The coronavirus disease 2019 (COVID-19) pandemic negatively affected antimicrobial stewardship programs at hospitals throughout Japan by diverting resources toward managing the pandemic. However, antimicrobial stewardship needs to continue regardless of hospital size or supervening crises. Herein, we discuss the impact of COVID-19 on antimicrobial stewardship at a small, local hospital in Japan.

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

Background: COVID-19 has presented hospitals with unique challenges. An SHEA Research Network survey showed that 40% reported “limited” or worse levels of personal protective equipment (PPE) and that 13% were self-producing PPE to address those deficits, including 3D-printed items. However, we do not know how efficiently, if at all, 3D-printed materials can be disinfected. Additionally, 2 filaments, PLACTIVE and PUREMENT, claim to be antimicrobial; they use copper nanocomposites and silver ions to reduce bacterial populations. We assessed how PLACTIVE and PUREMENT may be contaminated and how well they reduce contamination, and how readily polylactic acid (PLA), a standard 3D-printed material, may be disinfected. Methods: We grew methicillin-resistant and -susceptible Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae on 3D-printed disks and conducted bacterial survival assays to determine whether bacteria grow on PLA, PLACTIVE, and PUREMENT. We performed a time series (with 3- and 24-hour dry times) followed by serial dilutions to attain colony-forming unit (CFU) averages for each strain per disk. To determine whether 3D-printed material can be cleaned, we used 70% EtOH on PLA only. We conducted the same time series followed by a disinfectant time series (with dry times 30 seconds, 2.5, minutes, 5 minutes, and 10 minutes). Again, serial dilutions were performed to attain the PLA CFU averages with disinfectant. The CFU averages from the control group (PLA) and testing group (PLACTIVE and PUREMENT) were compared to see how well the antimicrobial material decreased bacterial load. We also compared the CFU averages of PLA with and without disinfectant to see how well 70% EtOH decreased bacterial load. Results: 3D-printed material is readily contaminated with bacteria common in hospitals and can sustain that contamination. Antimicrobial materials, PLACTIVE and PUREMENT, had lower levels of bacterial contamination when compared to PLA. However, disinfected disks had lower overall CFU averages than those that were not, but the level of disinfection was variable and bacterial populations recovered hours after disinfection application. Conclusions: Proper disinfection and using appropriate 3D-printed materials are essential to limiting bacterial contamination. 3D printers and their products can be invaluable for hospitals, especially when supplies are low and healthcare worker safety is paramount. Environmental services should be made aware of the presence of antimicrobial 3D-printed materials, and patients should be discouraged from printing their own items for use in hospital environments.

Disclosures: None

We surveyed clinicians to evaluate the perceived usefulness of a mnemonic, STORY, to improve penicillin allergy evaluation. Survey responses indicated that the perceived usefulness of STORY was high, and support for nurses’ involvement in penicillin allergy assessment was high. Future research may evaluate the feasibility of STORY implementation in clinical care.

Group Name: Duke Center for Antimicrobial Stewardship and Infection Prevention

Background: Wastewater drains in hospital patient rooms have been identified as environmental reservoirs for multidrug-resistant organisms, and they have been linked to outbreaks of carbapenem-resistant Enterobacteriaceae (CRE). We studied the colonization of wastewater drains in a new hospital bed tower. Methods: A patient care unit in a new bed tower opened on July 18, 2020. In-room sinks were located in each hospital room opposite the patient head wall. Patients admitted to this unit underwent weekly rectal cultures to survey for carbapenemase-producing CRE. Additionally, infection preventionists performed routine surveillance of all clinical cultures for CRE. Cultures were performed from all patient room sinks in this unit monthly beginning September 14, 2020. Samples were obtained from the drain cover, handles, and top of bowl using sponges soaked in neutralizing buffer and processed using the stomacher technique. The tail-pipe was sampled using a flocked mini-tip swab soaked in neutralizing buffer; the P-trap water was sampled with sterile tubing attached to a 50-mL syringe. All samples were plated on HARDYCHROM-ESBL and KPC Colorex media and were incubated at 37°C for 24 hours. Results: The first identified CRE-positive patient was admitted to the new unit on December 4, 2020; urine culture obtained at the time of admission grew KPC–producing Klebsiella pneumoniae (KPC-KP). The sink in this patient’s room had been sampled 3 prior times (most recently on November 9, 2020) and was negative for CRE. On December 7, 2020, KPC-KP was found on the drain cover (6,750 colony-forming units, CFU) and in the sink’s P-trap (1,840 CFU) of the index patient’s room during routine sink surveillance. Additional samples from other room surfaces were taken on December 9, 2020, and KPC-KP was recovered from the computer keyboard (452 CFU) and patient bedrails (880 CFU). The patient was discharged from this room December 13, 2020, and the room underwent enhanced terminal room cleaning including UV-C light. On the next routine sink sampling on January 4, 2021, KPC-KP was recovered again in the index room sink P-trap (9,800 CFU) but at no additional sites. MLST was performed, and all isolates were ST-258. Conclusions: In a new bed tower with no prior evidence of CRE-positive patients, the first identified case of a CRE (KPC-KP) in a patient resulted in widespread environmental contamination of the room after only 3 days of hospitalization and contamination of the in-room sink drain that persisted after 1 month. Given the ease with which CRE colonizes wastewater drains, new strategies are needed to mitigate drain colonization and to prevent CRE transmission to subsequent patients.

Funding: No

Disclosures: None

We surveyed healthcare professionals at a cancer center regarding their knowledge and perceptions of antibiotic use. Most knew the term “antimicrobial stewardship.” Nurses and other staff were less likely than pharmacists or providers to answer knowledge-based questions correctly. Opportunities exist to improve antibiotic knowledge among cancer center staff.

Background: Clinical pharmacists are a critical part of antibiotic stewardship. Stewardship often relies on relationships and persuasion, which may be affected by gender bias. Thus, we aimed to assess the association of sex with the acceptance of antibiotic stewardship recommendations. Methods: Between May and October 2019, medicine pharmacists at single hospital reviewed patients on antibiotics and–when a discharge was anticipated–led an antibiotic discussion (or “timeout”) prior to discharge. To explore differences in antibiotic timeout effectiveness by gender, we assessed the association of pharmacist sex with suggestion and acceptance of antibiotic changes using logistic regression controlling for patient characteristics. We also assessed whether hospitalist sex was associated with or moderated the effect of pharmacist sex on acceptance of timeout recommendations. Results: Between May 1, 2019, and October 31, 2019, pharmacists conducted 295 timeouts (patient characteristics in Fig. 1). Overall, 54% of timeouts were conducted by 12 female pharmacists and the remaining 46% were conducted by 8 male pharmacists. Overall, 82 (29%) of 295 timeouts resulted in a pharmacist recommending an antibiotic change, and male pharmacists were more likely to recommend a change: 52 (38%) of 137 versus 30 (19%) 158 (P Conclusions: In this discharge antibiotic intervention, timeouts conducted by women were less likely to result in an antibiotic change than those conducted by men. The difference in effectiveness resulted both from female pharmacists being less likely to recommend a change and from hospitalists being less likely to accept recommendations from a female pharmacist. These findings suggest that gender bias may play a role acceptance of antibiotic stewardship recommendations, which could affect antibiotic use, pharmacist job satisfaction, and patient outcomes.

Funding: None

Disclosures: None

Background: Sink drains can act as breeding grounds for multidrug-resistant (MDR) bacteria, leading to outbreaks. Drains provide a protected humid environment where nutrient-rich substances are available. Recent and growing installation of water and energy conservation devices have led to increased frequency of drain blockage due to biofilm accumulation. Ineffective drainage may lead to backflow and accumulation of water in the sink during use, increasing the risk of contaminated aerosols formation or direct contamination of surrounding material and equipment. Cleaning and disinfection procedures of sink drains need to be improved to prevent amplification and dispersion of MDR bacteria. The objective of this study was to investigate alternatives to reduce the biofilm and risk of contamination through aerosols. Methods: Sink drains from patient rooms were randomly selected in the neonatal intensive care unit of a 450-bed pediatric hospital. We tested 4 approaches: (1) new drain; (2) self-disinfecting heating-vibration drain; (3) chemical disinfection with 20 ppm chlorine for 30 minutes; and (4) thermal disinfection with > 90°C water for 30 minutes. A special device was used during disinfection to increase the disinfectant contact time with the biofilm. Treatments were conducted weekly, with prior sampling of drain water. Other drains were also sampled weekly, including a control drain with no intervention. Bacterial loads were evaluated using flow cytometry and heterotrophic plate counts. The drains were made of stainless steel, a heat-conductive material. Results: Preliminary results show that chlorine disinfection had a small impact (<1 log) on culturable bacteria at 48 hours after disinfection but not after a week or repeated weekly disinfection. Thermal disinfection using boiling water is promising, showing an important decrease of 4 log in culturable cells after 48 hours and a concentration still 100× lower 1 week after the disinfection. Repeated weekly thermal disinfection maintained lower culturable levels in the drain. No culturable cells were detected in water from the self-disinfecting drain 2 months after installation, whereas the new drain became fully colonized to concentrations similar to those of drains prior to interventions during the same period. Conclusions: Thermal disinfection of drains is a promising alternative to chlorine. This solution is interesting because it is nontoxic and easy to perform, requiring a small volume of hot water. The rapid recolonization of the new drain suggests that replacing contaminated drains is not a sustainable solution and would need to be paired with a thermal disinfection program to maintain low culturable cells.

Funding: No

Disclosures: None

A cluster of Rhizobium radiobacter isolates isolated from six unique surgical tissue cultures prompted an investigation ultimately identifying a pseudo-outbreak linked to errant laboratory tissue processing with contaminated, nonsterile saline. Timely response and multidisciplinary collaboration led to tangible system-level interventions and avoidance of unnecessary antibiotic exposures.

Objectives: Antimicrobial resistance is a serious threat to health and economic well-being worldwide. The impact of antibiotic-resistant infections is reflected by higher mortality, increased lengths of hospital stay (LOS), and increased healthcare costs. We analyzed the direct healthcare costs attributable to treating patients infected with methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacterales (CRE) in a tertiary-care referral hospital in Vietnam. Methods: A retrospective descriptive cross-sectional study was conducted in an intensive care unit (ICU) in the University Medical Center in Ho Chi Minh City from June 2018 to September 2019. Participants were ICU patients diagnosed with either MRSA or CRE infection, and patients infected with non–multidrug-resistant organisms (non-MDROs) were used as the comparison group. Medical records were obtained to collect data on medical services expenditures such as medications, diagnostic testing, medical procedures, and hospital rooms. Statistical significance was determined using the Mann-Whitney and Kruskal-Wallis tests for comparing the average costs and the χ2 test for comparing the proportions. Results: In total, 227 patients, including 37 MRSA-infected patients, 97 CRE-infected patients, and 93 non–MDRO-infected patients, were included in the study. The additional average healthcare costs for a treatment episode of a CRE infection case (367.7 million VND or ~US $16,000) and of a MRSA infection case (139.1 million VND or ~US $6,043) were 3.8 times higher (P < .001) and 1.5 times higher (P < .001), respectively, than the average cost for a non-MDRO case (94.8 million VND or ~US $4,121). Resource use for a CRE infection was higher than that for MRSA infection, with longer antibiotic treatment (13.4 additional days), greater LOS (15.8 additional days), and higher costs (additional 228.6 million VND or ~US $9,939). Conclusions: Multidrug-resistant infections create a heavy economic burden in a low- to middle-income country like Vietnam. The elevated cost was mainly due to longer antibiotic treatment and increased LOS.

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.

Background: Antibiotic overuse and the resulting patient outcomes span all hospitals. However, although antibiotic stewardship can improve antibiotic use, effective stewardship programs require expertise and an infrastructure that are not present in all hospitals. Rural hospitals have less access to resources, infectious disease expertise, and participation in academic research. Thus, we compared antibiotic overuse at discharge between rural and nonrural hospitals for patients diagnosed with community-associated pneumonia (CAP) or urinary tract infection (UTI)—the 2 most common hospital infections. Methods: To determine whether antibiotic overuse at discharge was higher among rural versus nonrural hospitals, we analyzed data from a 41-hospital prospective cohort of patients treated for CAP or UTI between July 1, 2017, and July 30, 2019, in Michigan. Antibiotic overuse was defined as treatment that was unnecessary (ie, patient did not have an infection), excessive (ie, duration >4 days for CAP), or included suboptimal fluoroquinolone use (ie, safer alternative available). Overuse was determined based on patient risk factors, symptoms, allergies, diagnostic results, and time to stability. Hospital rurality was defined using the Rural–Urban Continuum Codes (RUCC) score. We defined rural as a score ≥4 and very rural as a score of 7–9. We used t tests to compare the mean percentage of patients with antibiotic overuse at discharge between nonrural and rural (and very rural) hospitals. Results: Across 41 hospitals, we included 23,449 patients with CAP or UTI. There were 5 rural (and 3 very rural) hospitals with 2,039 (and 1,082) patients. Antibiotic overuse at discharge was present in 43.1% of patient cases in nonrural hospitals, 52.5% in rural hospitals (P = .04 vs nonrural) and 58.1% in very rural hospitals (P = .007 vs nonrural). Compared to nonrural hospitals, the mean percentage of cases with antibiotic overuse at discharge in rural hospitals was 9.4% higher (15.1% higher in very rural hospitals). Results were similar in a subgroup analysis of only patients with UTI (47.0% in rural vs 37.5% in nonrural, mean difference, 9.5%; P = .03) but were not statistically significant in patients with CAP (53.8% vs 48.0%, respectively; mean difference, 5.8%; P = 0.23). Conclusions: In this retrospective study, rural hospitals—especially very rural hospitals, had higher rates of antibiotic overuse at discharge than nonrural hospitals. Our findings suggest that antibiotic stewardship interventions tailored toward the unique differences in infrastructure, resources, and needs of rural hospitals are essential to community health.

Disclosures: None

We evaluated the impact of preliminary blood-culture antibiotic susceptibility testing on time to optimal antibiotic therapy in a cohort of 503 patients with monomicrobial bloodstream infections. The median time from blood-culture collection to optimal antibiotics was 17 hours earlier in the preliminary antibiotic susceptibility testing group.

Background: Pediatric patients often require central venous catheters (CVCs) for a variety of clinical indications, including medication administration, parenteral nutrition, and venous blood sampling. Patients with CVCs are at risk for central-line–associated bloodstream infections (CLABSI). These hospital-acquired infections are often preventable and may lead to increased morbidity and mortality. Clinicians at a 477-bed, freestanding pediatric academic hospital completed a quality improvement project to identify factors that place pediatric patients at increased risk for CLABSI and to outline strategies aimed at CLABSI reduction for our highest-risk patients. Methods: Project leaders completed a literature review to evaluate current research on the topic and then assembled a project team. The team completed a retrospective analysis and categorization of CLABSI cases and reviewed internal CLABSI root-cause analysis data. The group then completed a case–control analysis to identify risk factors in patients with CVCs who developed CLABSIs, compared to patients with CVCs who did not develop CLABSI. Following this analysis, the team created a CLABSI risk-factor tool for use by bedside nurses. This tool described patients with CLABSI risk factors and outlined best practices for CLABSI prevention. Results: Based upon literature review, root-cause analysis data, and retrospective CLABSI case review over the period from 2017 to 2021, an initial list of 9 potential CLABSI risk factors was compiled. A case–control analysis was performed comparing 97 CLABSI cases with 103 matched controls. Univariate, multivariate, and additional covariate analyses were employed to identify 3 factors placing pediatric patients at increased risk for CLABSI. These included (1) multiple enteral devices (ie, 2 or more devices, including gastrostomy tube, jejunostomy tube, gastrostomy or jejunostomy tube, ostomy, and peritoneal drain); (2) multiple CVC entries (ie, CVC used for medications and venous sampling); and (3) long-term CVC plus parenteral nutrition (CVC in place for >21 days and receiving parenteral nutrition and/or intralipids). Conclusions: Pediatric patients with central venous access are vulnerable to CLABSI, and certain patients may be at increased risk. Frontline clinicians may be able to identify these patients and adopt best practices to prevent infection. A tool for use by bedside nurses can be a useful adjunct to existing CLABSI prevention practices.

Disclosures: None

Background: Patients with recurrent urinary tract infections (rUTI) experience frequent exposure to antimicrobial regimens, leaving them at higher risk for developing antibiotic resistance. Little information on the prevalence of antibiotic resistance among patients with rUTI has been published. Although the IDSA recommends using a prior culture to guide empiric treatment, studies have not examined the predictive ability of a prior culture among patients meeting rUTI criteria. We constructed an antibiogram and evaluated test metrics, including sensitivity, specificity, and positive predictive value (PPV) and negative predictive values (NPV) of a prior culture (any organism), on predicting resistance (PPV) or susceptibility (NPV) of a future culture among patients with uncomplicated rUTI in an outpatient setting. Methods: We retrospectively extracted electronic health record data from outpatients aged ≥18 years who had an ICD-10 code for cystitis listed twice in 6 months or thrice in 12 months between November 1, 2016, and December 31, 2018. Patients sought care at either urology or primary care practices within an academic medical center in Houston, Texas. Patients with functional or structural abnormalities of the genitourinary tract, signs or symptoms of pyelonephritis, or pregnancy were excluded. Antibiogram data were reported for uropathogens with ≥30 isolates, and intermediate results were considered resistant. Test metrics and Bayes’ PPV and NPV were calculated using standard formulas. Results: We included 597 visits from 232 unique patients. Most were White (63%) and female (92%), and the cohort had a median age of 58 (IQR, 41–68). Among 310 rUTI episodes with a urine culture, 189 (61%) had at least 1 uropathogen isolated, and Escherichia coli (n = 130, 66%) was most common among all 196 uropathogens. E. coli isolates had >20% resistance to 10 of 18 antibiotics (Fig. 1). E. coli resistance to ciprofloxacin was 27.9%, resistance to nitrofurantoin was 5.5%, and resistance to trimethoprim-sulfamethoxazole was 38.0%. The PPVs for predicting resistance were highest for ceftriaxone (0.86; 95% CI, 0.60–0.96), ciprofloxacin (0.84; 95% CI, 0.63–0.94), and levofloxacin (0.84; 95% CI, 0.63–0.94). NPVs of resistance were highest for gentamicin (0.97; 95% CI, 0.83–1.00), ceftriaxone (0.94; 95% CI, 0.86–0.98), and cefepime (0.94; 95% CI, 0.84–0.98), whereas NPVs for cefuroxime, ciprofloxacin, levofloxacin, and nitrofurantoin were all >0.83. Conclusions: We detected considerable antibiotic resistance among patients with rUTI to commonly prescribed antibiotics. Prior urine culture susceptibility demonstrated moderate-to-high PPVs for predicting future resistance to ceftriaxone and fluoroquinolones as well as high NPVs for several cephalosporins and fluoroquinolones, which could inform empiric prescribing choices.

Funding: This investigator-initiated research study was funded by Rebiotix, a Ferring Company.

Disclosures: None