A self-selecting prophecy: prevalence of burnout in surgical fellows.

BACKGROUND: Burnout has become a prominent topic, yet there are limited data on the manifestation of this phenomenon among surgical fellows. The goal of this study is to elucidate the prevalence of burnout and determine if there are protective or predisposing factors in surgical fellowship training. METHODS: A confidential electronic survey was distributed to Fellowship Council accredited fellows during the 2020-2021 academic year. Demographic information and training characteristics were queried. The fellows were then asked to complete the Maslach Burnout Inventory (MBI), Perceived Stress Scale (PSS), Short Grit Scale (SGS), Satisfaction with Life Scale (SLS), and General Self-Efficacy Scale (SE). Data were analyzed using p values of ≤ 0.05 as statistically significant. RESULTS: At the end of the survey period, 92 out of 196 (46.9%) fellowship trainees responded. 69.6% of respondents identified as men, 29.7% as international medical school graduates (IMGs), and 15.3% non-US IMGs. Based on criteria defined by the MBI, there was an 8.4% rate of burnout. Most respondents noted low stress levels (62.3%), good satisfaction with life (58.9%), a moderate amount of grit, and a high level of self-esteem. On comparative analysis, fellows with burnout had significantly higher stress levels, lower levels of satisfaction with life, and less self-esteem. CONCLUSIONS: Overall, there was a low rate of burnout among fellows. We suggest this may be reflective of a self-selecting effect, as trainees who choose to undergo additional training may be less likely to experience this syndrome. In addition, there may be a protective factor during fellowship that results from inherent mentoring, increased specialization, and autonomy. Further investigation of the predisposing factors to burnout in fellowship trainees is warranted based on the results of this study.

Investigating Factors at Play in Hepatopancreatobiliary Fellowship Selection: Beliefs versus Reality.

BACKGROUND: Selection biases affecting candidate matches to fellowship programs directly influence diversity within the surgical community. The review of selection bias has never been distinctively investigated in the Hepatopancreatobiliary (HPB) surgery community. This study seeks to (i) evaluate factors affecting selection of candidates to HPB fellowships, (ii) examine explicit biases among program directors and faculty of HPB programs in North America, and (iii) compare the demography of the HPB faculty and recently graduated fellows to general surgery residents. STUDY DESIGN: An anonymous, self-reported survey consisting of 10 sets of fictional applications was distributed to 52 faculty members, including program directors, of AHPBA-affiliated HPB fellowships in North America. The respondents had to pick a preferred candidate between two abridged, fictional HPB fellow applications and give an open-ended response as to why they picked that candidate. The applications were nearly identical with one notable characteristic of interest. Demographic information of both faculty and their recent fellows was also collected. This survey was administered and collected between February and April, 2020. RESULTS: A total of 29 fully completed responses were received, comprising a 55.7% response rate. Respondents were 72.4% male, 69.0% Caucasian, and 79.3% held US medical degrees (MD). 50.0% of respondents preferred an MD candidate to a DO candidate, and 37% preferred US graduates to foreign-trained candidates. The respondents were unanimous in stating that gender, race, and family status were not a factor in their selection process. 5.0% said they would support an LGBTQ candidate when faced with otherwise similar applicants. Seventy-six HPB fellows from the past 5 years were 76.3% male, 56.6% Caucasian, and 51.3% US graduated Doctor of Medicine (US MD). CONCLUSION: This is the first study explicitly exploring the impact of demographic factors in the HPB fellowship selection process. The respondents unanimously and explicitly stated that race and gender do not play any role in their selection process. Yet, there is stark discordance between general surgery resident demographics and HPB fellow demographics. A greater effort to promote a more diverse HPB surgery community may be needed.

Overcoming the Arduous Transition for Robotic Hepatopancreatobiliary Cases: A Multi-Procedure Learning Curve Study Utilizing CUSUM Analysis.

BACKGROUND/OBJECTIVE: Quick optimization and mastery of a new technique is an important part of procedural medicine, especially in the field of minimally invasive surgery. Complex surgeries such as robotic pancreaticoduodenectomies (RPD) and robotic distal pancreatectomies (RDP) have a steep learning curve; therefore, findings that can help expedite the burdensome learning process are extremely beneficial. This single-surgeon study aims to report the learning curves of RDP, RPD, and robotic Heller myotomy (RHM) and to review the results' implications for the current state of robotic hepatopancreaticobiliary (HPB) surgery. STUDY DESIGN: This is a retrospective case series of a prospectively maintained database at a non-university tertiary care center. Total of 175 patients underwent either RDP, RPD, or RHM with the surgeon (DRJ) from January 2014 to January 2020. RESULTS: Statistical significance of operating room time (ORT) was noted after 47 cases for RDP (p < 0.05), 51 cases for RPD (p < 0.0001), and 18 cases for RHM (p < 0.05). Mean ORT after the statistical mastery of the procedure for RDP, RPD, and RHM was 124, 232, 93 min, respectively. No statistical significance was noted for estimated blood loss or length of stay. CONCLUSIONS: Robotic HPB procedures have significantly higher learning curves compared to non-HPB procedures, even for an experienced HPB surgeon with extensive laparoscopic experience. Our RPD curve, however, is quicker than the literature average. We suggest that this is because of the simultaneous implementation of HPB (RDP and RPD) and non-HPB robotic surgeries with a shorter learning curve-especially foregut procedures such as RHM-into an experienced surgeon's practice. This may accelerate the learning process without compromising patient safety and outcomes.

Frailty predicts worse outcomes after intracranial meningioma surgery irrespective of existing prognostic factors.

OBJECTIVE: Frailty has been recognized as a predictor of adverse surgical outcomes across multiple surgical disciplines, but until now the relationship between frailty and intracranial meningioma surgery has not been studied. The goal of the present study was to determine the relationship between increasing frailty (determined using the modified Frailty Index [mFI]) and intracranial meningioma resection outcomes (including hospital length of stay [LOS], discharge location, and reoperation and readmission rates). METHODS: This is a single-center retrospective cohort study of patients who underwent intracranial meningioma resection between August 2012 and May 2018. Seventy-six patients met the inclusion criteria. RESULTS: Frailty was associated with increased hospital LOS (p = 0.0218), increased reoperation rate (p = 0.029), and discharge to a higher level of care: an inpatient rehabilitation facility or a skilled nursing facility (p = 0.0002). After multivariable analysis, frailty was determined to be an independent risk factor for increased LOS, worse discharge disposition, and subsequent readmission. CONCLUSIONS: Frailty is an independent risk factor for worse outcomes following intracranial meningioma resection, including increased LOS, reoperations, and worse discharge disposition. Frailty may help stratify preoperative surgical risk, and thus may provide important clinical information to help neurosurgeons and elderly patients weigh the risks and benefits of resection.

Involving end-users in the design of an audit and feedback intervention in the emergency department setting - a mixed methods study.

BACKGROUND: Long length of stays (LOS) in emergency departments (ED) negatively affect quality of care. Ordering of inappropriate diagnostic tests contributes to long LOS and reduces quality of care. One strategy to change practice patterns is to use performance feedback dashboards for physicians. While this strategy has proven to be successful in multiple settings, the most effective ways to deliver such interventions remain unknown. Involving end-users in the process is likely important for a successful design and implementation of a performance dashboard within a specific workplace culture. This mixed methods study aimed to develop design requirements for an ED performance dashboard and to understand the role of culture and social networks in the adoption process. METHODS: We performed 13 semi-structured interviews with attending physicians in different roles within a single public ED in the U.S. to get an in-depth understanding of physicians' needs and concerns. Principles of human-centered design were used to translate these interviews into design requirements and to iteratively develop a front-end performance feedback dashboard. Pre- and post- surveys were used to evaluate the effect of the dashboard on physicians' motivation and to measure their perception of the usefulness of the dashboard. Data on the ED culture and underlying social network were collected. Outcomes were compared between physicians involved in the human-centered design process, those with exposure to the design process through the ED social network, and those with limited exposure. RESULTS: Key design requirements obtained from the interviews were ease of access, drilldown functionality, customization, and a visual data display including monthly time-trends and blinded peer-comparisons. Identified barriers included concerns about unintended consequences and the veracity of underlying data. The surveys revealed that the ED culture and social network are associated with reported usefulness of the dashboard. Additionally, physicians' motivation was differentially affected by the dashboard based on their position in the social network. CONCLUSIONS: This study demonstrates the feasibility of designing a performance feedback dashboard using a human-centered design approach in the ED setting. Additionally, we show preliminary evidence that the culture and underlying social network are of key importance for successful adoption of a dashboard.

Evaluation of a Digital Diabetes Prevention Program Adapted for Low-Income Patients, 2016-2018.

INTRODUCTION: We examined the effects of a digitally delivered, type 2 diabetes mellitus prevention program (DPP) for a low-income population. METHODS: We conducted a nonrandomized clinical trial with matched controls. The intervention group was offered a digital DPP, a web-based and mobile-based program including 52 weeks of participation in an educational curriculum, health coaching, and peer support. RESULTS: A total of 227 participants enrolled. At baseline, 34.6 was the mean body mass index, and 5.8 was the mean HbA1c. For the intervention group, mean weight loss was 4.4% at the 12-month follow-up. CONCLUSION: The modified DPP successfully engaged participants and resulted in weight loss. Low-income patients with prediabetes benefitted from a digitally delivered diabetes intervention. This prevention method should be accessible to a low-income population.

Site-specific DNA-antibody conjugates for specific and sensitive immuno-PCR.

Antibody conjugates are widely used as diagnostics and imaging reagents. However, many such conjugates suffer losses in sensitivity and specificity due to nonspecific labeling techniques. We have developed methodology to site-specifically conjugate oligonucleotides to antibodies containing a genetically encoded unnatural amino acid with orthogonal chemical reactivity. These oligobody molecules were used in immuno-PCR assays to detect Her2(+) cells with greater sensitivity and specificity than nonspecifically coupled fragments, and can detect extremely rare Her2(+) cells in a complex cellular environment. Such designed antibody-oligonucleotide conjugates should provide sensitive and specific reagents for diagnostics, as well as enable other unique applications based on oligobody building blocks.

The rate of transition to a suicide attempt among people with suicidal thoughts in the general population: A systematic review.

INTRODUCTION: While suicidal thoughts are relatively common in the general population, roughly affecting one in ten people during their lifetime, the transition from suicidal thoughts to a suicide attempt is rarer. There is limited consensus on the transition rate from suicidal ideation to suicide attempts. OBJECTIVE: To review and summarize evidence on the rate of transition from suicidal ideation to a suicide attempt, and the factors associated with this transition, in the general population. METHODS: A comprehensive search was conducted using MEDLINE, PsycINFO, and Embase for relevant articles published between January 1, 2000, and March 3, 2021. We identified 18 eligible studies that examined the transition from suicidal ideation to a suicide attempt in non-clinical populations. We assessed the quality of the included studies using the MASTER scale. The review has been registered with PROSPERO (CRD42021248325). RESULTS: Rates of transitioning to a suicide attempt among people with suicidal ideation varied substantially across studies, from 2.6 % to 37 %. Follow-up periods also varied substantially, from 12 to 300 months, impeding reliable comparisons across studies or pooling data for further analyses. The most examined risk factors were mental health disorders such as major depressive and anxiety disorders, which were typically associated with higher odds of transition to a suicide attempt. LIMITATIONS: High level of heterogeneity and limited quality of the studies. CONCLUSION: The risk of transition from suicidal thoughts to a suicide attempt is moderate to high. Further longitudinal research is required to refine the rate and explore social determinants of transition from suicidal ideation to suicide attempts.

Hiatal Hernia After Esophagectomy: A Single-Center Retrospective Analysis of a Rare Postoperative Phenomenon.

Development of a post-esophagectomy hiatal hernia (PEHH) is a rare, but problematic, sequela with the current reported prevalence ranging up to 20%. To determine the incidence rate of PEHH at our institution, a retrospective review of all transhiatal esophagectomies performed from 2012 to 2020 was conducted. Demographic, operative, and oncologic data were collected, rates of PEHH were calculated, and characteristics of subsequent repair were reviewed and analyzed. A total of 160 transhiatal esophagectomies were included, of which four patients (2.5%) developed a PEHH at a mean of 12 months postoperatively (range: 3-28 months) with symptomatology driving the diagnosis for three patients. The limited size of our study does not allow for statistically significant determinations regarding risk factors or method of repair. The true prevalence of a hiatal defect is likely higher than reported, as clinically asymptomatic patients are not captured in our current literature.

Is Cystogastrostomy a Definitive Operation for Pancreatitis Associated Pancreatic Fluid Collections?

BACKGROUND: Pancreatic-enteric drainage procedures have become standard therapy for symptomatic pancreatic pseudocysts and walled-off pancreatic necrosis. The need for pancreatic resection after cyst-enteric drainage procedure in the event of recurrence is not well studied. This study aimed to quantify the percentage of patients requiring resection due to recurrence after surgical cystogastrostomy and identify predictors of drainage failure. METHODS: A single-institution retrospective review was conducted to identify all patients undergoing surgical cystogastrostomy between 2012 and 2020. Demographic, disease, and treatment characteristics were identified. Failure of surgical drainage was defined as the need for subsequent pancreatic resection due to recurrence. Characteristics between failure and nonfailure groups were compared with identifying predictors of treatment failure. RESULTS: Twenty-four cystogastrostomies were performed during the study period. Three patients (12.5%) required a subsequent distal pancreatectomy after surgical drainage. There was no difference in comorbidities between drainage alone and failure of drainage groups. Mean cyst size seemed to be larger in patients that underwent drainage alone versus those that needed subsequent resection (15.2 vs 10.3 cm, P =0.05). Estimated blood loss at initial operation was similar between groups (126 vs 166 mL, P =0.36). CONCLUSION: Surgical pancreatic drainage was successful in the initial management of pancreatic fluid collections. We did not identify any predictors of failure of initial drainage. There was a trend suggesting smaller cyst size may be associated with cystgastrostomy failure. Resection with distal pancreatectomy for walled-off pancreatic necrosis and pancreatic pseudocysts can be reserved for cases of failure of drainage.

Contrasting roles of different mismatch repair proteins in basal-like breast cancer.

The mismatch repair (MMR) pathway is known as a tumor suppressive pathway and genes involved in MMR are commonly mutated in hereditary colorectal or other cancer types. However, the function of MMR genes/proteins in breast cancer progression and metastasis are largely unknown. We found that MSH2, but not MLH1, is highly enriched in basal-like breast cancer (BLBC) and that its protein expression is inversely correlated with overall survival time (OS). MSH2 expression is frequently elevated due to genomic amplification or gain-of-expression in BLBC, which results in increased MSH2 protein to pair with MSH6 (collectively referred to as MutSα). Genetic deletion of MSH2 or MLH1 results in a contrasting phenotype in metastasis, with MSH2-deletion leading to reduced metastasis and MLH1-deletion to enhanced liver or lung metastasis. Mechanistically, MSH2-deletion induces the expression of a panel of chemokines in BLBC via epigenetic and/or transcriptional regulation, which leads to an immune reactive tumor microenvironment (TME) and elevated immune cell infiltrations. MLH1 is not correlated with chemokine expression and/or immune cell infiltration in BLBC, but its deletion results in strong accumulation of neutrophils that are known for metastasis promotion. Our study supports the differential functions of MSH2 and MLH1 in BLBC progression and metastasis, which challenges the paradigm of the MMR pathway as a universal tumor suppressive mechanism.

Cytometric comparisons between circulating tumor cells from prostate cancer patients and the prostate-tumor-derived LNCaP cell line.

Many important experiments in cancer research are initiated with cell line data analysis due to the ease of accessibility and utilization. Recently, the ability to capture and characterize circulating tumor cells (CTCs) has become more prevalent in the research setting. This ability to detect, isolate and analyze CTCs allows us to directly compare specific protein expression levels found in patient CTCs to cell lines. In this study, we use immunocytochemistry to compare the protein expression levels of total cytokeratin (CK) and androgen receptor (AR) in CTCs and cell lines from patients with prostate cancer to determine what translational insights might be gained through the use of cell line data. A non-enrichment CTC detection assay enables us to compare cytometric features and relative expression levels of CK and AR by indirect immunofluorescence from prostate cancer patients against the prostate cancer cell line LNCaP. We measured physical characteristics of these two groups and observed significant differences in cell size, fluorescence intensity and nuclear to cytoplasmic ratio. We hope that these experiments will initiate a foundation to allow cell line data to be compared against characteristics of primary cells from patients.

Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors.

Circulating tumor cells (CTCs) have been implicated as a population of cells that may seed metastasis and venous thromboembolism (VTE), two major causes of mortality in cancer patients. Thus far, existing CTC detection technologies have been unable to reproducibly detect CTC aggregates in order to address what contribution CTC aggregates may make to metastasis or VTE. We report here an enrichment-free immunofluorescence detection method that can reproducibly detect and enumerate homotypic CTC aggregates in patient samples. We identified CTC aggregates in 43% of 86 patient samples. The fraction of CTC aggregation was investigated in blood draws from 24 breast, 14 non-small cell lung, 18 pancreatic, 15 prostate stage IV cancer patients and 15 normal blood donors. Both single CTCs and CTC aggregates were measured to determine whether differences exist in the physical characteristics of these two populations. Cells contained in CTC aggregates had less area and length, on average, than single CTCs. Nuclear to cytoplasmic ratios between single CTCs and CTC aggregates were similar. This detection method may assist future studies in determining which population of cells is more physically likely to contribute to metastasis and VTE.

Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology.

Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL⁻¹ (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL⁻¹. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in lung cancer patients.

Transduodenal resection for duodenal adenomas may be an underutilized tool - A single institution experience.

Background: Duodenal adenomas are pre-malignant lesions. Transduodenal resection and pancreaticoduodenectomy remain the only two surgical options. The optimal surgical management remains controversial between these two strategies. Methods: A retrospective review was conducted to identify patients who underwent intervention for duodenal adenomas. Patient were stratified by type of procedure, pancreaticoduodenectomy or transduodenal resection, and their demographic data as well as perioperative outcomes were compared. Results: 26 patients underwent surgery for duodenal adenomas. 11 underwent a pancreaticoduodenectomy (PD) (42.3%) and 15 underwent a transduodenal resection (TDR) (57.7%). Median operative time, median estimated blood loss, and mean length of stay were longer in the PD vs TDR group. Two patients (13.3%) in the TDR group developed recurrent adenomas. Conclusion: Transduodenal resection should be considered in patients who are suspected to harbor benign duodenal tumors. Duodenal tumors with high grade dysplasia or invasive cancer should undergo an oncologic procedure. Endoscopic surveillance appears to be indicated after transduodenal resection.

Hepatopancreatobiliary Fellowship Graduates: Where Do They Stand today?

BACKGROUND: The Americas Hepato-Pancreato-Biliary Association (AHPBA) Education and Training Committee standardized a Hepatopancreatobiliary (HPB) Surgery Fellowship certification process in 2010. Several classes of fellows have since graduated from HPB, combined Society of Surgical Oncology/AHPBA, and combined American Society of Transplant Surgeons/AHPBA fellowships, but there is little information on their career outcomes. We seek to offer long-term data on the careers of HPB fellowship graduates. METHODS: A 26-question anonymous survey was distributed among graduates of accredited programs for the last 10 years. We generated descriptive statistics from the responses. RESULTS: The respondents were evenly distributed in terms of graduation years between 2010 and 2019. Fifty-eight percent of fellows had completed a prior fellowship, 82% received 1 to 3 job offers during the fellowship, and 75% of respondents were still at their first job. The majority of graduates (>60%) were able to secure a job with a >50% HPB practice and >40 HPB cases per year within 3 years of graduation. Overall, >90% candidates rated their satisfaction with fellowship training greater than 8 out of 10. DISCUSSION: This survey helps shed light on the early formative years in the practices of HPB fellowship graduates. These data show that HPB fellowship training is essential and effective in providing job security and helps fellowship graduates develop a gratifying practice.

Whipple pancreatoduodenectomy: A technical illustration.

BACKGROUND: The Whipple procedure in its current form owes its evolution to the groundbreaking and innovative work of giants in the field of surgery. From being a multistep procedure with high morbidity and mortality, it is now ubiquitously performed in a single setting, often offered via minimally invasive approaches. Training to perform this procedure is an arduous task, and different training paradigms vary significantly. OBJECTIVES/METHODS: The purpose of this paper is to share a standard method by which the surgeon can perform the Whipple procedure in a systematic manner. Using illustrations to make the steps clearer, the authors will postulate that an improvement in mean operative time can be realistically achieved by most pancreatic surgeons. The focus is also on presenting this complex procedure as reproducible and teachable techniques for trainees. CONCLUSION: This illustrated review of the Whipple procedure as performed at our institution is intended to help facilitate a streamlined and stepwise progression through what is undoubtedly a challenging surgical procedure. Although the procedure described will not apply to all Whipple operations given the heterogeneity in anatomy and circumstances, our hope is that this will lead to a more efficient procedure and decreased operating room time and costs as well as provide a framework to teach and measure technical progress for surgical trainees.

Blueprint for safe transition from a low- to high-volume pancreatic surgery center.

We describe a straightforward model to implement a high volume specialty surgery program at a community hospital. Using pancreatic surgery as an example, we employed published processes in three arenas. First, mandatory multidisciplinary tumor board presentations captured all the patients considered for surgery. Then, perioperative protocols using tools such as enhanced recovery and teamwork in the perioperative arena created a reproducible and safe environment for complex surgery. We critically reviewed all complications using the Clavien-Dindo methodology, and confirmed our favorable outcomes via the targeted NSQIP program. These standard steps can be used for implementation of a new complex surgical procedure.

Esophagectomy in octogenarians: is it at a cost?

Background: Surgical intervention in the geriatric population has a higher risk of perioperative morbidity and mortality due to frailty, comorbidities, and lack of compensatory physiologic reserve. The literature on esophagectomy in octogenarians is limited and there is concern about elderly patients being with-held surgery. The purpose of this study is to analyze the outcomes of esophagectomies for esophageal cancer in octogenarians to assess the safety of esophagectomy in this population. Methods: 145 transhiatal esophagectomies performed for esophageal cancer between 2012 and 2020 were retrospectively reviewed in this IRB approved study. Two aborted esophagectomies were excluded. Patient demographics, surgical outcomes, and oncologic outcomes were reviewed. The octogenarian group was analyzed compared to patients younger than 80 years of age. Results: Among 143 esophagectomies, 136 patients were <80 years old while 7 were ≥80 years old. Octogenarians received significantly less neoadjuvant therapy compared to younger patients (42.9% vs 80.2%, p = 0.02). No statistically significant difference was noted in complication rate, length of stay (LOS), estimated blood loss (EBL), or mortality. However, octogenarians were found to have an increase in severity of complications compared to younger patients. Conclusion: This study demonstrates that esophagectomy can be performed in carefully selected octogenarians. This comes at a cost with increased severity of complications without an increase in complication rates or mortality. This data suggests that esophagectomy can be offered selectively to older patients with clear expectations and planning for the high risk of more severe post-operative complications.

Fosfomycin vs Ertapenem for Outpatient Treatment of Complicated Urinary Tract Infections: A Multicenter, Retrospective Cohort Study.

BACKGROUND: We sought to determine the comparative efficacy of fosfomycin vs ertapenem for outpatient treatment of complicated urinary tract infections (cUTIs). METHODS: We conducted a multicenter, retrospective cohort study involving patients with cUTI treated with outpatient oral fosfomycin vs intravenous ertapenem at 3 public hospitals in Los Angeles County between January 2018 and September 2020. The primary outcome was resolution of clinical symptoms 30 days after diagnosis. RESULTS: We identified 322 patients with cUTI treated with fosfomycin (n = 110) or ertapenem (n = 212) meeting study criteria. The study arms had similar demographics, although patients treated with ertapenem more frequently had pyelonephritis or bacteremia while fosfomycin-treated patients had more retained catheters, nephrolithiasis, or urinary obstruction. Most infections were due to extended-spectrum ß-lactamase-producing E. coli and Klebsiella pneumoniae, 80%-90% of which were resistant to other oral options. Adjusted odds ratios for clinical success at 30 days, clinical success at last follow-up, and relapse were 1.21 (95% CI, 0.68-2.16), 0.84 (95% CI, 0.46-1.52), and 0.94 (95% CI, 0.52-1.70) for fosfomycin vs ertapenem, respectively. Patients treated with fosfomycin had significant reductions in length of hospital stay and length of antimicrobial therapy and fewer adverse events (1 vs 10). Fosfomycin outcomes were similar irrespective of duration of lead-in intravenous (IV) therapy or fosfomycin dosing interval (daily, every other day, every third day). CONCLUSIONS: These results would support the conduct of a randomized controlled trial to verify efficacy. In the meantime, they suggest that fosfomycin may be a reasonable stepdown from IV antibiotics for cUTI.