kullanılır. Bu besiyerindeki içerik çeşitliliğinin farklı spektrumların oluşmasına neden olması mümkündür. Bu çalışmada, lipofilik M.furfur izolatlarının farklı besiyerlerinde üretilmeleriyle elde edilen MALDI-TOF MS spektrumları arasındaki ilişkinin incelenmesi ve rutin uygulamada kullanılabilirliğinin sorgulanması amaçlanmıştır. Araştırmaya alınan 17 M.furfur izolatı mDA, mLNA ve FFA agarda üretilmiştir. İzolatların MALDI-TOF MS spektrumlarının CI analizleri yapılmış ve CCI verileri karşılaştırılmıştır. Araştırmaya alınan izolatlar için FFA ve mLNA besiyerleri arasında CI değerleri arasında fark saptanmazken (p> 0.05), her iki besiyeri de mDA besiyerine göre daha yüksek CI değerlerine sahip bulunmuştur (p< 0.05). Besiyerleri için basıklık (kurtosis) değerleri FFA, mLNA ve mDA için sırasıyla 1.83, -0.56 ve -1.16 olarak hesaplanmıştır. Çalışmada mDA besiyerinin platikurtik verilere sahip olması, yaygın olarak kullanılmasına rağmen zaman kaybettirecek spektroskopik analizlere neden olacağını düşündürmektedir. Tween 60 ile hazırlanan FFA ve mLNA besiyerlerinde yüksek CI değerlerinin bulunması, MALDI-TOF MS gibi yöntemlerin M.furfur analizlerinde standardizasyon için daha kullanılabilir olduğunu göstermektedir. Tween farklılıkları, MALDI-TOF MS analizinde tween uzaklaştırma protokollerinin verimini de etkileyecektir. Farklı verilerin elde edilmesi, CI gibi küçük spektral verilerin işleme alınması protokollerinin besiyeri standardizasyonunda gereklilik olduğunu göstermektedir. Besiyeri birlikteliğinin sağlanması laboratuvarlar arasında karşılaştırılabilir verilerin elde edilmesini de kolaylaştıracaktır.
- 23 October 2025
- Published by Bilimsel Tip Publishing House in Mikrobiyoloji Bulteni
- Vol. 59 (4) , 517-524
Farklı Besiyerlerinin Malassezia furfur’un Kompozit Korelasyon İndeksine Dayalı MALDI-TOF MS Analizi Verilerine Etkisi
Matriks destekli lazer desorpsiyon iyonizasyon uçuş süresi kütle spektrometrisi [matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS)] mikrobiyoloji alanında oldukça geniş kullanım alanı bulmuştur. Cihazdan elde edilen spektrumlar ile küçük pik verilerin de analize alındığı kompozit indeks [composite indicator (CI)] analizleri mikrobiyal farklılıkların incelenmesinde önemli bir yöntemdir. Dış faktörlerin hücre kompozisyonu üzerine etkilerinin incelenmesinde birleşik korelasyon indeksi (CCI); spektrum verilerinin grup halinde analizine imkan tanımaktadır. Son yıllarda, klinik örneklerden giderek artan sayıda Malassezia furfur izolasyonu yapılmaktadır. Bu patojenin lipide bağlı üreme özelliği nedeniyle Sabouraud'un dekstroz agarı gibi rutin mikolojide kullanılan besiyerlerinde üremesi olmamaktadır. Gereksinim halinde her laboratuvarın kendine ait uygun besiyerini hazırlayarak kullanması önerilmektedir. Ancak Malassezia mayalarının üretilmesi için tanımlanan besiyerlerinde içerikler ve miktarları çok farklılıklar gösterir. Modifiye Dixon agar (mDA), modifiye Leeming and Notman agar (mLNA) ve FastFung agar (FFA) besiyerleri hem primer kültür ortamı olarak hem de araştırmalarda yaygın olarak kullanılır. Bu besiyerindeki içerik çeşitliliğinin farklı spektrumların oluşmasına neden olması mümkündür. Bu çalışmada, lipofilik M.furfur izolatlarının farklı besiyerlerinde üretilmeleriyle elde edilen MALDI-TOF MS spektrumları arasındaki ilişkinin incelenmesi ve rutin uygulamada kullanılabilirliğinin sorgulanması amaçlanmıştır. Araştırmaya alınan 17 M.furfur izolatı mDA, mLNA ve FFA agarda üretilmiştir. İzolatların MALDI-TOF MS spektrumlarının CI analizleri yapılmış ve CCI verileri karşılaştırılmıştır. Araştırmaya alınan izolatlar için FFA ve mLNA besiyerleri arasında CI değerleri arasında fark saptanmazken (p> 0.05), her iki besiyeri de mDA besiyerine göre daha yüksek CI değerlerine sahip bulunmuştur (p< 0.05). Besiyerleri için basıklık (kurtosis) değerleri FFA, mLNA ve mDA için sırasıyla 1.83, -0.56 ve -1.16 olarak hesaplanmıştır. Çalışmada mDA besiyerinin platikurtik verilere sahip olması, yaygın olarak kullanılmasına rağmen zaman kaybettirecek spektroskopik analizlere neden olacağını düşündürmektedir. Tween 60 ile hazırlanan FFA ve mLNA besiyerlerinde yüksek CI değerlerinin bulunması, MALDI-TOF MS gibi yöntemlerin M.furfur analizlerinde standardizasyon için daha kullanılabilir olduğunu göstermektedir. Tween farklılıkları, MALDI-TOF MS analizinde tween uzaklaştırma protokollerinin verimini de etkileyecektir. Farklı verilerin elde edilmesi, CI gibi küçük spektral verilerin işleme alınması protokollerinin besiyeri standardizasyonunda gereklilik olduğunu göstermektedir. Besiyeri birlikteliğinin sağlanması laboratuvarlar arasında karşılaştırılabilir verilerin elde edilmesini de kolaylaştıracaktır.