Overview of invasive fungal infections in children in South America - the threat of resistant Candida species and the role of climate change in the new geographic distribution of endemic systemic mycosis.

PURPOSE OF REVIEW: Invasive fungal infection (IFI) in children is a growing problem with crescent morbidity and mortality, well recognized in developed countries, affecting mainly immunocompromised children, including neonates and children in intensive care units. The burden of IFI in South American children is less well comprehended. In addition, the current epidemiology of endemic systemic mycoses in children may have changed over time. RECENT FINDINGS: Candida spp. infections are very prevalent in South America hospitalized children, especially in neonates, in a rate far superior compared to developed countries. C. auris, has already been responsible for outbreaks in neonates and children in Venezuela and Colombia. Sporotrichosis is well established as an urban zoonosis in impoverish families. Paracoccidioidomycosis and histoplasmosis are affecting new areas of Brazil, probably due to climate change, deforestation, and human migration. SUMMARY: This review aims to unveil the real dimension of these infections in South American children. Hopefully, the awareness brought by this review will help healthcare professionals to recognize IFI more easily and it will provide support for getting more resources for IFI treatment and prevention.

Changing epidemiology of dengue fever in children in South America.

PURPOSE OF REVIEW: Dengue is the most important arthropod-borne viral disease of public health significance. Its geographic distribution includes 128 countries worldwide, affecting 390 million people every year causing significant morbidity and mortality in children and adults everywhere. RECENT FINDINGS: In the past, severe dengue affected mostly adults in the Americas; this scenario has changed and now cases of dengue, severe dengue, and dengue deaths have increased in children under 15 years in Brazil and in Colombia. Dengue and COVID-19 co-infections have been reported in South America, with increased hospitalization. A dengue vaccine for 9-year-old children and older children and adults who have serological evidence of previous dengue has been licensed in many countries; a different dengue vaccine trial for 4-16-year-old children has demonstrated decrease in clinical dengue and decrease in dengue hospitalizations. SUMMARY: There is no specific treatment of dengue, and a changing climate, insecticide resistance and urban expansion have permitted the vector's spread, making the vector control almost impossible. The hope for dengue control relies on vaccine development; there is important research on this area with one vaccine already licensed and another one showing promising results.

Repurposing of Tetracyclines for COVID-19 Neurological and Neuropsychiatric Manifestations: A Valid Option to Control SARS-CoV-2-Associated Neuroinflammation?

The recent outbreak of coronavirus disease 2019 (COVID-19) has gained considerable attention worldwide due to its increased potential to spread and infect the general population. COVID-19 primarily targets the human respiratory epithelium but also has neuro-invasive potential. Indeed, neuropsychiatric manifestations, such as fatigue, febrile seizures, psychiatric symptoms, and delirium, are consistently observed in COVID-19. The neurobiological basis of neuropsychiatric COVID-19 symptoms is not fully understood. However, previous evidence about systemic viral infections pointed to an ongoing neuroinflammatory response to viral antigens and proinflammatory mediators/immune cells from the periphery. Microglia cells mediate the overproduction of inflammatory cytokines, free radicals, and damage signals, culminating with neurotoxic consequences. Semi-synthetic second-generation tetracyclines, including minocycline (MINO) and doxycycline (DOXY), are safe bacteriostatic agents that have remarkable neuroprotective and anti-inflammatory properties. Promising results have been obtained in clinical trials using tetracyclines for major psychiatric disorders, such as schizophrenia and major depression. Tetracyclines can inhibit microglial reactivity and neuroinflammation by inhibiting nuclear factor kappa B (NF-kB) signaling, cyclooxygenase 2, and matrix metalloproteinases (MMPs). This drug class also has a broad profile of activity against bacteria associated with community-based pneumonia, including atypical agents. COVID-19 patients are susceptible to secondary bacterial infections, especially those on invasive ventilation. Therefore, we suggest tetracyclines' repurposing as a potential treatment for COVID-19 neuropsychiatric manifestations. These drugs can represent a valuable multi-modal treatment for COVID-19-associated neuroinflammatory alterations based on their broad antimicrobial profile and neuroinflammation control.

Acute paracoccidioidomycosis with duodenal and cutaneous involvement and obstructive jaundice.

Paracoccidioidomycosis (PCM) is the most widespread endemic mycosis in LatinAmerica. If PCM is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. We report a case of PCM with duodenal and cutaneous involvement simulating cholangitis that was initially misdiagnosed as a lymphoproliferative disease. Clinicians should consider acute paracoccidioidomycosis in the differential diagnosis of jaundice and/or signs/symptoms of cholangitis developing in young patients from paracoccidioidomycosis endemic regions.

Successful control program to implement the appropriate antibiotic prophylaxis for Cesarean section.

OBJECTIVE: Describe implementation of a successful program to reduce doses (cefazolin 2 to 1 g) used for antimicrobial prophylaxis. METHODS: Evaluation of an intervention program to reduce prophylactic antimicrobial doses. The intervention included weekly staff discussions, automatic dispensation of 1g-vial of cefazolin by the pharmacy unless expressly requested by surgeon and increase in post-discharge surveillance as a strategy to reassure surgeons of the safety of the reduction. In the pre and post intervention periods, a prospective study of antimicrobial consumption and surgical site infections were measured. RESULTS: There were 5,164 and 5,204 deliveries in 2001-2002 and 2003-2004, respectively; 1,524 (29.5%) and 1,363 (26%) were cesarean sections. There was a 45% decrease in cefazolin vials used on average per cesarean section (2.29 to 1.25). Patients evaluated increased from 16% to 67% and the SSI rates in both periods were 3.34% to 2.42%, respectively. CONCLUSION: An ample intervention, including administrative and educational measures, led to high compliance with dose reduction and saved more than US$4,000 in cefazolin, considered important because government reimbursement in Brazil for cesarean section is $80.

Successful control program to implement the appropriate antibiotic prophylaxis for cesarean section

OBJECTIVE: Describe implementation of a successful program to reduce doses (cefazolin 2 to 1 g) used for antimicrobial prophylaxis. METHODS: Evaluation of an intervention program to reduce prophylactic antimicrobial doses. The intervention included weekly staff discussions, automatic dispensation of 1g-vial of cefazolin by the pharmacy unless expressly requested by surgeon and increase in post-discharge surveillance as a strategy to reassure surgeons of the safety of the reduction. In the pre and post intervention periods, a prospective study of antimicrobial consumption and surgical site infections were measured. RESULTS: There were 5,164 and 5,204 deliveries in 2001-2002 and 2003-2004, respectively; 1,524 (29.5 percent) and 1,363 (26 percent) were cesarean sections. There was a 45 percent decrease in cefazolin vials used on average per cesarean section (2.29 to 1.25). Patients evaluated increased from 16 percent to 67 percent and the SSI rates in both periods were 3.34 percent to 2.42 percent, respectively. CONCLUSION: An ample intervention, including administrative and educational measures, led to high compliance with dose reduction and saved more than US$4,000 in cefazolin, considered important because government reimbursement in Brazil for cesarean section is $80.

OBJETIVO: descrever a implantação de um programa de redução de doses usadas para profilaxia antimicrobiana em cesárea. MÉTODOS: Descrição a implantação de um programa de redução de profilaxia com cefazolina de 2 g para 1 g através de discussões semanais com profissionais, dispensação automática de frascos de 1 g de cefazolina pela farmácia exceto quando feito pedido expresso pelo cirurgião. Houve um trabalho para aumentar a vigilância pós alta, com o objetivo de tranquilizar os cirurgiões quanto à segurança da nova dose. Foi realizada uma avaliação prospectiva, antes e depois da implantação do programa, do consumo de cefazolina e das taxas de infecção obtidas por vigilância durante a hospitalização e após a alta. RESULTADOS: Houve 5.164 e 5.204 partos em 2001-2 e 2003-4, respectivamente, sendo que 1.524 (29,5 por cento) e 1.363 (26 por cento) foram cesáreas. Houve uma queda de consumo de frascos de cefazolina de 45 por cento (2,29 para 1,25 por cesárea). O número de pacientes avaliados para infecção hospitalar aumentou de 16 por cento para 67 por cento, e as taxas de infecção foram 3,34 por cento e 2,42 por cento, respectivamente. CONCLUSÃO: Uma intervenção ampla, que incluiu medidas administrativas e educacionais, levou a uma alta adesão ao programa de redução de dose profilática em cesárea e permitiu uma economia acima de US$ 4.000 apenas considerando custos com cefazolina. Esta pode ser considerada importante especialmente porque o reembolso do SUS para parto cesárea é aproximadamente US$ 80.

Implementing 1-dose antibiotic prophylaxis for prevention of surgical site infection.

HYPOTHESIS: Replacing a 24-hour regimen with a 1-dose antibiotic prophylaxis for elective surgery would not increase rates of surgical site infection and would decrease costs. DESIGN AND SETTING: Before-after trial in a tertiary, private general hospital in Ribeirão Preto, São Paulo, Brazil. PATIENTS: Surgery was performed on 6140 consecutive patients from February 2002 through October 2002 (period 1) and 6159 consecutive patients from December 2002 through August 2003 (period 2). Studied surgeries included orthopedic, gastrointestinal, urology, vascular, lung, head and neck, heart, gynecologic, oncology, colon, neurologic, and pediatric surgeries. The study excluded patients with infection at the time of surgery. INTERVENTION: Decreasing the 24-hour prophylactic antibiotic regimen to 1-dose antibiotic prophylaxis. MAIN OUTCOME MEASURES: Surgical site infections in both periods measured by in-hospital surveillance and postdischarge surveillance; compliance with 1-dose prophylaxis; and costs with cephazolin. RESULTS: We followed up 12,299 patients during their hospital stay; postdischarge surveillance increased significantly from 2717 patients (44%) to 3066 patients (50%, P<.001). One-dose prophylaxis was correctly followed in 6123 patients (99% compliance). The rate of surgical site infection did not change in either period (2% and 2.1% respectively, P = .67). The number of cephazolin vials purchased monthly decreased from 1259 to 467 with a corresponding monthly savings of $1980. CONCLUSIONS: One-dose antibiotic prophylaxis did not lead to an increase in rates of surgical site infection and brought a monthly savings of $1980 considering cephazolin alone. High compliance to 1-dose prophylaxis was achieved through an educational intervention encouraged by the hospital director and administrative measures that reduced access to extra doses.

Dengue virus infections.

Dengue is the most important arthropod-borne viral disease of public health significance. Its geographic distribution includes more than 100 countries worldwide, where more than 2.5 billion people are at risk for dengue infections. Most people will have asymptomatic infections, but the disease manifestations range from an influenza-like disease known as dengue fever to a severe, sometimes fatal disease characterized by hemorrhage and shock, known as dengue hemorrhagic fever/dengue shock syndrome. Dengue fever and dengue hemorrhagic fever/dengue shock syndrome are caused by the dengue viruses (dengue-1, dengue-2, dengue-3, and dengue-4) transmitted from viremic to susceptible humans mainly by the bites of Aedes aegypti. There is no specific management of dengue infections, no vaccine is commercially available, and vector control is the only alternative for stopping the spread of the disease. Knowledge of several aspects of dengue infections, especially of diagnosis and vaccine development, is continuously evolving, but several issues are still unresolved.