[Two Case of Rhino-Orbito-Cerebral Mucormicosis Developed After COVID-19 Infection]. / COVID-19 Enfeksiyonu Sonrasi Gelisen Iki Rino-Orbito-Serebral Mukormikoz Olgusu.

Coronavirus 2019 (COVID-19) infection causes excessive cytokine response and a decrease in cellular immune response and this increases susceptibility to fungal co-infections. Mucormycosis is a rare, lifethreatening invasive fungal infection. In this report, two cases who developed rhino-orbito-cerebral mucormycosis shortly after having COVID-19 infection were presented. The first case was a 68-year old woman who admitted to our clinic with orbital cellulitis in her left eye and had a known diagnosis of asthma and rheumatoid arthritis. She was diagnosed with COVID-19 pneumonia 40 days ago, stayed in the intensive care unit for a long time, and received pulse steroid (1000 mg methylprednisolone), interleukin-1 (IL-1) inhibitor (anakinra) and broad-spectrum antibiotic treatments together with antiviral therapy during this period. The second case was a 63-year-old male patient with known diabetes mellitus, hypertension and retinitis pigmentosa, with a history of hospitalization in the intensive care unit due to COVID-19 pneumonia 20 days ago and received pulse steroid therapy during this period. He admitted to our clinic with the complaints of droopy right eyelid, swelling, nausea and vomiting. In both cases, paranasal sinus tomography findings were consistent with invasive sinusitis. Functional endoscopic sinus surgery was performed immediately in less than 16 hours from the first admission in both cases. Histopathological examination of the both cases revealed results consistent with mucormycosis. Mucorales spp. was isolated in sinus tissue culture of the second case taken during the operation. Both of the patients received liposomal amphotericin B. First case died on the 19th day of the treatment. Second case was discharged with full recovery after nine weeks of treatment. The suppression of cellular immunity during the COVID-19 infection, and the use of steroids and interleukin inhibitors in the treatment of severe cases may increase secondary invasive fungal infections. Therefore, clinicians should more frequently consider possible fungal infections in patients with COVID-19.

Daptomycin vs. glycopeptides in the treatment of febrile neutropenia: results of the Izmir matched cohort study.

PURPOSE: In this multicentre, retrospective, matched cohort study we aimed to evaluate the outcomes of neutropenic fever cases that were treated with daptomycin or a glycopeptide (vancomycin or teicoplanin). METHODS: Data and outcomes of adult (aged > 18-years old) patients with neutropenic fever [(1) without clinical and radiological evidence of pneumonia, (2) who were treated with daptomycin or a glycopeptide (teicoplanin or vancomycin) for any reason and for at least 72 h] were extracted from the hospital databases. Matching was performed with all of the three following criteria: (1) underlying disease, (2) reason for starting daptomycin or glycopeptide (microbiologic evidence vs. microbiologic evidence, clinical infection vs. clinical infection and empirical therapy vs. empirical therapy) and (3) neutropenic status. RESULTS: Overall 128 patients [(69/123) (56.1%) in the daptomycin cohort (D) and 59/123 (48%) in the glycopeptide cohort (G)] had a resolution of fever at the end of 72 h antibiotic treatment (p = 0.25). There was no significant difference in cured, improved and (cured + improved) rates between (D) and (G) cohorts as well as fever of unknown origin cases or microbiologically confirmed infections or clinically defined infections subgroups (p > 0.05). There was also no significant difference (p > 0.05), in terms of persistent response in the (D) versus (G) cohorts, CONCLUSIONS: These findings suggest that although not better, daptomycin efficacy is comparable to vancomycin if used as empiric therapy in the treatment of adult febrile neutropenia. We conclude that daptomycin may be used at least as a salvage therapy alternative to glycopeptides in the treatment of adult febrile neutropenia cases. A large, randomized-controlled trial may further consolidate the evidence related to this question.

Comparative Evaluation of COVID-19 Associated Mucormycosis (CAM) and Non-COVID-19-associated Mucormycosis (non-CAM).

OBJECTIVE: To compare COVID-19 associated mucormycosis cases (CAM) with non-COVID-19 associated mucormycosis (non-CAM) cases followed as in-patients. STUDY DESIGN: Observational Study. PLACE AND DURATION OF STUDY: Department of Infectious Diseases and Clinical Microbiology, Adana City Training and Research Hospital, Health Sciences University (HSU), Adana, Turkey, between January 2018 and March 2022. METHODOLOGY: Patients with a diagnosis of mucormycosis (proven and probable) were dichotomised as COVID-19 associated mucormycosis and non-COVID-19 associated mucormycosis cases. Both groups were compared for underlying malignancy, chemotherapy, antifungal therapy related side effects and overall survival. RESULTS: Of the 35 cases enrolled in the study, 17 (48.6%) had CAM and 18 (51.4%) had non-CAM. A statistically significant difference was detected between non-CAM and CAM cases in terms of haematological malignancy, receiving chemotherapy, and antifungal therapy-related side effects (p=0.019, p=0.019, and p=0.027 respectively). Steroid use was found as a risk factor for the diabetic CAM cases (p<0.0001). The difference between the CAM and non-CAM cases in terms of overall survival was not statistically significant (p=0.088). CONCLUSION: Because of the ongoing COVID-19 pandemic and the increasing number of critical patients, treatment of COVID-19 should be performed cautiously in patients who have the risk of developing CAM, particularly those with diabetes and immunosuppression (haematologic malignancy, receiving steroid or chemotherapy, etc.) and these patients should be monitored closely. KEY WORDS: Mucormycosis, COVID-19, Mucormycosis associated with COVID-19, Diabetes mellitus, Turkey.

BNT162b2 or CoronaVac as the Third Dose against Omicron: Neutralizing Antibody Responses among Transplant Recipients Who Had Received Two Doses of CoronaVac.

We evaluated neutralizing antibodies against the Omicron variant and Anti-Spike IgG response in solid organ (SOT) or hematopoietic stem cell (HSTC) recipients after a third dose of BNT162b2 (BNT) or CoronaVac (CV) following two doses of CV. In total, 95 participants underwent SOT (n = 62; 44 liver, 18 kidney) or HSCT (n = 27; 5 allogeneic, 22 autologous) were included from five centers in Turkey. The median time between third doses and serum sampling was 154 days (range between 15 to 381). The vaccine-induced antibody responses of both neutralizing antibodies and Anti-Spike IgGs were assessed by plaque neutralizing assay and immunoassay, respectively. Neutralizing antibody and Anti-Spike IgG levels were significantly higher in transplant patients receiving BNT compared to those receiving CV (Geometric mean (GMT):26.76 vs. 10.89; p = 0.03 and 2116 Au/mL vs. 172.1 Au/mL; p < 0.001). Solid organ transplantation recipients, particularly liver transplant recipients, showed lower antibody levels than HSCT recipients. Thus, among HSCT recipients, the GMT after BNT was 91.29 and it was 15.81 in the SOT group (p < 0.001). In SOT, antibody levels after BNT in kidney transplantation recipients were significantly higher than those in liver transplantation recipients (GMT: 48.32 vs. 11.72) (p < 0.001). Moreover, the neutralizing antibody levels after CV were very low (GMT: 10.81) in kidney transplantation recipients and below the detection limit (<10) in liver transplant recipients. This study highlights the superiority of BNT responses against Omicron as a third dose among transplant recipients after two doses of CV. The lack of neutralizing antibodies against Omicron after CV in liver transplant recipients should be taken into consideration, particularly in countries where inactivated vaccines are available in addition to mRNA vaccines.

Necrotizing Fasciitis: Evaluation of 85 Cases and Usage of LRINEC Score.

Objective: The present study aims to define the characteristics of the necrotizing fasciitis (NF) cases followed at our hospital and to compare our results with the literature. Materials and Methods: In this study, NF cases followed and treated at our hospital from January 2005 to April 2019 were evaluated retrospectively. Results: A total of 85 cases of NF were included in the study. Of the cases, 33 (39%) were female and the median age was 59.8±13.1 years (range: 26-92 years). Diabetes mellitus (DM) (56%) was the most prevalent comorbid condition. Extremities were the most frequently involved field found in 41 (48%) of the cases followed by Fournier's gangrene found in 34 (40%) of the cases. All of the cases had undergone surgical intervention (debridement and/or amputation) and received broad-spectrum antibiotic therapy. Laboratory risk indicator for necrotizing fasciitis (LRINEC) score was calculated for 60 cases, and it was 6 or higher in 78% of them. Nineteen (22%) of 85 cases had died. Conclusion: Necrotizing fasciitis affects generally older male patients with DM. In NF cases to avoid the higher risk of mortality, the removal of necrotic tissue via surgical procedure together with antimicrobial therapy is required urgently; therefore, it is very important to differentiate NF from soft tissue infections as soon as possible. As the LRINEC score predicted NF among nearly 80% of our patients, this score could be used as an early diagnostic tool of NF. Level of Evidence: Level IV, case series.

Evaluation of the effect of the COVID-19 pandemic on mucormycosis studies with bibliometric analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is a relatively new concept in the literature that emerged during the pandemic. Bibliometric analysis is a type of analysis that uses mathematical and statistical methods to study the formal properties of knowledge areas. This study aimed to reveal the main themes, conceptual structures, and trends of bibliometric studies on mucormycosis in 2 different periods, pre-and during the pandemic. METHODS: This study consisted of 2 periods: pre-COVID-19 and COVID-19. Articles were collected from the Web of Science (WOS) Core Collection database. We provided AND and OR connectors for the keyword query and selected studies based on relevant keywords. Collected data were classified based on their publication date and examined using the R programming language (Version 4.0.3) package Bibliometrix and SciMAT Software. RESULTS: A total of 1261 articles were investigated, and performance and information structure analyses were conducted. Based on Bradford's law, the Journal of Fungi was the top-ranked journal in both periods. Cureus and mycoses were placed 2nd and 3rd in the second period. India is the largest contributor. In performance analysis, conceptual structures such as Rhizopus oryzae, epidemiology, diagnosis, management, treatment, and outcomes were at the forefront of mucormycosis publications during the COVID-19 period. CONCLUSIONS: Research trends have shifted to the clinical treatment and management of COVID-19. Therefore, pathogenesis, diagnosis, follow-up, and treatment strategies for CAM should be developed in the future.

Tenofovir disoproxil fumarate treatment in HbeAg-positive patients.

Tenofovir disoproxil fumarate (Tenofovir DF) is a nucleotide analogue. This multicentre study reports retrospectively the long-term efficacy and safety data with tenofovir DF treatment in nucleosid(t)e-naive, hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients. Thirty-one patients (11 females, 20 males) received 245 mg tenofovir DF per diem. All patients' initial serum hepatitis B virus (HBV) DNA levels were over 2,000 IU/ml. Serum alanine aminotransferase (ALT) levels, HBeAg, hepatitis B e antibodies (anti-HBe), hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (Anti-HBs), HBV DNA, creatinine and urea levels were evaluated at baseline, and at weeks 12, 24, 48 and 96 during therapy. Thirty-one patients completed 96 weeks of treatment. Mean age was 37.6 ± 9.4 years. The initial mean value of ALT was 79 ± 39.9 IU/L. At baseline, mean of fibrosis (Ishak) of liver biopsies was 2.3 ± 0.7. Two of the patients (5.9%) achieved HBV DNA less than 300 copies at week 12 of treatment and 97.1 % at week 96. HBeAg loss was observed in 6.7% of patients. At week 96, HBsAg loss was not observed in any of the patients. Mean ALT at week 48 was 32.7 U/L, at week 96 32.6 U/L. Renal safety was good. Creatinine remained stable. Tenofovir DF was well tolerated and produced potent, continuous viral suppression with increasing HBeAg loss.

Four-year study of entecavir efficacy and safety in nucleos(t)ide-naïve HBeAg positive chronic hepatitis B patients.

Entecavir is a guanosine analogue with activity against hepatitis B virus. The aim of this 4-year trial was to evaluate entecavir treatment in nucleos(t)ide-naïve HBeAg-positive chronic hepatitis B patients. Forty-nine patients received entecavir and nine of them withdrew from the trial at the end of week 96. The initial mean value of alanine aminotransferase was 79.4 +/- 41.5 IU/L, and at the end of the 4-year study period, 90% of patients had alanine aminotransferase values within the normal range. At week 96, 91.7% of patients had HBV DNA < 300 copies; at month 48, 90% of patients had HBV DNA < 50 IU/mL. HBeAg loss was recorded in 7.1% of patients at week 96 and in 12.5% at month 48. The rate of HBeAg seroconversion was 4.8% at week 96 and 7.5% at month 48. The rate of HBsAg seroconversion was 2.1% at week 96 and 2.5% at month 48. Entecavir as a potent and safe agent leading to continuous viral suppression proved to be safe and well tolerated therapy.