Google Flu Trends can detect regional outbreaks of influenza 7–10 days before conventional Centers for Disease Control and Prevention surveillance sy

Evaluation of Cryptococcus neoformans virulence in a number of nonmammalian hosts suggests that C. neoformans is a nonspecific pathogen. We used the killing of Galleria mellonella (the greater wax moth) caterpillar by C. neoformans to develop an invertebrate host model system that can be used to study cryptococcal virulence, host immune responses to infection, and the effects of antifungal compounds. All varieties of C. neoformans killed G. mellonella . After injection into the insect hemocoel, C. neoformans proliferated and, despite successful phagocytosis by host hemocytes, killed caterpillars both at 37°C and 30°C. The rate and extent of killing depended on the cryptococcal strain and the number of fungal cells injected. The sequenced C. neoformans clinical strain H99 was the most virulent of the strains tested and killed caterpillars with inocula as low as 20 CFU/caterpillar. Several C. neoformans genes previously shown to be involved in mammalian virulence ( CAP59 , GPA1 , RAS1 , and PKA1 ) also played a role in G. mellonella killing. Combination antifungal therapy (amphotericin B plus flucytosine) administered before or after inoculation was more effective than monotherapy in prolonging survival and in decreasing the tissue burden of cryptococci in the hemocoel. The G. mellonella - C. neoformans pathogenicity model may be a substitute for mammalian models of infection with C. neoformans and may facilitate the in vivo study of fungal virulence and efficacy of antifungal therapies.

Background. Microbiologic cultures, the current gold standard diagnostic method for invasive Candida infections, have low specificity and take up to 2–5 days to grow. We present the results of the first extensive multicenter clinical trial of a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of candidemia. Methods. Blood specimens were collected from 1801 hospitalized patients who had a blood culture ordered for routine standard of care; 250 of them were manually supplemented with concentrations from <1 to 100 colony-forming units (CFUs)/mL for 5 different Candida species. Results. T2MR demonstrated an overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%–99.6%) with a mean time to negative result of 4.2 ± 0.9 hours. Subanalysis yielded a specificity of 98.9% (95% CI, 98.3%–99.4%) for Candida albicans/Candida tropicalis, 99.3% (95% CI, 98.7%–99.6%) for Candida parapsilosis, and 99.9% (95% CI, 99.7%–100.0%) for Candida krusei/Candida glabrata. The overall sensitivity was found to be 91.1% (95% CI, 86.9%–94.2%) with a mean time of 4.4 ± 1.0 hours for detection and species identification. The subgroup analysis showed a sensitivity of 92.3% (95% CI, 85.4%–96.6%) for C. albicans/C. tropicalis, 94.2% (95% CI, 84.1%–98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%–93.7%) for C. krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C. krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C. parapsilosis. The negative predictive value was estimated to range from 99.5% to 99.0% in a study population with 5% and 10% prevalence of candidemia, respectively. Conclusions. T2MR is the first fully automated technology that directly analyzes whole blood specimens to identify species without the need for prior isolation of Candida species, and represents a breakthrough shift into a new era of molecular diagnostics. Clinical Trials Registration. NCT01752166.

The implementation of antimicrobial stewardship programs (ASPs) is a promising strategy to help address the problem of antimicrobial resistance. We sought to determine the efficacy of ASPs and their effect on clinical and economic parameters. We searched PubMed, EMBASE, and Google Scholar looking for studies on the efficacy of ASPs in hospitals. Based on 26 studies (extracted from 24,917 citations) with pre- and postimplementation periods from 6 months to 3 years, the pooled percentage change of total antimicrobial consumption after the implementation of ASPs was −19.1% (95% confidence interval [CI] = −30.1 to −7.5), and the use of restricted antimicrobial agents decreased by −26.6% (95% CI = −52.3 to −0.8). Interestingly, in intensive care units, the decrease in antimicrobial consumption was −39.5% (95% CI = −72.5 to −6.4). The use of broad-spectrum antibiotics (−18.5% [95% CI = −32 to −5.0] for carbapenems and −14.7% [95% CI = −27.7 to −1.7] for glycopeptides), the overall antimicrobial cost (−33.9% [95% CI = −42.0 to −25.9]), and the hospital length of stay (−8.9% [95% CI = −12.8 to −5]) decreased. Among hospital pathogens, the implementation of ASPs was associated with a decrease in infections due to methicillin-resistant Staphylococcus aureus (risk difference [RD] = −0.017 [95% CI = −0.029 to −0.005]), imipenem-resistant Pseudomonas aeruginosa (RD = −0.079 [95% CI = −0.114 to −0.040]), and extended-spectrum beta-lactamase Klebsiella spp. (RD = −0.104 [95% CI = −0.153 to −0.055]). Notably, these improvements were not associated with adverse outcomes, since the all-cause, infection-related 30-day mortality and infection rates were not significantly different after implementation of an ASP (RD = −0.001 [95% CI = −0.009 to 0.006], RD = −0.005 [95% CI = −0.016 to 0.007], and RD = −0.045% [95% CI = −0.241 to 0.150], respectively). Hospital ASPs result in significant decreases in antimicrobial consumption and cost, and the benefit is higher in the critical care setting. Infections due to specific antimicrobial-resistant pathogens and the overall hospital length of stay are improved as well. Future studies should focus on the sustainability of these outcomes and evaluate potential beneficial long-term effects of ASPs in mortality and infection rates.

Objective: The aim of this study was to explore the potential association of obesity and other chronic diseases with severe outcomes, such as intensive care unit (ICU) admission and invasive mechanical ventilation (IMV), in patients hospitalized with coronavirus disease 2019 (COVID‐19).Methods: This study analyzed a retrospective cohort of 103 patients hospitalized with COVID‐19. Demographic data, past medical history, and hospital course were collected and analyzed. A multivariate logistic regression analysis was implemented to examine associations.Results: From February 17 to April 5, 103 consecutive patients were hospitalized with COVID‐19. Among them, 44 patients (42.7%) were admitted to the ICU, and 29 (65.9%) required IMV. The prevalence of obesity was 47.5% (49 of 103). In a multivariate analysis, severe obesity (BMI ≥ 35 kg/m²) was associated with ICU admission (adjusted odds ratio [aOR]: 5.39, 95% CI: 1.13‐25.64). Moreover, patients who required IMV were more likely to have had heart disease (aOR: 3.41, 95% CI: 1.05‐11.06), obesity (BMI = 30‐34.9 kg/m²; aOR: 6.85, 95% CI: 1.05‐44.82), or severe obesity (BMI ≥ 35 kg/m²; aOR: 9.99, 95% CI: 1.39‐71.69).Conclusions: In our analysis, severe obesity (BMI ≥ 35 kg/m²) was associated with ICU admission, whereas history of heart disease and obesity (BMI ≥ 30 kg/m²) were independently associated with the use of IMV. Increased vigilance and aggressive treatment of patients with obesity and COVID‐19 are warranted.