[Distribution of the Prevalence of Human Leukocyte Antigen (HLA)-B*57:01 Positivity in HIV-1 Infected Individuals and Its Effects on Treatment: Türkiye Map-Buhasder Working Group]. / HIV-1 Enfekte Bireylerde Insan Lökosit Antijeni (HLA)-B*57:01 Pozitifligi Prevalansinin Dagilimi ve Tedavi Üzerine Etkileri: Türkiye Haritasi-BUHASDER Çalisma Grubu.

Human immunodeficiency virus (HIV)/acquired immundeficiency syndrome (AIDS) is a critical global public health problem that significantly affects both life expectancy and the overall quality of life of individuals in all age groups. The landscape of HIV infection has changed significantly in recent years due to the introduction of effective combination antiretroviral therapies (ART). A key component of first-line ART regimens for HIV treatment is abacavir, a nucleoside HIV reverse transcriptase inhibitor. Although abacavir is effective in suppressing viral replication and managing disease, its clinical utility is overshadowed by the potential for life-threatening hypersensitivity reactions in HLA-B*57:01-positive patients. In our country, local data obtained from various centers regarding the prevalence of HLA-B*57:01 in HIV-1-infected patients are available. In this study, it was aimed to determine the prevalence of the HLA-B*57:01 genotype in HIV-infected patients who were followed up and treated in many regions of our country. This retrospective study consists of the data of the patients aged 18 years and over diagnosed with HIV-1 infection between 01.01.2019 and 31.07.2022. Age, gender, place of birth, mode of transmission of the disease, death status, CD4+ T cell count and HIV RNA levels at the first clinical presentation, HLA-B*57:01 positivity, and the method used, clinical stage of the disease, virological response time with the treatment they received were recorded from the patient files. Data were collected from 16 centers and each center used different methods to detect HLA-B*57:01. These methods were sequence-specific oligonucleotide probe hybridization (SSOP), DNA sequence-based typing (SBT), single-specific primer-polymerase chain reaction (SSP-PCR), allele-specific PCR (AS-PCR) and quantitative PCR (Q-PCR). A total of 608 HIV-infected individuals, 523 males (86%) and 85 females (14%), were included in the study. The mean age of the patients was 36.9 ± 11.9 (18-73) years. The prevalence of HLA-B*57:01 allele was found to be 3.6% (22 patients). The number of CD4+ T lymphocytes in HLA-B*57:01 allele-positive patients was > 500/ mm3 in 10 patients (45.5%), while the number of CD4+ T lymphocytes in HLA-B*57:01 negative patients was > 500/mm3 in 216 patients (36.9%) (p> 0.05). Viral load at the time of diagnosis was found to be lower in patients with positive HLA-B*57:01 allele but it was not statistically significant (p> 0.05). Although different treatment algorithms were used in the centers following the patients, it was observed that the duration of virological response was shorter in HLA-B*57:01 positive patients (p= 0.006). Although the presence of the HLA-B*57:01 allele has a negative impact due to its association with hypersensitivity, it is likely to continue to attract interest due to its association with slower progression of HIV infection and reduced risk of developing AIDS. In addition, although the answer to the question of whether it is cost-effective to screen patients for HLA-B*57:01 before starting an abacavir-containing ART regimen for the treatment of HIV infection is being sought, it seems that HIV treatment guidelines will continue to recommend screening to identify patients at risk in this regard.

Investigation of in vitro efficacy of meropenem/polymyxin B and meropenem/fosfomycin combinations against carbapenem resistant Klebsiella pneumoniae strains.

The incidence of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasing worldwide, and very limited number of effective antibiotics are available for therapy. In our study, the in vitro efficacy of meropenem/polymyxin B and meropenem/fosfomycin combinations against CRKP strains was investigated. The efficiency of meropenem/polymyxin B and meropenem/fosfomycin combinations was tested by checkerboard microdilution and checkerboard agar dilution methods, respectively, against 21 CRKP strains containing major carbapenem resistant genes (7 blaKPC, 7 blaOXA-48 gene, and 7 blaOXA-48+ blaNDM), and seven additional CRKP strains without carbapenemase genes.Among the 28 CRKP strains, the meropenem/polymyxin B combination was synergistic in ten (35.7%), partially synergistic in 12 (42.8%), and indifferent in six (21.4%) isolates. The meropenem/fosfomycin combination was found to be synergistic in three isolates (10.7%), partially synergistic in 20 (71.4%), and indifferent in five (17.8%). In 21 strains containing carbapenem resistance genes, meropenem/polymyxin B and meropenem/fosfomycin combinations exhibited synergistic/partial synergistic effects in 15 (71.4%) and 16 (76.2%) strains, respectively, compared to 100% synergistic/partial synergistic efficiency in both combinations in seven strains free of carbapenemase genes. No antagonistic effect was detected in either combination.Regardless of presence or absence of carbapenem resistance genes, meropenem/polymyxin B and meropenem/fosfomycin combinations both demonstrated high synergistic and partial synergistic activity against 78.4% and 82.1% of CRKP strains, respectively. Also, they have no antagonistic effects and can be used successfully to prevent therapeutic failure with monotherapy, according to our in vitro studies.

[Evaluation of In vitro Efficacy of Meropenem/Colistin and Meropenem/Fosfomycin Combinations on Multidrug Resistant Gram-Negative Bacilli]. / Çok Ilaca Dirençli Gram-Negatif Basillerde Meropenem/Kolistin ve Meropenem/Fosfomisin Kombinasyonlarinin In vitro Etkinliginin Degerlendirilmesi.

The rate of extensively drug-resistant and pan-resistant gram-negative rods isolated as infectious agents is increasing around the world and in Türkiye. One of the important options in the treatment of these infections is the combined use of antibiotics. Therefore, the aim of this study was to investigate the in vitro effect of meropenem/colistin and meropenem/fosfomycin combinations on carbapenem-resistant gram-negative bacilli isolated as infectious agents. Escherichia coli (n= 6), Klebsiella pneumoniae (n= 10), Pseudomonas aeruginosa (n= 5), and Acinetobacter baumannii (n= 6) isolates were recovered from blood and tracheal aspirate samples of patients hospitalized in our hospital's intensive care unit were included in the study. In the first stage of the combination study, minimal inhibitory concentrations (MIC) were investigated by broth microdilution for meropenem and colistin, and agar dilution methods for fosfomycin. In the second stage of the study, synergy, partial synergy, indifference, and antagonistic effects were investigated with the checkerboard method for the meropenem/colistin combination and the agar dilution method for the meropenem/fosfomycin combination. The checkerboard results were interpreted as follows: fractional inhibitory concentration index (FICI) values ≤ 0.5 synergy, < 0.5-≤ 1 partial synergy, > 1-≤ 4 indifference and FIC values of > 4 antagonism. MIC values obtained in the study were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Of the 27 isolates studied with the broth microdilution method, 63% were found to be colistin-resistant and 37% susceptible. The MIC values of fosfomycin against Enterobacterales group bacteria were found to be in the range of 2-2048 mg/L. Two of the six E.coli isolates and nine of the 10 K.pneumoniae isolates were found to be resistant to fosfomycin (IV). The MIC values of ≥ 128 mg/L were found in all 11 non-fermentative gram-negative rods with intrinsic resistance to fosfomycin. In the combination of meropenem/ colistin, synergy and partial synergy were observed in 11 (40.7%) of 27 isolates, an indifference effect was observed in 13 (48.2%), and antagonistic effects were observed in three (11.1%) of the isolates. The synergy and partial synergy effects of this combination were 37.5% for Enterobacterales group bacteria, 50% for E.coli, and 30% for K.pneumoniae. Regarding the 11 non-fermentative gram-negative rods included in the study, 83.3% synergy and partial synergy was found in A.baumannii for the meropenem/colistin combination, while no synergy and partial synergistic effect was found in P.aeruginosa. Meropenem/fosfomycin synergy and partial synergy effects were 83.3% (5/6) for E.coli, 100% (8/8) for K.pneumoniae, 100% (6/6) for A.baumannii, and 25% (1/4) for P.aeruginosa. In all of the isolates studied, meropenem/fosfomycin combination was found to be more effective than the meropenem/colistin combination. It would be meaningful to support these data obtained in vitro with clinical efficacy results to be obtained as a result of the application of antibiotics in vivo, taking into account the pharmacokinetic and pharmacodynamic properties of the antibiotics used in this study.

Microorganisms isolated from the bile of the patients who have undergone cholecystectomy and their antibiotic resistance pattern: multicenter prospective study.

BACKGROUND: Gallbladder and biliary tract infections are diseases with high mortality rates if they are not treated properly. Microbiological evaluation of perioperatively collected samples both ensures proper treatment of patients and guides empirical treatment due to the determination of microorganism susceptibility. AIMS: This study aimed to isolate the microorganisms in bile cultures from patients who underwent cholecystectomy and to determine sensitivity results of these microorganisms. METHODS: This study was a multi-center and prospective design, included 360 patients, and was performed between 2019 and 2020. Culture results of bile taken during cholecystectomy were evaluated. RESULTS: Bacterial growth was found in the bile cultures of 84 out of 360 (23.3%) patients. Patients were divided into two groups according to whether they had risk factors for resistant microorganisms or not. While Escherichia coli (n = 11, 13%), Enterococcus spp. (n = 8, 9.5%), and Enterobacter spp. (n = 4, 4.7%) were detected most frequently in patients without risk. Staphylococcus spp. (n = 17, 20.2%), Enterococcus spp. (n = 16, 19%), and E. coli (n = 8, 9.5%) were the most frequently found microorganism at-risk patients. In multivariate analysis, bile culture positivity was found higher in patients who had history of biliary disease (p = 0.004), operation performed concurrently with a cholecystectomy (p = 0.035), and high rate of polymorphonuclear leukocytes (PNL) in total leukocyte count (p = 0.001). CONCLUSIONS: Our study shows that when starting empirical antibiotic treatment for bile ducts, whether patients are at risk for the development of resistant bacterial infection should be evaluated after which antibiotic selection should be made accordingly.

Hepatitis B immunization data of patients living with HIV/AIDS: a multi-centre study.

OBJECTIVES: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are the two leading viruses that cause the greatest number of virus-related morbidities in the world. HIV/HBV coinfection is correlated with high morbidity and mortality. For this particular reason hepatitis B vaccination is crucial for people living with HIV. METHODS: Patients who are being followed-up for HIV/AIDS and who have received a hepatitis B vaccine in 4 HIV clinics over a 5-year time period have been studied. Our multi-centered, retrospective, cross-sectional and observational study investigates factors that affect hepatitis B vaccination immune response of individuals living with HIV. The patients have been studied for the parameters such as age, sex, CD4 count at the time of diagnosis or vaccination, HIV-RNA levels, comorbidities, vaccine dosage, success of immunization after vaccination, and the demographics of the patients who have and have not developed immunity. RESULTS: Of 645 patients that are being followed-up in our clinics, 158 received hepatitis B vaccine; 39 of these 158 patients have been excluded from the study because they did not fulfil the inclusion criteria. Finally, 119 patients were evaluated in the study, 17 of the patients (14.3%) were females and 102 (85.7%) were males. The median age was 41.11 ± 10.09 (min-max: 18-75). Twenty-three of the patients (19.3%) were at the stage of AIDS during diagnosis while 80.7% were at the stage of HIV infection. Ninety-one of the patients (76.5%) have been administered a single dose hepatitis B vaccine on the standard 0, 1st, 6th month vaccination schedule, whereas 23.5% were administered a double dose on the same vaccination schedule. When further evaluated to find whether the patient was able to develop sufficient immunity (anti-HBs ≥ 10), it was found that the immune response was statistically significantly higher in the patients whose CD4 count was greater than 200 at the time of the first diagnosis and vaccination (p = 0.05 and p = 0.001, respectively). The patients have also been evaluated according to the number of doses they received (1 vs. 2). The immune response of the patients who received two doses was statistically significantly higher (p = 0.041). CONCLUSION: We can conclude that in the patients with CD4 count less than 200 at the time of their diagnosis and vaccination a high dose recombinant hepatitis B vaccine should definitely be administered as the normal dose and higher dose have similar side effect profiles and the higher dose provides greater immunity.

Effectiveness of ozone therapy in addition to conventional treatment on mortality in patients with COVID-19.

AIM: In this study, we aimed to investigate the effectiveness of ozone therapy, which is one of the integrative medicine applications that has been used safely for many years, on the prevalence of mortality in patients receiving COVID-19 treatment. METHODS: This was a prospective, controlled study conducted on patients with COVID-19 who were hospitalised. In this study, 55 patients were included. The patients were divided into two groups as the ozone and control group. Ozone therapy (major autohemotherapy) was applied to 37 patients who were being treated with the appropriate COVID-19 treatment protocol determined by the infectious diseases committee of our hospital. The ozone treatment protocol consisted of seven sessions (one session per day) of intravenous ozone administration, applied in a volume of 100 mL and a concentration of 30 µg/mL. Only the conventional COVID-19 treatment protocol was applied to 18 patients in the control group. Clinical follow-up was performed until the discharge of the patients from the hospital with successful treatment or until the mortality occurred. Factors affecting mortality were analysed using univariate regression analysis. RESULTS: Intensive care unit (ICU) hospitalisation was required in 6 of the 37 patients who were treated with ozone (16.2%), while 4 of 18 patients in the control group required ICU treatment (22.2%) (P = .713). When the mortality rates between the two groups were compared, mortality was lower in the ozone group (P = .032). As a result of univariate logistic regression analysis performed to investigate the factors affecting mortality, treatment with ozone therapy was determined as a risk factor for mortality. Patients receiving ozone therapy appear to have a lower mortality risk (odds ratio [OR]: 0.149, 95% confidence interval [CI] 0.026-0.863, P = .034). CONCLUSION: In this study, the findings suggested that the administration of ozone therapy along with the conventional medical treatment in patients hospitalised for COVID-19 could reduce mortality.

Clinicopathological profile of gastrointestinal tuberculosis: a multinational ID-IRI study.

Data are relatively scarce on gastro-intestinal tuberculosis (GITB). Most studies are old and from single centers, or did not include immunosuppressed patients. Thus, we aimed to determine the clinical, radiological, and laboratory profiles of GITB. We included adults with proven GITB treated between 2000 and 2018. Patients were enrolled from 21 referral centers in 8 countries (Belgium, Egypt, France, Italy, Kazakhstan, Saudi Arabia, UK, and Turkey). One hundred four patients were included. Terminal ileum (n = 46, 44.2%), small intestines except terminal ileum (n = 36, 34.6%), colon (n = 29, 27.8%), stomach (n = 6, 5.7%), and perianal (one patient) were the sites of GITB. One-third of all patients were immunosuppressed. Sixteen patients had diabetes, 8 had chronic renal failure, 5 were HIV positive, 4 had liver cirrhosis, and 3 had malignancies. Intestinal biopsy samples were cultured in 75 cases (78.1%) and TB was isolated in 65 patients (86.6%). PCR were performed to 37 (35.6%) biopsy samples and of these, 35 (94.6%) were positive. Ascites samples were cultured in 19 patients and M. tuberculosis was isolated in 11 (57.9%). Upper gastrointestinal endoscopy was performed to 40 patients (38.5%) and colonoscopy in 74 (71.1%). Surgical interventions were frequently the source of diagnostic samples (25 laparoscopy/20 laparotomy, n = 45, 43.3%). Patients were treated with standard and second-line anti-TB medications. Ultimately, 4 (3.8%) patients died and 2 (1.9%) cases relapsed. There was a high incidence of underlying immunosuppression in GITB patients. A high degree of clinical suspicion is necessary to initiate appropriate and timely diagnostic procedures; many patients are first diagnosed at surgery.

The diagnostic utility of the "Thwaites' system" and "lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients.

BACKGROUND: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. METHODS: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. RESULTS: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. CONCLUSION: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

Predictors of unfavorable outcome in neurosyphilis: Multicenter ID-IRI Study.

Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n = 55, 39%), fatigue (n = 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.

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.

Cranial imaging findings in neurobrucellosis: results of Istanbul-3 study.

OBJECTIVE: Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes. METHODS: Istanbul-3 study evaluated 263 adult patients with CNS brucellosis from 26 referral centers and reviewed their 242 magnetic resonance imaging (MRI) and 226 computerized tomography (CT) scans of the brain. RESULTS: A normal CT or MRI scan was seen in 143 of 263 patients (54.3 %). Abnormal imaging findings were grouped into the following four categories: (a) inflammatory findings: leptomeningeal involvements (44), basal meningeal enhancements (30), cranial nerve involvements (14), spinal nerve roots enhancement (8), brain abscesses (7), granulomas (6), and arachnoiditis (4). (b) White-matter involvement: white-matter involvement (32) with or without demyelinating lesions (7). (c) Vascular involvement: vascular involvement (42) mostly with chronic cerebral ischemic changes (37). (d) Hydrocephalus/cerebral edema: hydrocephalus (20) and brain edema (40). On multivariate logistic regression analysis duration of symptoms since the onset (OR 1.007; 95 % CI 1-28, p = 0.01), polyneuropathy and radiculopathy (OR 5.4; 95 % CI 1.002-1.013, p = 0.044), cerebrospinal fluid (CSF)/serum glucose rate (OR 0.001; 95 % CI 000-0.067, p = 0.001), and CSF protein (OR 2.5; 95 % CI 2.3-2.7, p = 0.0001) were associated with diffuse inflammation. CONCLUSIONS: In this study, 45 % of neurobrucellosis patients had abnormal neuroimaging findings. The duration of symptoms, polyneuropathy and radiculopathy, high CSF protein level, and low CSF/serum glucose rate were associated with inflammatory findings on imaging analyses.

Hydrocephalus and vasculitis delay therapeutic responses in tuberculous meninigitis: Results of Haydarpasa-III study.

AIMS: There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. MATERIALS AND METHODS: This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. RESULTS: In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27-86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for >9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68-19.57]). According to linear regression analysis, fever was significantly persisting (>7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. CONCLUSIONS: In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.

Results of a multinational study suggest the need for rapid diagnosis and early antiviral treatment at the onset of herpetic meningoencephalitis.

Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

Antituberculosis drug resistance patterns in adults with tuberculous meningitis: results of haydarpasa-iv study.

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem. This study aimed to evaluate drug resistance profiles of TBM isolates in adult patients in nine European countries involving 32 centers to provide insight into the empiric treatment of TBM. METHODS: Mycobacterium tuberculosis was cultured from the cerebrospinal fluid (CSF) of 142 patients and was tested for susceptibility to first-line antituberculosis drugs, streptomycin (SM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB). RESULTS: Twenty of 142 isolates (14.1 %) were resistant to at least one antituberculosis drug, and five (3.5 %) were resistant to at least INH and RIF, [multidrug resistant (MDR)]. The resistance rate was 12, 4.9, 4.2 and 3.5 % for INH, SM, EMB and RIF, respectively. The monoresistance rate was 6.3, 1.4 and 0.7 % for INH, SM and EMB respectively. There was no monoresistance to RIF. The mortality rate was 23.8 % in fully susceptible cases while it was 33.3 % for those exhibiting monoresistance to INH, and 40 % in cases with MDR-TBM. In compared to patients without resistance to any first-line drug, the relative risk of death for INH-monoresistance and MDR-TBM was 1.60 (95 % CI, 0.38-6.82) and 2.14 (95 % CI, 0:34-13:42), respectively. CONCLUSION: INH-resistance and MDR rates seemed not to be worrisome in our study. However, considering their adverse effects on treatment, rapid detection of resistance to at least INH and RIF would be most beneficial for designing anti-TB therapy. Still, empiric TBM treatment should be started immediately without waiting the drug susceptibility testing.

Impact of the COVID-19 Pandemic on Diabetic Foot Patients: A Shift in the Infectious Agent Profile Toward Nonfermentative Gram-Negative Bacilli.

BACKGROUND: Diabetes foot infection is a very important public health problem that causes serious health problems, mortality, and high health expenditures, and is one of the most important complications of diabetes mellitus. There are concerns that approaches such as limited personal visits to doctors, avoidance of hospitals, and restrictions on nonemergency surgical procedures during the coronavirus disease of 2019 pandemic pose a threat to those with diabetic foot problems, including diabetic foot ulcers (DFUs), ischemia, and infection, resulting in increased limb loss and mortality. METHODS: This multicenter, retrospective, cross-sectional study was conducted in 14 tertiary care hospitals from various regions of Turkey. A total of 1,394 patient records were evaluated, 794 of which were between January 1, 2019, and January 30, 2020 (prepandemic [Pre-P]), and 605 of which were between February 1, 2020, and February 28, 2021 (pandemic period [PP]). RESULTS: During the PP, diabetic foot patient follow-up decreased by 23.8%. In addition, the number of hospitalizations attributable to DFU has decreased significantly during the PP (P = .035). There was no difference between the groups regarding patient demographics, medical history, DFU severity, biochemical and radiologic findings, or comorbidities, but the mean duration of diabetes mellitus years was longer in patients in the Pre-P than in those in the PP (15.1 years versus 13.7 years). There was no difference between the two groups in terms of major complications such as limb loss and mortality, but infection recurrence was higher in the PP than in the Pre-P (12.9% versus 11.4%; P < .05). The prevalence of nonfermentative gram-negative bacteria as causative agents in DFU infections increased during the PP. In particular, the prevalence of carbapenem-resistant Pseudomonas spp. increased statistically during the PP. CONCLUSIONS: The rapid adaptation to the pandemic with the measures and changes developed by the multidisciplinary diabetic foot care committees may be the reasons why there was no increase in complications because of DFU during the pandemic in Turkey.

Latent Tuberculosis Infection Management in Solid Organ Transplantation Recipients: A National Snapshot.

OBJECTIVE:  Latent tuberculosis infection (LTBI) screening is strongly recommended in the pre-transplant evaluation of solid organ transplant (SOT) recipients, although it remains inadequate in many transplant centers. We decided to investigate pre-transplant TB risk assessment, LTBI treatment, and registry rates in Turkey. MATERIAL AND METHODS:  Adult SOT recipients who underwent tuberculin skin test (TST) and/or interferon-gamma release test (IGRA) from 14 centers between 2015 and 2019 were included in the study. An induration of ≥5 mm on TST and/or probable/positive IGRA (QuantiFERON-TB) was considered positive for LTBI. Demographic features, LTBI screening and treatment, and pre-/post-transplant TB history were recorded from the electronic database of transplantation units across the country and pooled at a single center for a unified database. RESULTS:  TST and/or IGRA were performed in 766 (33.8%) of 2266 screened patients most of whom were kidney transplant recipients (n = 485, 63.4%). LTBI screening test was positive in 359 (46.9%) patients, and isoniazid was given to 203 (56.5%) patients. Of the patients treated for LTBI, 112 (55.2%) were registered in the national registry, and 82 (73.2%) completed the treatment. Tuberculosis developed in 6 (1.06%) of 563 patients who were not offered LTBI treatment. CONCLUSION:  We determined that overall, only one-third of SOT recipients in our country were evaluated in terms of TB risk, only 1 of the 2 SOT recipients with LTBI received treatment, and half were registered. Therefore, we want to emphasize the critical importance of pretransplant TB risk stratification and registration, guided by revised national guidelines.

Unraveling the Complexity of Atypical Serological Profiles in Chronic Hepatitis B: Insights Into Disease Dynamics and Clinical Implications.

Introduction Chronic hepatitis B (CHB) continues to be a significant global public health problem. Conventional serological markers play a pivotal role in diagnosing and prognosticating CHB, but atypical serological profiles deviating from established norms pose challenges. Methods A cohort of 35 CHB patients who did not receive an antiviral treatment with atypical serological markers was followed for five years (2017-2022). Demographics, serological parameters, and changes were documented. Serological parameters and serum viral loads (hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) levels) were assayed at the central laboratory during their routine follow-ups. Three groups of atypical serological markers are defined: hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) positivity; hepatitis B e antigen (HBeAg) and anti-hepatitis B e-antigen (anti-HBe) positivity; and isolated core (anti-hepatitis B core (anti-HBc) immunoglobulin G (IgG)) positivity. Patients with concomitant HBsAg and anti-HBs were also stratified into seroreversion groups. Changes in serological markers and HBV-DNA levels across the study period were documented and evaluated at the end of the study period. Statistical analysis was conducted using the Kruskal-Wallis test and IBM SPSS Statistics software for Windows, Version 23.0 (IBM Corp., Armonk, NY, USA). Results In a cohort of 35 patients with atypical hepatitis B serology, demographic analysis revealed that 51.4% (n=18) were female and 48.6% (n=17) were male, with a mean age of 45.7 years. Educational distribution showed that 45.7% (n=16) completed primary education, 22.8% (n=8) had a high school education, and 31.5% (n=11) held university degrees. Among these patients, 10 displayed the concurrent presence of HBsAg and anti-HBs, with 60% (n=6) being female. Serum HBV-DNA was detectable in all cases. After five years, 60% (n=6) exhibited seroconversion from HBsAg to anti-HBs, particularly notable in females (66.7%). These patients showed lower HBsAg titers and serum HBV-DNA levels (p = 0.048, p = 0.036). A subset of 15 patients demonstrated simultaneous HBeAg and anti-HBe positivity. The HBeAg seropositivity waned over time, with 40% (n=6) and 26.7% (n=4) females and males, respectively, retaining positivity by the fifth year. During this period, serum HBV-DNA levels decreased. The remaining five patients sustained HBeAg and anti-HBe positivity. Among 10 patients solely positive for anti-HBc IgG, three had concurrent HBV-DNA positivity. Strikingly, three patients with negative HBV-DNA developed anti-HBs positivity after five years. Conclusion The complexity of CHB infection demands a comprehensive understanding. Atypical serological profiles suggest distinct disease stages, immune response variations, and viral mutations. This study enhances comprehension of viral replication, immune responses, and disease progression, potentially guiding tailored therapeutic strategies.

Risk factors for carbapenem-resistant Klebsiella pneumoniae infections in Intensive Care Units: a multicentre case-control study with a competing-risks analysis.

Aim: This study investigated the risk factors for the development of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in adult patients in Intensive Care Units (ICUs). Methods: A multicentre case-control study was conducted in ICUs in three tertiary hospitals in Turkey. The cases were patients culture-confirmed CRKP and a condition associated with healthcare-associated infections. Two controls were randomly selected for each case from among all other patients with an ICU stay at least as long as that of the corresponding case-patient. A proportional semiparametric subdistribution hazards regression model was used to assess risk factors for CRKP infection. ICU discharge and non-CRKP-related deaths were treated as competing risks. Results: A total of 120 patients, 44 cases and 76 controls were included in the analysis. Of the controls, 32 were discharged from the ICU and 44 died without acquiring CRKP infection. Endotracheal intubation (hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.00-3.868) and type 2 diabetes mellitus (HR: 1.57, 95% CI: 0.888-2.806) were associated with an increased risk of CRKP infection, whereas carbapenem exposure (HR: 0.47, 95% CI: 0.190-1.1175) and the presence of a nasogastric tube (HR: 0.49, 95% CI: 0.277-0.884) were associated with a decreased risk of CRKP infection. Conclusions: Enteral nutrition support via a nasogastric tube may be associated with a reduced risk of CRKP-resistant infections in ICU patients. This hypothesis should be tested with a well-designed study.

Tuberculosis in Solid-Organ Transplant Recipients in Turkey: Meta-Analysis From the Tuberculosis Study Group of Turkish Transplantation Society, Solid Organ Transplantation Infections.

OBJECTIVES: Tuberculosis risk in solid-organ transplant recipients is more than the general population, although tuberculosis incidence has been reported to decrease 5% in the last decade in Turkey. In Turkey, solid-organ transplants started in 1975; however, routine pretransplant tuberculosis risk screening programs are still not established. Therefore, we conducted a meta-analysis of tuberculosis prevalence, clinical forms, and prognosis of tuberculosis in solid-organ transplant recipients. MATERIALS AND METHODS: We searched PubMed, Web of Knowledge, Google Scholar, EBSCOhost, and Scopus databases in English and Turkish Medical Index of Turkish Academic Network and Information Center, Turkish Citation Index, Turkish Medline, Central Thesis of ULAKBIM databases in Turkish (from inception until December 2018) for national and international reference lists of all relevant papers. We used standard methodological procedures (Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009). RESULTS: We found 199 published studies in English and 26 in Turkish. After exclusion of noneligible studies, there were 10 retrospective research articles and 16 case reports. There were 148 (3.2%) tuberculosis cases with 4553 solid-organ transplant recipients (4031 renal, 522 liver). Of the tuberculosis cases, 50 (33.8%) were pulmonary, 21 (14.2%) were pulmonary and extrapulmonary, 13 (8.8%) were miliary, 27 (18.2%) were disseminated, and 37 (25.0%) were extra-pulmonary tuberculosis cases involving a maximum of 2 organs. There were 19 cases (12.8%) of graft lost. Of the patients with tuberculosis, 34 (19.9%) died resulting from either tuberculosis or other reasons. CONCLUSIONS: In this meta-analysis, most of the centers did not perform pretransplant risk evaluations; every center had different clinical procedures and follow-ups. Tuberculosis prevalence in solid-organ transplant recipients differs according to study population. Case reports were mostly about extrapulmonary tuberculosis. All such patients should be followed-up by a standard regimen during pretransplant and posttransplant periods. Prospective studies should be considered.

Foot self-care in diabetes mellitus: Evaluation of patient awareness.

AIMS: To assess diabetic patients' knowledge and practices regarding foot care. METHODS: This study was conducted as a cross-sectional study in 1030 patients between November 2017 and February 2018.The descriptive survey instrument was developed by the investigators. Survey content and format were based on prior surveys and guidelines. The survey sought socio-demographic characteristics of the patients and the level of knowledge about diabetic foot care practice. RESULTS: 29.5% of patients had bad foot care, 49.6% of patients had moderate foot care and 20.8% of patients had good foot care. There were no significant differences between patient groups in regard to age, gender, foot infection history and having undergone amputation surgery. We found that patients who good at foot care had higher education status (p<0.001), were more likely live in a city (p<0.001), had higher income (p<0.001), had been trained about foot care (p<0.001) and were more likely to have type I DM (p=0.015). Disease duration was longer in those who had good foot care compared to the other groups (p=0.010). CONCLUSIONS: The mean knowledge and practice scores of our patients were moderate, indicating that much is to be done for the education of patients on this matter. We also found that knowledge about the importance of this practice, education status and disease duration had significant influence on the practice of foot-care in patients with DM.