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A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (± standard error) Acute Physiology and Chronic Health Evaluation II score (16.8 ± 0.6 vs. 15.0 ± 0.7; P = .039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P = .08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P = .043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P = .02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.

Infection in neonates remains a substantial problem. Advances for this population are hindered by the absence of a consensus definition for sepsis. In adults, the Sequential Organ Failure Assessment (SOFA) operationalizes mortality risk with infection and defines sepsis. The generalizability of the neonatal SOFA (nSOFA) for neonatal late-onset infection-related mortality remains unknown. To determine the generalizability of the nSOFA for neonatal late-onset infection-related mortality across multiple sites. A multicenter retrospective cohort study was conducted at 7 academic neonatal intensive care units between January 1, 2010, and December 31, 2019. Participants included 653 preterm (<33 weeks) very low-birth-weight infants. Late-onset (>72 hours of life) infection including bacteremia, fungemia, or surgical peritonitis. The primary outcome was late-onset infection episode mortality. The nSOFA scores from survivors and nonsurvivors with confirmed late-onset infection were compared at 9 time points (T) preceding and following event onset. In the 653 infants who met inclusion criteria, median gestational age was 25.5 weeks (interquartile range, 24-27 weeks) and median birth weight was 780 g (interquartile range, 638-960 g). A total of 366 infants (56%) were male. Late-onset infection episode mortality occurred in 97 infants (15%). Area under the receiver operating characteristic curves for mortality in the total cohort ranged across study centers from 0.71 to 0.95 (T0 hours), 0.77 to 0.96 (T6 hours), and 0.78 to 0.96 (T12 hours), with utility noted at all centers and in aggregate. Using the maximum nSOFA score at T0 or T6, the area under the receiver operating characteristic curve for mortality was 0.88 (95% CI, 0.84-0.91). Analyses stratified by sex or Gram-stain identification of pathogen class or restricted to infants born at less than 25 weeks' completed gestation did not reduce the association of the nSOFA score with infection-related mortality. The nSOFA score was associated with late-onset infection mortality in preterm infants at the time of evaluation both in aggregate and in each center. These findings suggest that the nSOFA may serve as the foundation for a consensus definition of sepsis in this population.

Cryptococcal meningitis is a fungal infection that is most commonly thought of as an opportunistic infection affecting immunocompromised patients, classically patients with Human Immunodeficiency (HIV) infection. It is associated with a variety of complications including disseminated disease as well as neurologic complications including intracranial hypertension, cerebral infarcts, vision loss and other neurologic deficits. It is diagnosed by lumbar puncture with CSF studies, including fungal culture and cryptococcal antigen testing. We present a case of cryptococcal meningitis and fungemia in a previously healthy male patient who presented after multiple emergency department visits with persistent headache. After multiple visits, he underwent a lumbar puncture consistent with cryptococcal infection, and he was admitted to the hospital for initiation of antifungal therapy. His workup revealed no known underlying condition leading to immune compromise.

Background. Invasive aspergillosis (IA) is a leading cause of infection-related mortality following hematopoietic cell transplantation (HCT). The aim of this study was to determine the probability of survival and prognostic factors associated with outcomes over a long period of time. Methods. Cases of proven and probable IA diagnosed in HCT recipients at the Fred Hutchinson Cancer Research Center from 1 January 1990 through 31 December 2004 were included. Patient data were collected from a prospectively maintained database and by retrospective clinical chart review. Survival was estimated using Kaplan-Meier curves, and Cox regression models were used for multivariable analyses. Results. Four hundred five cases were identified. The probability of survival at 90 days after diagnosis was higher for patients identified as having IA between 2002 and 2004 than for patients whose IA was diagnosed in preceding years (45% vs. 22%; P < .001). Risk factors independently associated with all-cause mortality include impairment in pulmonary function before HCT, receipt of human leukocyte antigen—mismatched stem cells, neutropenia, elevated bilirubin and creatinine levels, receipt of corticosteroids at ≥2 mg/kg per day, disseminated and proven IA, and IA occurring>40 days after HCT. Factors associated with a decreased risk of all-cause mortality included receipt of nonmyeloablative conditioning and peripheral blood stem cells. In a subanalysis of attributable mortality restricted to patients receiving antifungal therapy, receipt of voriconazole was independently associated with protection from IA-related death. Conclusions. There has been a significant decrease in mortality in patients with a diagnosis of IA following HCT in recent years, coinciding with multiple changes in transplantation practices, including use of nonmyeloablative conditioning regimens, receipt of peripheral blood stem cells, more prompt diagnosis of IA, and use of voriconazole.

The purpose of this study was to compare the risk factors, clinical manifestations, and outcome of candidemia in immunocompromised (IC) and nonimmunocompromised (NIC) critically ill patients. Data were collected prospectively over a 2-year period (02/2000-01/2002) from patients in a 25-bed, medical-surgical intensive care unit (ICU). Eligible for participation in this study were patients who developed candidemia during their ICU stay. Patients under antifungal therapy and with a confirmed systemic fungal infection prior to the diagnosis of candidemia were excluded. Cultures of blood, urine, and stool were performed for all patients in the study, and all patients underwent endoscopy/biopsy of the esophagus for detection of Candida. Smears and/or scrapings of oropharyngeal and esophageal lesions were examined for hyphae and/or pseudohyphae and were also cultured for yeasts. During the study period, 1,627 patients were hospitalized in the ICU, 57% for primary medical reasons and 43% for surgical reasons. After application of the study's inclusion and exclusion criteria, 24 patients with candidemia (9 IC and 15 NIC) were analyzed. Total parenteral nutrition was more common in IC than in NIC patients (9/9 [100%] vs 8/15 [53%], p = 0.02). Oropharyngeal candidiasis was detected in 5 of 9 (55.5%) IC patients and in 1 of 15 (6.5%) NIC patients (p = 0.015). Esophageal candidiasis was also more common in IC than in NIC patients (4/9 [44%] vs 0/15 [0%], p = 0.012). Among the 9 IC patients, all except 2 died, resulting in a crude mortality of 78%; among the 15 NIC patients, 9 died, resulting in a crude mortality of 60% (p > 0.05). Autopsy was performed in two IC and in six NIC patients, with disseminated candidiasis found in one IC patient. Oropharyngeal and esophageal candidiasis are frequent in IC patients with candidemia. In contrast, this coexistence is rare in NIC critically ill patients with Candida bloodstream infections. A high mortality was noted in both IC and NIC critically ill patients with candidemia.

Early detection of fungal infections in and corresponding early treatment of febrile patients with neutropenia and cancer have been important issues and continue to be major challenges for clinicians. The use of nested PCR to make therapeutic decisions was studied. Sequential blood samples obtained from 42 patients with neutropenia and cancer were tested by nested PCR and culture. Instead of the empirical antifungal therapy strategy, amphotericin B treatment was initiated only for patients who had 2 consecutive positive results by nested PCR. A reduced mortality rate was observed for febrile patients with neutropenia and cancer who had fungal infections. Thus, this strategy, combined with the nested PCR for early detection of fungal infection in febrile patients with neutropenia, may be used as a guideline for antifungal therapy.

Although there are numerous studies of candidaemia in adults, data on paediatrics are still limited. The aim of this study was to compare risk factors, aetiology, therapy, and the outcome of nosocomial candidaemia among paediatric and adult patients in a large Brazilian tertiary hospital (1995-2003). During this period, 78 paediatrics and 113 adults were studied. Species other than Candida albicans caused 78.2% of episodes of candidaemia in paediatrics. Compared to adults, paediatrics received more frequently broad-spectrum antibiotics, vasopressors, blood transfusions, arterial catheter, chest tube, cardiothoracic surgery, mechanical ventilation, and parenteral nutrition. Candidaemia caused by Candida parapsilosis was more common in paediatrics, as was the isolation of Candida spp. from catheters. Amphotericin B treatment was more common in paediatrics. Mortality rate was higher in adults than in paediatrics with nosocomial candidaemia. We reinforce the necessity of continuous epidemiologic surveillance to follow the dynamics of candidaemia.

Dematiaceous (pigmented) fungi are increasingly recognized as a cause of opportunistic infections in humans. Since Lagerberg first described Hormonema dematioides, one case of infection (a localized skin infection) due to this fungus has been reported. We describe the first case of a systemic infection due to this organism.

Aspergillus species are infrequently isolated from blood cultures, and it may be difficult to interpret the significance of such fungemia in some cases. We report an unusual case of aspergillar fungemia in a 3-month-old infant with hepatoblastoma.

This is a retrospective study in consecutive cases with cultured-proven endogenous endophthalmitis (EE) treated at the largest tertiary medical center in middle Taiwan in the past 10 years. 83 eyes of 70 patients were enrolled. The mean interval between systemic diseases to the diagnosis of EE was 8.84 ± 6.94 days. The mean initial visual acuity (VA) in the logarithm of minimal angle of resolution (logMAR) was 1.63 ± 0.87. Type 2 diabetes mellitus was the most common predisposing medical illness (N = 53, 63.86%). The most common infectious sources were intra-abdominal abscess (N = 36, 43.37%), and the second most reason was urinary tract infection. The causative pathogen was Gram-negative predominant (N = 64, 77.11%). After aggressive treatment, 34.94% of eyes regain useful vision, and only six eyes underwent enucleation or evisceration. The binary multivariate logistic regression model revealed that female gender (95% CI 1.002–19.036, p = 0.05, OR 4.37), initial VA logMAR (95% CI 0.089–0.550, p = 0.01, OR 0.22), and more intravitreal injections (95% CI 0.368–0.927, p = 0.023, OR 0.58) were independent risk factors influencing final outcomes. Based on the results mentioned above, early diagnosis is recommended to gain better outcomes. The mean interval between systemic diseases to the diagnosis of EE was 8.84 ± 6.94 days in our sample population, clinicians should maintain a higher index of suspicion during this period when encountering patients with bacteremia or fungemia.