MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses-A Multicenter, Open-Label, Randomized Comparative Trial.

Background: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). Methods: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. Results: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). Conclusions: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. Clinical Trials Registration: NCT03572049.

Leptospirosis: Epidemiological and Clinical Characteristics at the National Reference Hospital in Panama.

Leptospirosis represents a public health problem in Panama, with an incidence rate of 1 in 100,000 inhabitants in 2014. Despite active surveillance and reports of outbreaks in the news, publications about human leptospirosis in Panama are scarce. The objective of this study was to describe the epidemiological and clinical features of leptospirosis in a cohort of patients admitted to the national reference hospital from January 2013 to December 2018. A total of 188 patients with suspected leptospirosis were identified, but only 56.9% (107 of 188) of the medical records could be retrieved. Microagglutination assays were completed in 45% (48 of 107) of the patients, confirming leptospirosis in 29.2% (14 of 48) of the patients. The most prevalent serogroup identified was Leptospira interrogans icterohemorrhagiae (4 of 14, 28.6%). The majority of patients with confirmed disease were middle-aged (36.4 ± 15.7 years), male (11 of 14, 78.6%), and symptomatic for 6.8 ± 0.7 days before admission. The predominant clinical presentation was fever (13 of 14, 92.9%), abdominal pain (7 of 14, 50%), and jaundice (8 of 14, 57.1%). Respiratory failure (8 of 14, 57.1%), elevated creatinine levels on admission (8 of 14, 57.1%), transfusion of blood-derived products (6 of 14, 42.9%), and required use of vasopressors (4 of 14, 28.6%) were common complications. Mortality was 28.6% (4 of 14). Empiric antibiotic therapy was initiated in almost all patients (10 of 12, 83.3%), and was appropriate in 90% (9 of 10) of them. Our study highlights the high prevalence of severe disease and reveals the diagnostic challenges concealing the true burden of leptospirosis in Panama. However, the small number of confirmed patients limits the generalization of these findings.

Omeprazol en la profilaxis temprana de sangrado digestivo alto en la Unidad de Cuidados Intensivos del Hospital Santo Tomás

Introducción: La profilaxis de sangrado digestivo alto con omeprazol es una práctica frecuente en pacientes admitidos a la UCI. Actualmente se investigan complicaciones infecciosas relacionadas con esta terapia. Objetivo: determinar la frecuencia con que se utiliza la profilaxis temprana con omeprazol en pacientes admitidos a la UCI y describir sus resultados clínicos. El objetivo secundario fue determinar los factores de riesgo asociados a úlceras de estrés más frecuentes.Método: se realizó un estudio retrospectivo, descriptivo en una muestra de pacientes admitidos a la UCI del Hospital Santo Tomás en el año 2019. Resultados: Se incluyeron 114 pacientes, con mediana de edad de 40 años (IQR, 28-58), predominio del sexo masculino (60.53%) y una mediana de tiempo en UCI de 12 días (IQR, 6-24). 111 pacientes (97.37%) recibieron profilaxis temprana con omeprazol. En el grupo que recibió profilaxis temprana, se presentó sangrado digestivo alto en 2.70% de los casos; 40 pacientes (36.04%) presentaron neumonía nosocomial y 1 paciente (0.90) presentó infección por Clostridium difficile. En la muestra estudiada, 110 pacientes (96.49%) utilizaron ventilación mecánica; 85 pacientes (74.56%) presentaron shock y 44 pacientes (38.60%) desarrollaron lesión renal aguda. Conclusiones: La profilaxis temprana con omeprazol es una práctica habitual en pacientes admitidos a UCI. El sangrado digestivo alto se presentó con poca frecuencia. Un tercio de los pacientes que recibió este tratamiento presentó neumonía nosocomial, siendo la infección por Clostridium difficile una rara complicación. El uso de ventilación mecánica y el shock fueron los factores de riesgo de úlceras de estrés más frecuentes. (provisto por Infomedic International)

Introduction: Upper gastrointestinal bleeding prophylaxis with omeprazole is a frequent practice in patients admitted to the ICU. Infectious complications related to this therapy are currently being investigated. Objective: to determine the frequency with which early omeprazole prophylaxis is used in patients admitted to the ICU and to describe its clinical outcomes. The secondary objective was to determine the risk factors associated with the most frequent stress ulcers. Methods: a retrospective, descriptive study was conducted in a sample of patients admitted to the ICU of Hospital Santo Tomás in 2019. Results: 114 patients were included, with a median age of 40 years (IQR, 28-58), male predominance (60.53%) and a median time in ICU of 12 days (IQR, 6-24). 111 patients (97.37%) received early prophylaxis with omeprazole. In the group that received early prophylaxis, upper gastrointestinal bleeding occurred in 2.70% of cases; 40 patients (36.04%) presented nosocomial pneumonia and 1 patient (0.90) presented Clostridium difficile infection. In the sample studied, 110 patients (96.49%) used mechanical ventilation; 85 patients (74.56%) presented shock and 44 patients (38.60%) developed acute kidney injury. Conclusions: Early prophylaxis with omeprazole is a common practice in patients admitted to ICU. Upper gastrointestinal bleeding occurred infrequently. One third of the patients who received this treatment presented nosocomial pneumonia, being Clostridium difficile infection a rare complication. The use of mechanical ventilation and shock were the most frequent risk factors for stress ulcers. (provided by Infomedic International)

It is time to define an organizational model for the prevention and management of infections along the surgical pathway: a worldwide cross-sectional survey.

BACKGROUND: The objectives of the study were to investigate the organizational characteristics of acute care facilities worldwide in preventing and managing infections in surgery; assess participants' perception regarding infection prevention and control (IPC) measures, antibiotic prescribing practices, and source control; describe awareness about the global burden of antimicrobial resistance (AMR) and IPC measures; and determine the role of the Coronavirus Disease 2019 pandemic on said awareness. METHODS: A cross-sectional web-based survey was conducted contacting 1432 health care workers (HCWs) belonging to a mailing list provided by the Global Alliance for Infections in Surgery. The self-administered questionnaire was developed by a multidisciplinary team. The survey was open from May 22, 2021, and June 22, 2021. Three reminders were sent, after 7, 14, and 21 days. RESULTS: Three hundred four respondents from 72 countries returned a questionnaire, with an overall response rate of 21.2%. Respectively, 90.4% and 68.8% of participants stated their hospital had a multidisciplinary IPC team or a multidisciplinary antimicrobial stewardship team. Local protocols for antimicrobial therapy of surgical infections and protocols for surgical antibiotic prophylaxis were present in 76.6% and 90.8% of hospitals, respectively. In 23.4% and 24.0% of hospitals no surveillance systems for surgical site infections and no monitoring systems of used antimicrobials were implemented. Patient and family involvement in IPC management was considered to be slightly or not important in their hospital by the majority of respondents (65.1%). Awareness of the global burden of AMR among HCWs was considered very important or important by 54.6% of participants. The COVID-19 pandemic was considered by 80.3% of respondents as a very important or important factor in raising HCWs awareness of the IPC programs in their hospital. Based on the survey results, the authors developed 15 statements for several questions regarding the prevention and management of infections in surgery. The statements may be the starting point for designing future evidence-based recommendations. CONCLUSION: Adequacy of prevention and management of infections in acute care facilities depends on HCWs behaviours and on the organizational characteristics of acute health care facilities to support best practices and promote behavioural change. Patient involvement in the implementation of IPC is still little considered. A debate on how operationalising a fundamental change to IPC, from being solely the HCWs responsibility to one that involves a collaborative relationship between HCWs and patients, should be opened.

Antiretroviral therapy use in selected countries in Latin America during 2013-2017: results from the Latin American Workshop in HIV Study Group.

OBJECTIVE: To document antiretroviral use in Latin America during the last decade. METHODS: We collected indicators from 79 HIV health care centres in 14 Latin American Spanish-speaking countries for 2013-2017. Indicators were analysed by age, sex and other characteristics and weighted by the estimated people under care (PUC) population in each country. RESULTS: We gathered information on 116 299 PUC. One-third belonged to centres reporting a shortage of at least one antiretroviral therapy (ART) drug for >30 days during 2017. At end 2017, 95.1% of PUC were receiving ART. During 2013-2017, 45 329 people living with HIV were admitted to 39 centres. ART initiated during the first year after admission increased from 76.7% in 2013 to 83.8% in 2017. In 35 centres across the study period, 71.7% of PUC started ART with tenofovir disoproxil fumarate and lamivudine, and zidovudine use decreased. The third most common ART drug, EFV, reached 64.8%. Raltegravir and other alternatives increased annually to almost 10% of total use in 2017. CONCLUSIONS: Initial ART in Latin America is not based on the most recent scientific evidence and recommendations; use of drugs with higher efficacy and safety profiles and guarantee of ART availability continues to be a public health challenge.

Histoplasmosis.

Histoplasmosis is one of the commonest endemic mycoses in the Americas yet is often underdiagnosed and neglected as a public health priority. This review outlines the evolving understanding of its epidemiology and the clinical syndromes of histoplasmosis, in addition to up-to-date diagnostic and treatment guidelines. A focus on histoplasmosis in advanced HIV is included. The challenges pertinent to histoplasmosis management in Latin America, with recommendations made through international expert consensus are discussed.

Tracing the Evolutionary History and Global Expansion of Candida auris Using Population Genomic Analyses.

Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. aurisIMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

Isolation of Candida auris from 9 patients in Central America: Importance of accurate diagnosis and susceptibility testing.

Candida auris is an emerging multidrug-resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing.

Chikungunya virus infection: first detection of imported and autochthonous cases in Panama.

Chikungunya virus (CHIKV) is a mosquito-borne pathogen that was only endemic in Africa and south Asia until 2005 and 2006, when the virus spread into the Indian Ocean islands, Europe, and Asia. Autochthonous CHIKV transmission in the Caribbean islands was reported in December of 2013. In Panama, two febrile cases were detected in May of 2014: one traveling from Haiti, and the other traveling from the Dominican Republic. After other imported cases were detected, the first autochthonous case was reported in August of the same year. We detected CHIKV viral RNA and isolated the virus from serum samples. The phylogenetic analysis of the two imported isolates and one autochthonous CHIKV isolate indicated that the viruses belong to the Asian lineage in the Caribbean clade and are related to viruses recently identified in Saint Martin island, British Virgin Islands, China, and the Philippines. Although the circulating CHIKV lineages in the Americas have not yet been described, our results suggest that the Asian lineage is circulating in most American countries reporting autochthonous infection.

Sensitivity changes over the course of infection increases the likelihood of resistance against fusion but not CCR5 receptor blockers.

As HIV-1 evolves over the course of infection, resistance against antiretrovirals may arise in the absence of drug pressure, especially against receptor and fusion blockers because of the extensive changes observed in the envelope glycoprotein. Here we show that viruses from the chronic phase of disease are significantly less sensitive to CCR5 receptor and fusion blockers compared to early infection variants. Differences in susceptibility to CCR5 antagonists were observed in spite of no demonstrable CXCR4 receptor utilization. No significant sensitivity differences were observed to another entry blocker, soluble CD4, or to reverse transcriptase, protease, or integrase inhibitors. Chronic as compared to early phase variants demonstrated greater replication when passaged in the presence of subinhibitory concentrations of fusion but not CCR5 receptor inhibitors. Fusion antagonist resistance, however, emerged from only one chronic phase virus culture. Because sensitivity to receptor and fusion antagonists is correlated with receptor affinity and fusion capacity, respectively, changes that occur in the envelope glycoprotein over the course of infection confer greater ability to use the CCR5 receptor and increased fusion ability. Our in vitro passage studies suggest that these evolving phenotypes increase the likelihood of resistance against fusion but not CCR5 receptor blockers.