Background Patients hospitalized with COVID-19 are at increased risk of healthcare-associated infections especially with prolonged hospital stays. We sought to identify incidence, antimicrobial susceptibilities, and outcomes associated with bacterial/fungal secondary infections in a large cohort of patients with COVID-19. Methods We evaluated adult patients diagnosed with COVID-19 between March 2 to May 31, 2020 and hospitalized >24 hours. Data extracted from medical records included diagnoses, vital signs, laboratory results, microbiological data, and antibiotic use. Microbiologically-confirmed bacterial and fungal pathogens from clinical cultures were evaluated to characterize community- and healthcare-associated infections, including describing temporal changes in predominant organisms on presentation and throughout hospitalization. Univariable and multivariable logistic regression analyses were performed to investigate risk factors for healthcare-associated infections. Results A total of 3,028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) with positive cultures met criteria for infection. Community-associated co-infections were identified in 183 (6%) patients, whereas healthcare-associated infections occurred in 350 (12%) patients. 57% of healthcare-associated infections were caused by Gram-negative bacteria and 19% by fungi. Antibiotic resistance increased with longer hospital stays, with incremental increases in the proportion of vancomycin-resistance among enterococci and ceftriaxone- and carbapenem-resistance among Enterobacterales. ICU stay, invasive mechanical ventilation, and steroids were associated with healthcare-associated infections. Conclusions Healthcare-associated infections occur in a small proportion of patients hospitalized with COVID-19 and are most often caused by Gram-negative and fungal pathogens. Antibiotic resistance is more prevalent with prolonged hospital stays. Antimicrobial stewardship is imperative in this population to minimize unnecessary broad-spectrum antibiotics.
Androgen receptor (AR) signaling pathways are important for the survival and proliferation of prostate cancer cells. Because AR activity is facilitated by distinct coregulatory factors and complexes, it is conceivable that some of these proteins might also play a role in promoting prostate oncogenesis. The multisubunit Mediator complex is an important coactivator for a broad range of regulatory transcriptional factors including AR, yet its role in prostate cancer is unclear. Here, we used RNA interference to knock down the expression of two integral Mediator components, MED1/TRAP220 and MED17, in prostate cancer cells. MED1/TRAP220 plays a particularly important role in androgen signaling in that it serves as a direct binding target for AR. We found that the knockdown of either subunit markedly decreases transcription from transiently transfected androgen-responsive reporter genes, as well as inhibits androgen-dependent expression of endogenous AR target genes. We show for the first time that loss of either MED1/TRAP220 or MED17 in prostate cancer cells significantly decreases both androgen-dependent and -independent cellular proliferation, inhibits cell cycle progression, and increases apoptosis. Furthermore, we show that MED1/ TRAP220 is overexpressed in both AR-positive and -negative prostate cancer cells lines, as well as in 50% (10 of 20) of the clinically localized human prostate cancers we examined, thus suggesting that MED1/TRAP220 hyperactivity may have implications in prostate oncogenesis. In sum, our data suggest that Mediator plays an important coregulatory role in prostate cancer cell proliferation and survival, and therefore, may represent a new target for therapeutic intervention. [Cancer Res 2007;67(9):4034-41]
The native esophageal microbiome is similar in composition to the oral microbiome, with a high relative abundance of the phylum Firmicutes and the genus Streptococcus. Limited studies to date suggest that there are certain microbiome alterations associated with esophageal diseases. Additionally, it may be possible to indirectly assess the esophageal microbiome via non-endoscopic means. This raises the possibility that non-invasive microbiome analysis could be used for disease screening and monitoring. Further understanding of the role of the esophageal microbiome in disease pathogenesis, as well as methods for microbiome alteration, may help elucidate future targets for disease modifying therapies, or minimally invasive screening tools in patients at high risk for development of various esophageal conditions.
The role of procalcitonin in identifying community-associated bacterial infections among patients with coronavirus disease 2019 is not yet established. In 2443 patients with 148 bacterial co-infections, mean procalcitonin levels were significantly higher with any bacterial infection (13.16 ± 51.19 ng/mL, p=0.0091) and with bacteremia (34.25 ± 85.01 ng/mL, p=0.0125) than without infection (2.00 ±15.26 ng/mL). Procalcitonin (cutoff 0.25 or 0.50 ng/mL) did not reliably identify bacterial co-infections, but may be useful in excluding bacterial infection.
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