Ilges, Dan

Abstract Background We investigated the relationship between cumulative, historical antibiotic therapy and the presence of ceftriaxone-resistant (CRO-R) Enterobacterales bloodstream infections (BSI) from urinary sources. Methods Adult patients established with primary care at Mayo Clinic with a first episode of monomicrobial Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis BSI from a urinary source from May 2019 to May 2023 were included. Antibiotic therapy over the year prior to BSI was quantified as days of therapy (DOT), cumulative modified Antibiotic Spectrum Index (mASI), and cumulative Days of Antibiotic Spectrum Coverage (DASC) using prescription data. Patients with CRO-R urinary pathogens prior to antibiotic therapy assessment were excluded. Results In total, 721 adults had monomicrobial gram-negative BSI, including 70 patients (9.7%) with a CRO-R pathogen and 651 patients (90.3%) with a ceftriaxone-susceptible (CRO-S) pathogen. In the 12 months prior to BSI, levels of antibiotic DOT, mASI, and DASC were significantly greater among patients with CRO-R BSI than CRO-S BSI (P < .001). The median time from blood culture collection to appropriate antibiotic therapy was significantly longer in the CRO-R group (24 hours, interquartile range [IQR] 16–48) than the CRO-S group (1 hour, IQR 0–2) (P < .001). Increasing cumulative antibiotic therapy prior to BSI, as quantified by the mASI, was significantly associated with increased risk of 1-year CDI after BSI (P = .027). Conclusions Patients with first episode CRO-R Enterobacterales BSI had significantly greater prior antibiotic exposure than patients with CRO-S BSI and experienced significant delay of appropriate therapy. Routine quantitation and reporting of prior antibiotic therapy may improve empiric prescribing.

ABSTRACT Trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis can prevent Pneumocystis jirovecii pneumonia (PJP) and other opportunistic infections (OI). We sought to assess the frequency, causative factors, and impact of early TMP/SMX discontinuation in abdominal solid organ transplant (SOT). This is a single‐center, retrospective cohort study of abdominal SOT recipients at Mayo Clinic Arizona (MCA) between January 2021 and June 2023. Primary study goals were to determine the rate and reasons behind early TMP/SMX discontinuation and whether TMP/SMX prophylaxis was reinitiated. Secondary outcomes included mean duration of therapy, alternative prophylactic agent utilized, and incidence of TMP/SMX‐preventable OI. A total of 930 abdominal SOT recipients were included (592 kidney, 253 liver, 85 multiorgan transplants). TMP/SMX was discontinued early in 184 (20%) patients: 77 kidney, 84 liver, 23 multiorgan. Predominant reasons for discontinuation were hyperkalemia (39%) and cytopenias (35%). Median duration of TMP/SMX prophylaxis before discontinuation was 54.5 (18.0, 93.2) days. TMP/SMX was not resumed in 62% of cases (36% kidney, 89% liver, 52% multi‐organ). The predominant reason for non‐resumption was alternative prophylaxis with no clear intent to rechallenge TMP/SMX (70%). Alternative prophylaxis included pentamidine (43%), none (30%), dapsone (22%), and atovaquone (5%). Of patients reinitiated, 86% (59/69) successfully remained on TMP/SMX through the prophylaxis period. One TMP‐SMX‐preventable OI (nocardiosis) was observed in the TMP/SMX discontinuation group. TMP/SMX is often discontinued prematurely in SOT recipients without resumption despite resolution of the offending cause. TMP/SMX prophylaxis should be maintained where possible, as alternative therapy may not offer the same broad spectrum of protection against OI.

Abstract Objective: To retrospectively observe procalcitonin (PCT) and antibiotic ordering practices in patients hospitalized with community-acquired pneumonia (CAP). Design: Retrospective, exact matched, multicenter cohort study from October 1, 2018 – March 31, 2023. Setting: All hospitals across the Mayo Clinic Enterprise. Participants: Adult patients with CAP, identified using pneumonia diagnosis codes and receipt of systemic antibiotics with an indication of “respiratory tract infection” within 48 hours of hospitalization. Methods: PCT testing within the first 7 days of hospitalization was compared to non-PCT care (nPCT). The primary outcomes were treatment duration, antibiotic days of therapy (DOT), and length of stay (LOS). Results: 15364 patients met inclusion criteria. PCT testing occurred in 42.4% (6515/15364) of encounters, totaling 8214 PCT results. 12880 unique patient encounters were matched 1:1, 6440 in each group. Treatment duration was longer in the PCT group compared to the nPCT group (5.1 vs 4.6 days, respectively, P < 0.001). Patients in the PCT group also received more DOT (8.6 vs 7.6 DOT, P < 0.001) and had a longer LOS (6.8 vs 5.9 days, P < 0.001), respectively. There was no difference in 30-day all-cause mortality or C. difficile infection between groups. In a sensitivity analysis of nPCT patients compared to those with a peak value <0.25 ng/mL (i.e. normal result) there was no difference in treatment duration (4.6 days nPCT vs 4.7 days normal PCT, P = 0.104) or LOS (5.9 days nPCT vs 6.0 days normal PCT, P = 0.134). Conclusion: PCT testing in patients hospitalized with CAP was not associated with reduced antimicrobial utilization, LOS, or 30-day all-cause mortality.

Abstract Reducing antimicrobial exposure by limiting the duration of therapy is an effective antimicrobial stewardship strategy. In this article, we describe the impact of modification of the electronic health record to remove default durations of therapy on ambulatory antibiotic prescriptions issued from emergency departments in a large, multicenter health system.

Background: Cefazolin is a preferred treatment option for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Recent studies have suggested a potential impact on clinical outcomes in patients with hypoalbuminemia treated with highly protein-bound antimicrobials. Objective: The purpose of this study was to determine if there are any differences in clinical outcomes between normoalbuminemic and hypoalbuminemic patients treated with cefazolin for bacteremia. Methods: A retrospective, multicentered cohort study of patients hospitalized between 2019 and 2023 with MSSA bacteremia treated with cefazolin for at least 24 hours prior to culture clearance. Patients were divided into hypoalbuminemia (serum albumin ≤2.5 g/dL) or normoalbuminemia groups. The primary outcome was time to culture clearance. Results: Of 69 patients included (50 in normoalbuminemia group and 19 in hypoalbuminemia group), the most common sources of bacteremia were line-related, osteoarticular, and infective endocarditis. Deep-seated infections were present in 24% of the normoalbuminemia group and 58% of the hypoalbuminemia group. Patients with hypoalbuminemia had a significantly longer mean hospital length of stay (12 vs 7 days, P = 0.016). After adjusting for deep-seated infection, hypoalbuminemia was associated with increased time to culture clearance by 1.2 days ( P = 0.039). In-hospital mortality was significantly higher in the hypoalbuminemia group (26% vs 4%, P = 0.015). Conclusion and Relevance: Limited research is available describing the relationship between serum albumin levels and clinical outcomes. Our study suggests patients with hypoalbuminemia treated with cefazolin for MSSA bacteremia have significantly longer time to culture clearance, increased mortality, and longer length of stay.

Abstract Background Trimethoprim-sulfamethoxazole (TS) prophylaxis can prevent Pneumocystis jirovecii (PCP) and other opportunistic infections (OIs), such as intestinal protozoa, Toxoplasma, Listeria, and Nocardia. We sought to assess the frequency, causative factors, and impact of early TS discontinuation in abdominal SOT recipients. Methods This is a single-center, retrospective cohort study of adult abdominal SOT recipients at Mayo Clinic Arizona between 1/1/2021 and 6/30/2023. Objectives included the rate and reasons behind early TS discontinuation and whether TS prophylaxis was reinitiated. Early discontinuation was defined as cessation of TS prophylaxis within 6 months post-transplant for ≥7 days. Secondary outcomes included median duration of therapy, alternative prophylactic agent utilized, and incidence of TS preventable OI. Patients were excluded if they had no TS ordered, died &lt;180 days from transplant, or received a thoracic organ transplant. Results 942 abdominal SOT recipients were identified. Thus far 171 liver, 11 Kidney, and 29 liver/kidney have been reviewed and included in the current analysis. TS was discontinued early in 60 (28%) patients. Predominant reasons for discontinuation were hyperkalemia (45%), cytopenias (17%), and acute kidney injury (15%). Allergy was the indication for discontinuation in 1 patient. Median duration of TS before discontinuation was 39 days (IQR 66). TS was not resumed in 78% of cases. The predominant reason for non-resumption was alternative prophylaxis with no clear intent to rechallenge TS (70%). The main discontinuation reason had resolved in 70% that stopped due to cytopenias, 67% that stopped due to liver injury, and 96% that stopped due to hyperkalemia. Alternative prophylaxis included pentamidine (50%), dapsone (32%), atovaquone (5%), none (13%). No patients developed PCP or other TS preventable OI during 9-month follow-up post-SOT. Conclusion TS is discontinued prematurely in a significant number of SOT recipients and is often not resumed despite resolution of the offending cause. Given its proven track record in preventing several OIs in SOT recipients, providers should document reason(s) for TS discontinuation and consider resumption of TS after reasons for discontinuation resolve. Disclosures All Authors: No reported disclosures

Abstract Background Optimizing antimicrobial prescribing for urinary tract infections (UTI) represents an area of opportunity for ambulatory antimicrobial stewardship programs. A pre-populated, ambulatory antibiotic order panel for UTI was implemented in the Mayo Clinic Enterprise on 5/16/2022. The order panel provides antimicrobial regimens which align with both institutional and national treatment guidelines based on patient comorbidities, complicating factors, and beta-lactam allergy status. We aimed to assess the impact of panel use on antibiotic prescribing for complicated and uncomplicated cystitis in the ambulatory setting. Methods This retrospective review included ambulatory encounters from the Mayo Clinic Enterprise in 2022 and 2023. Eligible encounters were randomly selected and included those with a primary ICD-10 code of cystitis performed by primary care or urgent care clinicians. Encounters were excluded if patients had symptoms indicative of pyelonephritis, underwent urinary instrumentation within 30 days, or had a urinary pathogen isolated within 90 days. The primary outcome was concordance with institutional guidelines. Secondary outcomes included repeat healthcare contact and therapy duration. Outcomes were analyzed with Pearson's chi-squared and Wilcoxon rank sum tests (α level = 0.05). Results 793 encounters (397 panel vs. 396 non-panel) were included. Prescribing was guideline concordant in 79.3% and 64.9% (p&lt; 0.001) of panel and non-panel encounters, respectively. Inappropriate duration was the most common reason for non-concordance in the panel use cohort. There was no difference between groups for repeat healthcare contact incidence. Antimicrobials prescribed differed between panel and no-panel groups (Table 1), with higher use of sulfamethoxazole/trimethoprim and lower use of cefdinir in the panel cohort. Numerically shorter durations were seen in the panel group, with more 3- and 5-day regimens than the no-panel group. Conclusion Use of a pre-populated antimicrobial order panel for outpatient cystitis encounters resulted in greater adherence to institutional guideline recommendations, particularly in terms of antimicrobial selection, without adversely impacting repeat healthcare contact. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun Biopharma: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|F2G: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support