Understanding clinical outcomes and factors influencing mortality in intensive care unit patients with COVID-19-associated candidemia.

BACKGROUND: During the COVID pandemic, research has shown an increase in candidemia cases following severe COVID infection and the identification of risk factors associated with candidemia. However, there is a lack of studies that specifically explore clinical outcomes and mortality rates related to candidemia after COVID infection. OBJECTIVES: The aim of this international study was to evaluate the clinical outcomes and identify factors influencing mortality in patients who developed candidemia during their COVID infection. PATIENTS/METHODS: This study included adult patients (18 years of age or older) admitted to the intensive care unit (ICU) and diagnosed with COVID-associated candidemia (CAC). The research was conducted through ID-IRI network and in collaboration with 34 medical centres across 18 countries retrospectively, spanning from the beginning of the COVID pandemic until December 2021. RESULTS: A total of 293 patients diagnosed with CAC were included. The median age of the patients was 67, and 63% of them were male. The most common Candida species detected was C. albicans. The crude 30-day mortality rate was recorded at 62.4%. The logistic regression analysis identified several factors significantly impacting mortality, including age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07, p < .0005), SOFA score (OR 1.307, 95% CI 1.17-1.45, p < .0005), invasive mechanical ventilation (OR 7.95, 95% CI 1.44-43.83, p < .017) and duration of mechanical ventilation (OR 0.98, 95% CI 0.96-0.99, p < .020). CONCLUSIONS: By recognising these prognostic factors, medical professionals can customise their treatment approaches to offer more targeted care, leading to improved patient outcomes and higher survival rates for individuals with COVID-associated candidemia.

Invasive fusariosis in acute leukaemia patients-An outbreak in the haematology ward.

Fusarium, a common fungus, emerges as a pathogen in severely immunocompromised patients. We present a series of patients who developed invasive fusariosis (IF) during admission to an acute leukaemia ward: an outbreak of 12 cases in June and July 2018, followed by four sporadic cases until 2021. No case was reported earlier. All patients were clustered in the same location with indoor air and water installations found to be contaminated with Fusarium spp. thus a nosocomial outbreak was assumed. Following the water installation replacement, the number of Fusarium cases dramatically dropped to one or two isolated instances per year in the same location. All 16 patients had acute leukaemia and developed IF during severe neutropenia following induction therapy. IF diagnosis was based on positive blood cultures (14 patients) and/or on tissue biopsies (3 patients). The median time from admission to the IF onset was 20 days, and from the first day of severe neutropenia (≤500/mm3) was 11.5 days. All patients were febrile, eight had moderate-to-severe myalgias, eight had respiratory involvements: lung lesions and/or sinusitis and seven had characteristic skin lesions. Follow-up: 12 out of 16 (75%) were alive on Day 90; nine out of 15 (60%) were alive on Month 6. All with intractable neutropenia died. In severely neutropenic febrile patients, the triad of respiratory involvement/skin lesions/severe myalgia may suggest Fusarium aetiology. The ability to recover from neutropenia is critical to surmount IF. The indoor environment in immunocompromised dedicated settings must be constantly controlled.

Fusarium ramigenum, a novel human opportunist in a patient with common variable immunodeficiency and cellular immune defects: case report.

BACKGROUND: Fusarium species are ubiquitous environmental fungi that occasionally provoke serious invasive infections in immunocompromised hosts. Among Fusarium species, Fusarium ramigenum, belonging to the Fusarium fujikuroi species complex, has thus far never been found to cause human infections. Here we describe the first case of invasive fusariosis caused by Fusarium ramigenum in a human and also identify immunological deficiencies that most likely contributed to invasiveness. CASE PRESENTATION: A 32-year-old Caucasian male with a seemingly insignificant medical history of mild respiratory illness during the preceding two years, developed invasive pulmonary fusariosis. Detailed immunological assessment revealed the presence of common variable immunodeficiency, complicated by a severe impairment of the capacity of T-cells to produce both gamma-interferon and interleukin-17. In-depth microbiological assessment identified the novel human opportunistic pathogen Fusarium ramigenum as cause of the infection. CONCLUSION: This report demonstrated that an opportunistic invasive fungal infection may indicate an underlying cellular immune impairment of the host. The unexpected invasive infection with Fusarium ramigenum in this case unmasked a complex combined humoral and cellular immunological deficiency.

Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review.

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed of white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells, and platelets. Immune cells, cytokines, chemokines, and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate proinflammatory and procoagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated "cytokine storm", platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2-associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism with chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalized patients with severe disease that would target the crossroads of inflammatory and coagulation pathways.

Pulmonary Thrombosis despite Therapeutic Anticoagulation in COVID-19 Pneumonia: A Case Report and Literature Review.

The rate of thrombotic complications in COVID-19 patients is high and could be associated with the risk of unfavourable outcomes. Moreover, pulmonary thrombotic events can occur even in patients already on anticoagulant treatment. We present the case of a patient with severe COVID-19 pneumonia, without traditional risk factors for thrombosis, who developed massive pulmonary thrombosis (PT) despite therapeutic anticoagulation. The diagnosis was challenging, and the case raised concerns about the protective role of conventional anticoagulant treatment in COVID-19 pneumonia. Thus, we searched for literature reports on COVID-19 patients who developed PT despite being under anticoagulation therapy. We identified 13 cohort studies including 4058 patients of which 346 (8.5%) developed PT and nine case reports/series enrolling 14 patients. Four cohorts were further analysed, which reported data on risk factors for thrombosis, outcomes and biological characteristics. We found that there were no differences between patients with and without PT regarding the classical risk factors for thrombosis. PT occurred regardless of the anticoagulation regimen, and the risk factor identified was severe COVID-19 pneumonia and a stay in an intensive care unit (ICU). Pulmonary thrombotic events in patients with COVID-19 are rather inflammation-related than correlated with traditional thromboembolic risk factors, and the therapeutic approach must take into consideration this aspect.

Antiphospholipid Antibodies Occurrence in Acute SARS-CoV-2 Infection without Overt Thrombosis.

We sought to determine the prevalence of antiphospholipid antibodies (aPLs) and their correlation with COVID-19 severity (in terms of clinical and laboratory parameters) in patients without thrombotic events during the early phase of infection. This was a cross-sectional study with the inclusion of hospitalized COVID-19 patients from a single department during the COVID-19 pandemic (April 2020-May 2021). Previous known immune disease or thrombophilia along with long-term anticoagulation and patients with overt arterial or venous thrombosis during SARS-CoV-2 infection were excluded. In all cases, data on four criteria for aPL were collected, namely lupus anticoagulant (LA), IgM and IgG anticardiolipin antibodies (aCL), as well as IgG anti-ß2 glycoprotein I antibodies (aß2GPI). One hundred and seventy-nine COVID-19 patients were included, with a mean age of 59.6 (14.5) years and a sex ratio of 0.8 male: female. LA was positive in 41.9%, while it was strongly positive in 4.5%; aCL IgM was found in 9.5%, aCL IgG in 4.5%, and aß2GPI IgG in 1.7% of the sera tested. Clinical correlation: LA was more frequently expressed in severe COVID-19 cases than in moderate or mild cases (p = 0.027). Laboratory correlation: In univariate analysis, LA levels were correlated with D-dimer (p = 0.016), aPTT (p = 0.001), ferritin (p = 0.012), C-reactive protein (CRP) (p = 0.027), lymphocyte (p = 0.040), and platelet (p < 0.001) counts. However, in the multivariate analysis, only the CRP levels correlated with LA positivity: OR (95% CI) 1.008 (1.001-1.016), p = 0.042. LA was the most common aPL identified in the acute phase of COVID-19 and was correlated with infection severity in patients without overt thrombosis.

Neurological Manifestations of SARS-CoV2 Infection: A Narrative Review.

The COVID-19 virus frequently causes neurological complications. These have been described in various forms in adults and children. Headache, seizures, coma, and encephalitis are some of the manifestations of SARS-CoV-2-induced neurological impairment. Recent publications have revealed important aspects of viral pathophysiology and its involvement in nervous-system impairment in humans. We evaluated the latest literature describing the relationship between COVID-19 infection and the central nervous system. We searched three databases for observational and interventional studies in adults published between December 2019 and September 2022. We discussed in narrative form the neurological impairment associated with COVID-19, including clinical signs and symptoms, imaging abnormalities, and the pathophysiology of SARS-CoV2-induced neurological damage.

Anthrax meningoencephalitis complicated with brain abscess - A case report.

Bacillus anthracis is a sporulating gram-positive rod whose main route of entry into the human body is cutaneous. Anthrax meningitis is usually fulminant and fatal. We present here a successfully treated case of anthrax meningoencephalitis complicated with brain abscess. The patient was a shepherd, with disease onset 7 days prior to hospital admission with fever, chills, occipital headache, and vertigo, followed by right hemiplegia, motor aphasia, agitation and coma. He had cutaneous lesions with black eschar on the limbs, which was a clue (along with his occupation), for diagnosis suspicion. The polymerase chain reaction for B. anthracis DNA was positive in both cerebrospinal fluid and cutaneous lesions. The cerebrospinal fluid was compatible with bacterial meningitis without being haemorrhagic. Magnetic resonance imaging showed meningeal enhancement and multiple intraparenchymal heterogeneous lesions with an important haemorrhagic component in the left parietal lobe, surrounded by vasogenic oedema with maintenance, 22 days later, of the left parietal lobe lesion, having a ring contrast enhancement and a central diffusion restriction, compatible with an abscess. From admission, he was intensively treated with combined large-spectrum antibiotics; this could be the most valuable factor in the successful outcome.

Vector-borne and zoonotic infections and their relationships with regional and socioeconomic statuses: An ID-IRI survey in 24 countries of Europe, Africa and Asia.

BACKGROUND: In this cross-sectional, international study, we aimed to analyze vector-borne and zoonotic infections (VBZI), which are significant global threats. METHOD: VBZIs' data between May 20-28, 2018 was collected. The 24 Participatingcountries were classified as lower-middle, upper-middle, and high-income. RESULTS: 382 patients were included. 175(45.8%) were hospitalized, most commonly in Croatia, Egypt, and Romania(P = 0.001). There was a significant difference between distributions of VBZIs according to geographical regions(P < 0.001). Amebiasis, Ancylostomiasis, Blastocystosis, Cryptosporidiosis, Giardiasis, Toxoplasmosis were significantly more common in the Middle-East while Bartonellosis, Borreliosis, Cat Scratch Disease, Hantavirus syndrome, Rickettsiosis, Campylobacteriosis, Salmonellosis in Central/East/South-East Europe; Brucellosis and Echinococcosis in Central/West Asia; Campylobacteriosis, Chikungunya, Tick-borne encephalitis, Visceral Leishmaniasis, Salmonellosis, Toxoplasmosis in the North-Mediterranean; CCHF, Cutaneous Leishmaniasis, Dengue, Malaria, Taeniasis, Salmonellosis in Indian Subcontinent; Lassa Fever in West Africa. There were significant regional differences for viral hemorrhagic fevers(P < 0.001) and tick-borne infections(P < 0.001), and according to economic status for VBZIs(P < 0.001). The prevalences of VBZIs were significantly higher in lower-middle income countries(P = 0.001). The most similar regions were the Indian Subcontinent and the Middle-East, the Indian Subcontinent and the North-Mediterranean, and the Middle-East and North-Mediterranean regions. CONCLUSIONS: Regional and socioeconomic heterogeneity still exists for VBZIs. Control and eradication of VBZIs require evidence-based surveillance data, and multidisciplinary efforts.

Triazole-resistant Aspergillus fumigatus harbouring G54 mutation: Is it de novo or environmentally acquired?

Triazole resistance in Aspergillus fumigatus develops in patients with chronic lung diseases receiving long-term azole therapy or by environmental selection of resistant A. fumigatus. Here we report for the first time the isolation of triazole-resistant A. fumigatus (TRAF) harbouring the G54E mutation from environmental samples in India, Romania and Tanzania. This mutation in the cyp51A azole target gene of A. fumigatus is so far considered as de novo occurring in patients due to prolonged exposure to azoles. A total of 81 soil and woody debris samples from India, Romania and Tanzania were processed for detection of TRAF and determination of their susceptibility to medical triazoles and fungicides. cyp51A sequencing and real-time PCR were performed for detection of mutations. The isolates were genotyped by microsatellite typing. Overall, 25% of samples (20/81) from India, Romania and Tanzania harboured TRAF. Of the 20 samples harbouring TRAF, a single resistance mechanism, the G54E mutation, was found in 16 samples from three countries. This mechanism was responsible for 46.4% of resistant isolates from Tanzania, 30.4% from Romania and 20.0% from India. The G54E isolates revealed high MICs of itraconazole and posaconazole and were cross-resistant to agricultural fungicides. The majority of the Romanian and Tanzanian G54E isolates had an identical genotype. The present report describes the genetic heterogeneity of TRAF strains harbouring the G54E mutation in the environment of India, Romania and Tanzania. It may be anticipated that long-term exposure of A. fumigatus to fungicides may induce selection of G54 mutants in the environment.

Immune reconstitution inflammatory syndrome in central nervous system tuberculosis.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) related to tuberculosis (TB) is an exacerbation of an inflammatory response that most often occurs in HIV-infected patients but it has also been observed in non-HIV immunocompromised hosts. We describe two cases of TB associated IRIS with CNS involvement, one in a patient diagnosed with HIV infection and the other in a patient with immunosuppression due to anti tumor necrosis factor treatment. CASE REPORT; The first case was a 40-year-old man, newly diagnosed with HIV infection, who developed right hemiplegia and expressive aphasia. Lumbar puncture and MRI sustained the diagnosis of TB meningoencephalitis. He initially improved understandard antituberculous therapy (ATT). After 6 weeks of ATT antiretroviral treatment (ART) was initiated and one week later the patient experienced worsening of his symptoms (left hemiparesis and mixed aphasia), of CSF and MRI changes. He improved after he was starting on corticosteroids in tapering doses, with clinical deterioration at lower doses over a 5-month period. The second case was a 56-year-old male, treated for 3 years with Infliximab for ankylosing spondylitis. He was diagnosed with disseminated TB (CNS tuberculomas and pulmonary TB), histological and bacteriological confirmed the diagnosis. His neurological symptoms improved after starting ATT but after 2 weeks of therapy he presented with diplopia and generalized tonic-clonic seizures. These symptoms improved only after corticosteroids were added (tapering doses during the next 6 months). CONCLUSION: TB-associated IRIS with CNS involvement is potentially life threatening. Corticosteroids should be used to control the IRIS symptoms in those patients. The dosing and duration should be tailored to each patient.

Characteristics of late presenters in Bucharest.

INTRODUCTION: Late presentation is associated with increased healthcare costs, rates of HIV transmission and poor outcome. In Romania, in 2012, one third of individuals with new HIV diagnosis were late presenters (LP). OBJECTIVE: The aim of the study was to evaluate the epidemiological and clinical characteristics associated with late presentation. METHODS: We retrospectively studied patients over 18 years old, notified in our institution between January 2012 and December 2013, including 499 out of 727 newly diagnosed patients in Bucharest. LP were defined as patients presenting with CD4 T-cell count below 350 cells/mm(3) or with an AIDS defining event. Patients with advanced HIV disease (AHD) were defined as persons with a CD4 T-cell count below 200 cells/mm(3). Differences between groups were analyzed using the Mann-Whitney U test for continuous variables and the chi-square test for dichotomous variables. Multivariable analysis was performed using binary logistic regression. RESULTS: Out of 499 patients included, 362 (72%) were male. The median age was 30 (IQR 26-36). A total of 302 (61%) were LP and 184 (37%) were patients with AHD. A total of 170 (34%) were asymptomatic and 114 (23%) presented with an AIDS-defining event. The median CD4 count was 293 cells/mm(3) (IQR 125-471) and the median HIV viral load was 100,191 copies/mL (IQR 34,560-272,936). Characteristics of LP compared with non-LP are shown in Table 1. Stage C disease has been shown by multivariable analysis to be associated with LP (p<0.001, OR=11.56, 95% CI 4.94-27.03). CONCLUSIONS: More than half of newly HIV diagnosed patients in Bucharest were LP. The proportion of LP was highest among heterosexually acquired cases. Although most our patients were young, late presentation was associated with age over 35 years. The lower proportion of LP among IVDU compared with those heterosexually infected could be explained by a higher proportion of HIV screening tests among IVDU.

[The fever of international travel]. / Febra dupa calatorii internationale.

Between 20 and 70 percent of the 50 million people who travel from the industrialized world to the developing world each year report some illness associated with their travel. Although most illness reported by travellers are mild, 20-70% of travellers become ill enough to seek medical attention, either during or immediately after travel. The full spectrum of health complaints is unknown. Nevertheless the usual presentation of a returned traveller is a particular syndrome-fever, respiratory infection, diarrhoea, eosinophilia, or skin and soft tissue infection- or screening for asymptomatic infection. The most common diseases diagnosed in returning travellers are more often of cosmopolitan than exotic origin. However, fever in returned travelers always should raise suspicion for a severe or potentially life-threatening tropical infection. Therefore, fever in a returned traveller requires prompt investigation focused on infections that are life-threatening, treatable or transmissible. Careful assessment of the travel history, likely incubation period, exposure history, associated signs and symptoms, duration of fever, immunization status, use or non-use of antimalarial chemoprophylaxis and degree of compliance with the prescribed regimen, if used, helps to establish the diagnosis. Determining an approximate incubation period can be particularly helpful in ruling out possible causes of fever. Malaria is the most important cause of fever in the returned traveller. While most travel-related infections present within 6 months of return, some infections with long latent periods or potential for lifetime persistence might be seen in those who have lived abroad.

[Differential diagnosis of febrile exanthema]. / Diagnosticul diferential al exantemului febril.

Febrile exanthema (FE) is an extremely polymorphous clinical entity, frequently seen in daily clinical practice. FE is characterized by diffuse rash and fever. FE is classified in 4 types, depending on the primary skin lesion: macular, maculopapular, vesicular, and bullous exanthema. It is of infectious and non-infectious cause. Among the infectious causes the most frequent is the viral one. FE may affect all ages, but especially children and young people. Usually, FE raises important issues of differential diagnosis, because its clinical and etiological complexity. To decide the most appropriate therapeutic and prophylactic measures for FE, it is important to know the clinical criteria and the specific diagnostic methods.