HIV-Associated Histoplasmosis

Impaired immunity induced by HIV is one of the main causes of disseminated histoplasmosis in endemic areas, and thus from 1987 WHO and then the CDC classified this condition as an AIDS-defining illness. Host factors associated independently with histoplasmosis are low level of CD4 ( 200 cell/mm3. In advanced disease, the most frequent manifestation is as disseminated histoplasmosis often acute and severe, with complications such as respiratory failure, circulatory shock, and disseminated intravascular coagulation. The subacute presentation is frequent, associated with moderate involvement of the reticuloendothelial system, with great variability of clinical manifestation. Guidelines for diagnosing and managing histoplasmosis among people living with HIV have been published from WHO, IDSA, NIH, but limited data was based on randomized clinical trials

Epidemiology of Histoplasmosis

More prevalent than initially considered, histoplasmosis is primarily a non-contagious disease of the reticuloendothelial system, producing a broad spectrum of clinical manifestations, ranging from asymptomatic or self-limited infection, in immunocompetent patients to life-threatening, disseminated disease in immunocompromised ones. The causative agent is H. capsulatum, a thermally dimorphic, intracellular fungus, discovered in 1906, by the pathologist Samuel Darling, when examined tissues from a young man whose death was mistakenly attributed to miliary tuberculosis. Since then, histoplasmosis was described on six continents, with high and low endemicity areas. H. capsulatum is a soil-based fungus, commonly associated with river valleys in the temperate zone, and with the presence of bird and bat guano. Infection occurs when saprophytic spores are inhaled and change to the pathogenic yeast in the lungs, where H. capsulatum overcomes many obstacles to cause host injuries. Depending on geographic distribution, morphology, and clinical symptoms, three varieties have been historically recognized, two of them (var. capsulatum and var. duboisii) being pathogen to humans, and the third (var. farciminosum) has predominantly been described as an equine pathogen. In endemic areas, patients with AIDS or people who receive immunosuppressive therapies should be counseled to avoid high-risk activities; otherwise, precautionary measures should be taken

ACQUIRED DRUG RESISTANCE TO NRTI CLASS IN TREATMENT-EXPERIENCED HIV INFECTED PATIENTS FROM THE CONSTANTA COUNTY: THERAPEUTIC IMPLICATIONS

Objective. To determine the prevalence of acquired drug resistance (ADR) and of resistance patterns in treatment-experienced HIV infected patients from Constanta in order to establish the best therapeutic options in NRTI class. Material and methods. A retrospective study which included 144 treatment-experienced HIV patients with confirmed viral failure. The strains isolated from these patients were analysed in the Molecular Genetic Laboratory of „Matei Bals“ National Institute of Infectious Diseases, Bucharest and the resulting sequences were saved in FASTA format. The HIV-1 subtyping was based on „REGA HIV01&2 Automated subtyping tool version 2.0“ algorithm. „Stanford HIVdb Program version 8.4“ was used in order to determine the therapeutic options. For statistical calculations, the R-Project software was used. Graphic representations were performed using GNUPLOT program. Results. The prevalence of the acquired drug resistance was 92.36%. The most frequent mutation occurred at the level of the codon 184. The TAM-2 path was more frequently selected compared to TAM-1. Association between TAM1 and TAM 2 were also found, mutation K65R being rarely met. Conclusions. The prevalence of the acquired drug resistance in our study was high, The most valuable therapeutic option in the INRT class remains tenofovir, due to the mutational profile, which was selected on account of the extensive use of thymidine analogues

REZISTENŢA LA INRT LA PACIENŢII MULTIPLU EXPERIMENTAŢI DIN CONSTANŢA: IMPLICAŢII TERAPEUTICE

Obiective. Identificarea prevalenţei rezistenţei dobândite la INRT (inhibitorii non-nucleozidici de reverstranscriptază) şi al profilelor de rezistenţă la un lot de pacienţi cu multiple scheme de terapie antiretrovirală din Constanţa şi evaluarea opţiunilor terapeutice remanente. Material şi metode. Studiu retrospectiv ce a inclus 144 pacienţi seropozitivi HIV, multiplu experimentaţi terapeutic, aflaţi în eşec virusologic. Tulpinile izolate de la aceşti pacienţi au fost analizate în Laboratorul de Genetică Moleculară al Institutului Naţional de Boli Infecţioase „Matei Balş“ din Bucureşti, secvenţele rezultate fiind salvate în format Fasta. Subtiparea HIV-1 s-a efectuat pe baza algoritmului „REGA HIV-1&2 Automated subtyping tool version 2.0“. Pentru determinarea opţiunile terapeutice s-a utilizat „Stanford HIVdb Program version 8.4“. Datele au fost prelucrate statistic cu programul R-Project. Reprezentările grafice au fost realizate cu programul GNUPLOT. Rezultate. Prevalenţa rezistenţei dobândite a fost de 92,36%. Cea mai frecventă mutaţie a fost la nivelul codonului 184. Calea TAM-2 a fost mai frecvent selectată decât TAM-1, existând şi asociaţii între cele douăcăi; în schimb, mutaţia K65R a fost rar întâlnită. Concluzii. Prevalenţa rezistenţei dobândite la INRT a fost crescută. Opţiunea terapeutică cea mai valoroasă în clasa INRT a ramas tenofovirul, datorită profilului mutaţional selectat, mai ales din cauza neutilizării lui şi a folosirii extensive anterioare a analogilor timidinici

In-Hospital Antibiotic Use for COVID-19: Facts and Rationales Assessed through a Mixed-Methods Study

It is well known that during the coronavirus disease 2019 (COVID-19) pandemic, antibiotics were overprescribed. However, less is known regarding the arguments that have led to this overuse. Our aim was to understand the factors associated with in-hospital antibiotic prescription for COVID-19, and the rationale behind it. We chose a convergent design for this mixed-methods study. Quantitative data was prospectively obtained from 533 adult patients admitted in six hospitals (services of internal medicine, infectious diseases and pneumology). Fifty-six percent of the patients received antibiotics. The qualitative data was obtained from interviewing 14 physicians active in the same departments in which the enrolled patients were hospitalized. Thematic analysis was used for the qualitative approach. Our study revealed that doctors based their decisions to prescribe antibiotics on a complex interplay of factors regarding the simultaneous appearance of consolidation on the chest computer tomography together with a worsening of clinical conditions suggestive of bacterial infection and/or an increase in inflammatory markers. Besides these features which might suggest bacterial co-/suprainfection, doctors also prescribed antibiotics in situations of uncertainty, in patients with severe disease, or with multiple associated comorbidities

SARS-CoV-2 Infection and Emery-Dreifuss Syndrome in a Young Patient with a Family History of Dilated Cardiomyopathy

Emery–Dreifuss muscular dystrophy (EDMD) is a rare genetic disease that affects the musculoskeletal system, including the heart, causing rhythm disorders and cardiomyopathy, sometimes requiring an implantable cardioverter-defibrillator (ICD) or heart transplantation due to severe heart damage. The case described herein concerns a 16-year-old girl, with grade II obesity, without other known pathological antecedents or cardiac pathology diagnosis given an annual history of cardiological investigations. She was admitted to the Infectious Diseases Department with SARS-CoV-2 virus infection. The anamnesis showed that the cardiological investigations performed in the past were completed due to the medical history antecedents of her sister, who had been diagnosed with dilated cardiomyopathy, having undergone the placement of an ICD and a heart transplant. Numerous investigations were performed during hospitalization, which revealed high levels of high-sensitive cardiac troponin I (hs-cTnI), creatine kinase (CK) and N-terminal pro b-type natriuretic peptide (NT-proBNP). Dynamic electrocardiographic evaluations showed ventricular extrasystoles, without clinical manifestations. The patient presented stage 2 arterial hypertension (AHT) during hospitalization. A cardiac ultrasound was also performed, which revealed suspected mild subacute viral myocarditis with cardiomyopathy, and antihypertensive medication was initiated. A heart MRI was performed, and the patient was diagnosed with dilated cardiomyopathy, refuting the suspicion of viral subacute myocarditis. After discharge, as the patient developed gait disorders with an impossible heel strike upon walking and limitation of the extension of the arms and ankles, was hospitalized in the Neurology Department. Electrocardiograms (ECGs) were dynamically performed, and because the rhythm disorders persisted, the patient was transferred to the Cardiology Department. On Holter monitoring, non-sustained ventricular tachycardia (NSVT) was detected, so antiarrhythmic treatment was initiated, and placement of an ICD was subsequently decided and was diagnosed with EDMD. Genetic tests were also performed, and a mutation of the lamin A/C gene was detected (LMNA gene exon 2, variant c448A > C (p.Thr150pro), heterozygous form, AD)

Antibiotic Prescription and In-Hospital Mortality in COVID-19: A Prospective Multicentre Cohort Study

Background: Since the beginning of the COVID-19 pandemic, empiric antibiotics (ATBs) have been prescribed on a large scale in both in- and outpatients. We aimed to assess the impact of antibiotic treatment on the outcomes of hospitalised patients with moderate and severe coronavirus disease 2019 (COVID-19). Methods: We conducted a prospective multicentre cohort study in six clinical hospitals, between January 2021 and May 2021. Results: We included 553 hospitalised COVID-19 patients, of whom 58% (311/553) were prescribed antibiotics, while bacteriological tests were performed in 57% (178/311) of them. Death was the outcome in 48 patients—39 from the ATBs group and 9 from the non-ATBs group. The patients who received antibiotics during hospitalisation had a higher mortality (RR = 3.37, CI 95%: 1.7–6.8), and this association was stronger in the subgroup of patients without reasons for antimicrobial treatment (RR = 6.1, CI 95%: 1.9–19.1), while in the subgroup with reasons for antimicrobial therapy the association was not statistically significant (OR = 2.33, CI 95%: 0.76–7.17). After adjusting for the confounders, receiving antibiotics remained associated with a higher mortality only in the subgroup of patients without criteria for antibiotic prescription (OR = 10.3, CI 95%: 2–52). Conclusions: In our study, antibiotic treatment did not decrease the risk of death in the patients with mild and severe COVID-19, but was associated with a higher risk of death in the subgroup of patients without reasons for it