Transmission of bacteria between animals and humans in domestic households is increasingly recognized. We evaluated the presence of antimicrobial-resistant fecal bacteria in 8 dog-owner–dog pairs before and after the dog received amoxicillin-clavulanate. The study identified shared flora in the humans and dogs that were affected by antimicrobial administration.

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

Background: Clinical antibiotic susceptibility testing (AST) interpretations based on minimum inhibitory concentrations (MIC) breakpoints are important for both clinical decision making and some reportable condition criteria. Standardization of MIC breakpoints across clinical laboratories is lacking; AST instruments are often validated for outdated Clinical and Laboratory Standards Institute (CLSI) MIC breakpoint guidelines. In this study, we analyzed the agreement between the reported clinical laboratory AST interpretations and the guideline CLSI interpretation. Methods: Clinical laboratory AST data collected from the Multisite Gram-Negative Surveillance Initiative (MuGSI) carbapenem-resistant Enterobacterales (CRE) surveillance program in Tennessee between 2019 and 2021 were utilized. MIC values from the clinical instrument were used to calculate CLSI standard interpretations following the 2019–2021 CLSI M100 guidelines. Agreement between the clinical laboratory and CLSI interpretations of the reported MIC values were measured using a weighted Cohen κ calculated in SAS version 9.4 software. Total matches were isolates with identical CLSI and clinical laboratory interpretations. Results: In total, 14 antibiotics were assessed. Of those, 9 antibiotics had at least moderate agreement (κ > 0.41) between interpretations. Agreement between the clinical laboratory and the CLSI interpretations were near perfect (κ > 0.81) for 3 antibiotics. Agreement between the clinical laboratory and the CLSI interpretations were poor for cefazolin (0.06) and ertapenem (0.14). Cefotaxime (−0.07) was the only antibiotic that suggested no agreement. Conclusions: Of the antibiotics included in the analysis, 36% had less than moderate agreement between clinical laboratory and CLSI AST interpretations. Given the increases in antimicrobial resistance globally and the emphasis placed on antibiotic stewardship, standardization across clinical AST panels should be prioritized. Inconsistencies have the potential to contribute to inappropriate antibiotic use in addition to under- or overidentification of reportable conditions, including CRE.

Disclosures: None

Background: Blood cultures are commonly ordered for patients with low risk of bacteremia. Liberal blood-culture ordering increases the risk of false-positive results, which can lead to increased length of stay, excess antibiotics, and unnecessary diagnostic procedures. We implemented a blood-culture indication algorithm with data feedback and assessed the impact on ordering volume and percent positivity. Methods: We performed a prospective cohort study from February 2022 to November 2022 using historical controls from February 2020 to January 2022. We introduced the blood-culture algorithm (Fig. 1) in 2 adult surgical intensive care units (ICUs). Clinicians reviewed charts of eligible patients with blood cultures weekly to determine whether the blood-culture algorithm was followed. They provided feedback to the unit medical directors weekly. We defined a blood-culture event as ≥1 blood culture within 24 hours. We excluded patients aged <18 years, absolute neutrophil count <500, and heart and lung transplant recipients at the time of blood-culture review. Results: In total, 7,315 blood-culture events in the preintervention group and 2,506 blood-culture events in the postintervention group met eligibility criteria. The average monthly blood-culture rate decreased from 190 blood cultures per 1,000 patient days to 142 blood cultures per 1,000 patient days (P < .01) after the algorithm was implemented. (Fig. 2) The average monthly blood-culture positivity increased from 11.7% to 14.2% (P = .13). Average monthly days of antibiotic therapy (DOT) was lower in the postintervention period than in the preintervention period (2,200 vs 1,940; P < .01). (Fig. 3) The ICU length of stay did not change before the intervention compared to after the intervention: 10 days (IQR, 5–18) versus 10 days (IQR, 5–17; P = .63). The in-hospital mortality rate was lower during the postintervention period, but the difference was not statistically significant: 9.24% versus 8.34% (P = .17). The all-cause 30-day mortality was significantly lower during the intervention period: 11.9% versus 9.7% (P < .01). The unplanned 30-day readmission percentage was significantly lower during the intervention period (10.6% vs 7.6%; P < .01). Over the 9-month intervention, we reviewed 916 blood-culture events in 452 unique patients. Overall, 74.6% of blood cultures followed the algorithm. The most common reasons overall for ordering blood cultures were severe sepsis or septic shock (37%), isolated fever and/or leukocytosis (19%), and documenting clearance of bacteremia (15%) (Table 1). The most common indications for inappropriate blood cultures were isolated fever and/or leukocytosis (53%). Conclusions: We introduced a blood-culture algorithm with data feedback in 2 surgical ICUs and observed decreases in blood-culture volume without a negative impact on ICU LOS or mortality rate.

Disclosure: None

The standardized antibiotic administration ratio (SAAR) enables comparison of antibiotic use (AU) within and between hospitals and identifies target locations and antimicrobials for stewardship interventions. Thousands of institutions have already been submitting AU to the National Healthcare Safety Network. We highlight the benefits and meaningful utilization of SAAR in conjunction with antimicrobial stewardship interventions to improve antimicrobial prescribing in the clinical setting.

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.

Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) is a multidrug-resistant gram-negative bacteria (MDR-GNB) that is rapidly emerging as a life-threatening nosocomial disease in many countries. We sought to identify the risk factors associated with mortality for carriage of CRE in patients at a tertiary-care teaching hospital. Methods: A retrospective observational study was conducted between January 2020 to December 2021 in a tertiary-care teaching healthcare facility, University Malaya Medical Centre in Malaysia. The study included all inpatients aged ≥18 years who had a CRE infection or were colonized during the study period. The genotype was identified by polymerase chain reaction (PCR). Statistical analysis of data including a multivariate logistic regression analysis was conducted using SPSS version 23.0 software. Results: In total, 176 cases of CRE (130 infection and 46 colonized) were identified, and the mortality rate was 31.8%. The main sources of CRE were rectal swab (61.9%), blood (11.9%), and respiratory sources (11.9%). Klebsiella pneumoniae (55.7%) was the predominant species, followed by Escherichia coli (21.6%). Among the isolates, 17.7% were non–CPE-CRE and 82.3% were CPE-CRE: NDM (69.3%) and OXA (10.8%). In multivariate analysis, the factors associated with mortality were older age (OR, 1.040; 95% CI, 1.012–1.069), longer length of stay (OR, 0.974; 95% CI, 0.955–0.994), use of central venous catheter (OR, 0.287; 95% CI, 0.094–0.878), and arterial lines (OR, 0.292; 95% CI, 0.095–0.891). Conclusion: Patients with CRE had a high mortality rate. Older age, longer duration of stay, indwelling CVC and arterial line were independent risk factors for death. Infection prevention and control measures to reduce CRE, such as active surveillance, contact precautions, compliance to intravenous catheter care bundles, healthcare worker education, and hand hygiene adherence, should be implemented.

We examined the effect of an antimicrobial stewardship program (ASP), procalcitonin testing and rapid blood-culture identification on hospital mortality in a prospective quality improvement project in critically ill septic adults. Secondarily, we have reported antimicrobial guideline concordance, acceptance of ASP interventions, and antimicrobial and health-resource utilization.

In clinical settings where airborne pathogens, such as Mycobacterium tuberculosis, are prevalent, they constitute an important threat to health workers and people accessing healthcare. We report key insights from a 3-year project conducted in primary healthcare clinics in South Africa, alongside other recent tuberculosis infection prevention and control (TB-IPC) research. We discuss the fragmentation of TB-IPC policies and budgets; the characteristics of individuals attending clinics with prevalent pulmonary tuberculosis; clinic congestion and patient flow; clinic design and natural ventilation; and the facility-level determinants of the implementation (or not) of TB-IPC interventions. We present modeling studies that describe the contribution of M. tuberculosis transmission in clinics to the community tuberculosis burden and economic evaluations showing that TB-IPC interventions are highly cost-effective. We argue for a set of changes to TB-IPC, including better coordination of policymaking, clinic decongestion, changes to clinic design and building regulations, and budgeting for enablers to sustain implementation of TB-IPC interventions. Additional research is needed to find the most effective means of improving the implementation of TB-IPC interventions; to develop approaches to screening for prevalent pulmonary tuberculosis that do not rely on symptoms; and to identify groups of patients that can be seen in clinic less frequently.

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.