Detection of a Human Adenovirus Outbreak, Including Some Critical Infections, Using Multipathogen Testing at a Large University, September 2022-January 2023.

Background: Human adenoviruses (HAdVs) can cause outbreaks of flu-like illness in university settings. Most infections in healthy young adults are mild; severe illnesses rarely occur. In Fall 2022, an adenovirus outbreak was identified in university students. Methods: HAdV cases were defined as university students 17-26 years old who presented to the University Health Service or nearby emergency department with flu-like symptoms (eg, fever, cough, headache, myalgia, nausea) and had confirmed adenovirus infections by polymerase chain reaction (PCR). Demographic and clinical characteristics were abstracted from electronic medical records; clinical severity was categorized as mild, moderate, severe, or critical. We performed contact investigations among critical cases. A subset of specimens was sequenced to confirm the HAdV type. Results: From 28 September 2022 to 30 January 2023, 90 PCR-confirmed cases were identified (51% female; mean age, 19.6 years). Most cases (88.9%) had mild illness. Seven cases required hospitalization, including 2 critical cases that required intensive care. Contact investigation identified 44 close contacts; 6 (14%) were confirmed HAdV cases and 8 (18%) reported symptoms but never sought care. All typed HAdV-positive specimens (n = 36) were type 4. Conclusions: While most students with confirmed HAdV had mild illness, 7 otherwise healthy students had severe or critical illness. Between the relatively high number of hospitalizations and proportion of close contacts with symptoms who did not seek care, the true number of HAdV cases was likely higher. Our findings illustrate the need to consider a wide range of pathogens, even when other viruses are known to be circulating.

Host-specific induction of Escherichia coli fitness genes during human urinary tract infection.

Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of uncomplicated urinary tract infection (UTI), manifested by inflammation of the urinary bladder, in humans and is a major global public health concern. Molecular pathogenesis of UPEC has been primarily examined using murine models of UTI. Translational research to develop novel therapeutics against this major pathogen, which is becoming increasingly antibiotic resistant, requires a thorough understanding of mechanisms involved in pathogenesis during human UTIs. Total RNA-sequencing (RNA-seq) and comparative transcriptional analysis of UTI samples to the UPEC isolates cultured in human urine and laboratory medium were used to identify novel fitness genes that were specifically expressed during human infection. Evidence for UPEC genes involved in ion transport, including copper efflux, nickel and potassium import systems, as key fitness factors in uropathogenesis were generated using an experimental model of UTI. Translational application of this study was investigated by targeting Cus, a bacterial copper efflux system. Copper supplementation in drinking water reduces E. coli colonization in the urinary bladder of mice. Additionally, our results suggest that anaerobic processes in UPEC are involved in promoting fitness during UTI in humans. In summary, RNA-seq was used to establish the transcriptional signature in UPEC during naturally occurring, community acquired UTI in women and multiple novel fitness genes used by UPEC during human infection were identified. The repertoire of UPEC genes involved in UTI presented here will facilitate further translational studies to develop innovative strategies against UTI caused by UPEC.

Impact of a critical pathway on inpatient management of diabetic ketoacidosis.

To assess the management of diabetic ketoacidosis (DKA) and evaluate if introduction of a critical pathway improves management, we studied adults admitted with DKA to the Medicine and Critical Care Services in a US teaching hospital. Patients admitted with DKA in 1997 before implementation of the critical pathway were the control group (n=72). In 1998, housestaff and nurses in the emergency department (ED) and on the General Medicine and Critical Care Services were instructed in the use of the critical pathway. Patients admitted with DKA during 1998 (n=77) were the intervention group. Length of stay (LOS), hospital cost, adherence to guidelines, and medical outcomes to be avoided were compared, and regression analyses were performed to correlate processes and outcomes of care. Mean LOS and variability in LOS decreased during the intervention period, especially in patients treated without endocrinology consultation (EC) (5.2 +/- 10.6 vs. 2.4 +/- 2.1 days, P=0.01), and hospital cost and variability in cost tended to decrease ($6441 +/- 15,204 vs. $3625 +/- 3478, P=0.24). More intervention subjects received the recommended intravenous fluid volume (88 vs. 71%, P=0.013), education in sick-day management (77 vs. 54%, P=0.006), and EC (38 vs. 21%, P=0.03). Insulin management was not changed. We conclude that implementation of a DKA critical pathway reduced practice variation and was associated with shorter LOS and a trend toward decreased cost. Some processes of care were improved but many require additional interventions.