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Invasive candidiasis encompassing Candida bloodstream infections and deep-seated candidiasis can become a persistent health problem. These infections are caused by Candida species and have high morbidity and mortality rates. Species distribution, access to diagnosis, treatment and mortality are different around the world. The mortality rate is high in South America (30–70%), and Candida albicans is the most prevalent species in this region. However, a global epidemiological shift to non-albicans species has been observed. In this group, C. parapsilosis is the species most frequently detected, followed by C. tropicalis, and at a slower rate, C. glabrata, which has also increased, in addition to the emerging C. auris, resistance to several drugs. This article summarizes relevant aspects of candidemia pathogenesis, such as the mechanisms of fungal invasion, immune response, and the impact of genetic defects that increase host susceptibility to developing the infection. We also discuss relevant aspects of treatment and future challenges in South America.

This work examines cellular immunity against SARS-CoV-2 in patients from Córdoba, Argentina, during two major waves characterized by different circulating viral variants and different social behavior. Using flow cytometry, we evaluated the main lymphocyte populations of peripheral blood from hospitalized patients with moderate and severe COVID-19 disease. Our results show disturbances in the cellular immune compartment, as previously reported in different cohorts worldwide. We observed an increased frequency of B cells and a significant decrease in the frequency of CD3 + T cells in COVID-19 patients compared to healthy donors (HD). We also found a reduction in Tregs, which was more pronounced in severe patients. During the first wave, the frequency of GZMB, CD107a, CD39, and PD-1-expressing conventional CD4 + T (T conv) cells was significantly higher in moderate and severe patients than in HD. During the second wave, only the GZMB + T conv cells of moderate and severe patients increased significantly. In addition, these patients showed a decreased frequency in IL-2-producing T conv cells. Interestingly, we identified two subsets of circulating CD8 + T cells with low and high CD8 surface expression in both HD and COVID-19 patients. While the percentages of CD8 hi and CD8 lo T cells within the CD8 + population in HD are similar, a significant increase was observed in CD8 lo T cell frequency in COVID-19 patients. CD8 lo T cell populations from HD as well as from SARS-CoV-2 infected patients exhibited lower frequencies of the effector cytokine-producing cells, TNF, IL-2, and IFN-γ, than CD8 hi T cells. Interestingly, the frequency of CD8 lo T cells increased with disease severity, suggesting that this parameter could be a potential marker for disease progression. Indeed, the CD8 hi /CD8 lo index helped to significantly improve the patient’s clinical stratification and disease outcome prediction. Our data support the addition of, at least, a CD8 hi /CD8 lo index into the panel of biomarkers commonly used in clinical labs, since its determination may be a useful tool with impact on the therapeutic management of the patients.

COVID-19 severity has been linked to an increased production of inflammatory mediators called \"cytokine storm\". Available data is mainly restricted to the first international outbreak and reports highly variable results. This study compares demographic and clinical features of patients with COVID-19 from Córdoba, Argentina, during the first two waves of the pandemic and analyzes association between comorbidities and disease outcome with the \"cytokine storm\", offering added value to the field. We investigated serum concentration of thirteen soluble mediators, including cytokines and chemokines, in hospitalized patients with moderate and severe COVID-19, without previous rheumatic and autoimmune diseases, from the central region of Argentina during the first and second infection waves. Samples from healthy controls were also assayed. Clinical and biochemical parameters were collected. Comparison between the two first COVID-19 waves in Argentina highlighted that patients recruited during the second wave were younger and showed less concurrent comorbidities than those from the first outbreak. We also recognized particularities in the signatures of systemic cytokines and chemokines in patients from both infection waves. We determined that concurrent pre-existing comorbidities did not have contribution to serum concentration of systemic cytokines and chemokines in COVID-19 patients. We also identified immunological and biochemical parameters associated to inflammation which can be used as prognostic markers. Thus, IL-6 concentration, C reactive protein level and platelet count allowed to discriminate between death and discharge in patients hospitalized with severe COVID-19 only during the first but not the second wave. Our data provide information that deepens our understanding of COVID-19 pathogenesis linking demographic features of a COVID-19 cohort with cytokines and chemokines systemic concentration, presence of comorbidities and different disease outcomes. Altogether, our findings provide information not only at local level by delineating inflammatory/anti-inflammatory response of patients but also at international level addressing the impact of comorbidities and the infection wave in the variability of cytokine and chemokine production upon SARS-CoV-2 infection.

Antifungal stewardship is a critical component of healthcare management that focuses on optimizing the use of antifungal medications to improve patient outcomes, minimize resistance, and reduce healthcare costs.  In resource-limited settings, the prevalence of fungal infections remains a significant health concern, often exacerbated by factors such as compromised immune systems, inadequate diagnostic capabilities, and limited access to antifungal agents. This paper reviews the current state of antifungal stewardship practices in developing countries, addressing the unique socioeconomic and healthcare landscape.

Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are two forms of a disease caused by Candida spp. β-defensin (BD) is one of the most important families of antimicrobial peptides in the female genital tract and includes molecules that exert essential local functions as antimicrobial and PMN chemoattractant peptides. However, the information on their role during murine and human VVC and RVVC is limited. Thus, we analyzed the behavior and contribution of BD1 to the local response in a VVC mice model and the local cytokine profile and human BD1 and BD3 expression in cervicovaginal lavage from patients with VVC and RVVC. We demonstrated that, in patients with RVVC BD1, mRNA and protein expression were severely diminished and that the aspartate proteinase and lipase secreted by C. albicans are involved in that decrease. This study provides novel information about the pathogenesis of VVC and describes a highly efficient C. albicans escape strategy for perpetuating the infection; these results may contribute to the development of new or combined treatment approaches.

This study sought to determine whether a specific polymerase chain reaction (PCR) for enterotoxigenic Escherichia coli (ETEC) toxins after chaotropic extraction of DNA from stool would increase the detection of ETEC over that of conventional oligonucleotide probe hybridization of 5 E. coli colonies per stool sample (a standard method). By DNA hybridization, 29 (21%) of 140 patients were positive for ETEC, and 59 (42%) of 140 were positive for ETEC when PCR was used. Sensitivity of the PCR assay was confirmed through spiked stool experiments to be ∼100–1000 ETEC colonies per sample. Specificity of the assay was determined by showing an absence of ETEC by the PCR technique in a subgroup of 48 subjects and by confirming the presence of ETEC DNA of positive samples by dot blot procedure. PCR technique detected significantly more ETEC infections in these subjects than did the hybridization method (P < .0001).

Eighty United States students in Mexico received either loperamide (an initial dose of 4 mg, followed by 2 mg after passage of each unformed stool, up to 8 mg/d; 40 patients) or loperamide (at the same dosage schedule) plus an oral rehydration therapy (ORT) preparation (500 mL initially, followed by 250 mL after each subsequently passed unformed stool, up to 1,000 mL per 24 hours; 40 patients). The ORT preparation was a modification of the World Health Organization-recommended solution, adjusted to a sodium concentration of 60 mEq/L. All treatments were given for 48 hours. The study demonstrated equivalent clinical responses with regard to diminishment of diarrhea or subjective findings such as abdominal pain/cramps, headache, dry mouth, dizziness, or thirst. Stool number (by form) and specific gravity of urine postenrollment were similar in the groups. Administration of loperamide plus ORT for the management of traveler's diarrhea, in cases in which subjects were encouraged to drink ad libitum, offered no benefit over administration of loperamide alone.

The syndrome of peripheral fat wasting (lipodystrophy) with central adiposity, hyperlipidemia, and insulin resistance has been associated with the use of HIV-1 protease inhibitors. To date, the mechanisms of these effects have been only hypothesized. Two cases of breast hypertrophy in association with abdominal swelling and thinning of the thighs in women treated with indinavir have been reported. A proposed hypothesis explains breast hypertrophy in women as being secondary to the default accumulation of fat by more metabolically active breast adipocytes in the presence of estrogen. We describe two HIV-1-infected men with normal testosterone and estrogen levels, in whom gynecomastia developed in association with indinavir therapy.

Background Gram-negative bacteremia (GNB) in neutropenic patients is a major cause of infection-related mortality. Our objective was to identify factors associated with 7-day and 30-day mortality during GNB episodes in neutropenic patients. Methods Prospective multicenter study. Episodes of GNB in adult neutropenic cancer and hematopoietic stem cell transplant (HSCT) patients were included in 10 centers of Argentina, from May 2014 to January 2018. To identify factors associated with 7-day and 30-day mortality, variables with P < 0.05 in univariate analysis were included in a logistic regression model for multivariate analysis. Results Four hundred and seventy-six episodes of GNB were included. From these, 68.06% had hematological malignancies, 22.90% HSCT and 9.03% solid tumors. Seven-day and 30-day mortality were 19.53 and 26.47%, respectively. In multivariate analysis, factors independently associated with 7-day mortality were: Meropenem-resistant GNB (OR 8.60, 95% CI 3.06–24.14, P ≤ 0.0001), respiratory source (OR 3.67, 95% CI 1.21–11.10, P = 0.021), skin and soft tissue source (OR 3.89, 95% CI 1.01–14.94, P = 0.048), Charlson score > 4 (OR 2.76, 95% CI 1.06–7.19, P = 0.037) and shock (OR 7.13, 95% CI 2.50–20.33, P ≤ 0.0001). Independent factors for 30-day mortality were: Meropenem-resistant GNB (OR 7.06, 95% CI 2.83–17.64, P ≤ 0.0001), respiratory source (OR 4.41, 95% CI 1.53–12.73, P = 0.006), skin and soft tissue source (OR 3.66, 95% CI 1.00–13.42, P = 0.049), Charlson score > 4 (OR 3.81, 95% CI 1.62–8.91, P = 0.002), intensive care unit requirement (OR 2.46, 95% CI 1.00–6.04, P = 0.049), shock (OR 10.90, 95% CI 4.12–29.85, P ≤ 0.0001) and refractory cancer (OR 4.30, 95% CI 1.57–11.78, P = 0.005). Conclusion The identification of certain prognostic factors would allow the stratification of neutropenic patients at high risk for mortality during GNB episodes. The appropriate medical intervention of a multidisciplinary team on these factors could improve the outcome of these patients. Since Meropenem-resistant GNB is one of strongest prognostic factors, it is essential to identify the patients at risk and treat them appropriately. Disclosures All authors: No reported disclosures.