Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI.

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.

Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI.

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat due to multi-drug resistance development among the CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, we found that E. faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.

A Description of Outcomes Experienced by Patients Whose Orders for Peripheral Artery Revascularization Were Reviewed by a Nondenial Prior Authorization Program.

OBJECTIVE: After a nondenial prior authorization program evaluates orders for peripheral artery revascularization (PAR), ordering physicians sometimes withdraw their orders based upon program recommendations. Some patients with withdrawn orders receive PAR if claudication does not resolve. To characterize patient outcomes under this program, we evaluated whether associations existed between the withdrawal of patients' initial PAR orders and the presence of claims for PAR and claims mentioning intermittent claudication (IC) in the following 16 weeks. METHODS: Orders for PAR placed from 1/1/19 to 9/30/19 for patients with Medicare Advantage health plans were extracted from a national healthcare organization's database. Claims data from 0 to 16 weeks following the order were reviewed to determine if patients had downstream PAR claims, or if they had emergency department or hospital claims mentioning IC. Chi-square tests were used to assess the association between order withdrawal and downstream PAR, as well as claims mentioning IC. Multivariate logistic regressions were run to assess the same, controlling for patient age, sex, urbanicity, local median income, state obesity rate, type of PAR, ordering physician specialty, and whether PAR was ordered in a hospital setting. RESULTS: Of 1588 orders meeting inclusion criteria, 71.9% (1038/1444) of authorized orders and 61.1% (88/144) of withdrawn orders were followed by PAR within 16 weeks, a significant difference (P < .01). Relatedly, 69.8% (1008/1444) of authorized orders and 70.8% (102/144) of withdrawn orders were followed by IC claims, an insignificant difference. Multivariate logistic regressions showed patients with withdrawn PAR orders had significantly lower adjusted odds of PAR (OR: 0.63; 95% CI: 0.44-0.91), but an insignificant difference in their adjusted odds of IC (OR: 1.10; CI: 0.76-1.64). CONCLUSIONS: Although patients with withdrawn PAR orders were significantly less likely to receive PAR in the subsequent 16 weeks, no association was found between withdrawn PAR orders and subsequent claims mentioning IC.