The safety and adverse event profile of favipiravir in the treatment of COVID-19 patients, Turkey.

INTRODUCTION: Favipiravir (FVP) is an antiviral and used to treat COVID-19. We aimed to document the safety and adverse events associated with FVP on the outcome of COVID-19 treatment. METHODOLOGY: The study included 225 adult patients with moderate COVID-19 infection (World Health Organization scale-5). The adverse events (AEs) were evaluated using a grading scale supported by the Food and Drug Administration. Safety was assessed by the frequency of serious AEs. RESULTS: The AEs associated with FVP treatment were hepatotoxicity (87/225, 38.7%), weakness (32/225, 14.2%), nephrotoxicity (26/225, 11.6%), nausea (18/225, 8.0%), diarrhea (8/225, 3.6%), vomiting (5/225, 2.2%), and insomnia (4/225, 1.8%); rash was not detected. Hepatotoxicity was observed more frequently in patients who also developed nephrotoxicity (57.7% vs 36.2%, p = 0.03). The deceased patients were significantly older and had higher prevalence of hypertension, congestive heart failure (CHF), coronary artery disease, cancer, nephrotoxicity. and angiotensin- converting enzyme inhibitors/angiotensin receptor blocker use. While male gender (OR: 5.38 CI: 1.64-17.67) and CHF (OR: 6.8 CI: 1.92-24.74) were significantly associated with nephrotoxicity, age (OR: 1.06 CI: 1.02-1.10), cancer (OR: 3.9 CI: 1.10-14.22) and nephrotoxicity (OR: 5.5 CI: 1.74-17.74) were associated with mortality. CONCLUSIONS: Serious AEs were detected at very low levels that would not require discontinuation of treatment or any AE-related death. Since SARS-CoV-2 itself and drug interactions may differ, FVP-related AEs might vary in COVID-19 patients. Our study shows that FVP can be used safely with a low AE profile. More extensive evidence is required to evaluate the long-term AEs of FVP.

Diagnostic Efficacy of Aspergillus Galactomannan Lateral Flow Assay in Patients with Hematological Malignancies: A Prospective Multicenter Study.

BACKGROUND: A rapid and reliable diagnostic test is needed to reduce mortality through early diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies. OBJECTIVE: To evaluate the efficacy of serum and bronchoalveolar lavage (BAL) Aspergillus galactomannan lateral flow assay (GM-LFA) in IA diagnosis and determine the correlation of GM-LFA with GM enzyme immunoassay (GM-EIA) in patients with hematological malignancies. METHODS: In this prospective multicenter study, we used serum and BAL fluid samples from patients with hematological malignancies and suspected IA and performed GM-LFA and GM-EIA. According to the EORTC/MSGERC criteria, patients were grouped as proven (n = 6), probable (n = 22), possible IA (n = 55), or no IA (n = 88). The performance of serum GM-LFA at 0.5 optical density index (ODI) and area under the curve (AUC) were calculated. Spearman's correlation analysis and kappa statistics were performed to determine the agreement between the tests. RESULTS: GM-LFA showed an AUC of 0.832 in proven/probable IA (sensitivity [SEN], specificity [SPE], negative predictive value [NPV], and diagnostic accuracy were 75%, 100%, 92.6%, and 93.9%, respectively, at a 0.5 ODI) versus that in no IA. A moderate positive correlation was noted between the GM-LFA and GM-EIA scores (p = 0.01). The observed agreement between the tests at 0.5 ODI was almost perfect (p < 0.001). After excluding patients who received mold-active antifungal prophylaxis or treatment, the SEN, SPE, NPV, and diagnostic accuracy for proven/probable IA were 76.2%, 100%, 93.3%, and 94.5%, respectively. CONCLUSIONS: Serum GM-LFA demonstrated high discriminatory power and good diagnostic performance for IA in patients with hematological malignancies.

Consideration of Severe Coronavirus Disease 2019 As Viral Sepsis and Potential Use of Immune Checkpoint Inhibitors.

Taking into consideration the multisystemic clinical and autopsy findings in "severe" coronavirus disease 2019 patients, viral sepsis would be a more accurate term to describe the whole clinical picture. The most significant pathophysiological components of this picture are intense cytokine release, prolonged inflammation, immunosuppression with T cell exhaustion, and the development of organ dysfunctions. Currently, the optimal treatment for severe coronavirus disease 2019 is uncertain. Supportive treatment and immunomodulators have a critical place in the treatment of severe patients until effective antivirals are developed. Interleukin-6 antagonists, one of the immunomodulating agents, appears to be effective in the treatment of cytokine storm, but some patients continue to have severe lymphopenia and immunosuppression. We believe it can be useful as immunomodulator therapy in critical coronavirus disease 2019 patients because of the benefits of immune checkpoint inhibitors in cancer and sepsis patients.

Candida urinary tract infections in adults.

Candiduria is commonly seen in hospitalized patients and most of the patients are asymptomatic, but it may be due to cystitis, pyelonephritis, prostatitis, epididymo-orchitis or disseminated candidiasis. Major risk factors are diabetes mellitus, indwelling urinary catheters, use of broad-spectrum antibiotics, urinary obstruction, and admission to intensive care units. Candida urinary tract infections can be caused by hematogenous spread following candidemia, or retrograde route via the urethra. The presence of Candida species in urine in asymptomatic patients does not warrant antifungal therapy except neutropenic patients, very low-birth-weight infants and patients undergoing urologic procedures. Fluconazole is the treatment of choice for symptomatic infections, it achieves high urinary levels. The other azole antifungals and echinocandins do not reach sufficient urine levels. Amphotericin B deoxycholate is the alternative antifungal agent if fluconazole can not be used because of resistance, allergy or failure.

Diagnosis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Turkish Expert Opinion (TEO-2).

One of the most problematic issues in hematological malignancies is the diagnosis of invasive fungal diseases. Especially, the difficulty of mycological diagnosis and the necessity of immediate intervention in molds have led to the adoption of "surrogate markers" that do not verify but rather strongly suggest fungal infection. The markers commonly used are galactomannan (GM), beta-glucan, and imaging methods. Although there are numerous studies on these diagnostic approaches, none of these markers serve as a support for the clinician, as is the case in human immunodeficiency virus (HIV) or cytomegalovirus (CMV) infections. This paper has been prepared to explain the diagnostic tests. As molecular tests have not been standardized and are not used routinely in the clinics, they will not be mentioned here.

Outcomes of fecal carriage of extended-spectrum ß-lactamase after transrectal ultrasound-guided biopsy of the prostate.

OBJECTIVE: To determine the prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (PE) fecal carriage in patients that undergo transrectal ultrasonography-guided biopsy (TRUSbx) and its relationship with post-biopsy infections. METHODS: A prospective clinical study in 4 different tertiary hospitals between 2008 and 2010 was conducted. Four hundred men with sterile urine who were to undergo a TRUSbx because of the suspicion of prostate cancer were included and followed for 14 days after biopsy. Rectal swab culture specimens were acquired immediately before the procedure. Demographic data, prophylaxis choice, quinolone or any other antibiotic consumption within the past 2 months, history of prostatitis, repeat biopsy, intensive care unit admission, hospitalization, urethral catheterization, diabetes mellitus (DM), and steroid usage were recorded. RESULTS: ESBL carriage was detected in 19% of patients and quinolone use within the last 2 months; other antibiotic use within the last 2 months and DM were found to be significantly associated (P <.05). Symptomatic urinary tract infection (UTI) on the third day after biopsy was seen in 9% of patients and was associated with fluoroquinolone (FQ) consumption before biopsy. Although ESBL-PE carriage was associated with post-biopsy UTI symptoms, it was not found to be associated with post-biopsy symptomatic UTI. Urosepsis was seen in 2 patients (0.5%) after biopsy, and both the patients were ESBL-PE carriers. CONCLUSION: The presence of ESBL-PE was associated with DM and FQ consumption before biopsy. ESBL-PE carriage was associated with a high rate of post-biopsy UTI symptoms requiring further elucidation; however, it was not associated with microbiologically proven infections. FQ consumption before TRUSbx was also associated with post-biopsy infections.

Toll-like receptor expression in monocytes in patients with chronic kidney disease and haemodialysis: relation with inflammation.

BACKGROUND: Inflammation is one of the main contributors to atherosclerosis in haemodialysis (HD) patients. Activation of Toll-like receptors (TLRs) leads to inflammatory response. In this study, we aimed to evaluate the expression of TLRs on monocytes and relate their expression with inflammation in chronic kidney disease (CKD) and HD patients. METHODS: Thirty-four age- and gender-matched controls and stage 3-4 CKD patients and thirty-two HD patients were included in each study group. The effect of HD on the expression of Toll-like receptor-2 (TLR-2) and Toll-like receptor-4 (TLR-4) on CD14( +) monocytes was determined at the beginning (baseline), during (120 min) and following (300 min and 24 h) HD and compared with control and stage 3-4 CKD groups. The HD procedure was performed by using low-flux polysulphone dialysers. In addition, serum IL-6 levels were evaluated in both groups at baseline and after a HD session. RESULTS: The percentage of CD14( +) monocytes expressing TLR-2 were similar in all of the study groups, whereas the percentage of CD14( +) monocytes expressing TLR-4 were significantly lower in both stage 3-4 CKD and HD patients at baseline than in controls. The mean fluorescence intensities (MFI) of TLR-2 were significantly lower in controls than in stage 3-4 CKD and HD patients at baseline. The MFI of TLR-4 was similar in all of the groups. The percentage of CD14( +) monocytes expressing TLR-2 did not change during and after HD. The MFI of TLR-2 decreased at 120 min of HD compared with baseline (1837 ± 672 vs 1650 ± 578, P < 0.05), and recovered back to baseline values at 300 min and at 24 h post-HD. MFI of TLR-4 increased at 24 h compared with baseline (941 ± 294 vs 1087 ± 441, P < 0.05). Serum IL-6 levels correlated with MFI of TLR-2 and TLR-4 in stage 3-4 CKD patients and in HD patients at baseline and after HD in univariate analysis. Stepwise multiple regression analysis revealed that MFI of TLR-2 was an independent determinant of serum IL-6 concentrations in stage 3-4 CKD and in HD patients at baseline, at 300 min and at 24 h post-HD. Conclusions. Our study demonstrates that TLR-2 is associated with the inflammatory response of non-dialysed and dialysed CKD patients.

Complete heart block in a neutropenic patient with invasive aspergillosis.

A patient with leukemia who developed complete heart block after the diagnosis of pulmonary aspergillosis is reported. The patient had probable invasive pulmonary aspergillosis with a sudden tachypnea, dyspnea, fever, bilateral pulmonary infiltrates and acute respiratory insufficiency after chemotherapy. On the sixth day of antifungal therapy, she developed complete atrioventricular block. Complete heart block has not been reported during liposomal amphotericin B (LAMB) therapy. Local or hematogenous involvement of the myocardium with aspergillosis may be the most likely explanation of the complete heart block.

Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.

The Glucatell (1-->3)- beta-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of >or=60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and >or=96% for >or=2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.