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Our objective was to evaluate whether patients with bacteraemic urinary tract infection (UTI) who receive inadequate empirical therapy have worse outcomes than those with adequate therapy. This was a retrospective cohort study of patients with bacteraemic UTI. The exposure variable was adequate versus inadequate empirical antibiotic therapy (AEAT versus IEAT) within 24 h of culture collection. Primary endpoint was time to cure. The primary analysis used propensity score models with inverse probability of treatment weights. A secondary Cox proportional hazards modelling approach was used to test the robustness of this finding, and to evaluate other patient and pathogen predictors of time to cure. Of 469 patients with bacteraemic UTI, 368 (78.5%) received AEAT. There was no significant difference in mortality between those receiving AEAT and those receiving IEAT (adjusted OR 0.86, 95%CI 0.47-1.58). Receipt of AEAT had no association with time to cure (HR 0.93, 95%CI 0.73-1.19, p 0.55) or time to normalization of individual clinical variables. Cox proportional hazards modelling revealed that longer time to cure was associated with liver disease (HR 0.25, 95%CI 0.08-0.76, p 0.015), prior stroke (HR 0.73, 95%CI 0.54-0.99, p 0.044), empirical receipt of piperacillin-tazobactam (HR 0.77, 95%CI 0.59-0.99, p 0.044), qSOFA score1 (HR 0.68, 95%CI 0.55-0.84, p 0.001), and hospital-onset UTI (HR 0.53, 95%CI 0.39-0.71, p 0.001). In conclusion, we found no association between AEAT and time to cure for patients with bacteraemic UTI. It may be appropriate to accept a higher risk threshold when choosing empirical antibiotic regimens, even in centres with high rates of resistant uropathogens.

OBJECTIVES To evaluate long-term uptake of an antimicrobial stewardship audit-and-feedback program along with potential predictors of stewardship suggestions and acceptance across a diverse ICU population. DESIGN A retrospective cohort study. SETTING An urban, academic medical institution. PATIENTS Patients admitted to an ICU who received an antimicrobial stewardship program suggestion between June 2010 and September 2019. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS The antimicrobial stewardship program provided 7,749 antibiotic assessments over the study period and made a suggestion to alter therapy in 2,826 (36%). Factors associated with a higher likelihood of receiving a suggestion to alter therapy included shorter hospital length of stay prior to antimicrobial stewardship program review (odds ratio 1.15 for ≤ 5 d; 95% CI 1.00-1.32), admission to cardiovascular (1.37; 1.06-1.76) or burn surgery (1.88; 1.50-2.36) versus general medicine, and preceding duration of antibiotic use greater than 5 days (1.33; 1.10-1.60). Assessment of aminoglycosides (2.91; 1.85-4.89), carbapenems (1.93; 1.54-2.41), and vancomycin (2.71; 2.19-3.36) versus ceftriaxone was more likely to result in suggestions to alter therapy. The suggestion acceptance rate was 67% (1,895/2,826), which was stable throughout the study period. Admission to a level 3 ICU was associated with higher likelihood of acceptance of suggestions (1.50; 1.14-1.97). Factors associated with lower acceptance rates were admission to burn surgery (0.64; 0.45-0.91), treatment of pneumonia (0.64; 0.42-0.97 for community-acquired and 0.65; 0.44-0.94 for ventilator-acquired), unknown source of infection (0.66; 0.48-0.92), and suggestion types of "narrow spectrum" (0.65; 0.45-0.94), "change formulation of antibiotic" (0.42; 0.27-0.64), or "change agent of therapy" (0.63; 0.40-0.97) versus "change of dose". CONCLUSIONS An antimicrobial stewardship program implemented over a decade resulted in sustained suggestion and acceptance rates. These findings support the need for a persistent presence of audit-and-feedback over time with more frequent suggestions to alter potentially nephrotoxic agents, increased efforts toward specialized care units, and further work approaching infectious sources that are typically treated without pathogen confirmation and identification.

Background There exists a knowledge gap in identifying the spectrum of infectious pathogens and syndromes that lead to fulminant decline and death. The aim of this study was to better characterize patient-, pathogen-, and disease-related factors in the phenomenon of unexpected infectious deaths. Methods We conducted a population-based, retrospective cohort study of all community-based, unexpected infectious deaths in Ontario, Canada between January 2016 and December 2017. Patient-related information, infection-related information, and circumstances around the death were extracted for each case to facilitate descriptive analyses. Results Of the 7506 unexpected deaths over the study period, 418 (6%) were due to infectious diseases. Bacterial pneumonia (43%) was the most common infectious syndrome, followed by disseminated infection with no clear focus (12%), peritonitis (10%), myocarditis (6%), and pyelonephritis (5%). A pathogen was identified in 210 cases (50%), with the most common being Staphylococcus aureus (n = 35), Streptococcus pneumoniae (n = 30), Streptococcus pyogenes (n = 25), Klebsiella spp. (n = 23), and Escherichia coli (n = 19). Prodromal symptoms were present in 68% of persons before death, with a median (interquartile range) duration of only 1.0 (0.0–4.0) days; just 30% of those who died had had recent healthcare contact before their death. Conclusion Infectious diseases have the capacity to cause fulminant decline and death. The most common cause of unexpected infectious death is bacterial pneumonia, with a predominance of gram-positive bacteria. Given the rapidity of these deaths, preventing a majority of them would require upstream strategies to reduce infection susceptibility and transmission., This population-wide cohort study highlights the phenomenon of unexpected deaths due to infectious disease, with respect to the key pathogens involved, the most prominent clinical syndromes, characteristics of those who died, and opportunities and challenges for prevention.

Glucose transporter (GLUT) proteins play a key role in the transport of monosaccharides across cellular membranes, and thus, blood sugar regulation and tissue metabolism. Patterns of GLUT expression, including the insulin-responsive GLUT4, have been well characterized in mammals. However, relatively little is known about patterns of GLUT expression in birds with existing data limited to the granivorous or herbivorous chicken, duck and sparrow. The smallest avian taxa, hummingbirds, exhibit some of the highest fasted and fed blood glucose levels and display an unusual ability to switch rapidly and completely between endogenous fat and exogenous sugar to fuel energetically expensive hovering flight. Despite this, nothing is known about the GLUT transporters that enable observed rapid rates of carbohydrate flux. We examined GLUT (GLUT1, 2, 3, & 4) expression in pectoralis, leg muscle, heart, liver, kidney, intestine and brain from both zebra finches (Taeniopygia guttata) and ruby-throated hummingbirds (Archilochus colubris). mRNA expression of all four transporters was probed using reverse-transcription PCR (RT-PCR). In addition, GLUT1 and 4 protein expression were assayed by western blot and immunostaining. Patterns of RNA and protein expression of GLUT1-3 in both species agree closely with published reports from other birds and mammals. As in other birds, and unlike in mammals, we did not detect GLUT4. A lack of GLUT4 correlates with hyperglycemia and an uncoupling of exercise intensity and relative oxidation of carbohydrates in hummingbirds. The function of GLUTs present in hummingbird muscle tissue (e.g. GLUT1 and 3) remain undescribed. Thus, further work is necessary to determine if high capillary density, and thus surface area across which cellular-mediated transport of sugars into active tissues (e.g. muscle) occurs, rather than taxon-specific differences in GLUT density or kinetics, can account for observed rapid rates of sugar flux into these tissues.