Prognostic Trends and Current Challenges in Candidemia: A Comparative Analysis of Two Multicenter Cohorts within the Past Decade.

Candidemia remains a major public health challenge due to its high mortality rates, especially in developing countries. Monitoring epidemiological trends may provide insights for better clinical outcomes. This study aimed to describe trends in the epidemiology, therapeutic practices, and mortality in candidemia through a retrospective comparative analysis between two surveillance cohorts of all candidemic adults at eleven tertiary hospitals in Brazil, from 2010-2011 (Period I) versus 2017-2018 (Period II). A total of 616 cases were diagnosed, with 247 being from Period II. These patients were more likely to have three or more coexisting comorbidities [72 (29.1%) vs. 60 (16.3%), p < 0.001], had a prior history of in-hospital admissions more often [102 (40.3%) vs. 79 (21.4%), p = 0.001], and presented with candidemia earlier after admission, within 15 days (0-328) vs. 19 (0-188), p = 0.01. Echinocandins were more frequently prescribed [102 (41.3%) vs. 50 (13.6%), p = 0.001], but time to antifungal initiation [2 days (0-14) vs. 2 (0-13), p = 0.369] and CVC removal within 48 h [90/185 (48.6%) vs. 148/319 (46.4%), p = 0.644] remained unchanged. Additionally, many patients went untreated in both periods I and II [87 (23.6%) vs. 43 (17.4%), p = 0.07], respectively. Unfortunately, no improvements in mortality rates at 14 days [123 (33.6%) vs. 93 (37.7%), p = 0.343] or at 30 days [188 (51.4%) vs. 120 (48.6%), p = 0.511] were observed. In conclusion, mortality rates remain exceedingly high despite therapeutic advances, probably associated with an increase in patients' complexity and suboptimal therapeutic interventions. Management strategies should be tailored to suit epidemiological changes, expedite diagnosis to reduce the number of untreated eligible patients and guarantee early antifungal initiation and source control.

Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection.

BACKGROUND: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking. METHODS: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out. RESULTS: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective. CONCLUSIONS: Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

A risk score for predicting death in COVID-19 in-hospital infection: A Brazilian single-center study.

BACKGROUND: There is a paucity of information about Brazilian COVID-19 in-hospital mortality probability of death combining risk factors. OBJECTIVE: We aimed to correlate COVID-19 Brazilian in-hospital patients' mortality to demographic aspects, biomarkers, tomographic, echocardiographic findings, and clinical events. METHODS: A prospective study, single tertiary center in Brazil, consecutive patients hospitalized with COVID-19. We analyzed the data from 111 patients from March to August 2020, performed a complete transthoracic echocardiogram, chest thoracic tomographic (CT) studies, collected biomarkers and correlated to in-hospital mortality. RESULTS: Mean age of the patients: 67 ± 17 years old, 65 (58.5%) men, 29 (26%) presented with systemic arterial hypertension, 18 (16%) with diabetes, 11 (9.9%) with chronic obstructive pulmonary disease. There was need for intubation and mechanical ventilation of 48 (43%) patients, death occurred in 21/111 (18.9%) patients. Multiple logistic regression models correlated variables with mortality: age (OR: 1.07; 95% CI 1.02-1.12; p: 0.012; age >74 YO AUC ROC curve: 0.725), intubation need (OR: 23.35; 95% CI 4.39-124.36; p < 0.001), D dimer (OR: 1.39; 95% CI 1.02-1.89; p: 0.036; value >1928.5 ug/L AUC ROC curve: 0.731), C-reactive protein (OR: 1.18; 95% CI 1.05-1.32; p < 0.005; value >29.35 mg/dl AUC ROC curve: 0.836). A risk score was created to predict intrahospital probability of death, by the equation: 3.6 (age >75 YO) + 66 (intubation need) + 28 (C-reactive protein >29) + 2.2 (D dimer >1900). CONCLUSIONS: A novel and original risk score were developed to predict the probability of death in Covid 19 in-hospital patients concerning combined risk factors.

Performance of a multidisciplinary team and the impact of bundles for reducing health care associated infections in adult intensive care unit: 22 years of experience.

A retrospective cohort study was conducted to evaluate the bundle of techniques developed by the multidisciplinary team to minimize infections in an adult intensive care unit over a 22-year span. Two periods were analyzed: 1996-2006 and 2007-2017. Bloodstream infections, urinary tract infections, and ventilator-associated pneumonia declined 58.6%, 56.7%, and 82.6%, respectively (P < .05) from 2007 to 2017 compared with these same infections during 1996-2006.

Clostridioides difficile laboratory diagnostic techniques: a comparative approach of rapid and molecular methods.

Clostridioides difficile infection is a public health problem because of it is easily spread; with harmful consequences, it is essential to reduce hospital costs and prevent its dissemination by having a precise diagnosis. The gold standard for its diagnosis is polymerase chain reaction (PCR); however, the technique is not available for all laboratories due to the high cost. New approaches using non-molecular tests to detect C. difficile and toxin A/B production has been proposed to improve cost benefits. The objective of this study is to compare molecular methods (PCR) and rapid methods (immunochromatographic test and enzymatic immunoassay). A series of tests comprising these diagnostic techniques was performed with 50 patients with a clinical diagnosis for Clostridioides difficile on GeneXpert® devices test; a calculation of the sensitivity was executed, followed by a comparison of the efficiency of all techniques. Greater sensitivity was observed in the PCR-based methods (BD MAX™ and BioFire FilmArray®) and the GDH-based assays (RIDASCREEN® and Alere Techlab®). The proposed algorithm represents minor monetary disadvantages but a significant temporal optimization of 10%. Future studies concerning both positive and negative results could be advantageous because of the possibility of calculating more method concordance indexes, such as the specificity and Kappa index, in addition to being able to indicate a monetary profit if the proposed algorithm was applied due to the nonproceeding PCR cases.

Severe Strongyloides stercoralis infection in kidney transplant recipients: a multicenter case-control study

BACKGROUND: Severe Strongyloides stercoralis infection in kidney transplant recipients is associated with considerable morbidity and mortality, although little is known about the risk factors for such infection. METHODOLOGY/Principal findings This was a retrospective, multicenter, case­control study in which we assessed the risk factors for and clinical outcomes of severe S. stercoralis infections in kidney transplant recipients in Brazil. We included 138 kidney transplant recipients: 46 cases and 92 controls. Among the cases, the median number of days from transplantation to diagnosis was 117 (interquartile range [IQR], 73.5­965) and the most common clinical findings were gastrointestinal symptoms (in 78.3%) and respiratory symptoms (in 39.1%), whereas fever and eosinophilia were seen in only 32.6% and 43.5%, respectively. The 30-day all-cause mortality among the cases was 28.3% overall and was significantly higher among the cases of infection occurring within the first three months after transplantation (47% vs. 17.2%, P = 0.04). The independent risk factors were receiving a transplant from a deceased donor (odds ratio [OR] = 6.16, 95% confidence interval [CI] = 2.05­18.5), a history of bacterial infection (OR = 3.04, 95% CI = 1.2­7.5), and a cumulative corticosteroid dose (OR = 1.005, 95% CI = 1.001­1.009). The independent predictors of mortality were respiratory failure (OR = 98.33, 95% CI = 4.46­2169.77) and concomitant bacteremia (OR = 413.00, 95% CI = 4.83­35316.61). CONCLUSIONS/Significance Severe S. stercoralis infections are associated with considerable morbidity and mortality after kidney transplantation. In endemic areas, such infection may occur late after transplantation, although it seems to be more severe when it occurs earlier after transplantation. Specific risk factors and clinical manifestations can identify patients at risk, who should receive prophylaxis or early treatment. (AU)

A randomized clinical trial comparing Nitrofurazone-coated and uncoated urinary catheters in kidney transplant recipients: Results from a pilot study.

BACKGROUND: Urinary tract infections are frequent complications early after kidney transplantation, and the use of antimicrobial coated catheters in settings other than transplantation has shown promising results for infection prevention. The purpose of this study was to compare the efficacy of Nitrofurazone-coated silicone urinary catheters with non-impregnated silicone urinary catheters in reducing bacteriuria and urinary tract infections in kidney transplant recipients. METHODS: This single-center study, randomized controlled trial at the Hospital do Rim, a tertiary referral center in kidney transplantation, located in São Paulo, Brazil. Subjects involved living donor kidney transplant recipients, and were randomized 1:1 ratio with a computer-generated system to a Nitrofurazone-coated silicone urinary catheter and non-impregnated silicone urinary catheter from March 2013 to December 2014. Patients with asymptomatic bacteriuria or urinary tract infection at baseline, deceased kidney transplant donors, patients with known hypersensitivity to nitrofurantoin, pregnancy, and those refusing to sign the informed consent form were excluded from the study. RESULTS: Two hundred fourteen subjects were randomized and one hundred seventy-six completed the study. There were no differences in the rates of asymptomatic bacteriuria (12.5% in the Nitrofurazone group and 11.4% in the control group, P = 0.99) and urinary tract infection (8% and 6.8%, P = 0.99) and the incidence of side effects was more frequent in the Nitrofurazone-impregnated silicone urinary catheter group (46.6% and 26.1%, P = 0.007). CONCLUSION: The study suggests that there is no beneficial effect of the employment of Nitrofurazone-coated urinary catheter. TRIAL REGISTRATION NUMBER: ISRCTN57888785.

Epidemiology and Microbiologic Characterization of Nosocomial Candidemia from a Brazilian National Surveillance Program.

Candidemia is a growing problem in hospitals all over the world. Despite advances in the medical support of critically ill patients, candidiasis leads to prolonged hospitalization, and has a crude mortality rate around 50%. We conducted a multicenter surveillance study in 16 hospitals distributed across five regions of Brazil to assess the incidence, species distribution, antifungal susceptibility, and risk factors for bloodstream infections due to Candida species. From June 2007 to March 2010, we studied a total of 2,563 nosocomial bloodstream infection (nBSI) episodes. Candida spp. was the 7th most prevalent agent. Most of the patients were male, with a median age of 56 years. A total of 64 patients (46.7%) were in the ICU when candidemia occurred. Malignancies were the most common underlying condition (32%). The crude mortality rate of candidemia during the hospital admission was 72.2%. Non-albicans species of Candida accounted for 65.7% of the 137 yeast isolates. C. albicans (34.3%), Candida parapsilosis (24.1%), Candida tropicalis (15.3%) and Candida glabrata (10.2%) were the most prevalent species. Only 47 out of 137 Candida isolates were sent to the reference laboratory for antifungal susceptibility testing. All C. albicans, C. tropicalis and C. parapsilosis isolates were susceptible to the 5 antifungal drugs tested. Among 11 C. glabrata isolates, 36% were resistant to fluconazole, and 64% SDD. All of them were susceptible to anidulafungin and amphotericin B. We observed that C. glabrata is emerging as a major player among non-albicans Candida spp. and fluconazole resistance was primarily confined to C. glabrata and C. krusei strains. Candida resistance to echinocandins and amphotericin B remains rare in Brazil. Mortality rates remain increasingly higher than that observed in the Northern Hemisphere countries, emphasizing the need for improving local practices of clinical management of candidemia, including early diagnosis, source control and precise antifungal therapy.

Extensive cervical lymphadenitis mimicking bacterial adenitis as the first presentation of Kawasaki disease / Extensa linfadenite cervical mimetizando adenite bacteriana como primeira manifestação da doença de Kawasaki

Cervical adenitis >1.5cm in diameter is the less frequently observed criteria in patients with Kawasaki disease and it is usually found in association with other symptoms during the acute phase. Moreover, the finding of fever and lymphadenitis with intense local signs of inflammation and phlegmon is rarely seen as the initial manifestation of Kawasaki disease. We report the case of a 7-year-old boy who had cervical lymphadenitis with adjacent cellulitis and phlegmon mimicking bacterial adenitis as the first presentation of Kawasaki disease. The patient had fever, cervical lymphadenitis with adjacent cellulitis, and severe headache. Cefadroxil was prescribed based on the clinical diagnosis of bacterial adenitis. Because he remained febrile and phlogistic signs worsened, after 1 day of hospitalization, antibiotics were administrated intravenously (ceftriaxone and oxacillin). The computed tomography of the neck showed primary infectious/inflammatory process. On the fourth day, the patient had dry and scaly lips, and treatment with oxacillin was replaced by clindamycin because the patient was still febrile. On the ninth day, he presented non-exudative bilateral conjunctival injection. On the tenth day of febrile disease, a rash appeared on his trunk, hands and feet. Patient’s symptoms resolved after intravenous administration of immunoglobulin (2g/kg/dose), and he was discharged 2 days later. On the 14th day, the patient had lamellar desquamation of fingers. Kawasaki disease should be considered as a differential diagnosis in children with febrile cervical lymphadenitis unresponsive to empiric antibiotics even if they have adjacent cellulitis and phlegmon.

Adenite cervical >1,5cm é o critério menos frequentemente observado em pacientes com doença de Kawasaki e manifesta-se habitualmente em associação com os demais sintomas da fase aguda. Entretanto, linfadenite febril isolada com intensos sinais flogísticos e flegmão é raramente observada como primeira manifestação da doença de Kawasaki. Assim, relatou-se aqui um caso de uma criança que apresentou linfadenite cervical com celulite adjacente e flegmão mimetizando adenite bacteriana como primeira manifestação da doença de Kawasaki. Paciente previamente hígido, 7 anos, masculino, iniciou quadro de febre, adenite cervical com celulite adjacente e cefaleia intensa, sendo prescrita cefadroxila devido ao diagnóstico clínico de linfadenite bacteriana. Por se manter febril e com piora dos sinais flogísticos, após 1 dia foi internado para receber antibioticoterapia endovenosa (oxacilina e ceftriaxona). Tomografia computadorizada da região cervical mostrou processo infeccioso/inflamatório primário. No quarto dia, apresentou lábios ressecados e descamativos, sendo a oxacilina substituída por clindamicina devido à persistência da febre e sinais flogísticos. No nono dia, iniciou hiperemia ocular não exsudativa. No décimo dia de febre, apresentou exantema em tronco, membros, mãos e pés. Recebeu gamaglobulina endovenosa (2g/kg/dose), evoluiu com resolução dos sintomas e, após 2 dias, recebeu alta hospitalar. No 14odia, apresentou descamação lamelar dos dedos das mãos. Portanto, doença de Kawasaki deve ser considerada no diagnóstico diferencial das linfadenites cervicais febris na infância não responsivas à antibioticoterapia empírica, mesmo que esteja presentes celulite adjacente e flegmão.

Extensive cervical lymphadenitis mimicking bacterial adenitis as the first presentation of Kawasaki disease.

Cervical adenitis >1.5cm in diameter is the less frequently observed criteria in patients with Kawasaki disease and it is usually found in association with other symptoms during the acute phase. Moreover, the finding of fever and lymphadenitis with intense local signs of inflammation and phlegmon is rarely seen as the initial manifestation of Kawasaki disease. We report the case of a 7-year-old boy who had cervical lymphadenitis with adjacent cellulitis and phlegmon mimicking bacterial adenitis as the first presentation of Kawasaki disease. The patient had fever, cervical lymphadenitis with adjacent cellulitis, and severe headache. Cefadroxil was prescribed based on the clinical diagnosis of bacterial adenitis. Because he remained febrile and phlogistic signs worsened, after 1 day of hospitalization, antibiotics were administrated intravenously (ceftriaxone and oxacillin). The computed tomography of the neck showed primary infectious/inflammatory process. On the fourth day, the patient had dry and scaly lips, and treatment with oxacillin was replaced by clindamycin because the patient was still febrile. On the ninth day, he presented non-exudative bilateral conjunctival injection. On the tenth day of febrile disease, a rash appeared on his trunk, hands and feet. Patient's symptoms resolved after intravenous administration of immunoglobulin (2g/kg/dose), and he was discharged 2 days later. On the 14th day, the patient had lamellar desquamation of fingers. Kawasaki disease should be considered as a differential diagnosis in children with febrile cervical lymphadenitis unresponsive to empiric antibiotics even if they have adjacent cellulitis and phlegmon.

Early invasive pulmonary aspergillosis in a kidney transplant recipient caused by aspergillus lentulus: first brazilian report

We report the first Brazilian case of pulmonary invasive aspergillosis caused by Aspergillus lentulus, a new opportunistic Aspergillus species included in the section fumigati that is usually resistant to amphotericin B and azoles

Early invasive pulmonary aspergillosis in a kidney transplant recipient caused by Aspergillus lentulus: first Brazilian report.

We report the first Brazilian case of pulmonary invasive aspergillosis caused by Aspergillus lentulus, a new opportunistic Aspergillus species included in the section fumigati that is usually resistant to amphotericin B and azoles.

Nosocomial bloodstream infections in Brazilian pediatric patients: microbiology, epidemiology, and clinical features.

BACKGROUND: Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality and are the most frequent type of nosocomial infection in pediatric patients. METHODS: We identified the predominant pathogens and antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric patients (≤16 years of age) in the Brazilian Prospective Surveillance for nBSIs at 16 hospitals from 12 June 2007 to 31 March 2010 (Br SCOPE project). RESULTS: In our study a total of 2,563 cases of nBSI were reported by hospitals participating in the Br SCOPE project. Among these, 342 clinically significant episodes of BSI were identified in pediatric patients (≤16 years of age). Ninety-six percent of BSIs were monomicrobial. Gram-negative organisms caused 49.0% of these BSIs, Gram-positive organisms caused 42.6%, and fungi caused 8.4%. The most common pathogens were Coagulase-negative staphylococci (CoNS) (21.3%), Klebsiella spp. (15.7%), Staphylococcus aureus (10.6%), and Acinetobacter spp. (9.2%). The crude mortality was 21.6% (74 of 342). Forty-five percent of nBSIs occurred in a pediatric or neonatal intensive-care unit (ICU). The most frequent underlying conditions were malignancy, in 95 patients (27.8%). Among the potential factors predisposing patients to BSI, central venous catheters were the most frequent (66.4%). Methicillin resistance was detected in 37 S. aureus isolates (27.1%). Of the Klebsiella spp. isolates, 43.2% were resistant to ceftriaxone. Of the Acinetobacter spp. and Pseudomonas aeruginosa isolates, 42.9% and 21.4%, respectively, were resistant to imipenem. CONCLUSIONS: In our multicenter study, we found a high mortality and a large proportion of gram-negative bacilli with elevated levels of resistance in pediatric patients.

Brazilian guidelines for the management of candidiasis - a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical

Candida infections account for 80% of all fungal infections in the hospital environment, including bloodstream, urinary tract and surgical site infections. Bloodstream infections are now a major challenge for tertiary hospitals worldwide due to their high prevalence and mortality rates. The incidence of candidemia in tertiary public hospitals in Brazil is approximately 2.5 cases per 1000 hospital admissions. Due to the importance of this infection, the authors provide a review of the diversity of the genus Candida and its clinical relevance, the therapeutic options and discuss the treatment of major infections caused by Candida. Each topography is discussed with regard to epidemiological, clinical and laboratory diagnostic and therapeutic recommendations based on levels of evidence.

Brazilian guidelines for the management of candidiasis - a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical.

Candida infections account for 80% of all fungal infections in the hospital environment, including bloodstream, urinary tract and surgical site infections. Bloodstream infections are now a major challenge for tertiary hospitals worldwide due to their high prevalence and mortality rates. The incidence of candidemia in tertiary public hospitals in Brazil is approximately 2.5 cases per 1000 hospital admissions. Due to the importance of this infection, the authors provide a review of the diversity of the genus Candida and its clinical relevance, the therapeutic options and discuss the treatment of major infections caused by Candida. Each topography is discussed with regard to epidemiological, clinical and laboratory diagnostic and therapeutic recommendations based on levels of evidence.