Objective: To determine the impact of an inpatient stewardship intervention targeting fluoroquinolone use on inpatient and postdischarge Clostridioides difficile infection (CDI). Design: We used an interrupted time series study design to evaluate the rate of hospital-onset CDI (HO-CDI), postdischarge CDI (PD-CDI) within 12 weeks, and inpatient fluoroquinolone use from 2 years prior to 1 year after a stewardship intervention. Setting: An academic healthcare system with 4 hospitals. Patients: All inpatients hospitalized between January 2017 and September 2020, excluding those discharged from locations caring for oncology, bone marrow transplant, or solid-organ transplant patients. Intervention: Introduction of electronic order sets designed to reduce inpatient fluoroquinolone prescribing. Results: Among 163,117 admissions, there were 683 cases of HO-CDI and 1,104 cases of PD-CDI. In the context of a 2% month-to-month decline starting in the preintervention period (P <.01), we observed a reduction in fluoroquinolone days of therapy per 1,000 patient days of 21% after the intervention (level change, P <.05). HO-CDI rates were stable throughout the study period. In contrast, we also detected a change in the trend of PD-CDI rates from a stable monthly rate in the preintervention period to a monthly decrease of 2.5% in the postintervention period (P <.01). Conclusions: Our systemwide intervention reduced inpatient fluoroquinolone use immediately, but not HO-CDI. However, a downward trend in PD-CDI occurred. Relying on outcome measures limited to the inpatient setting may not reflect the full impact of inpatient stewardship efforts.

Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. Recently, the ninth allele of the mobile colistin resistance (mcr) gene family, designated mcr-9, was reported. However, its clinical and public health significance remains unclear. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 from a convenience sample of clinical isolates collected between 2012 and 2017 through the Georgia Emerging Infections Program, a population- and laboratory-based surveillance program. Isolates underwent phenotypic characterization and whole-genome sequencing. Phenotypic characteristics, genomic features, and clinical outcomes of mcr-9-positive and -negative CRE cases were then compared. Among 235 sequenced CRE genomes, 13 (6%) were found to harbor mcr-9, all of which were Enterobacter cloacae complex. The median MIC and rates of heteroresistance and inducible resistance to colistin were similar between mcr-9-positive and -negative isolates. However, rates of resistance were higher among mcr-9-positive isolates across most antibiotic classes. All cases had significant health care exposures. The 90-day mortality was similarly high in both mcr-9-positive (31%) and -negative (7%) CRE cases. Nucleotide identity and phylogenetic analysis did not reveal geotemporal clustering. mcr-9-positive isolates had a significantly higher number of median [range] antimicrobial resistance (AMR) genes (16 [4 to 22] versus 6 [2 to 15]; P, 0.001) than did mcr-9-negative isolates. Pangenome tests confirmed a significant association of mcr-9 detection with mobile genetic element and heavy metal resistance genes. Overall, the presence of mcr-9 was not associated with significant changes in colistin resistance or clinical outcomes, but continued genomic surveillance to monitor for emergence of AMR genes is warranted.

Objective: To describe the epidemiology of carbapenem-resistant Enterobacterales (CRE) bacteriuria and to determine whether urinary catheters increase the risk of subsequent CRE bacteremia. Design: Using active population- and laboratory-based surveillance we described a cohort of patients with incident CRE bacteriuria and identified risk factors for developing CRE bacteremia within 1 year. Setting: The study was conducted among the 8 counties of Georgia Health District 3 (HD3) in Atlanta, Georgia. Patients: Residents of HD3 with CRE first identified in urine between 2012 and 2017. Results: We identified 464 patients with CRE bacteriuria (mean yearly incidence, 1.96 cases per 100,000 population). Of 425 with chart review, most had a urinary catheter (56%), and many resided in long-term care facilities (48%), had a Charlson comorbidity index >3 (38%) or a decubitus ulcer (37%). 21 patients (5%) developed CRE bacteremia with the same organism within 1 year. Risk factors for subsequent bacteremia included presence of a urinary catheter (odds ratio [OR], 8.0; 95% confidence interval [CI], 1.8-34.9), central venous catheter (OR, 4.3; 95% CI, 1.7-10.6) or another indwelling device (OR, 4.3; 95% CI, 1.6-11.4), urine culture obtained as an inpatient (OR, 5.7; 95% CI, 1.3-25.9), and being in the ICU in the week prior to urine culture (OR, 2.9; 95% CI, 1.1-7.8). In a multivariable analysis, urinary catheter increased the risk of CRE bacteremia (OR, 5.3; 95% CI, 1.2-23.6). Conclusions: In patients with CRE bacteriuria, urinary catheters increase the risk of CRE bacteremia. Future interventions should aim to reduce inappropriate insertion and early removal of urinary catheters.

Coronavirus disease 2019 (COVID-19) changed healthcare across the world. With this change came an increase in healthcare-associated infections (HAIs) and a concerning concurrent proliferation of MDR organisms (MDROs). In this narrative review, we describe the impact of COVID-19 on HAIs and MDROs, describe potential causes of these changes, and discuss future directions to combat the observed rise in rates of HAIs and MDRO infections.

Objectives: To describe the epidemiology of patients with nonintestinal carbapenem-resistant Enterobacterales (CRE) colonization and to compare clinical outcomes of these patients to those with CRE infection. Design: A secondary analysis of Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae 2 (CRACKLE-2), a prospective observational cohort. Setting: A total of 49 US short-term acute-care hospitals. Patients: Patients hospitalized with CRE isolated from clinical cultures, April, 30, 2016, through August 31, 2017. Methods: We described characteristics of patients in CRACKLE-2 with nonintestinal CRE colonization and assessed the impact of site of colonization on clinical outcomes. We then compared outcomes of patients defined as having nonintestinal CRE colonization to all those defined as having infection. The primary outcome was a desirability of outcome ranking (DOOR) at 30 days. Secondary outcomes were 30-day mortality and 90-day readmission. Results: Of 547 patients with nonintestinal CRE colonization, 275 (50%) were from the urinary tract, 201 (37%) were from the respiratory tract, and 71 (13%) were from a wound. Patients with urinary tract colonization were more likely to have a more desirable clinical outcome at 30 days than those with respiratory tract colonization, with a DOOR probability of better outcome of 61% (95% confidence interval [CI], 53%-71%). When compared to 255 patients with CRE infection, patients with CRE colonization had a similar overall clinical outcome, as well as 30-day mortality and 90-day readmission rates when analyzed in aggregate or by culture site. Sensitivity analyses demonstrated similar results using different definitions of infection. Conclusions: Patients with nonintestinal CRE colonization had outcomes similar to those with CRE infection. Clinical outcomes may be influenced more by culture site than classification as "colonized"or "infected."

The ongoing coronavirus pandemic has emphasized the importance of diagnostic medicine to both health professionals and the broader public. With rapid development and introduction of testing for SARS-CoV-2, much attention has been given to evaluating the reliability of these tests. However, as advanced diagnostics become increasingly used in healthcare worldwide, both performance characteristics of the test and the interpretation of results must be considered before implementation. Prior to widespread availability of SARS-CoV-2 testing, many clinicians used rapid viral diagnostics, including influenza PCR and multiplex respiratory PCR panels to look for evidence of alternative diagnoses in patients presenting with influenza-like illnesses. Common human coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1) which typically cause mild upper respiratory tract infections are targets in several commercial multiplex PCR panels, however none in March 2020, detected SARS CoV-2 (the cause of COVID-19)[1].

The coronavirus disease 2019 (COVID-19) pandemic has caused unfathomable changes across society. This challenge, like the 1918 influenza pandemic, has highlighted the importance of physicians who can rigorously answer critical research questions. As was the case then, we are now confronted by daunting, pressing needs spanning basic, translational, and clinical research. Now more than ever, there is widespread, progressive appreciation of the devastating ways in which structural racism, social determinants of health, and health disparities tragically enhance and perpetuate the pathogenesis of infectious diseases (ID), as well as associated disease and deaths. Among the many lessons learned from this first year of the COVID-19 pandemic, a critically important one is the way in which a nimble, effective, well-funded ID research community is needed to immediately pivot and respond to public health emergencies in real-time.

Objective: To determine the effect of an electronic medical record (EMR) nudge at reducing total and inappropriate orders testing for hospital-onset Clostridioides difficile infection (HO-CDI).Design: An interrupted time series analysis of HO-CDI orders 2 years before and 2 years after the implementation of an EMR intervention designed to reduce inappropriate HO-CDI testing. Orders for C. difficile testing were considered inappropriate if the patient had received a laxative or stool softener in the previous 24 hours.Setting: Four hospitals in an academic healthcare network.Patients: All patients with a C. difficile order after hospital day 3.Intervention: Orders for C. difficile testing in patients administered a laxative or stool softener in <24 hours triggered an EMR alert defaulting to cancellation of the order (nudge).Results: Of the 17,694 HO-CDI orders, 7% were inappropriate (8% prentervention vs 6% postintervention; P <.001). Monthly HO-CDI orders decreased by 21% postintervention (level-change rate ratio [RR], 0.79; 95% confidence interval [CI], 0.73-0.86), and the rate continued to decrease (postintervention trend change RR, 0.99; 95% CI, 0.98-1.00). The intervention was not associated with a level change in inappropriate HO-CDI orders (RR, 0.80; 95% CI, 0.61-1.05), but the postintervention inappropriate order rate decreased over time (RR, 0.95; 95% CI, 0.93-0.97).Conclusion: An EMR nudge to minimize inappropriate ordering for C. difficile was effective at reducing HO-CDI orders, and likely contributed to decreasing the inappropriate HO-CDI order rate after the intervention.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates can frequently retain susceptibility to traditional antipseudomonal β-lactams including cefepime, ceftazidime and piperacillin/tazobactam. OBJECTIVES: This observational study aimed to determine the proportion of CRPA isolates that were susceptible to all tested other traditional antipseudomonal β-lactams (S-CRPA) and assess whether patients with S-CRPA had improved 30 day mortality compared with patients with NS-CRPA (non-susceptible to cefepime, ceftazidime or piperacillin/tazobactam). METHODS: Patients with CRPA isolated from normally sterile sites, urine, lower respiratory tracts and wounds were identified using active population- and laboratory-based surveillance through the Georgia Emerging Infections Program from August 2016 to July 2018 in Atlanta, GA, USA. Only unique patients who were hospitalized at the time of, or within 1 week of, culture were included. We excluded patients with cystic fibrosis. Multivariable logistic regression estimated the association between S-CRPA and 30 day mortality. RESULTS: Among 635 adults hospitalized with CRPA, 219 (34%) had S-CRPA. Patients with S-CRPA were more likely to be white (50% versus 38%, P = 0.01) and live in a private residence prior to culture (44% versus 28%, P < 0.01), and less likely to have required ICU care within the prior week (23% versus 36%, P < 0.01) compared with patients with NS-CRPA. Compared with those with NS-CRPA, patients with S-CRPA had an increased 30 day mortality (18% versus 15%, adjusted OR 1.9; 95% CI 1.2-3.1). CONCLUSIONS: S-CRPA was associated with higher 30 day mortality than NS-CRPA in hospitalized patients. The reason for this observed increase in mortality deserves further investigation.

The coronavirus disease 2019 (COVID-19) pandemic has affected many providers, but its impact on Infectious Diseases (ID) fellows in the United States is largely undescribed. In this study, we discuss key issues that emerged from the first national ID Fellows Call with respect to the ID fellow's role during the COVID-19 pandemic, teaching/learning, and research.