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ABSTRACT Background: Invasive fungal infections (IFIs) affect >1.5 million people per year. Nevertheless, IFIs are usually neglected and underdiagnosed. IFIs should be considered as a public-health problem and major actions should be taken to tackle them and their associated costs. Aim To report the incidence of IFIs in four Mexican hospitals, to describe the economic cost associated with IFIs therapy and the impact of adverse events such as acute kidney injury (AKI), liver damage (LD), and ICU stay. Methods: This was a retrospective, transversal study carried-out in four Mexican hospitals. All IFIs occurring during 2016 were included. Incidence rates and estimation of antifungal therapy's expenditure for one year were calculated. Adjustments for costs of AKI were done. An analysis of factors associated with death, AKI, and LD was performed. Results: Two-hundred thirty-eight cases were included. Among all cases, AKI was diagnosed in 16%, LD in 25%, 35% required ICU stay, with a 23% overall mortality rate. AKI and LD showed higher mortality rates (39% vs 9% and 44% vs 18%, respectively, p < 0.0001). The overall incidence of IFIs was 4.8 cases (95% CI = 0.72–8.92) per 1000 discharges and 0.7 cases (95% CI = 0.03–1.16) per 1000 patients-days. Invasive candidiasis showed the highest incidence rate (1.93 per 1000 discharges, 95% CI = −1.01 to 2.84), followed by endemic IFIs (1.53 per 1000 discharges 95% CI = −3.36 to 6.4) and IA (1.25 per 1000 discharges, 95% CI = −0.90 to 3.45). AKI increased the cost of antifungal therapy 4.3-fold. The total expenditure in antifungal therapy for all IFIs, adjusting for AKI, was $233,435,536 USD (95% CI $6,224,993 to $773,810,330). Conclusions: IFIs are as frequent as HIV asymptomatic infection and tuberculosis. Costs estimations allow to assess cost-avoidance strategies to increase targeted driven therapy and decrease adverse events and their costs.

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ABSTRACT Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is spreading worldwide, but little is known about the epidemiology of this pathogen in Brazil. Objective: To evaluate clinical and microbiological features of children with S. aureus infections admitted to a university hospital. Methods: This was a cross-sectional study evaluating the potential risk factors for CA-MRSA, and a retrospective cohort evaluating in-hospital clinical outcomes. To include patients with both community and hospital-associated infections, we screened the results of the microbiological laboratory tests from January 1, 2012, to December 31, 2016. According to the phenotype, we classified the isolates in Methicillin-Susceptible S. aureus (MSSA), Hospital-Associated Methicillin-Resistant S. aureus (HA-MRSA), and CA-MRSA. Clinical data were collected from the patients’ medical records. Results: We identified 279 cases of S. aureus infections (MSSA = 163, CA-MRSA = 69, HA-MRSA = 41). Overall, the incidence density of CA-MRSA and MSSA infections increased while the HA-MRSA incidence density decreased over the study period. CA-MRSA infected patients were more likely to present with skin and soft tissue infections (OR: 2.83, 95%CI: 1.54–5.33, p < 0.001) and osteomyelitis (OR: 4.76; 95%CI: 1.16–22.71, p = 0.014) when compared to MSSA and HA-MRSA infections. Unadjusted case fatality rates were similar between MSSA-infected patients (3.14%, 5/159) and CA-MRSA infected patients (3.80%, 3/79, p = 0.792), while HA-MRSA infected patients were more likely to die in the hospital (12.20%, 5/41, p = 0.013). Conclusions: CA-MRSA is an emergent pediatric pathogen in Brazil. Our results highlight the relevance of choosing an appropriate initial antimicrobial drug for treating children with severe S. aureus infections.

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ABSTRACT Background: Influenza continues to drive seasonal morbidity, particularly in settings with low vaccine coverage. Objectives: To describe the influenza cases and viral circulation among hospitalized patients. Methods: A prospective study based on active surveillance of inpatients with influenza-like illness from a tertiary hospital in Bucharest, Romania, in the season 2016/17. Results: A total of 446 patients were tested, with a balanced gender distribution. Overall, 192 (43%) patients tested positive for influenza, with the highest positivity rate in the age groups 3–13 years and >65 years. Peak activity occurred between weeks 1 and 16/2017, with biphasic distribution: A viruses were replaced by B viruses from week 9/2017; B viruses predominated (66.1%). Among the 133 (69.3%) subtyped samples, all influenza A were subtype H3 (n = 57) and all influenza B were B/Victoria (n = 76). Patients who tested positive for influenza presented fewer comorbidities (p = 0.012), except for the elderly, in whom influenza was more common in patients with comorbidities (p = 0.050). Disease evolution was generally favorable under antiviral treatment. The length of hospital stay was slightly longer in patients with influenza-like illness who tested patients negative for influenza (p = 0.031). Conclusions: Distinctive co-circulation of A/H3 and B/Victoria in Bucharest, Romania in the 2016/17 influenza season was found. While the A/H3 subtype was predominant throughout Europe that season, B/Victoria appears to have circulated specifically in Romania and the Eastern European region, predominantly affecting preschoolers and school children.

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ABSTRACT Objectives: To determine the factors associated with Mycobacterium tuberculosis complex-positive blood culture. Methods: Case-control study. Sociodemographic, clinical and laboratory data were collected from 2000 to 2015. Results: We reviewed medical records of 533 patients with culture-proven tuberculosis, of whom 27.2% (145/533) had blood culture available. Patients with mycobacteremia presented more frequently with abdominal tuberculosis, body mass index <18 kg/m2, and had lower hemoglobin and albumin levels. No differences were observed regarding HIV status. Conclusions: Few studies have reported on the characteristics associated with Mycobacterium tuberculosis complex bacteremia, especially among Human Immunodeficiency Virus-negative patients. Out of 145 tuberculosis-infected patients with blood culture results available, 21 turned out positive. Anemia, hypoalbuminemia, and a body mass index < 18 kg/m2 were associated with mycobacteremia.

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ABSTRACT Background: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated. Objective: To identify predictive genetic markers of immune response to ART. Methods: Case–control study. Out of 176 HIV-infected patients recruited in the city of Recife, Northeast Brazil, 67 patients with no immunologic response were the cases and the remaining 109 patients who responded were the controls. A set of 94 selected single nucleotide polymorphisms (SNPs) involved in antiretroviral drugs pharmacodynamic pathways and immune system homeostasis were genotyped, while the remaining 48 were ancestry informative markers (AIMs) for controlling for eventual hidden population structure. Results: Male patients were overrepresented in non-responder group (p = 0.01). Non-responders also started with lower absolute CD4+ T cell counts (p < 0.001). We found five SNPs significantly associated with the outcome, being three more frequent in non-responders than responders: rs2243250 (IL4) A allele (p = 0.04), rs1128503 (ABCB1) A allele (p = 0.03) and rs707265 (CYP2B6) A allele (p = 0.02), whereas the other two were less frequent in non-responders: rs2069762 (IL2) C allele (p = 0.004) and rs4646437 (CYP3A4) A allele (p = 0.04). Conclusion: Some significant univariate associations remained independently associated at multivariate survival analysis modeling, such as pre-treatment CD4+ T cells counts, IL2 and ABCB1 genotypes, and use of protease inhibitors, yielding a predictive model for the probability for immune response. More studies are needed to unravel the genetic basis of ART immunological non-response.

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ABSTRACT Objectives: The role of viral co-detection in children with severe acute respiratory infection is not clear. We described the viral detection profile and its association with clinical characteristics in children admitted to the Pediatric Intensive Care Unit (PICU) during the 2009 influenza A(H1N1) pandemic. Method: Longitudinal observational retrospective study, with patients aged 0–18 years, admitted to 11 PICUs in Rio de Janeiro, with suspected H1N1 infection, from June to November, 2009. The results of respiratory samples which were sent to the Laboratory of Fiocruz/RJ and clinical data extracted from specific forms were analyzed. Results: Of 71 samples, 38% tested positive for H1N1 virus. Of the 63 samples tested for other viruses, 58 were positive: influenza H1N1 (43.1% of positive samples), rhinovirus/enterovirus (41.4%), respiratory syncytial vírus (12.1%), human metapneumovirus (12.1%), adenovirus (6.9%), and bocavirus (3.5%). Viral codetection occured in 22.4% of the cases. H1N1-positive patients were of a higher median age, had higher frequency of fever, cough and tachypnea, and decreased leukometry when compared to H1N1-negative patients. There was no difference in relation to severity outcomes (number of organic dysfunctions, use of mechanical ventilation or amines, hospital/PICU length of stay or death). Comparing the groups with mono-detection and co-dection of any virus, no difference was found regarding the association with any clinical variable. Conclusions: Other viruses can be implicated in SARI in children. The role of viral codetection has not yet been completely elucidated.

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ABSTRACT Background: Perinatally HIV-infected children are surviving into adulthood, and getting pregnant. There is a scarcity of information on health and pregnancy outcomes in these women. Aim: To evaluate characteristics related to HIV disease and pregnancy outcomes in perinatally infected women, and to compare these women with a group of youth with behaviorally acquired HIV-infection, at a reference hospital in Rio de Janeiro, Brazil. Methods: A cohort study. Epidemiological, clinical, and laboratory data were compared between perinatally (PHIV) and behaviorally HIV-infected (BHIV) pregnant youth with the primary aim to study pregnancy outcomes in the PHIV group and compare with outcomes to BHIV group. Results: Thirty-two pregnancies occurred in PHIV group, and 595 in BHIV group. A total of seven (22%) PHIV women and 64 (11%) BHIV women had a premature delivery (p = 0.04), however, when adjusting for younger age at pregnancy, and antiretroviral therapy initiation in 1st trimester of pregnancy (OR = 18.66, 95%CI = 5.52–63.14), the difference was no longer significant. No cases of mother-to-child HIV transmission (MTCT) were observed in the PHIV group while there was a 2% MTCT rate in BHIV group. Conclusion: Pregnancy among PHIV was as safe as among BHIV. The differences between those groups were probably related to treatment and prolonged care in the first group.

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ABSTRACT The Brazilian Public Health Service provides freely αPEG-IFN to treat patients infected with HCV. The primary goal of HCV therapy is the long-term elimination of HCV from the blood to reduce the risk of HCV associated complications and death. Patient viremia affects the treatment duration and response, thus influencing clinical decisions. We developed a high-throughput method to perform the quantification of RNA hepatitis C virus (HCV) virus load in plasma samples to monitor patients under treatment. The method is based on a duplex detection, in a one-step real-time RT-PCR assay and it has been validated according to the rules established by the official Brazilian regulatory agency (ANVISA). This new method was compared to a commercial kit (Cobas/Taqman HCV Test v2.0 - Roche), showing virus load results with significant correlation between them (p= 0,012) using commercial and clinical panels. In addition, 611 samples from patients treated with peguilated alfa-interferon (αPEG-IFN) from different regions of Brazil were analyzed. Our one-step real-time RT-PCR assay demonstrated good performance in viral load measurement and in treatment course monitoring, with acceptable sensitivity and specificity values.

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ABSTRACT Introduction: Nontyphoidal Salmonella serotypes are the main cause of human food-borne infection, including several hospitalization cases in the developing countries. Aim: To detect the main serotypes and to characterize the antibiotic resistance of human non-enteric and enteric nontyphoidal Salmonella from clinical isolates in Brazil. Methods: Salmonella serotypes were identified by microbiological and molecular methods. Susceptibility testing to antibiotics was performed by agar disk diffusion. Real-time PCRs were carried out for the detection of the genus Salmonella as well as serotypes Typhimurium and Enteritidis. Results: A total of 307 nontyphoidal Salmonella were isolated from 289 different patients in a reference laboratory (LACEN-RS) from Southern Brazil in a six-year period (2010–2015). There were 45 isolates from emerging cases and 244 from sporadic cases in hospitalized patients. Non-enteric isolates were detected in 42.6% of the patients from sources such as urine, blood and other clinical fluids. Serological and PCR-specific tests demonstrated that Typhimurium (48.4%) and Enteritidis (18.3%) were the most frequent serotypes. Typhimurium isolates were generally resistant to three or more antibiotic classes, while Enteritidis isolates to one or two classes. Typhimurium was the most frequent serotype in all samples (48.4%), mainly among the hospitalized patients (55.6%), and presented the highest rates of multidrug resistance (59.3% of the isolates of this serotype). Further, the prevalence of this serotype increased along the years of the study in comparison to other nontyphoidal Salmonella serotypes. Conclusion: Greater public health attention should be given to prevent salmonellosis in the community and in hospital settings to reduce the rates of Typhimurium strains with multidrug resistance.

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ABSTRACT Objective: To determine the incidence of surgical site infection in patients undergoing craniotomy and to compare 12-month and 3-month post-discharge surveillance periods in terms of their impact on the incidence of surgical site infection in those patients. Methods: This was a retrospective cohort study involving 173 adult patients submitted to “clean” craniotomy, with or without implants, during the six-month period, at a university hospital in the city of São Paulo, Brazil. All the patients were evaluated in the pre-, trans- and postoperative periods and were followed for 12 months to analyze the development of surgical site infections. Results: Of the 173 patients undergoing craniotomy during the study period, 20 developed an surgical site infection during the first, and 12 months after discharge, the overall incidence of surgical site infection therefore being 11.56%, compared with a 1-month incidence of 8.67% and a 3-month incidence of 10.98%. Among the 106 patients who received implants, the 1-, 3-, and 12-month incidence of surgical site infection was 7.54% (n= 8), 8.49% (n= 9), and 9.43% (n= 10), respectively. Among the 67 patients who did not receive implants, the 1-, 3-, and 12-month incidence of surgical site infection was 10.44% (n= 7), 14.92% (n= 10), and 14.92% (n= 10), respectively. Conclusion: The incidence of surgical site infection after craniotomy is high. Reducing the duration of the post-discharge surveillance period from 12 months to 3 months did not cause significant losses in the numbers of surgical site infection identified or a substantial decrease in their incidence.

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ABSTRACT Acinetobacter baumannii is one of the most frequent Gram-negative opportunistic pathogens associated with hospital-acquired infection worldwide. We briefly describe A. baumannii isolates that were recovered from surrounding ICU bed surfaces, exhibiting multidrug resistance phenotype and belonging to some widely spread clonal complexes of clinical A. baumannii isolates.

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ABSTRACT A 19-year-old patient who mistakenly received two doses of influenza vaccine 10 days before presentation, was admitted with malaise, weakness, and a purpuric non-blanching rash most prominent on the ankles followed by abdominal pain and hematochezia 72 h later. The diagnosis of influenza vaccine-related Henoch–Schonlein vasculitis was made. This complication, although rare, is the most common vasculitis related to immunization.