Evaluation of CpxRA as a Therapeutic Target for Uropathogenic Escherichia coli Infections.

CpxRA is an envelope stress response system found in all members of the family Enterobacteriaceae; CpxA has kinase activity for CpxR and phosphatase activity for phospho-CpxR, a transcription factor. CpxR also accepts phosphate groups from acetyl phosphate, a glucose metabolite. Activation of CpxR increases the transcription of genes encoding membrane repair and downregulates virulence determinants. We hypothesized that activation of CpxR could serve as an antimicrobial/antivirulence strategy and discovered compounds that activate CpxR in Escherichia coli by inhibiting CpxA phosphatase activity. As a prelude to testing such compounds in vivo, here we constructed cpxA (in the presence of glucose, CpxR is activated because of a lack of CpxA phosphatase) and cpxR (system absent) deletion mutants of uropathogenic E. coli (UPEC) CFT073. By RNA sequencing, few transcriptional differences were noted between the cpxR mutant and its parent, but in the cpxA mutant, several UPEC virulence determinants were downregulated, including the fim and pap operons, and it exhibited reduced mannose-sensitive hemagglutination of guinea pig red blood cells in vitro In competition experiments with mice, both mutants were less fit than the parent in the urine, bladder, and kidney; these fitness defects were complemented in trans Unexpectedly, in single-strain challenges, only the cpxA mutant was attenuated for virulence in the kidney but not in the bladder or urine. For the cpxA mutant, this may be due to the preferential use of amino acids over glucose as a carbon source in the bladder and urine by UPEC. These studies suggest that CpxA phosphatase inhibitors may have some utility for treating complex urinary tract infections.

Etiology and utility of hospital-onset bacteremia as a safety metric for targeted harm reduction.

BACKGROUND: Hospital acquired infections (HAIs) are a major driver of morbidity and cost in health systems. Central line-associated bloodstream infections (CLABSIs) require intensive surveillance and review. All-cause hospital-onset bacteremia (HOB) may be a simpler reporting metric, correlates with CLABSI, and is viewed positively by HAI experts. Despite the ease in the collection, the proportion of HOBs that are actionable and preventable is unknown. Moreover, quality improvement strategies targeting it may be more challenging. In this study, we describe the bedside provider-perceived sources of HOB in order to provide insight into this new metric as a target for HAI prevention. METHODS: All cases of HOBs in 2019 from an academic tertiary care hospital were retrospectively reviewed. Information was collected to assess provider-perceived etiology and associated clinical factors (microbiology, severity, mortality, and management). HOB was categorized as preventable or not preventable based on the perceived source from the care team and management decisions. Preventable causes included device-associated bacteremias, pneumonias, surgical complications, and contaminated blood cultures. RESULTS: Of the 392 instances of HOB, 56.0% (n = 220) had episodes that were determined not preventable by providers. Excluding blood culture contaminates, the most common cause of preventable HOB was secondary to CLABSIs (9.9%, n = 39). Of the HOBs that were not preventable, the most common sources were gastrointestinal and abdominal (n = 62), neutropenic translocation (n = 37), and endocarditis (n = 23). Patients with HOB were generally medically complex with an average Charlson comorbidity index of 4.97. This translated into a higher average length of stay (29.23 vs 7.56, P < .001) and higher inpatient mortality (odds ratio 8.3, confidence interval [6.32-10.77]) when compared to admissions without HOB. CONCLUSIONS: The majority of HOBs were not preventable and the HOB metric may be a marker of a sicker patient population making it a less actionable target for quality improvement. Standardization across the patient mix is important if the metric becomes linked to reimbursement. If the HOB metric were to be used in lieu of CLABSI, large tertiary care health systems that house sicker patients may be unfairly financially penalized for caring for more medically complex patients.

Candida auris outbreak at a tertiary care hospital during the COVID-19 pandemic.

BACKGROUND: Candida auris (C auris) is a fungal pathogen that has the potential for environmental persistence leading to outbreaks in health care settings. There has been a worldwide surge in C auris outbreaks during the COVID-19 pandemic. In this report, we describe an outbreak of C auris, its control, patient outcomes, and lessons learned. METHODS: The outbreak occurred in a 600-bed adult academic tertiary care hospital. Contact tracing was initiated immediately after identification of the index case and surveillance testing for C auris was obtained from patients who were exposed to the index case. Infection prevention measures were closely followed. RESULTS: A total of 560 cultures were performed on 453 unique patients between August 2021 and December 2021. Of those, 31 cultures (5.5%) were positive for C auris; 27 (87.1%) were colonized with C auris, while 4 patients developed a clinical infection (12.9%). The secondary attack rate was 6.8% (31/453). The 30-day all-cause mortality rate for all patients who tested positive for C auris was 9.7%. DISCUSSION: C auris can cause protracted outbreaks that result in colonization and invasive infections. Multidisciplinary work to improve adherence to infection prevention measures as well as targeted admission screening are essential to limit outbreaks.

In-person classroom instruction and risk of SARS-CoV-2 infection among undergraduates at Indiana University, Fall 2020.

Objective: To examine how in-person classroom instruction was related to risk of SARS-CoV-2 infection in undergraduate students. Participants: Indiana University undergraduate students (n = 69,606) enrolled in Fall 2020, when courses with in-person and remote instruction options were available. Methods: Students participated weekly in mandatory SARS-CoV-2 RT-PCR asymptomatic testing by random selection, supplemented with symptomatic testing as needed. We used log-binomial regression models to estimate the association between number of in-person credit hours and the risk of SARS-CoV-2 infection over the course of the semester. Results: Overall 5,786 SARS-CoV-2 cases were observed. Increased in-person credit hour exposures were not associated with increased risk of SARS-CoV-2 overall [aRR (95% CI): 0.98 (0.97,0.99)], nor within specific subgroups (Greek affiliation and class). Conclusions: In-person instruction did not appear to increase SARS-CoV-2 transmission in a university setting with rigorous protective measures in place, prior to mass vaccine rollout and prior to delta variant emergence.

Two-step algorithm-based Clostridioides difficile testing as a tool for antibiotic stewardship.

OBJECTIVES: Diagnosis of Clostridium difficile infection (CDI) can be challenging due to high colonization rates. Unlike PCR-only testing, two-step algorithm testing (that includes toxin and PCR) may help differentiate colonization from active infection, but it is unknown if this type of testing impacts treatment decisions. We examined the association between changing CDI diagnostic methods, the way the testing results were displayed, and the rates of CDI-specific treatment. METHODS: We performed a retrospective analysis of positive C. difficile cases over 2 years, a year preceding and following our institution's transition from PCR to two-step testing. During the PCR period, results were displayed in the electronic medical record as 'positive'. In the two-step period, positive results were either displayed as 'likely colonized' or 'toxin positive'. Rates of CDI-specific therapy and adverse patient outcomes (30-day mortality and intensive care unit admission) were compared among the three groups. RESULTS: A total of 610 patients had positive results over the study period. Of the 354 patients in the PCR group, 329 (93%) were treated with CDI-specific therapy. Of the 142 patients in the likely colonized group, 59 (42%) were treated. All 114 patients in the toxin-positive group were treated. Multivariate analysis of patients who were PCR positive or likely colonized showed that tests sent in the two-step era were less likely to be associated with treatment for CDI (odds ratio 0.05, 95% CI 0.03-0.09). DISCUSSION: We found a correlation between changing the type of test and the way the results were displayed and reduction in CDI-specific antibiotic use without restricting clinician diagnostic ordering.

Clinical comparison and agreement of PCR, antigen, and viral culture for the diagnosis of COVID-19: Clinical Agreement Between Diagnostics for COVID19.

The aim of this study is to compare the COVID-19 nasopharyngeal PCR (NP PCR) to antigen, nasal PCR, and viral culture. One-hundred-and-fourteen risk-stratified patients were tested by culture, nasal PCR, NP PCR, and Ag testing. Twenty (48%) of the high risk and 23 (32%) of the low risk were NP PCR positive. Compared with NP PCR, the sensitivity of nasal PCR, Sofia Ag, BinaxNOW Ag, and culture were 44%, 31%, 37%, and 15%. In the high risk group, the sensitivity of these tests improved to 71%, 37%, 50%, and 22%. Agreement between tests was highest between nasal PCR and both antigen tests. Patients who were NP PCR positive but antigen negative were more likely to have remote prior COVID-19 infection (p<0.01). Nasal PCR and antigen positive patients were more likely to have symptoms (p = 0.01).

Real world utilization of nurse-driven urinary catheter removal protocol in patients with epidural pain catheters.

BACKGROUND: Surgeons use indwelling bladder catheters (IBCs) to avoid urinary retention in patients with epidural analgesic catheters. Reduction of IBC-days is associated with improved catheter-associated urinary tract infection rates (CAUTI). This study investigates real world application of a Nurse-Driven Catheter Removal Protocol (NDCRP) to reduce IBC-days in this patient population. METHODS: Patients with epidural catheters and IBC were targeted for IBC removal on post-operative day 1 (POD1). Patients were followed for application of the NDCRP, catheterization need, IBC re-anchoring, and complications. RESULTS: One hundred and thirty-three patients had IBCs removed on POD1 (Protocol Group) and 50 patients did not (Non-Protocol Group). There was a reduction in IBC-days in the Protocol Group despite incomplete adherence to the NDCRP (1.55 days vs 4.64 days; P < .001). Ninety-three patients (70%) were able to spontaneously void after early IBC removal. Fourteen patients (11%) were able to spontaneously void after serial in-and-out catheterization (I/O). No significant difference in re-anchoring was found between the protocol and non-protocol groups (26 vs 4 patients; P = .09). CONCLUSIONS: Early removal of IBCs (POD1) in patients with epidural catheters with the assistance of an NDCRP is a safe and successful strategy to reduce IBC-days in the hospital.

Clinical characteristics, outcomes and prognosticators in adult patients hospitalized with COVID-19.

BACKGROUND: COVID-19 is a novel disease caused by SARS-CoV-2. METHODS: We conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into 3 groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV, and those who received MV and died during hospitalization. RESULTS: There were 140 hospitalizations; 22 deaths (mortality rate 15.7%), 83 (59%) survived and did not receive MV, 35 (25%) received MV and survived; 18 (12.9%) received MV and died. Thee mean age of each group was 57.8, 55.8 and 72.7 years, respectively (P = .0001). Of those who received MV and died, 61% were male (P = .01). More than half the patients (n = 90, 64%) were African American. First measured d-dimer >575.5 ng/mL, procalcitonin > 0.24 ng/mL, lactate dehydrogenase >445.6 units/L, and brain natriuretic peptide (BNP) >104.75 pg/mL had odds ratios of 10.5, 5, 4.5 and 2.9, respectively for MV (P < .05 for all). Peak BNP >167.5 pg/mL had an odds ratio of 6.7 for inpatient mortality when mechanically ventilated (P = .02). CONCLUSIONS: Age and gender may impact outcomes in COVID-19. D-dimer, procalcitonin, lactate dehydrogenase and BNP may serve as early indicators of disease trajectory.

Use of an intraoperative sodium oxychlorosene-based infection prevention protocol to safely decrease postoperative wound infections after spine surgery.

OBJECTIVE: Postoperative infection remains prevalent after spinal surgical procedures. Institutional protocols for infection prevention have improved rates of infection after spine surgery. However, prior studies have focused on only elective surgical patients. The aim of this study was to determine the efficacy of a multiinstitutional intraoperative sodium oxychlorosene-based infection prevention protocol for decreasing rate of infection after instrumented spinal surgery. METHODS: A retrospective analysis was performed at two tertiary care institutions with level I trauma programs, and patients who underwent posterior instrumented spinal fusion between January 1, 2011, and May 31, 2019, were included. Postoperative deep wound infection rates were captured before and after implementation of a multiinstitutional infection prevention protocol. Possible adverse outcomes related to infection prevention techniques were also examined. In addition, consecutive patients treated from January 1, 2018, to May 31, 2019, were prospectively included in a database to collect preoperative and postoperative spine-specific quality of life measures and to assess the impact of postoperative infection on quality of life. RESULTS: A total of 5047 patients fit the inclusion criteria. Of these, 1043 patients underwent surgery prior to protocol implementation. The infection rate of this cohort (3.5%) decreased significantly after protocol implementation (1.2%, p < 0.001). Postoperative sterile seroma rates did not differ between the preprotocol and postprotocol groups (0.7% vs 0.7%, p = 0.5). In the 1031 patients who underwent surgery between January 2018 and May 2019, the fusion rate was 89.2%. Quality of life outcomes between patients with infection and those without infection were similar, although statistical power was limited owing to the low rate of infection. Notably, 2 of 10 patients who developed deep wound infection died of infection-related complications. CONCLUSIONS: An intraoperative sodium oxychlorosene-based infection prevention protocol helped to significantly decrease the rate of infection after spine surgery without negatively impacting other postoperative procedure-related metrics. Postoperative wound infection may be associated with higher-than-expected rate of postoperative mortality.

Seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies among healthcare workers with differing levels of coronavirus disease 2019 (COVID-19) patient exposure.

Healthcare employees were tested for antibodies against severe acute respiratory coronavirus virus 2 (SARS-CoV-2). Among 734 employees, the prevalence of SARS-CoV-2 antibodies was 1.6%. Employees with heavy coronavirus disease 2019 (COVID-19) exposure had similar antibody prevalence as those with limited or no exposure. Guidelines for PPE use seem effective for preventing COVID-19 infection in healthcare workers.

Changing the culture of urine culturing: Utilizing Agile Implementation to improve diagnostic stewardship in the ICU.

Over diagnosis of catheter-associated urinary tract infection (CAUTI) contributes to unnecessary and excessive antibiotic use, selection for resistant organisms, increased risk for Clostridiodes difficile infections, as well as a false elevation in CAUTI rates. Utilizing agile implementation to implement a urine culture algorithm achieved statistically significant reduction in CAUTI rates in a critical care unit resulting in sustainment and spread throughout the system.

Utilizing a real-time discussion approach to improve the appropriateness of Clostridioides difficile testing and the potential unintended consequences of this strategy.

We report electronic medical record interventions to reduce Clostridioides difficile testing risk 'alert fatigue.' We used a behavioral approach to diagnostic stewardship and observed a decrease in the number of tests ordered of ~4.5 per month (P < .0001). Although the number of inappropriate tests decreased during the study period, delayed testing increased.

Why do clinicians order inappropriate Clostridium difficile testing? An exploratory study.

BACKGROUND: The drivers behind Clostridium difficile testing are not well understood. METHODS: C difficile testing orders were reviewed. An algorithm that sequentially considered the presence of diarrhea, leukocytosis, fever, and laxative use was created. Tests deemed potentially inappropriate were discussed with the ordering team. RESULTS: Of 128 orders reviewed, 62% (n = 79) were appropriate. Patients whose testing was deemed inappropriate had longer lengths of stay. Diarrhea and laxative use were common and similarly distributed in those appropriately or inappropriately tested. The most commonly cited reason for ordering an inappropriate test was the reporting of diarrhea to the clinician by the patient or nursing that was not documented in the electronic health record. The next most common reason was clinician perception of risk. Demographics, laxative use, fever, leukocytosis, and diarrhea were similarly distributed between patients testing positive or negative by C difficile polymerase chain reaction. DISCUSSION: The discriminating value of diarrhea or laxative use in assessing for C difficile infection is poor. Multiple streams of information add to the complexities of decision making around C difficile testing. Inconsistent definitions of diarrhea likely contribute to this complexity. Clinician-perceived risk to the patient, partially driven by length of stay, may be a large driver of testing practices. CONCLUSIONS: Without understanding the knowledge, attitudes, and values that underlie clinician behavior, interventions targeting ordering practices may not succeed.

Strategies for the successful implementation of disinfecting port protectors to reduce CLABSI in a large tertiary care teaching hospital.

Disinfecting port protectors are a supplement to the central line-associated bloodstream infection prevention bundle as an optional recommendation from the Centers for Disease Control and Prevention. Despite evidence of effectiveness, few centers have successfully reported systematic, sustained implementation of these devices. In this article, we discuss a successful implementation in a large tertiary care teaching hospital, using an evidence-based, multidisciplinary approach. Infection prevention; Bacteremia; Ethanol caps; Bundle measures; Quality improvement; Hub infection.

Using the agile implementation model to reduce central line-associated bloodstream infections.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are among the most common hospital-acquired infections and can lead to increased patient morbidity and mortality rates. Implementation of practice guidelines and recommended prevention bundles has historically been suboptimal, suggesting that improvements in implementation methods could further reductions in CLABSI rates. In this article, we describe the agile implementation methodology and present details of how it was successfully used to reduce CLABSI. METHODS: We conducted an observational study of patients with central line catheters at 2 adult tertiary care hospitals in Indianapolis from January 2015 to June 2017. RESULTS: The intervention successfully reduced the CLABSI rate from 1.76 infections per 1,000 central line days to 1.24 (rate ratio = 0.70; P = .011). We also observed reductions in the rates of Clostridium difficile and surgical site infections, whereas catheter-associated urinary tract infections remained stable. CONCLUSIONS: Using the AI model, we were able to successfully implement evidence-based practices to reduce the rate of CLABSIs at our facility.

Assessing patient risk of central line-associated bacteremia via machine learning.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) contribute to increased morbidity, length of hospital stay, and cost. Despite progress in understanding the risk factors, there remains a need to accurately predict the risk of CLABSIs and, in real time, prevent them from occurring. METHODS: A predictive model was developed using retrospective data from a large academic healthcare system. Models were developed with machine learning via construction of random forests using validated input variables. RESULTS: Fifteen variables accounted for the most significant effect on CLABSI prediction based on a retrospective study of 70,218 unique patient encounters between January 1, 2013, and May 31, 2016. The area under the receiver operating characteristic curve for the best-performing model was 0.82 in production. DISCUSSION: This model has multiple applications for resource allocation for CLABSI prevention, including serving as a tool to target patients at highest risk for potentially cost-effective but otherwise time-limited interventions. CONCLUSIONS: Machine learning can be used to develop accurate models to predict the risk of CLABSI in real time prior to the development of infection.