Enterobacterales represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. We previously demonstrated that positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-sorbitol (18F-FDS) can selectively detect Enterobacterales infections in murine models. Here, we demonstrate that uptake of 18F-FDS by bacteria occurs via a metabolically conserved sorbitol-specific pathway with rapid in vitro 18F-FDS uptake noted in clinical strains, including MDR isolates. Whole-body 18F-FDS PET/computerized tomography (CT) in 26 prospectively enrolled patients with either microbiologically confirmed Enterobacterales infection or other pathologies demonstrated that 18F-FDS PET/CT was safe, could rapidly detect and localize Enterobacterales infections due to drug-susceptible or MDR strains, and differentiated them from sterile inflammation or cancerous lesions. Repeat imaging in the same patients monitored antibiotic efficacy with decreases in PET signal correlating with clinical improvement. To facilitate the use of 18F-FDS, we developed a self-contained, solid-phase cartridge to rapidly (<10 min) formulate ready-to-use 18F-FDS from commercially available 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) at room temperature. In a hamster model, 18F-FDS PET/CT also differentiated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from secondary Klebsiella pneumoniae pneumonia—a leading cause of complications in hospitalized patients with COVID-19. These data support 18F-FDS as an innovative and readily available, pathogen-specific PET technology with clinical applications.
Drugs for treating giardiasis.
BACKGROUND & AIMS Despite advances in critical care medicine, the mortality rate is high among critically ill patients with cirrhosis. We aimed to identify factors that predict early (7 d) mortality among patients with cirrhosis admitted to the intensive care unit (ICU) and to develop a risk-stratification model. METHODS We collected data from patients with cirrhosis admitted to the ICU at Indiana University (IU–ICU) from December 1, 2006, through December 31, 2009 (n = 185), or at the University of Pennsylvania (Penn–ICU) from May 1, 2005, through December 31, 2010 (n = 206). Factors associated with mortality within 7 days of admission (7-d mortality) were determined by logistic regression analyses. A model was constructed based on the predictive parameters available on the first day of ICU admission in the IU–ICU cohort and then validated in the Penn–ICU cohort. RESULTS Median Model for End-stage Liver Disease (MELD) scores at ICU admission were 25 in the IU–ICU cohort (interquartile range, 23–34) and 32 in the Penn–ICU cohort (interquartile range, 26–41); corresponding 7-day mortalities were 28.3% and 53.6%, respectively. MELD score (odds ratio, 1.13; 95% confidence interval [CI], 1.07–1.2) and mechanical ventilation (odds ratio, 5.7; 95% CI, 2.3–14.1) were associated independently with 7-day mortality in the IU–ICU. A model based on these 2 variables separated IU–ICU patients into low-, medium-, and high-risk groups; these groups had 7-day mortalities of 9%, 27%, and 74%, respectively (concordance index, 0.80; 95% CI, 0.72– 0.87; P < 10−8). The model was applied to the Penn–ICU cohort; the low-, medium-, and high-risk groups had 7-day mortalities of 33%, 56%, and 71%, respectively (concordance index, 0.67; 95% CI, 0.59–0.74; P < 10−4). CONCLUSIONS A model based on MELD score and mechanical ventilation on day 1 can stratify risk of early mortality in patients with cirrhosis admitted to the ICU. More studies are needed to validate this model and to enhance its clinical utility.
Short-term moderate alcohol discontinuation adversely impacted hepatic IR in Latinos which was influenced by level of ALT at baseline independent of etiology. Although reduction in ALT through weight loss and HCV eradication remains a priority in improving IR, the observed nonharmful effect of moderate alcohol use represents a potentially confounding variable that warrants further study.
Purpose of review To discuss available information on the effectiveness of anti-toxoplasma therapy for ocular toxoplasmosis and to provide clinicians with a practical approach to the disease. Recent findings Only eleven randomized studies were identified. In the three studies for acute retinitis, there was a clear trend in favor of treatment. In the two studies for the prevention of recurrences, trimethoprim–sulfamethoxazole prophylaxis was superior to placebo. In the six studies comparing different regimens, there was no statistically significant difference between the regimens. In the setting of acute posterior uveitis suspected to be caused by toxoplasma, serological testing should always be obtained, and anti-toxoplasma drug treatment, and corticosteroids should be instituted for at least 6 weeks. Toxoplasmic chorioretinitis during pregnancy represents a particular challenge. Summary Treatment with at least two drugs and corticosteroids should be offered to patients with active toxoplasmic chorioretinitis. Pregnant women with confirmed acute infection and concomitant acute retinitis should be treated for the ocular lesion(s) and to prevent vertical transmission. Pregnant women with chronic Toxoplasma infection acquired prior to gestation and concomitant retinitis by reactivation should be treated for the retinitis and monitored for vertical transmission.
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