The usefulness of anti-HCV signal to cut-off ratio in predicting hepatitis C viremia and the effect of genotype differences on signal to cut-off ratio.

OBJECTIVE: In the hepatitis C virus (HCV) diagnostic algorithm, an anti-HCV screening test is recommended first. In countries with low HCV prevalence, anti-HCV testing can often give false-positive results. This may lead to unnecessary retesting, increased costs, and psychological stress for patients. METHODS: In this study, the most appropriate S/Co (signal-cutoff) value to predict HCV viremia in anti-HCV test(+) individuals was determined, and the effect of genotype differences was evaluated. Of the 96,515 anti-HCV tests performed between 2020 and 2023, 934 were reactive. A total of 332 retests and 65 patients without HCV-ribonucleic acid (RNA) analysis were excluded. Demographic data were calculated for 537 patients, and 130 patients were included in the study. RESULTS: The average age of 537 patients was 55±18 years, and 57.1% were women. The anti-HCV positivity rate was 0.62% (602/96,515), and the actual anti-HCV positivity rate was 0.13% (130/96,515). Anti-HCV levels were higher in HCV-RNA(+) patients than in HCV-RNA-negative individuals (p<0.0001) (Table 1). Receiver operating characteristic curve analysis identified the optimal S/Co value to be 10.86 to identify true positive cases. Sensitivity was 96.1%, specificity was 61.2%, positive predictive value (PPV) was 44.2%, and negative predictive value (NPV) was 98% (Figure 2). A total of 107 (82.3%) of the patients were identified as GT1, and the most common subtype was GT1b (n=100). CONCLUSION: If anti-HCV S/Co is ≥10.86, direct HCV RNA testing may be recommended; However, the possibility of false positivity should be considered in patients with a S/Co value below 10.86.

High antibiotic resistance rates in Helicobacter pylori strains in Turkey over 20 years: implications for gastric disease treatment.

OBJECTIVE: Helicobacter pylori (Hp) eradication therapy is crucial for preventing the development of gastritis, peptic ulcers, and gastric cancer. An increase in resistance against antibiotics used in the eradication of Hp is remarkable. This meta-analysis aims to examine the resistance rates of Hp strains isolated in Turkey over the last 20 years against clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LVX), tetracycline (TET), and amoxicillin (AMX) antibiotics. BASIC METHODS: Literature search was carried out in electronic databases, by searching articles published in Turkish and English with the keywords ' helicobacter pylori ' or 'Hp' and 'antibiotic resistance' and 'Turkey'. That meta-analysis was carried out using random-effect model. First, the 20-year period data between 2002 and 2021 in Turkey were planned to be analyzed. As a second stage, the period between 2002 and 2011 was classified as Group 1, and the period between 2012 and 2021 as Group 2 for analysis, with the objective of revealing the 10-year temporal variation in antibiotic resistance rates. MAIN RESULTS: In gastric biopsy specimens, 34 data from 29 studies were included in the analysis. Between 2002-2021, CLR resistance rate was 30.9% (95% CI: 25.9-36.2) in 2615 Hp strains. Specifically, in Group 1, the CLR resistance rate was 31% in 1912 strains, and in Group 2, it was 30.7% in 703 strains. The MTZ resistance rate was found to be 31.9% (95% CI: 19.8-45.4) in 789 strains, with rates of 21.5% in Group 1 and 46.6% in Group 2. The overall LVX resistance rate was 25.6%, with rates of 26.9% in Group 1 and 24.8% in Group 2. The 20-year TET resistance rate was 0.8%, with 1.50% in Group 1 and 0.2% in Group 2. The overall AMX resistance rate was 2.9%, 3.8% between 2002-2011, and 1.4% between 2012-2021. PRINCIPAL CONCLUSION: Hp strains in Turkey exhibit high resistance rates due to frequent use of CLR, MTZ, and LVX antibiotics. However, a significant decrease has been observed in TET and AMX resistance to Hp in the last 10 years. Considering the CLR resistance rate surpasses 20%, we suggest reconsidering the use of conventional triple drug therapy as a first-line treatment. Instead, we recommend bismuth-containing quadruple therapy or sequential therapies (without bismuth) for first-line treatment, given the lower rates of TET and AMX resistance. Regimens containing a combination of AMX, CLR, and MTZ should be given priority in second-line therapy. Finally, in centers offering culture and antibiogram opportunities, regulating the Hp eradication treatment based on the antibiogram results is obviously more appropriate.

Molecular epidemiological investigation of carbapenem resistant Klebsiella pneumoniae isolated from intensive care unit patients of six geographical regions of Turkey.

INTRODUCTION: Klebsiella pneumonia causes serious infections in hospitalized patients. In recent years, carbapenem-resistant infections increased in the world. The molecular epidemiological investigation of carbapenem-resistant K. pneumoniae isolates was aimed in this study. METHODOLOGY: Fifty carbapenem-resistant K. pneumoniae isolates from six geographical regions of Turkey between September 2019-2020 were included in the study. The disk diffusion method was used for the antibiotic susceptibility testing. The microdilution confirmed colistin susceptibility. Genetic diversity was investigated by MLST (Multi-Locus Sequence Typing). RESULTS: The resistance rates were as follows: 49 (98%) for meropenem, 47 (94%) imipenem, 50 (100%) ertapenem, 30 (60%) colistin and amoxicillin-clavulanate, 49 (98%) ceftriaxone, 48 (96%) cefepime, 50 (100%) piperacillin-tazobactam, 47 (94%) ciprofloxacin, 40 (80%) amikacin, 37 (74%) gentamicin. An isolate resistant to colistin by disk diffusion was found as susceptible to microdilution. ST 2096 was the most common (n:16) sequence type by MLST. ST 101 (n:7), ST14 (n:6), ST 147 and ST 15 (n:4), ST391 (n:3), ST 377 and ST16 (n:2), ST22, ST 307, ST 985, ST 336, ST 345, and ST 3681 (n:1) were classified in other isolates. In Istanbul and Ankara ST2096 was common. Among Turkey isolates, the most common clonal complexes (CC) were CC14 (n:26) and CC11 (n = 7). CONCLUSIONS: In Turkey, a polyclonal population of CC14 throughout the country and inter-hospital spread were indicated. The use of molecular typing tools will highlight understanding the transmission dynamics.

A meta-analysis of antibiotic resistance rates in Pseudomonas aeruginosa isolated in blood cultures in Turkey between 2007 and 2017.

OBJECTIVE: The prevalence of Pseudomonas aeruginosa has remained stable in recent years, and resistant strains has increased dramatically. In this meta-analysis, we aimed to analyze the P. aeruginosa strains isolated from blood cultures in Turkey during the last 11 years and to reveal their antimicrobial susceptibility. METHODS: Data collected between 2007 and 2017 were divided into two groups as Group-1; 2007-2011 and Group-2; 2012-2017. The differences in antibiotic resistance rates between Group-1 and Group-2 were analyzed. The study data were included according to PRISMA criteria, then meta-analysis was performed. RESULTS: A total of 30 study data from 25 studies were included in the study. The prevalence rate of meropenem (MEM) resistance in P. aeruginosa in Turkey was 25.1% (95% Cl: 20.65-29.83) according to a meta-analysis of 637 isolates. MEM resistance rates in Group-1 and Group-2 were 23.4% (95% Cl: 18.34-28.99) and 29.3% (95% Cl: 21.23-38.23), respectively. The prevalence rate of imipenem (IMP) resistance in P. aeruginosa in Turkey was 26.8% (%95 Cl: 23.40-30.35) according to a meta-analysis of 1421 isolates. IMP resistance rates in Group-1 and Group-2 were 26.2% (95% Cl: 22.41-30.27) and 28.4% (95% Cl: 21.57-35.88), respectively. Ciprofloxacin (CIP) resistance rate was 27.04% (95% Cl: 21.88-32.52) in 1388 isolates. CIP resistance rates in Group-1 and Group-2 were 30.8% (95% Cl: 24.35-37.56) and 18.6% (95% Cl: 10.72-28.11), respectively. The prevalence rate of piperacillin-tazobactam (TZP) resistance in P. aeruginosa in Turkey was 29.2% (95% Cl: 21.058-38.088) according to a meta-analysis of 1030 isolates. TZP resistance rates in Group-1 and Group-2 were 26.1% (95% Cl: 17.76-35.31) and 38.2% (95% Cl: 18.48-60.27), respectively. CONCLUSION: There is a remarkable increase in resistance rates in P. aeruginosa to MEM and TZP in Turkey due to frequent use. Other antibiotics with antipseudomonal effect should be prioritized in the treatment of these infections.

Real-World Data from Turkey: Is Sofosbuvir/Ledipasvir With or Without Ribavirin Treatment for Chronic Hepatitis C Really Effective?

BACKGROUND: In this study, we aimed to investigate the efficacy and safety of sofosbuvir-based therapies in the treatment of chronic hepatitis C in real-world clinical practice. METHODS: Data from patients with chronic hepatitis C treated with SOF/LDV ± RBV or SOF/RBV in 31 centers across Turkey between April 1, 2017, and August 31, 2018, were recorded in a nationwide database among infectious disease specialists. Demographics, clinical, and virological outcomes were analyzed. RESULTS: A total of 552 patients were included in the study. The mean age of the patients was 51.28 ± 14.2, and 293 (55.8%) were female. The majority had HCV genotype 1b infection (65%), 75.04% of the patients underwent treatment, and non-cirrhosis was present at baseline in 381 patients (72.6%). SOF/LDV ± RBV treatment was given to 477 patients and 48 patients received SOF/RBV according to HCV genotype. The total SVR12 rate was 99% in all patients. Five patients experienced disease relapse during the study and all of them were genotype 2. In patients infected with HCV GT2, SVR12 was 77.3%. SVR was 100% in all patients infected with other HCV genotypes. All treatments were well tolerated by patients without causing severe adverse events. Side effects and side effects-associated treatment discontinuation rates were 28.2% and 0.4%, respectively. Weakness (13.7%) was the common side effect. CONCLUSION: The present real-world data of 525 patients with HCV genotypes 1, 1a, 1b, 3, 4, and 5 who underwent SOF/LDV ± RBV treatment in Turkey demonstrated a high efficacy and safety profile. HCV GT2 patients should be treated with more efficacious treatment.

Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients.

BACKGROUND AND OBJECTIVES: An effective treatment option is not yet available for SARS-CoV2, which causes the COVID-19 pandemic and whose effects are felt more and more every day. Ivermectin is among the drugs whose effectiveness in treatment has been investigated. In this study; it was aimed to investigate the presence of gene mutations that alter ivermectin metabolism and cause toxic effects in patients with severe COVID-19 pneumonia, and to evaluate the effectiveness and safety of ivermectin use in the treatment of patients without mutation. MATERIALS AND METHODS: Patients with severe COVID19 pneumonia were included in the study, which was planned as a prospective, randomized, controlled, single-blind phase 3 study. Two groups, the study group and the control group, took part in the study. Ivermectin 200 mcg/kg/day for 5 days in the form of a solution prepared for enteral use added to the reference treatment protocol -hydroxychloroquine + favipiravir + azithromycin- of patients included in the study group. Patients in the control group were given only reference treatment with 3 other drugs without ivermectin. The presence of mutations was investigated by performing sequence analysis in the mdr1/abcab1 gene with the Sanger method in patients included in the study group according to randomization. Patients with mutations were excluded from the study and ivermectin treatment was not continued. Patients were followed for 5 days after treatment. At the end of the treatment and follow-up period, clinical response and changes in laboratory parameters were evaluated. RESULTS: A total of 66 patients, 36 in the study group and 30 in the control group were included in the study. Mutations affecting ivermectin metabolism was detected in genetic tests of six (16.7%) patients in the study group and they were excluded from the study. At the end of the 5-day follow-up period, the rate of clinical improvement was 73.3% (22/30) in the study group and was 53.3% (16/30) in the control group (p = 0.10). At the end of the study, mortality developed in 6 patients (20%) in the study group and in 9 (30%) patients in the control group (p = 0.37). At the end of the follow-up period, the average peripheral capillary oxygen saturation (SpO2) values of the study and control groups were found to be 93.5 and 93.0%, respectively. Partial pressure of oxygen (PaO2)/FiO2 ratios were determined as 236.3 ± 85.7 and 220.8 ± 127.3 in the study and control groups, respectively. While the blood lymphocyte count was higher in the study group compared to the control group (1698 ± 1438 and 1256 ± 710, respectively) at the end of the follow-up period (p = 0.24); reduction in serum C-reactive protein (CRP), ferritin and D-dimer levels was more pronounced in the study group (p = 0.02, p = 0.005 and p = 0.03, respectively). CONCLUSIONS: According to the findings obtained, ivermectin can provide an increase in clinical recovery, improvement in prognostic laboratory parameters and a decrease in mortality rates even when used in patients with severe COVID-19. Consequently, ivermectin should be considered as an alternative drug that can be used in the treatment of COVID-19 disease or as an additional option to existing protocols.

Demographic, clinical and laboratory characteristics for differential diagnosis of peripheral lymphadenopathy (LAP) and the etiologic distribution of LAP in adults; a multicenter, nested case-control study including 1401 patients from Turkey.

Peripheral lymphadenopathy (LAP) is an important and common abnormal finding of the physical exam in general medical practice. We aimed to reveal the LAP etiology and demographic, clinical and laboratory variables that may be useful in the differential evaluation of LAP. This multicenter, nested case-control study including 1401 patients between 2014 and 2019 was conducted in 19 tertiary teaching and research hospitals from different regions in Turkey. The ratio of infectious, malign and autoimmune/inflammatory diseases was 31.3%, 5% and 0.3%, respectively. In 870 (62%) of patients had nonspecific etiology. Extrapulmonary tuberculosis (n: 235, 16.8%) was the most frequent cause of LAP. The ratio of infective etiology of LAP was significantly lower in patients older than 65 years-old compared to younger patients with the rate of 66.67% and 83.84%, respectively (p 0.016, OR 0.386, 95% Cl 0.186-0.803). The probability of malign etiology was higher both in patients who are older than 45 years-old (p < 0.001, OR 3.23, 95% Cl 1.99-5.26) and older than 65 years-old (p 0.002, OR 3.36, 95% Cl 1.69-6.68). Age, localization and duration of LAP, leukocytosis, anemia, thrombocytopenia, CRP and sedimentation rate were important parameters to differentiate infections. Size of lymph node and splenomegaly in addition to the parameters above were useful parameters for differentiating malign from benign etiology. Despite the improvements in diagnostic tools, reaching a definite differential diagnosis of lymphadenopathy is still challenging. Our results may help clinicians to decide in which cases they need an aggressive workup and set strategies on optimizing the diagnostic approach of adulthood lymphadenopathy.

Evaluation of 170 Followed-up Cases Treated for Hydatid Disease: A Multicentre Study.

OBJECTIVE: To determine the clinical characteristics of patients with cystic echinococcosis and the diagnostic and therapeutic approaches used. METHODS: This is a multicentre, retrospective study. Patients from six centres who were diagnosed with hydatid cysts in the last five years were evaluated. RESULTS: The mean age was 45.4±17.4 years, and 54.7% were female. The most common complaints were abdominal pain, nausea and vomiting, and the most common physical examination finding was abdominal tenderness. Most patients were diagnosed within 2-6 months. Anaemia and eosinophilia were the most common laboratory findings. The liver was the most commonly involved organ (n=153, 90%). One hundred twenty-five (73.5%) patients underwent ultrasonography. The largest cyst was present in the liver at stage four, and its diameter was 160x170 mm. The rates of the negative, grey zone and positive results were 9.4%, 8.8% and 81.8%. Surgery was more common (n=72, 42.4%) than puncture, aspiration, injection, and re-aspiration treatments (n=14, 8.2%). Of the 47 patients who had a recurrence, 22 (46.8%) had a history of hydatid cyst treatment. CONCLUSION: Hydatid disease, which is endemic in our country, is diagnosed at a late stage. In terms of disease diagnosis, serological tests may be misleading. It was not possible to compare the success rates according to the treatment choices because of the lack of randomisation of stages and sizes of the lesions.

Difference in Toxoplasma gondii Seroprevalence Rates Due to Low and High CD4 Counts in Patients with HIV/AIDS

Objective: Since symptomatic toxoplasmosis in in human immunodeficiency virus (HIV)/Acquired immunodeficiency syndrome (AIDS) almost always occurs as a result of reactivation of chronic infection, screening Toxoplasma serology has an important role in the follow up of the main disease in these populations. In this meta-analysis, we aimed to reveal the difference in the seroprevalence rates of Toxoplasma gondii infection between groups in relation to CD4 counts (CD4-counts ≥200 and <200 cells/mm3) HIV-infected population. Methods: The meta-analysis was performed by searching for the studies in English that were published in the last 20-year period in databases including PubMed, Google Scholar, Embase, Science Direct and Web of Science. The process of searching was carried out using the keywords: "Acquired immunodeficiency syndrome", "AIDS", "Human immunodeficiency virus", "HIV", "Toxoplasma", "Toxoplasmosis", "Toxoplasma gondii", "seroprevalence", "prevalence" and "immunoglobulin G". Results: A total of 16 studies including 3982 seropositive samples of T. gondii, 2792 of which were in first group (HIV positive patients with CD4-counts ≥200 cells/mm3) and 1190 were in second group (HIV positive patients with CD4-counts <200 cells/mm3), were included in the meta-analysis. The seroprevalence of T. gondii was 40.03% in HIV-positive patients with CD4 counts ≥200 cells/mm3, and 43.5% in the group with CD4 counts <200 cells/mm3. Seroprevalence rates in the studies included in the meta-analysis showed variability (heterogeneity) in both groups and heterogeneity between studies was higher in group 1 [Group 1; Cochran Q=994.16, DF=15, I²=98.49%, p<0.0001 and group 2; Cochran Q=368.50, DF=15, I²=95.93%, p<0.0001]. Conclusion: We concluded that HIV/AIDS patients with low CD4 counts have higher epidemiological risk as well as immunological risk of toxoplasmosis. To the best of our knowledge, this is the first meta-analysis evaluating the seroprevalence of T. gondii in AIDS/HIV population by comparing the seroprevalance of T. gondii in subgroups formed according to CD4 counts.

Overuse of prophylaxis in HBsAg and/or anti-HBc positive patients after increasing awareness to prevent reactivation in patients receiving immunosuppressive therapies: How rational are our prophylaxis decisions according to the literature?

Screening prior to initiation of immunosuppressive therapy, and decision making between the initiation of hepatitis B virus (HBV) prophylaxis and monitoring with the intent of on-demand anti-HBV therapy initiation are the key determinants to prevent reactivation of HBV. Patients over 18 years of age with HBsAg and/or anti-HBc positivity, who received HBV prophylaxis due to immunosuppressive treatments between 2013 and 2019, enrolled in this retrospective descriptive study. We tried to create awareness about the reactivation of hepatitis among clinicians in our hospital from the beginning of 2017, via warnings at the hospital data management system and via in-service training activities. Changes or differences between two-time period groups (first group between 2013 and 2016, the second between 2017 and 2018) and between four reactivation risk groups (low, moderate, high and very high) were analyzed. Of 125 patients who received immunosuppressive therapies and HBV prophylaxis, 52 (41.6%) were HBsAg positive while 73 (58.4%) were anti-HBc positive/HBsAg negative. Eighteen of the patients were in the 1st-period-years and 107 were in the second. The ratio of anti-HBc positive/HBsAg negative patients increased from 22.22% (n: 4) to 64.49% (n: 69) in the 2nd period (p: 0.001). In the 1st period, 16.67% of the patients had hepatitis B surface antibodies (anti-HBs), which increased to 46.73% during the 2nd period. The ratio of patients with HBV DNA positivity was found to be 55.56% in the first period and 33.87% in the second. Patients in the moderate (1-10%) and high (10-30%) reactivation risk groups were predominant, with rates of 38.89% and 33.33% of all the patients during the 1st period, respectively. However, the number of patients with a low reactivation risk increased 19-fold (from 2 to 38) and reached a proportion of 35.51% of all patients during the 2nd period. There was also a 6.33-fold increase (from 6 to 38) in the number of patients with high reactivation risk, reaching a rate of 35.51% during the 2nd period. None of the patients developed HBV reactivation when HBV prophylaxis was initiated before (n:11), concurrently (n:81) with or after (n:33) the immunosuppressive therapy. Awareness of HBV reactivation among clinicians has significantly increased in recent years mainly due to in-service training activities in our hospital. This rapid progress in awareness resulted in increased rates of screening for HBV and therefore increased the number of anti-HBc positive/HBsAg negative patients. However, it also led to the overuse of HBV prophylaxis even in low-risk patients.