We report the complete genome sequence of a clinical isolate of Providencia stuartii strain CMC-4104, isolated from a splenic abscess. Oxford Nanopore Technologies (ONT) and Illumina sequencing reads were assembled using Geneious to generate a 4,504,925-bp circular chromosome containing multiple copies of the NDM-1 and PER-1 genes in a genomic resistance island.

Introduction This study aimed to evaluate the clinical and economic outcomes of implementing a Clostridiodes difficile infection (CDI) Treatment Optimization and Access Pathway (treatment pathway) directing first-line use of fidaxomicin for CDI. Methods This was a retrospective, quasi-experimental study of adult patients with CDI using Electronic Health Record data from a single center. The primary intervention was implementation of a treatment pathway directing first-line use of fidaxomicin for patients with first/second CDI episode and at high risk of recurrence. The primary clinical outcome was CDI recurrence within 30 days of completing therapy in patients achieving clinical cure. Secondary clinical outcomes included clinical cure and sustained response evaluated at 90 days after completion of CDI treatment. Economic outcomes included costs associated with hospital stay at index admission and 30- and 90-day readmission. Differences between the pre- and post-implementation cohorts were assessed for baseline characteristics, CDI treatment utilization, clinical outcomes, and economic outcomes. The budget impact was calculated for the pre- vs. post-implementation cohorts, each normalized to 100 patients. Results Post- vs. pre-implementation, 30-day recurrence (6.4% vs. 18.0%., p = 0.001), 90-day recurrence (14.9% vs. 27.1%, p = 0.009), and 30-day (4.6% vs. 12.7%, p = 0.007) and 90-day CDI-related readmissions (8.5% vs. 18.9%, p = 0.007) were lower. The clinical cure (94.1% vs. 84.4%, p = 0.002) and 90-day sustained response rates were higher (73.3% vs. 55.9%, p < 0.001). Median total costs were also lower in the post- vs. pre-implementation cohorts at index admission ($11,934.64 vs. $14,523.27, p = 0.048), and 30-day ($7685.82 vs. $12,424.44, p = 0.102) and 90-day CDI-related readmission episodes ($8246.69 vs. $12,729.57, p = 0.042). The budget impact analyses of 100 patients post- vs. pre-implementation found saving of $222,895 overall and $9432 per CDI-readmission avoided. Conclusions Implementation of the CDI treatment pathway was associated with better clinical outcomes and hospital cost savings. The findings help validate real-world value of fidaxomicin for CDI disease management.

Providencia stuartii (Ps) is a clinically significant opportunistic pathogen often associated with “difficult-to-treat resistance” (DTR) infections due to pan-resistance to first-line antimicrobials. We report the clinical diagnosis and rapid genomic characterization of strain Ps-CMC-4104, recovered from a human splenic abscess in a patient with infected necrotizing pancreatitis. To resolve the complex genetic architecture of this strain, we utilized hybrid sequencing combining Oxford Nanopore (long-read) and Illumina (short-read) technologies. Analysis revealed a 4,504,925 bp circular chromosome featuring a unique genomic resistance island (GRI) closely related to Salmonella SGI1. Notably, the PsGRI contains multiple copies of NDM-1 and PER-1 carbapenem-resistance and -inhibitor genes, a repetitive structure typically unresolvable by standard short-read methods. Additionally, a large 278,489 bp low-copy circular plasmid harbored single copies of these carbapenemase and extended-spectrum β-lactamase genes alongside other antimicrobial resistance determinants and ISCR1 insertion sequences. Nanopore technology allowed us to precisely identify the duplications, providing critical insights into the strain’s pan-resistant phenotype. This study serves as proof-of-concept for the importance of integrating long-read sequencing into clinical workflows to identify complex resistance mechanisms in DTR pathogens, facilitating targeted antimicrobial stewardship and infection control.

Background: Clostridioides difficile infection (CDI) causes a significant national health care burden. Literature has demonstrated lower rates of CDI recurrence with fidaxomicin compared with oral vancomycin. However, patients are sometimes switched to oral vancomycin before completing a fidaxomicin course. Objective: The objective of this study is to evaluate rates of CDI recurrence in full courses of fidaxomicin versus partial courses of fidaxomicin followed by a switch to oral vancomycin. Methods: In this single-center, retrospective, cohort study of adults with CDI, patients were screened for inclusion if they received either a full 10-day course of fidaxomicin or partial course of fidaxomicin followed by a switch to oral vancomycin. The primary outcome was the rate of CDI recurrence within 30 days after completion of initial therapy determined by a positive CDI test and initiation of treatment. Results: Ninety-nine patients received a full course of fidaxomicin, and 95 patients received a partial course of fidaxomicin followed by oral vancomycin. Mean age was lower in the full course group compared with the partial course (65.3 years vs 71.5 years, P < 0.002). Clostridioides difficile infection recurrence occurred in 5.1% of the full course group and 7.4% of the partial therapy group ( P = 0.503) at 30 days and 13.1% versus 14.7% ( P = 0.747) at 90 days. Clostridioides difficile infection–related readmissions at 30 days were similar in the full course and partial course groups (7.1% vs 4.2%, P = 0.389). Conclusion and Relevance: Partial courses of fidaxomicin followed by oral vancomycin had similar 30-day CDI recurrence compared with full course fidaxomicin.