Diagnostic approach of tuberculous lymphadenitis in a multicenter study.

INTRODUCTION: Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the demographic, clinical, and laboratory variables that differentiate TBLN from non-tuberculous lymphadenitis (NTBLN), as well as the etiology of lymphadenopathy in adults. METHODOLOGY: Patients who were over 18 years old and were referred to the infectious disease outpatient clinics with complaints of swollen peripheral lymph nodes, and who underwent lymph node biopsy between 1 January 2010 and 1 March 2021, were included in this multicenter, nested case-control study. RESULTS: A total of 812 patients at 17 tertiary teaching and research hospitals in Turkiye were included in the study. TBLN was the most frequent diagnosis (53.69%). The proportion of patients diagnosed with TBLN was higher among females; and among those who had a higher erythrocyte sedimentation rate, positive purified protein derivative test, and positive interferon-gamma release test result (p < 0.05). However, TBLN was less frequent among patients with generalized lymphadenopathy, bilateral lymphadenopathy, axillary lymphadenopathy, inguinal lymphadenopathy, hepatomegaly, splenomegaly, leukocytosis, and moderately increased C reactive protein levels (p < 0.05). CONCLUSIONS: Identifying the variables that predict TBLN or discriminate TBLN from NTBLN will help clinicians establish optimal clinical strategies for the diagnosis of adult lymphadenopathy.

Impact of vaccination on ICU admissions of hospitalized COVID-19 patients in a country with a heterologous vaccine policy.

INTRODUCTION: Vaccination against coronavirus disease-19 (COVID-19) is highly effective in preventing severe disease and mortality. Adenoviral vector and mRNA vaccines were effective against intensive care unit (ICU) admission, but the effectiveness of inactivated vaccine on ICU admission was unclear. We aimed to evaluate the effect of vaccination status on ICU admission in hospitalized COVID-19 patients in a country with heterologous vaccination policy. METHODOLOGY: This is a retrospective multicenter study conducted in three hospitals in Izmir, Turkey between 1 January 2021 and 31 March 2022. Patients aged ≥ 18 years and hospitalized due to COVID-19 were included in the study. Patients who had never been vaccinated and patients who had been vaccinated with a single dose were considered unvaccinated. A logistic regression analysis was performed for evaluating risk factors for ICU admission. RESULTS: A total of 2,110 patients were included in the final analysis. The median age was 66 years (IQR, 53-76 years) and 54% of the patients were vaccinated. During the study period, 407 patients (19.3%) were transferred to the ICU due to disease severity. Patients who were admitted to the ICU were older (median age 68 vs. 65 years, p < 0.001); and the number of unvaccinated individuals was higher among ICU patients (57% vs. 45%, p < 0.001). In multivariate regression analysis, being unvaccinated was found to be the most important independent risk factor for ICU admission with an OR of 2.06 (95% CI, 1.64-2.59). CONCLUSIONS: Vaccination against COVID-19 is effective against ICU admission and hospital mortality.

Surgical Antimicrobial Prophylaxis Compliance in Turkey: Data from the Prospective, Observational, Multicenter Survey Including 7,978 Surgical Patients.

Background: Surgical antimicrobial prophylaxis (SAP) is the peri-operative administration of antimicrobial agents. Compliance rates vary worldwide from 15% to 84.3%, with studies in Turkey not exceeding 35%. The aim of this multicenter study was to determine the rate of appropriate antibiotic class, timing, and duration as well as discharge prescriptions in Turkey. Thus, we aimed to determine the rate of full compliance with SAP procedures in our country Patients and Methods: This multicenter, prospective, observational, descriptive study was conducted in 47 hospitals from 28 provinces in seven different regions of Turkey. Patients over 18 years of age in all surgical units between June 6, 2022, and June 10, 2022, were included in the study. Results: Of the 7,978 patients included in the study, 332 were excluded from further analyses because of pre-existing infection, and SAP compliance analyses were performed on the remaining 7,646 cases. The antibiotic most commonly used for SAP was cefazolin (n = 4,701; 61.5%), followed by third-generation cephalosporins (n = 596; 7.8%). The most common time to start SAP was within 30 minutes before surgery (n = 2,252; 32.5%), followed by 30 to 60 minutes before surgery (n = 1,638; 23.6%). Surgical antimicrobial prophylaxis duration was <24 hours in 3,516 (50.7%) patients and prolonged until discharge in 1,505 (21.7%) patients. Finally, the actual proportion of patients compliant with SAP was 19% (n = 1,452) after omitting 4,458 (58.3%) patients who were prescribed oral antibiotic agents at discharge as part of a prolonged SAP. Conclusions: Surgical antimicrobial prophylaxis compliance rates are still very low in Turkey. Prolonged duration of SAP and especially high rate of antibiotic prescription at discharge are the main reasons for non-compliance with SAP.

Assessment of mimicking by EBV-CMV immunoglobulin M of anti-HLA antibodies.

OBJECTIVE: We aimed to show the cross-reactivity that may occur between immunoglobulin (Ig) M antibodies that form against Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) and human leukocyte antigens (HLA). METHODS: Complement-dependent cytotoxicity (CDC) cross-reactivity between serum samples of 57 patients with IgM positive CMV and/or EBV infections and T and B cells from 15 healthy donors were evaluated. Dithiothreitol was used to distinguish cross-reactivity caused by IgM antibodies from IgG. RESULTS: The cross-reactivity ratio between pathogenic IgM antibodies with T cell of the 12th donor, and B cell of the 3rd, 4th, and 8th donors was significantly higher (p = 0.011, <0.001, <0.001 and 0.013, respectively). The ratio of B cell CDC cross-reactivity of all donors (26.4%) was higher than the ratio of T cell CDC cross-reactivity (5.2%) (p < 0.001). The ratio of T cell CDC cross-reactivity of sera containing both anti-CMV IgM and anti-EBV IgM antibodies was significantly higher than those of sera containing only anti-CMV IgM or only anti-EBV IgM antibodies (p = 0.002 and p < 0.001, respectively). There was no difference between B cell CDC cross-reactivity rates according to the presence of anti-CMV and/or anti-EBV IgM antibodies. CONCLUSION: Cross-reactivity may occur between anti-CMV and anti-EBV IgM antibodies with HLA molecules. Thus, in graft recipients, pathogenic IgMs can also act as de novo anti-HLA antibodies and aggravate the rejection process.

What Is the Place of Intermediate Care Unit in Patients with COVID-19? A Single Center Experience.

Introduction: COVID-19 pandemic has led to an increased rate of intensive care unit (ICU) stays. Intermediate care units (IMCUs) are a useful resource for the management of patients with severe COVID-19 that do not require ICU admission. In this research, we aimed to determine survival outcomes and parameters predicting mortality in patients who have been admitted to IMCU. Materials and Methods: Patients who were admitted to IMCU between April 2019 and January 2021 were analyzed retrospectively. Sociodemographics, clinical characteristics, and blood parameters on admission were compared between the patients who died in IMCU and the others. Blood parameters at discharge were compared between survived and deceased individuals. Survival analysis was performed via Kaplan-Meier analysis. Blood parameters predicting mortality were determined by univariate and multivariate Cox regression analysis. Results: A total of 140 patients were included within the scope of this study. The median age was 72.5 years, and 77 (55%) of them were male and 63 (45%) of them were female. A total of 37 (26.4%) patients deceased in IMCU, and 40 patients (28.5%) were transferred to ICU. Higher platelet count (HR 3.454; 95% CI 1.383-8.625; p=0.008), procalcitonin levels (HR 3.083; 95% CI 1.158-8.206; p=0.024), and lower oxygen saturation (HR 4.121; 95% CI 2.018-8.414; p < 0.001) were associated with an increased risk of mortality in IMCU. At discharge from IMCU, higher procalcitonin levels (HR 2.809; 95% CI 1.216-6.487; p=0.016), lower platelet count (HR 2.269; 95% CI 1.012-5.085; p=0.047), and noninvasive mechanic ventilation requirement (HR 2.363; 95% CI 1.201-4.651; p=0.013) were associated with an increased risk of mortality. Median OS was found as 41 days. The overall survival rate was found 40% while the IMCU survival rate was 73.6%. Conclusions: IMCU seems to have a positive effect on survival in patients with severe COVID-19 infection. Close monitoring of these parameters and early intervention may improve survival rates and outcomes.

The Spectrum of Infections in Patients with Lung Cancer.

Although diagnostic and therapeutic advances in lung cancer (LC) have increased the survival of patients, infection and its complications are still among the most important causes of mortality. The disruption of tissue caused by tumor mass, management of cancer therapy and alteration in the humoral/cellular immune systems due to both cancer itself and therapy considerably increase susceptibility to infection in cancer patients. Particularly, opportunistic microorganisms should be considered, then applying rapid and sensitive diagnostic methods for them. Thus, cancer patients who are already exposed to difficult, long-term and expensive treatments can be prevented from dying from complications related to infections.

Efficacy and Safety of Direct-Acting Antivirals in Elderly Patients with Chronic Hepatitis C: A Nationwide Real-Life, Observational, Multicenter Study from Turkey.

BACKGROUND: The number and proportion of elderly patients living with chronic hepatitis C are expected to increase in the coming years. We aimed to compare the real-world efficacy and safety of direct-acting antiviral treatment in elderly and younger Turkish adults infected with chronic hepatitis C. METHODS: In this multicenter prospective study, 2629 eligible chronic hepatitis C patients treated with direct-acting antivirals between April 2017 and December 2019 from 37 Turkish referral centers were divided into 2 age groups: elderly (≥65 years) and younger adults (<65 years) and their safety was compared between 2 groups in evaluable population. Then, by matching the 2 age groups for demographics and pretreatment risk factors for a non-sustained virological response, a total of 1516 patients (758 in each group) and 1244 patients (622 in each group) from the modified evaluable population and per-protocol population were included in the efficacy analysis and the efficacy was compared between age groups. RESULTS: The sustained virological response in the chronic hepatitis C patients was not affected by the age and the presence of cirrhosis both in the modified evaluable population and per-protocol population (P = .879, P = .508 for modified evaluable population and P = .058, P = .788 for per-protocol population, respectively). The results of the per-protocol analysis revealed that male gender, patients who had a prior history of hepatocellular carcinoma, patients infected with non-genotype 1 hepatitis C virus, and patients treated with sofosbuvir+ribavirin had a significantly lower sustained virological response 12 rates (P < .001, P = .047, P = .013, and P = .025, respectively). CONCLUSION: Direct-acting antivirals can be safely used to treat Turkish elderly chronic hepatitis C patients with similar favorable efficacy and safety as that in younger adults.

SARS-CoV-2 (Covid-19) vaccines structure, mechanisms and effectiveness: A review.

The world has been suffering from COVID-19 disease for more than a year, and it still has a high mortality rate. In addition to the need to minimize transmission of the virus through non-pharmacological measures such as the use of masks and social distance, many efforts are being made to develop a variety of vaccines to prevent the disease worldwide. So far, several vaccines have reached the final stages of safety and efficacy in various phases of clinical trials, and some, such as Moderna/NIAID and BioNTech/Pfizer, have reported very high safety and protection. The important point is that comparing different vaccines is not easy because there is no set standard for measuring neutralization. In this study, we have reviewed the common platforms of COVID-19 vaccines and tried to present the latest reports on the effectiveness of these vaccines.

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.

Fever of unknown origin (FUO) on a land on cross-roads between Asia and Europa; a multicentre study from Turkey.

AIMS: The differential diagnosis of Fever of Unknown Origin (FUO) is still a major clinical challenge despite the advances in diagnostic procedures. In this multicentre study, we aimed to reveal FUO aetiology and factors influencing the final diagnosis of FUO in Turkey. METHODS: A total of 214 patients with FUO between the years 2015 and 2019 from 13 tertiary training and research hospitals were retrospectively evaluated. RESULTS: The etiologic distribution of FUO was infections (44.9%), malignancies (15.42%), autoimmune/inflammatory (11.68%) diseases, miscellaneous diseases (8.41%) and undiagnosed cases (19.62%). Brucellosis (10.25%), extrapulmonary tuberculosis (6.54%) and infective endocarditis (6.54%) were the most frequent three infective causes. Solid malignancies (7.1%) and lymphoma (5.6%), adult-onset still's disease (6.07%) and thyroiditis (5.14%) were other frequent diseases. The aetiological spectrum did not differ in elderly people (P < .05). Infections were less frequent in Western (34.62%) compared with Eastern regions of Turkey (60.71%) (P < .001, OR: 0.31, 95% Cl: 0.19 to 0.60). The ratio of undiagnosed aetiology was significantly higher in elderly people (p: 0.046, OR: 2.34, 95% Cl: 1.00 to 5.48) and significantly lower in Western Turkey (P: .004, OR: 3.07, 95% Cl: 1.39 to 6.71). CONCLUSIONS: Brucellosis, extrapulmonary tuberculosis and infective endocarditis remain to be the most frequent infective causes of FUO in Turkey. Solid tumours and lymphomas, AOSD and thyroiditis are the other common diseases. The aetiological spectrum did not differ in elderly people, on the other hand, infections were more common in Eastern Turkey. A considerable amount of aetiology remained undiagnosed despite the state-of-the-art technology in healthcare services.

The Course of COVID-19 in Four Patients with HIV During the Pandemic.

BACKGROUND: The clinical spectrum of SARS-CoV-2 infection may vary from simple colds to a severe acute respiratory syndrome, metabolic acidosis, septic shock, and multiple organ failure. Current evidence indicates that the risk of severe illness increases with age, in the male sex, and with certain chronic medical problems. Many people living with HIV have other conditions that increase their risk. ; Case presentation: In the first 3 months of the pandemic, four patients with HIV were hospitalized in our clinic because of COVID-19. The disease severity was mild in two patients with normal CD4+ T count. However, one patient with a low CD4+T count died and the other developed retinal detachment one month after discharge. The deceased patient had a malignancy. ; Conclusion: In this study, the effect of the immunological status of the patients on the course of COVID-19 and the developing vascular complications was evaluated in 4 patients with HIV.

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.

Assessment of prophylactic antibiotic usage habits of the general surgeons in Turkey.

INTRODUCTION: One of the most important aspects of inappropriate antibiotic use among general surgeons in Turkey is the use of surgical antibiotic prophylaxis (SP). In order to shed light on the current situation, we conducted a survey of general surgeons in our country. Our aim was to evaluate the approach taken by our general surgeons in prescribing SP, while providing data pertinent to the effectiveness of the 'Rational Drug Use' (AIK) national action plan. METHODOLOGY: A questionnaire on the subject of personal SP usage and compliance with guidelines was distributed amongst general surgeons between 2018-2019. The questions related to individual approaches taken by surgeons when treating patients with either clean or clean-contaminated wounds. Results of the questionnaires were collated and compliance with ASHP guidelines was evaluated. RESULTS: A total of 317 completed questionnaires were evaluated. According to the questionnaire results, the rate of total compliance with ASHP guidelines was 26.8%. The compliance rate for preoperative SP was 69.7% in the clean wound group and 54.6% in the clean-contaminated wound group. Although 96.5% of the participants reported correct timing for the first dose of SP, this number dropped to 79.5% apropos the adminstration of further doses of prophylaxis. The percentage of surgeons prescribing continued antibiotics at discharge for clean and clean-contaminated cases was 22.7% and 38.5%, respectively. CONCLUSIONS: The results of this study indicate that inappropriate use of SP is widespread in our country, and that antibiotics continue to be prescribed at discharge.

Role of quantitative hepatitis B surface antigen levels in predicting liver biopsy time in treatment-naive chronic hepatitis B patients.

AIM OF THE STUDY: The quantitative hepatitis B surface antigen (qHBsAg) level indicates the amount of transcriptional activity of covalently closed circular DNA (cccDNA) and integrated DNA in hepatocytes which plays a role in development of chronic hepatitis B (CHB) and may help decide whether the treatment is necessary or not. The aim of this study is to evaluate the association between serum qHBsAg levels and viral replication and stage of liver fibrosis in treatment-naive CHB patients and to determine the role of qHBsAg levels in predicting when liver biopsy is necessary. MATERIAL AND METHODS: 967 patients were included in the study. Because of refusal of liver biopsy the study was conducted on 123 patients. The association between qHBsAg levels with HBV DNA, a-fetoprotein, fibrosis stage and histology activity index was evaluated. RESULTS: Of the patients, mean age was 48 ±11.2 years and 56.1% were male. We found that patients with HBV DNA ≥ 2000 IU/ml had a higher qHBsAg titer in comparison with HBV DNA < 2000 IU/ml. However, there was no relationship between qHBsAg titer and liver necroinflammation or fibrosis stage. CONCLUSIONS: Monitoring of qHBsAg together with HBV DNA may be helpful in CHB management. However, qHBsAg level does not provide knowledge about the timing of biopsy or the decision of CHB treatment.

Long-Term Effects of Tenofovir on Liver Histopathology in Patients with Chronic Viral Hepatitis B Infection.

OBJECTIVE: The aim of this study to evaluate histopathological improvement and virological, serological and biochemical response rates in patients with chronic hepatitis B (CHB) who were treated with tenofovir disoproxil fumarate (TDF). MATERIAL AND METHOD: A total of 91 nucleosid(t)e-naive CHB patients who received TDF were evaluated. Virological, serological and biochemical test results were assessed at baseline and every 12 weeks. Liver biopsy specimens were assessed according to the modified Ishak scoring. RESULTS: The study was conducted on 52 patients. The mean age was 40±10 years and 40.4% were female. The mean follow-up period was 33±11 months. HBsAg seroclearance occurred in none of the patients. The serum level of HBV-DNA became undetectable in 94.2% of the patients. Mean histological activity index at baseline and on-treatment were 8.2±2.3 and 6.2±2.0 and the mean fibrosis scores were 2.65±1.3 and 2.33±1.1, respectively. CONCLUSION: We determined that TDF therapy provided remarkably good HBV DNA suppression and biochemical response rates, but low seroconversion. Improvement of liver necroinflammation was detected, but no significant change observed in fibrosis.

Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience

SUMMARY OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.

RESUMO O recente desenvolvimento de agentes antivirais de ação direta (DAAs) mudou drasticamente o tratamento da hepatite C crônica, e os regimes livres de interferon tornaram-se pobres escolhas para tratamento na prática clínica. Hoje os DAAs oferecem terapias curativas mais curtas, bem toleradas e altamente eficazes. O objetivo deste estudo foi avaliar a eficácia e segurança dos DAAs em pacientes com doença renal em estágio terminal e infecção pelo genótipo 1 do HCV na prática clínica real. MÉTODOS Trinta e seis pacientes, que se inscreveram em nossa clínica com diagnóstico de hepatite C crônica (CHC), inclusive no programa de hemodiálise, e preencheram os critérios de idade >18 anos, foram considerados para infecção pelo genótipo 1 com nível detectável de RNA do HCV. Os pacientes com infecção por GT1a receberam OBV/PTV/r mais DSV mais RBV por 12 semanas. Os pacientes infectados com GT1b receberam este regime sem RBV por 12 semanas. RESULTADOS O estudo foi realizado em 33 pacientes. A idade média foi de 52,30±13,77 anos e 70% deles eram do sexo masculino. Na semana 4 do tratamento, os níveis de ARN do VHC diminuíram para menos de 15 UI/ml em todos os pacientes. A taxa de resposta virológica sustentada (RVS) 12 foi de 100%. Nove pacientes apresentaram efeitos colaterais durante o tratamento. Dos pacientes com efeitos colaterais, 89,9% estavam no grupo 1a e 11,1% no grupo 1b. CONCLUSÃO Neste estudo, o tratamento com OBV/PTV/r e DSV com ou sem RBV resultou em altas taxas de resposta virológica sustentada em pacientes infectados pelo VGC GT1 com doença renal em estágio final (ESRD). A RVS foi alcançada em todos os pacientes com poucos efeitos colaterais.

An evaluation of the effect of ertapenem in rats with sepsis created by cecal ligation and puncture.

BACKGROUND: Intra-abdominal adhesions are still a major problem which is expected to be reduced by the provision of bacterial decontamination. Various antibiotics have been used to prevent the formation of adhesion in the septic abdomen. This study aims to investigate the efficacy of ertapenem in sepsis of rats induced by cecal ligation and puncture. METHODS: Twenty-eight Wistar rats were divided into four groups randomly. In all groups, bacterial peritonitis was created by cecal ligation and puncture method. Group 1 was considered as sham group. Groups 2, 3 and 4 were given, respectively, saline, a single dose of ertapenem and a dose of ertapenem intraperitoneally every day. Intra-abdominal adhesions were assessed seven days after surgery by histopathological examination. Microbiological examination was performed through the ascites obtained. TNF-α was measured from blood taken from rats. RESULTS: Adhesion score decreased significantly by the application of ertapenem (p<0.001) and fibrosis scores were found to be significantly lower (p=0.005). Among all groups, the relationship between the decrease in the number of colonies and antibiotics application was not statistically significant (p=0.109). No statistically significant difference was found between the group given a single dose of ertapenem and the group given multiple ertapenem (p=1). CONCLUSION: Peritoneal lavage with ertapenem appears to be effective in preventing the adhesion in the septic abdomen. As no difference was detected at the end of a single dose and multiple-dose administration of antibiotics in the adhesion scores, a single dose after surgery seems to be enough. The findings suggest that the results should be evaluated in a clinical trial.

A new antibiotic stewardship program approach is effective on inappropriate surgical prophylaxis and discharge prescription.

INTRODUCTION: This study aims to evaluate the efficacy of a new antimicrobial stewardship program (ASP) on surgical antibiotic prophylaxis (SP) and antibiotics in discharge prescriptions used as a continuation of SP. METHODOLOGY: The study included elective patients with clean and clean-contaminated wounds. The accuracy of the assigned SP was evaluated according to international guidelines. Primary outcome measures comprised appropriateness of prophylactic antibiotic indication, correct timing of initial dose, discontinuation of SP within 24 hours, and antibiotic prescription at discharge. A secondary outcome measure was to determine whether the effect of ASP was sustained long-term. RESULTS: The total compliance rate for all stages of SP increased from 8% to 52.1% after the intervention (p < 0.05). When analyzed according to individual SP components, it was found that although ASP did not change first dose timing rates, it did affect the rates of prophylactic antibiotic indication, discontinuation of SP within 24 hours and antibiotic prescription at discharge, with statistical significance (p < 0.05). In addition, ASP continued to increase its effectiveness throughout the 3rd year. CONCLUSIONS: Based on the findings of our study, it seems clear that the modified ASP introduced in our general surgery clinic can be used effectively and simply; in addition, this ASP increases its efficacy with time.

Risk factors for noncatheter-related Candida bloodstream infections in intensive care units: A multicenter case-control study.

Candida bloodstream infections are associated with high mortality among critically ill patients in intensive care units (ICUs). Studies that explore the risk factors for candidemia may support better patient care in intensive care units. We conducted a retrospective, multicenter case-control study to investigate the risk factors for noncatheter-related Candida bloodstream infections (CBSI) in adult ICUs. Participants selected controls randomly on a 1:1 basis among all noncase patients stayed during the same period in ICUs. Data on 139 cases and 140 controls were deemed eligible. Among the controls, 69 patients died. The stratified Fine-Gray model was used to estimate the subdistribution Hazard ratios. The subdistribution hazards and 95% confidence intervals for final covariates were as follows: prior exposure to antimycotic agents, 2.21 (1.56-3.14); prior exposure to N-acetylcysteine, 0.11 (0.03-0.34) and prior surgical intervention, 1.26 (0.76-2.11). Of the patients, those exposed to antimycotic drugs, 87.1% (54/62) had breakthrough candidemia. Serious renal, hepatic, or hematologic side effects were comparable between patients those exposed and not-exposed to systemic antimycotic drugs. Untargeted administration of antimycotic drugs did not improve survival among candidemic patients (not-exposed, 63.6% [49/77]; exposed % 66.1 [41/62]; P = .899). This study documented that exposure to an antifungal agent is associated with increased the risk of subsequent development of CBSIs among nonneutropenic adult patients admitted to the ICU. Only two centers regularly prescribed N-acetylcysteine. Due to the limited number of subjects, we interpreted the positive effect of N-acetylcysteine on the absolute risk of CBSIs with caution.

Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe.

BACKGROUND: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. METHODS: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. RESULTS: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties. CONCLUSIONS: Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.