Background: Central line-associated bloodstream infections (CLABSI) and catheter-associated urinary tract infections (CAUTI) are key healthcare-associated infection (HAI) quality metrics. In this qualitative analysis, we aimed to identify common issues contributing to CLABSIs and CAUTIs occurring during the COVID-19 pandemic. Methods: In an academic healthcare network in Atlanta, GA, four hospitals perform real-time, apparent cause analyses (ACAs) for all CLABSIs and CAUTIs. Contributing factors are entered as free text into an electronic database. We analyzed data from 8/2020–8/2022. We first performed a qualitative open card sort of all reported contributing factors to CLABSI and created a novel framework based on mutually defined critical tasks (e.g., line insertion) and cross-cutting issues (e.g., communication breakdown). Contributing factors could describe ≥1 critical task and/or ≥1 cross-cutting issue. After establishing interrater reliability, a multidisciplinary group applied this framework to classify each contributing factor. For CAUTI, we used the same set of cross-cutting issues but identified new critical tasks via open card sorting. We then used the framework to classify each CAUTI contributing factor. We used descriptive statistics to identify frequent critical tasks and cross-cutting issues. Results: We reviewed 350 CLABSI ACAs with 602 contributing factors and 240 CAUTI ACAs with 405 contributing factors (Figure 1). Our classification framework comprised 11 cross-cutting issues and 9 critical tasks for CLABSI and 7 critical tasks for CAUTI (Figure 2). CLABSI: The critical tasks most often reported were bathing (19%), central line dressing maintenance (15%), and assessing central line indication (8%; Figure 3). Within these tasks, the most frequent issues described for bathing were the task not being performed (20%) and unclear documentation (18%); for dressing maintenance, the task was not performed (15%), not documented (15%), or poorly performed due to lack of competency (15%); and for assessing line indication, there was frequent communication breakdown (33%). CAUTI: The critical tasks most often reported were urinary catheter care (26%) and assessing the indication for urinary catheter (22%; Figure 4). Within these tasks, urinary catheter care was frequently not documented (38%) or not performed (16%); assessing urinary catheter necessity was often not documented (29%) or involved breakdown of communication (19%). Conclusion: We created a novel framework to evaluate common causes of HAIs in an academic healthcare network. This framework can be used to identify and track gaps over time and to develop quality improvement initiatives targeting key tasks and associated factors, such as communication difficulties when assessing device indications.

Disclosure: Colleen Kraft: Consultant - REbiotix/Ferring; Scientific Advisory Board - Seres, LLC

Background: Antibiotics alone are often insufficient to treat recurrent C. difficile infection (rCDI) because they have no activity against C. difficile spores that germinate within a disrupted microbiome. SER-109, an investigational, oral, microbiome therapeutic comprised of purified Firmicutes spores, was designed to reduce rCDI through microbiome repair. We report an integrated efficacy analysis through week 24 for SER-109 from phase 3 studies, ECOSPOR III and ECOSPOR IV. Methods: ECOSPOR III was a randomized, placebo-controlled phase 3 trial conducted at 56 US or Canadian sites that included 182 participants with ≥2 CDI recurrences, confirmed via toxin EIA testing. Participants were stratified by age (<65 years or ≥65 years) and antibiotic regimen (vancomycin, fidaxomicin) and were randomized 1:1 to placebo or SER-109 groups. ECOSPOR IV was an open-label, single-arm study conducted at 72 US or Canadian sites including 263 participants with rCDI enrolled in 2 cohorts: (1) rollover participants from ECOSPOR III who experienced on-study recurrence diagnosed by toxin EIA (n = 29) and (2) participants with ≥1 CDI recurrence (diagnosed by PCR or toxin EIA), inclusive of the current episode (n = 234). In both studies, the investigational product was administered orally as 4 capsules over 3 consecutive days following symptom resolution after standard-of-care antibiotics. The primary efficacy end point was rCDI (recurrent toxin-positive diarrhea requiring treatment) through week 8. Other end points included CDI recurrence rates and safety through 24 weeks. Results: These 349 participants received at least 1 dose of SER-109 in ECOSPOR III or ECOSPOR IV (mean age 64.2; 68.8% female). Overall, 77 participants (22.1%) enrolled with their first CDI recurrence. Four participants received blinded SER-109 in ECOSPOR III followed by a second dose of open-label SER-109 in ECOSPOR IV. Overall, the proportion of participants who received any dose of SER-109 with rCDI at week 8 was 9.5% (33 of 349; 95% CI, 6.6 %–13.0%), and the CDI recurrence rate remained low through 24 weeks (15.2%, 53 of 349; 95% CI, 11.6%–19.4%), corresponding to sustained clinical response rates of 90.5% (95% CI, 87.0%–93.4%) and 84.8% (95% CI, 80.6%–88.4%), respectively (Fig. 1). Most rollover participants (25 of 29, 86.2%) were from the placebo arm; 13.8% had rCDI by week 8. Conclusions: In this integrated analysis, the rates of rCDI were low and durable in participants who received the investigational microbiome therapeutic SER-109, with sustained clinical response rates of 90.5% and 84.8% at weeks 8 and 24, respectively. These data further support the potential benefit of microbiome repair with SER-109 following antibiotics for rCDI to prevent recurrence in high-risk patients.

Financial support: This study was funded by Seres Therapeutics.

Disclosure: None

Hospitals caring for patients with high-consequence pathogens may need to safely manage large volumes of category A waste. Using biological indicators to assess for successful sterilization, autoclave cycle parameters that would inactivate 4 categories of waste were identified and validated utilizing a STERIS Amsco 630LS Steam Sterilizer.

Group Name: The Emory COVID-19 Quality and Clinical Research Collaborative

Background: Patients hospitalized with COVID-19 are at risk of secondary infections—10%–33% develop bacterial pneumonia and 2%–6% develop bloodstream infection (BSI). We conducted a retrospective cohort study to identify the prevalence, microbiology, and outcomes of secondary pneumonias and BSIs in patients hospitalized with COVID-19. Methods: Patients aged ≥18 years with a positive SARS-CoV-2 real-time polymerase chain reaction assay admitted to 4 academic hospitals in Atlanta, Georgia, between February 15 and May 16, 2020, were included. We extracted electronic medical record data through June 16, 2020. Microbiology tests were performed according to standard protocols. Possible ventilator-associated pneumonia (PVAP) was defined according to Centers for Disease Control and Prevention (CDC) criteria. We assessed in-hospital mortality, comparing patients with and without infections using the χ2 test. SAS University Edition software was used for data analyses. Results: In total, 774 patients were included (median age, 62 years; 49.7% female; 66.6% black). In total, 335 patients (43.3%) required intensive care unit (ICU) admission, 238 (30.7%) required mechanical ventilation, and 120 (15.5%) died. Among 238 intubated patients, 65 (27.3%) had a positive respiratory culture, including 15 with multiple potential pathogens, for a total of 84 potential pathogens. The most common organisms were Staphylococcus aureus (29 of 84; 34.5%), Pseudomonas aeruginosa (16 of 84; 19.0%), and Klebsiella spp (14 of 84; 16.7%). Mortality did not differ between intubated patients with and without a positive respiratory culture (41.5% vs 35.3%; P = .37). Also, 5 patients (2.1%) had a CDC-defined PVAP (1.7 PVAPs per 1,000 ventilator days); none of them died. Among 536 (69.3%) nonintubated patients, 2 (0.4%) had a positive Legionella urine antigen and 1 had a positive respiratory culture (for S. aureus). Of 774 patients, 36 (4.7%) had BSI, including 5 with polymicrobial BSI (42 isolates total). Most BSIs (24 of 36; 66.7%) had ICU onset. The most common organisms were S. aureus (7 of 42; 16.7%), Candida spp (7 of 42; 16.7%), and coagulase-negative staphylococci (5 of 42; 11.9%); 12 (28.6%) were gram-negative. The most common source was central-line–associated BSI (17 of 36; 47.2%), followed by skin (6 of 36; 16.7%), lungs (5 of 36; 13.9%), and urine (4 of 36; 11.1%). Mortality was 50% in patients with BSI versus 13.8% without (p < 0.0001). Conclusions: In a large cohort of patients hospitalized with COVID-19, secondary infections were rare: 2% bacterial pneumonia and 5% BSI. The risk factors for these infections (intubation and central lines, respectively) and causative pathogens reflect healthcare delivery and not a COVID-19–specific effect. Clinicians should adhere to standard best practices for preventing and empirically treating secondary infections in patients hospitalized with COVID-19.

Funding: No

Disclosures: None

Background: Antibiotics targeted against Clostridioides difficile bacteria are necessary, but insufficient, to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome. ECOSPOR-III evaluated SER-109, an investigational, biologically derived microbiome therapeutic of purified Firmicute spores for treatment of rCDI. Herein, we present the interim analysis in the ITT population at 8 and 12 weeks. Methods: Adults ≥18 years with rCDI (≥3 episodes in 12 months) were screened at 75 US and CAN sites. CDI was defined as ≥3 unformed stools per day for <48 hours with a positive C. difficile assay. After completion of 10–21 days of vancomycin or fidaxomicin, adults with symptom resolution were randomized 1:1 to SER-109 (4 capsules × 3 days) or matching placebo and stratified by age (≥ or <65 years) and antibiotic received. Primary objectives were safety and efficacy at 8 weeks. Primary efficacy endpoint was rCDI (recurrent toxin+ diarrhea requiring treatment); secondary endpoints included efficacy at 12 weeks after dosing. Results: Overall, 287 participants were screened and 182 were randomized (59.9% female; mean age, 65.5 years). The most common reason for screen failure was a negative C. difficile toxin assay. A significantly lower proportion of SER-109 participants had rCDI after dosing compared to placebo at week 8 (11.1% vs 41.3%, respectively; relative risk [RR], 0.27; 95% confidence interval [CI], 0.15–0.51; p-value <0.001). Efficacy rates were significantly higher with SER-109 vs placebo in both stratified age groups (Figure 1). SER-109 was well-tolerated with a safety profile similar to placebo. The most common treatment-emergent adverse events (TEAEs) were gastrointestinal and were mainly mild to moderate. No serious TEAEs, infections, deaths, or drug discontinuations were deemed related to study drug. Conclusions: SER-109, an oral live microbiome therapeutic, achieved high rates of sustained clinical response with a favorable safety profile. By enriching for Firmicute spores, SER-109 achieves high efficacy while mitigating risk of transmitting infectious agents, beyond donor screening alone. SER-109 represents a major paradigm shift in the clinical management of patients with recurrent CDI. Clinicaltrials.gov Identifier NCT03183128. These data were previously presented as a late breaker at American College of Gastroenterology 2020.

Funding: Seres Therapeutics

Disclosures: None

Figure 1.

In total, 13 facilities changed C. difficile testing to reflexive testing by enzyme immunoassay (EIA) only after a positive nucleic acid-amplification test (NAAT); the standardized infection ratio (SIR) decreased by 46% (range, −12% to −71% per hospital). Changing testing practice greatly influenced a performance metric without changing C. difficile infection prevention practice.

Background: High-level personal protective equipment (PPE) protects healthcare workers (HCWs) during the care of patients with serious communicable diseases. Doffing body fluid–contaminated PPE presents a risk of self-contamination. A study assessing HCW failure modes and self-contamination with viruses during PPE doffing found that, of all PPE items, the highest number of doffing failure modes and highest self-contamination risk occurred during removal of the 1-layer powered air-purifying respirator (PAPR) hood. Hood type may affect contamination risk; however, no experimental evidence exists comparing hood types. Objective: We quantified and compared the risk of self-contamination with viruses during doffing of a 1e-layer versus a 2-layer PAPR hood. Methods: In this study, 8 HCWs with experience using high-level PPE donned PPE contaminated on 4 prespecified areas with 2 surrogate human viruses, bacteriophage MS2 (a nonenvelope virus) and Φ6 (an enveloped virus). They completed a clinical task then doffed PPE according to a standard protocol. Following doffing, inner gloves, hands, face, and scrubs were sampled for viral contamination using infectivity assays. HCWs performed the entire sequence twice, first with a 1-layer hood with 1 shroud then with a 2-layer hood with 2 shrouds. The Wilcoxon rank-sum test was used to compare viral contamination between the 2 hood types. HCWs were video-recorded to identify failure modes in their doffing process using a failure modes and effects analysis to identify ways that individual actions deviated from optimal behavior. Results: Φ6 transfer to hands, inner gloves, and scrubs were observed for 1 HCW using the 1-layer hood versus scrubs only for 1 HCW using the 2-layer hood. MS2 transfer to hands was observed for 2 HCWs using the 1-layer hood versus none using the 2-layer hood. Inner glove contamination was observed for 6 of 8 HCWs using the 1-layer hood versus 2 of 8 using the 2-layer hood. Conclusions: A significantly higher number of MS2 virus was recovered on the inner gloves of HCWs using the 1-layer versus the 2-layer hood (median difference, 2.27×104; P = .03). In addition, 31 failure modes were identified during removal of the 2-layer hood versus 13 failure modes for the 1-layer hood. The magnitude of self-contamination depends on the type of PAPR hood used. The 2-layer hood resulted in significantly less inner glove contamination than the 1-layer hood. However, more failure modes were identified during the doffing process for the 2-layer hood. In conclusion, the failure modes identified during the use of the 2-layer hood were less likely to result in self-contamination compared to the failure modes identified during use of the 1-layer hood.

Funding: None

Disclosures: None

Background: US hospitals are required to report C. difficile infections (CDIs) to the NHSN as a performance measure tied to payment penalties for poor scores. Currently, only the charted CDI test results performed last in reflex testing scenarios are reported to the NHSN (CDI events). We describe the reduction in NHSN CDI events from the addition of a reflex toxin enzyme immunoassay (EIA) after a positive nucleic acid amplification test (NAAT) in teaching and nonteaching hospitals, and we estimate the impact on standardized infection ratios (SIR). Methods: Reporting of all CDI test results, by test method, occurred during April 2018–July 2019 to the Georgia Emerging Infections program (funded by the Centers for Disease Control and Prevention), which conducts active population-based surveillance in an 8-county Atlanta area (population, 4 million). Among facilities starting reflex EIA testing, results were aggregated by test method during months of reflex testing to calculate facility-specific reduction in NHSN CDI events (% reduction; 1-[no. EIA+/no. NAAT+]). Differences in percent reduction between facilities by characteristic were compared using the Kruskal-Wallis test. We simulated expected changes in the SIR for a range of reductions, assuming equal effect on both community-onset (CO) and hospital-onset (HO) tests. Each facility’s historical NHSN CDI events prior to reflex testing were used to estimate changes to facility-specific SIRs by reducing values by the corresponding facility’s percent reduction. Results: Overall, 13 acute-care hospitals (bed size, 52–633; ICU bed size, 6–105) started reflex testing during the study period (mean, 7 months, 15,800 admissions, 66,400 patient days), resulting in 550 +NAAT tests reflexing to 180 +EIA tests (pooled mean 58% reduction). Percent reduction varied (mean, 67%; range, 42%–81%) but did not differ between larger (≥217 beds) and smaller hospitals (61 vs 50% reduction; P > .05) or by outsourced versus inhouse testing (65% vs 54% reduction; P > .05). Simulations identified a threshold reduction at which point effect on HO counteract the effects on CO events enough to reduce the SIR; thresholds for nonteaching and teaching were 26% and 32% reduction, respectively (Fig. 1). The estimated reductions in facility-specific SIRs using measured percent reductions on historic NHSN CDI events closely paralleled the simulation, and the mean estimated change in SIR was −46% (range, −12% to −71%) (Fig. 1). Conclusions: Although the magnitude of the effect varied, all 13 facilities experienced dramatic reductions in CDI events reportable to NHSN due to reflex testing; applying these reductions to historical NHSN data illustrates anticipated reductions in their facility-specific SIRs due to this testing change.

Funding: None

Disclosures: Scott Fridkin, consulting fee, vaccine industry (various) (spouse)