Efficacy and safety of co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-positive patients: real-world data

Objectives: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a recommended and widely used regimen for HIV infection. In this study, we aimed to determine the efficacy and safety of E/C/F/TAF in people living with HIV (PLWH), who are either treatment-naive or switched from any tenofovir disoproxil fumarate-containing regimen. For switched patients, we aimed to determine the impact of switching from tenofovir disoproxil fumarate (TDF) to TAF on lipid profile and kidney functions. Methods: ACTHIV-IST Study Group produced a database, and five dedicated HIV centres in Istanbul entered data of PLWH who switched from any TDF-containing regimen to E/C/F/TAF and treatment-naive patients who were initiated with the E/C/F/TAF regimen between January 2017 and December 2019. Clinical findings, viral parameters, lipid studies, renal function tests, adverse events and adherence to the treatment were recorded in this prospective observational study. Results: The study included a total of 614 switched and treatment-naive patients. Of 430 treatment-experienced patients, 89% (382) were men, and the mean age was 42 +/- 12 years. Among them, 47% (181/382) self-identified as men who have sex with men (MSM). The median duration of HIV diagnosis was 54 +/- 29 months. The median duration of E/C/F/TAF use was 20 +/- 36 months and that of previous treatment was 23 +/- 18 months. HIV-RNA was undetectable at baseline and month 12 in 84.1% (360/428) and 86.1% (328/381) of patients, respectively (p > 0.05). Mean CD4 counts were 708 +/- 287 cells/mu L and 802 +/- 305 cells/mu L at baseline and month 12, respectively (p < 0.001). Serum creatinine levels remained stable during the treatment period. Mean total cholesterol levels at baseline and month 12 were 172 and 211 mg/dL (p < 0.01), LDL-cholesterol 104 and 138 mg/dL (p < 0.01), HDL-cholesterol 39 and 49 mg/dL (p < 0.01) and triglycerides 134 and 174 mg/dL (p < 0.01), respectively. The treatment was generally well tolerated. Eight patients discontinued the therapy (drug interaction: 3; lost to follow-up: 1; pregnancy: 1; pulmonary tuberculosis: 1; side effect: 1; patient's decision: 1). Of 184 treatment-naive patients, 88% (162) were men, and the mean age was 36.5 +/- 12 years. Among them, 50% (81/162) self-identified as MSM. The mean duration of HIV infection was 21.6 +/- 17.1 months. The mean duration of E/C/F/TAF use was 16 +/- 4 months. HIV-RNA was undetectable at baseline and month 12 in 1% and 89.1% of patients, respectively. Mean CD4 counts at baseline and month 12 were 469 +/- 223 cells/mu L and 740 +/- 298 cells/mu L, respectively. During the treatment period, creatinine levels remained stable. Total cholesterol, LDL-cholesterol, triglyceride and also HDL-cholesterol levels increased. Mean total cholesterol levels at baseline and month 12 were 167 and 211 mg/dL (p < 0.01), LDL-cholesterol 108 and 143 mg/dL (p < 0.01), HDL-cholesterol 41 and 47 mg/dL (p < 0.01) and triglycerides 136 and 172 mg/dL, respectively (p < 0.01). The treatment was generally well tolerated. Three patients discontinued the therapy (drug interaction: 1; non-responder: 1; patient's decision: 1). Conclusion: Starting with or switching to E/C/F/TAF in PLWH effectively suppresses HIV infection, is associated with an increase in CD4 cell count and is well tolerated in a real-life setting. Renal functions remained stable during the treatment

Tuberculous and brucellosis meningitis differential diagnosis.

BACKGROUND: The Thwaites and Lancet scoring systems have been used in the rapid diagnosis of tuberculous meningitis (TBM). However, brucellar meningoencephalitis (BME) has similar characteristics with TBM. The ultimate aim of this study is to infer data to see if BME should be included in the differential diagnosis of TBM when these two systems suggest the presence of TBM. METHOD: BME and TBM patients from 35 tertiary hospitals were included in this study. Overall 294 adult patients with BME and 190 patients with TBM were enrolled. All patients involved in the study had microbiological confirmation for either TBM or BME. Finally, the Thwaites and Lancet scoring systems were assessed in both groups. RESULTS: The Thwaites scoring system more frequently predicted BME cases (n = 292, 99.3%) compared to the TBM group (n = 182, 95.8%) (P = 0.017). According to the Lancet scoring system, the mean scores for BME and TBM were 9.43 ± 1.71 and 11.45 ± 3.01, respectively (P < 0.001). In addition, TBM cases were classified into "probable" category more significantly compared to BME cases, and BME cases were categorized into the "possible" category more frequently. CONCLUSIONS: When the Thwaites or Lancet scoring systems indicate TBM, brucellar etiology should also be taken into consideration particularly in endemic countries

Causative pathogens and antibiotic resistance in diabetic foot infections: A prospective multi-center study.

AIM: Clinical practice guidelines for the management of diabetic foot infections developed by the Infectious Diseases Society of America (IDSA) are commonly used worldwide. The issue of whether or not these guidelines need to be adjusted for local circumstances, however, has seldom been assessed in large prospective trials. METHODS: The Turk-DAY trial was a prospective, multi-center study in which infectious disease specialists from centers across Turkey were invited to participate (NCT02026830). RESULTS: A total of 35 centers throughout Turkey enrolled patients in the trial. Overall, investigators collected a total of 522 specimens from infected diabetic foot wounds for culture from 447 individual patients. Among all isolates, 36.4% were gram-positive organisms, with Staphylococcus aureus the most common among these (11.4%). Gram-negative organisms constituted 60.2% of all the isolates, and the most commonly isolated gram-negative was Escherichia coli (15%). The sensitivity rates of the isolated species were remarkably low for several antimicrobials used in the mild infection group. CONCLUSIONS: Based on our findings, several of the antimicrobials frequently used for empirical treatment, including some also recommended in the IDSA guidelines, would not be optimal for treating diabetic foot infections in Turkey. Although the IDSA guideline recommendations may be helpful to guide empiric antimicrobial therapy of DFIs, they should be adjusted to local conditions

Tuberculous and brucellosis meningitis differential diagnosis

Background: The Thwaites and Lancet scoring systems have been used in the rapid diagnosis of tuberculous meningitis (TBM). However, brucellar meningoencephalitis (BME) has similar characteristics with TBM. The ultimate aim of this study is to infer data to see if BME should be included in the differential diagnosis of TBM when these two systems suggest the presence of TBM.Method: BME and TBM patients from 35 tertiary hospitals were included in this study. Overall 294 adult patients with BME and 190 patients with TBM were enrolled. All patients involved in the study had microbiological confirmation for either TBM or BME. Finally, the Thwaites and Lancet scoring systems were assessed in both groups.Results: The Thwaites scoring system more frequently predicted BME cases (n = 292, 99.3%) compared to the TBM group (n = 182, 95.8%) (P = 0.017). According to the Lancet scoring system, the mean scores for BME and TBM were 9.43 +/- 1.71 and 11.45 +/- 3.01, respectively (P < 0.001). In addition, TBM cases were classified into "probable" category more significantly compared to BME cases, and BME cases were categorized into the "possible" category more frequently.Conclusions: When the Thwaites or Lancet scoring systems indicate TBM, brucellar etiology should also be taken into consideration particularly in endemic countries. (C) 2015 Elsevier Ltd. All rights reserved

Causative pathogens and antibiotic resistance in diabetic foot infections: A prospective multi-center study

PMID = 2696579

infections: A prospective multi-center study

Aim: Clinical practice guidelines for the management of diabetic foot infections developed by the Infectious Diseases Society of America (IDSA) are commonly used worldwide. The issue of whether or not these guidelines need to be adjusted for local circumstances, however, has seldom been assessed in large prospective trials.Methods: The Turk-DAY trial was a prospective, multi-center study in which infectious disease specialists from centers across Turkey were invited to participate (NCT02026830).Results: A total of 35 centers throughout Turkey enrolled patients in the trial. Overall, investigators collected a total of 522 specimens from infected diabetic foot wounds for culture from 447 individual patients. Among all isolates, 36.4% were gram-positive organisms, with Staphylococcus aureus the most common among these (11.4%). Gram-negative organisms constituted 60.2% of all the isolates, and the most commonly isolated gram-negative was Escherichia coli (15%). The sensitivity rates of the isolated species were remarkably low for several antimicrobials used in the mild infection group.Conclusions: Based on our findings, several of the antimicrobials frequently used for empirical treatment, including some also recommended in the IDSA guidelines, would not be optimal for treating diabetic foot infections in Turkey. Although the IDSA guideline recommendations may be helpful to guide empiric antimicrobial therapy of DFIs, they should be adjusted to local conditions. (C) 2016 Elsevier Inc. All rights reserved

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. © 2016, Springer-Verlag Berlin Heidelberg

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