Background
Histoplasmosis is highly endemic in the American continent. This condition is associated with a high mortality, particularly in people living with HIV/AIDS (PLWHA). Diagnosis of histoplasmosis is usually late in South America, as
Histoplasma
antigen detection is rarely available. Here we determined the prevalence, risk factors, and outcome of histoplasmosis in PLWHA in Brazilian hospitals.
Methods
This was a prospective cohort study (2016–2018) involving 14 tertiary medical centers in Brazil. We included hospitalized PLWHA presenting with fever and additional clinical findings. Patients were investigated at each participant center with classical mycology methods. Also,
Histoplasma
antigen detection was performed in urine samples (IMMY). Probable/proven histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria.
Results
From 616 eligible patients, 570 were included. Histoplasmosis was identified in 21.6% (123/570) of patients. Urine antigen testing increased the diagnostic yield in 53.8%, in comparison with standard mycology methods. Variables independently associated with histoplasmosis were CD4+ count <50 cells/mm
3
, use of an antiretroviral (protective effect), and sample collection in the Northeast region of Brazil. Dyspnea at presentation was independently associated with death. Histoplasmosis was more frequent than tuberculosis in patients with low CD4+ counts. Overall 30-day mortality was 22.1%, decreasing to 14.3% in patients with antigen-based diagnosis.
Conclusions
Histoplasmosis is a very frequent condition affecting PLWHA in Brazil, particularly when CD4+ counts are lower than 50 cells/mm
3
. Antigen detection may detect earlier disease, with a probable impact on outcomes. Access to this diagnostic tool is needed to improve clinical management of PLWHA in endemic countries.
Resistance to antimicrobial agents is increasing worldwide and imposes significant life-threatening risks to several different populations, especially those in intensive care units (ICUs). Bacteria can quickly develop or acquire resistance to antimicrobial drugs, and combined with their intrinsic potential to cause disease in humans, these bacteria can become deadly. Among Gram-negative bacteria, Acinetobacter baumannii is notorious as a frequent opportunistic pathogen associated with critically ill patients, and understanding the genetic basis of A. baumannii resistance to beta-lactams among patients in ICUs will result in better protocols to prevent the development of resistance as well as improved treatment regimens. In this study, we assessed 1333 patients in five ICUs, 56 of whom developed A. baumannii infections. Most of the A. baumannii isolates were resistant to beta-lactam antimicrobial drugs, specifically, 3rd- and 4th-generation cephalosporins and carbapenems, and 91.1% of the isolates were multi-drug resistant (MDR). The most frequent OXA gene present was OXA-23 (55.1%), which is significantly associated with MDR strains. Most of the A. baumannii isolates (76.8%) were capable of forming a biofilm. The antimicrobial drug classes that were effective against most of these isolates were polymyxins and tigecycline. The molecular profile of the isolates allowed detection of 12 different clusters comprising 2 to 8 isolates each. In conclusion, our data indicate a high incidence of resistance to carbapenems as well as MDR strains among the observed A. baumannii isolates, most of which exhibited a high prevalence of OXA-23 gene expression. Only a few selective drugs were effective, reinforcing the notion that bacterial resistance is an emerging problem that should be prioritized in every healthcare facility.
Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. Three hundred eighty-four patients were included; the median age was 39 years and 283 (73.7%) were men. Hosts were 304 (79.2%) HIV-positive, 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplanted (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). Two hundred and seventy-one (70.6%) patients were discharged home and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional AMB mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Patients with CNS cryptococcosis had lower mortality (83/313, 26.5%) when compared with the other categories (P = 0.017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death [odds ratio (OR), 1.03; 95% Confidence Interval (CI), 1.01 to 1.05; P = 0.008 and OR, 1.84; 95% CI, 1.01 to 3.53; P = 0.048, respectively]. Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.
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