Antibiotic-associated Adverse Events Research Articles

Inappropriate Diagnosis of Pneumonia Among Hospitalized Adults

Little is known about incidence of, risk factors for, and harms associated with inappropriate diagnosis of community-acquired pneumonia (CAP). To characterize inappropriate diagnosis of CAP in hospitalized patients. This prospective cohort study, including medical record review and patient telephone calls, took place across 48 Michigan hospitals. Trained abstractors retrospectively assessed hospitalized patients treated for CAP between July 1, 2017, and March 31, 2020. Patients were eligible for inclusion if they were adults admitted to general care with a discharge diagnostic code of pneumonia who received antibiotics on day 1 or 2 of hospitalization. Data were analyzed from February to December 2023. Inappropriate diagnosis of CAP was defined using a National Quality Forum-endorsed metric as CAP-directed antibiotic therapy in patients with fewer than 2 signs or symptoms of CAP or negative chest imaging. Risk factors for inappropriate diagnosis were assessed and, for those inappropriately diagnosed, 30-day composite outcomes (mortality, readmission, emergency department visit, Clostridioides difficile infection, and antibiotic-associated adverse events) were documented and stratified by full course (>3 days) vs brief (≤3 days) antibiotic treatment using generalized estimating equation models adjusting for confounders and propensity for treatment. Of the 17 290 hospitalized patients treated for CAP, 2079 (12.0%) met criteria for inappropriate diagnosis (median [IQR] age, 71.8 [60.1-82.8] years; 1045 [50.3%] female), of whom 1821 (87.6%) received full antibiotic courses. Compared with patients with CAP, patients inappropriately diagnosed were older (adjusted odds ratio [AOR], 1.08; 95% CI, 1.05-1.11 per decade) and more likely to have dementia (AOR, 1.79; 95% CI, 1.55-2.08) or altered mental status on presentation (AOR, 1.75; 95% CI, 1.39-2.19). Among those inappropriately diagnosed, 30-day composite outcomes for full vs brief treatment did not differ (25.8% vs 25.6%; AOR, 0.98; 95% CI, 0.79-1.23). Full vs brief duration of antibiotic treatment among patients was associated with antibiotic-associated adverse events (31 of 1821 [2.1%] vs 1 of 258 [0.4%]; P = .03). In this cohort study, inappropriate diagnosis of CAP among hospitalized adults was common, particularly among older adults, those with dementia, and those presenting with altered mental status. Full-course antibiotic treatment of those inappropriately diagnosed with CAP may be harmful.

Protocol for a parallel cluster randomized trial of a participatory tailored approach to reduce overuse of antibiotics at hospital discharge: the ROAD home trial

BackgroundAntibiotic overuse at hospital discharge is common, costly, and harmful. While discharge-specific antibiotic stewardship interventions are effective, they are resource-intensive and often infeasible for hospitals with resource constraints. This weakness impacts generalizability of stewardship interventions and has health equity implications as not all patients have access to the benefits of stewardship based on where they receive care. There may be different pathways to improve discharge antibiotic prescribing that vary widely in feasibility. Supporting hospitals in selecting interventions tailored to their context may be an effective approach to feasibly reduce antibiotic overuse at discharge across diverse hospitals. The objective of this study is to evaluate the effectiveness of the Reducing Overuse of Antibiotics at Discharge Home multicomponent implementation strategy (“ROAD Home”) on antibiotic overuse at discharge for community-acquired pneumonia and urinary tract infection.MethodsThis 4-year two-arm parallel cluster-randomized trial will include three phases: baseline (23 months), intervention (12 months), and postintervention (12 months). Forty hospitals recruited from the Michigan Hospital Medicine Safety Consortium will undergo covariate-constrained randomization with half randomized to the ROAD Home implementation strategy and half to a “stewardship as usual” control. ROAD Home is informed by the integrated-Promoting Action on Research Implementation in Health Services Framework and includes (1) a baseline needs assessment to create a tailored suite of potential stewardship interventions, (2) supported decision-making in selecting interventions to implement, and (3) external facilitation following an implementation blueprint. The primary outcome is baseline-adjusted days of antibiotic overuse at discharge. Secondary outcomes include 30-day patient outcomes and antibiotic-associated adverse events. A mixed-methods concurrent process evaluation will identify contextual factors influencing the implementation of tailored interventions, and assess implementation outcomes including acceptability, feasibility, fidelity, and sustainment.DiscussionReducing antibiotic overuse at discharge across hospitals with varied resources requires tailoring of interventions. This trial will assess whether a multicomponent implementation strategy that supports hospitals in selecting evidence-based stewardship interventions tailored to local context leads to reduced overuse of antibiotics at discharge. Knowledge gained during this study could inform future efforts to implement stewardship in diverse hospitals and promote equity in access to the benefits of quality improvement initiatives.Trial registrationClinicaltrials.gov NCT06106204 on 10/30/23

Guideline concordance and antibiotic-associated adverse events between Veterans administration and non-Veterans administration dental settings: a retrospective cohort study.

Background: Antibiotics prescribed as infection prophylaxis prior to dental procedures have the potential for serious adverse drug events (ADEs). However, the extent to which guideline concordance and different dental settings are associated with ADEs from antibiotic prophylaxis is unknown. Aim: The purpose was to assess guideline concordance and antibiotic-associated ADEs and whether it differs by VA and non-VA settings. Methods: Retrospective cohort study of antibiotic prophylaxis prescribed to adults with cardiac conditions or prosthetic joints from 2015 to 2017. Multivariable logistic regression models were fit to assess the impact of ADEs, guideline concordance and dental setting. An interaction term of concordance and dental setting evaluated whether the relationship between ADEs and concordance differed by setting. Results: From 2015 to 2017, 61,124 patients with antibiotic prophylaxis were identified with 62 (0.1%) having an ADE. Of those with guideline concordance, 18 (0.09%) had an ADE while 44 (0.1%) of those with a discordant antibiotic had an ADE (unadjusted OR: 0.84, 95% CI: 0.49-1.45). Adjusted analyses showed that guideline concordance was not associated with ADEs (OR: 0.78, 95% CI: 0.25-2.46), and this relationship did not differ by dental setting (Wald χ^2 p-value for interaction = 0.601). Conclusion: Antibiotic-associated ADEs did not differ by setting or guideline concordance.

Adherence to stewardship recommendations for antibiotic discontinuation reduces antibiotic-associated adverse drug events.

Inappropriate antibiotic use may lead to increased adverse drug events (ADEs). This study assessed whether an antimicrobial stewardship recommendation to discontinue antibiotics in patients with low likelihood for bacterial infection reduced antibiotic duration and antibiotic-associated ADEs. At a 4-hospital system, hospitalized adult patients receiving empiric antibiotics for suspected infection were identified between May 2, 2016 and June 30, 2018. For those patients who were deemed unlikely to have a bacterial infection, a note was left by an infectious diseases physician recommending antibiotic discontinuation. Patient cases were considered "adherent" to recommendations if antibiotics were discontinued within 48 hours of the note and "non-adherent" to recommendations if antibiotics were continued beyond this. Duration of antibiotics and potential antibiotic-associated ADEs were collected retrospectively. Attribution of the adverse event to the antibiotic was decided upon by the investigators. The incidence of ADEs and duration of antibiotics between the adherent and non-adherent groups were compared. Of 253 patients deemed unlikely to have a bacterial infection, 114 (45%) treatment teams stopped antibiotics within 48 hours of the recommendation, and 139 (55%) continued antibiotics. The total number of ADEs was significantly higher in the non-adherent group compared to the adherent group (34 ADEs vs 9 ADEs, P = .001). The median number of total prescribed antibiotic days was higher in the non-adherent group than in the adherent group (5 days vs 1 day, P < .001). This study demonstrates that stewardship programs may prevent ADEs by recommending antibiotic discontinuation in patients with low suspicion for bacterial infection.

Understanding the role of antibiotic-associated adverse events in influencing antibiotic decision-making.

To (1) understand the role of antibiotic-associated adverse events (ABX-AEs) on antibiotic decision-making, (2) understand clinician preferences for ABX-AE feedback, and (3) identify ABX-AEs of greatest clinical concern. Focus groups. Academic medical center. Medical and surgical house staff, attending physicians, and advanced practice practitioners. Focus groups were conducted from May 2022 to December 2022. Participants discussed the role of ABX-AEs in antibiotic decision-making and feedback preferences and evaluated the prespecified categorization of ABX-AEs based on degree of clinical concern. Thematic analysis was conducted using inductive coding. Four focus groups were conducted (n = 15). Six themes were identified. (1) ABX-AE risks during initial prescribing influence the antibiotic prescribed rather than the decision of whether to prescribe. (2) The occurrence of an ABX-AE leads to reassessment of the clinical indication for antibiotic therapy. (3) The impact of an ABX-AE on other management decisions is as important as the direct harm of the ABX-AE. (4) ABX-AEs may be overlooked because of limited feedback regarding the occurrence of ABX-AEs. (5) Clinicians are receptive to feedback regarding ABX-AEs but are concerned about it being punitive. (6) Feedback must be curated to prevent clinicians from being overwhelmed with data. Clinicians generally agreed with the prespecified categorizations of ABX-AEs by degree of clinical concern. The themes identified and assessment of ABX-AEs of greatest clinical concern may inform antibiotic stewardship initiatives that incorporate reporting of ABX-AEs as a strategy to reduce unnecessary antibiotic use.

Comparison of Adjuvant Clindamycin vs Linezolid for Severe Invasive Group A Streptococcus Skin and Soft Tissue Infections.

Linezolid may be an option for severe group A Streptococcus (GAS) infections based on its potent in vitro activity and antitoxin effects, but clinical data supporting its use over clindamycin are limited. This study evaluated treatment outcomes in patients with severe GAS skin and soft tissue infections who received either linezolid or clindamycin. This retrospective single-center cohort study examined patients with GAS isolated from blood and/or tissue cultures with invasive soft tissue infection or necrotizing fasciitis who underwent surgical debridement and received linezolid or clindamycin for at least 48 hours. The primary outcome was percentage change in Sequential Organ Failure Assessment (SOFA) score from baseline through 72 hours of hospitalization. After adjustment for time to first surgical intervention among patients with a baseline SOFA score >0 (n = 23 per group), there was no difference in reduction of SOFA score over the first 72 hours in patients receiving clindamycin vs linezolid. In the entire cohort (n = 26, clindamycin; n = 29, linezolid), there was no difference in inpatient mortality (2% vs 1%) or any secondary outcomes, including duration of vasopressor therapy, intensive care unit length of stay, and antibiotic-associated adverse drug events. There was no difference in reduction of critical illness as measured by SOFA score between baseline and 72 hours among patients treated with clindamycin vs linezolid. Given its more favorable side effect profile, linezolid may be a viable option for the treatment of serious GAS infections and should be further studied.

Trimethoprim-Sulfamethoxazole for Pediatric Osteoarticular Infections.

Trimethoprim-sulfamethoxazole (TMP-SMX) is active against most Staphylococcus aureus isolates but is not widely used for treatment of pediatric osteoarticular infections. This was a comparative effectiveness study of hospitalized patients ≤18 years treated with TMP-SMX versus other antibiotic regimens for acute osteoarticular infections between 2016 and 2021 at three hospitals using inverse probability of treatment weighted propensity score analysis. The primary outcome was treatment failure, a composite of unanticipated emergency department (ED) or outpatient visits, hospital readmissions, extension or change of antibiotic therapy due to inadequate clinical response, or death, all within 6 months after completing antibiotics. The secondary outcome was antibiotic-associated adverse events (AEs) within 6 months. The exposed group for the treatment failure analysis included children who received ≥7 days of TMP-SMX and did not experience treatment failure while on another antibiotic. Children receiving at least one dose of TMP-SMX were the exposed group for the AE analysis. 116 patients met eligibility criteria; 26 (22.4%) patients were classified into the TMP-SMX cohort and 90 (77.6%) into the other antibiotics cohort (most commonly clindamycin, vancomycin, and cefazolin). There was no significant difference in treatment failure between TMP-SMX and other antibiotics (43% vs 19%; 95% CI 0.9-10.4). More patients in the TMP-SMX cohort experienced an unplanned ED or outpatient visit (OR 4.8, 95% CI 1.3-17.8). There was no difference in hospital readmission, antibiotic change, or duration extension. Exposure to TMP-SMX was associated with more AEs (41% vs 19%, p=0.012). Treatment with TMP-SMX was not associated with greater clinical failure but was associated with more AEs compared to alternative agents for the treatment of pediatric acute osteoarticular infections.

Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot randomised controlled trial

BackgroundSelf-reported penicillin allergies are highly prevalent in hospitalised patients and are associated with poor health and health service outcomes. Critically ill patients have historically been underrepresented in prospective delabelling studies in part due to concerns around clinical stability and reliability of penicillin skin testing. Allergy assessment tools exist to identify low-risk penicillin allergy phenotypes and facilitate direct oral challenge delabelling. PEN-FAST is a clinical decision rule that has been validated to predict true penicillin allergy in a cohort of non-critically ill patients. There is however limited evidence regarding the feasibility, safety and efficacy of direct oral challenges and the use of delabelling clinical decisions rules in the intensive care setting.MethodsCritically ill patients in the intensive care unit (ICU) with low-risk penicillin allergy phenotypes (PEN-FAST score < 3) will be randomised 1:1 to direct oral penicillin challenge (single dose 250 mg oral amoxicillin or implicated penicillin) or routine care, followed by a 2-h observation period. Patients will receive a second oral challenge/observation prior to hospital discharge (with subsequent observation for 2 h). An assessment for antibiotic-associated adverse events will also be undertaken at 24 h and 5 days post each challenge/observation and again at 90 days post-randomisation. The primary outcome measures are feasibility (proportion of eligible patients recruited and protocol compliance) and safety (proportion of patients who experience an antibiotic-associated immune-mediated adverse event or serious adverse event).DiscussionWe will report the feasibility and safety of point-of-care penicillin direct oral challenge in this first randomised controlled trial of low-risk penicillin allergy in critically ill hospitalised patients. Upon completion of the project, important findings will inform the design of planned large prospective multi-centre clinical trials in Australian and international ICUs, further examining safety and efficacy and exploring antimicrobial prescribing-related outcomes following penicillin oral challenge.Trial registrationAustralian New Zealand Clinical Trials RegistryRegistration Number: ACTRN12621000051842Date registered: 20/01/2021https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379735&isReview=true

Understanding clinician perspectives on antibiotic associated adverse events to inform feedback

Background: Feedback regarding antibiotic-associated adverse events (ABX-AEs) may assist clinicians with antibiotic decision making. We sought to understand how clinicians account for ABX-AEs when prescribing and their preferences for ABX-AE feedback. Methods: We conducted 1-hour virtual focus groups with 3–5 physicians or advance practice practitioners (APPs) per session at Johns Hopkins Hospital. Participants discussed the role of ABX-AEs in antibiotic decision making and feedback preferences. Participants evaluated prespecified categorization (mildly, moderately, or very concerning) of several ABX-AEs. Focus groups were recorded and transcribed. Transcripts were coded inductively by 2 independent reviewers; discrepancies were resolved by consensus. Codes were used to conduct thematic analysis. Results: Overall, 3 focus groups were conducted with 12 participants: 41.6% were house staff, 16.7% were attending physicians, and 41.6% were APPs. Most were female (91.6%) and were white (41.7%) or Asian (41.7%). Clinicians generally agreed with the prespecified categorizations of ABX-AEs based on degree of clinical concern (Table). We identified 5 themes: (1) The risk of ABX-AE is considered during initial prescribing but influences agent selection more than the decision to prescribe antibiotics. (2) The occurrence of an ABX-AE leads to assessment of need for continued antibiotic therapy. (3) The impact of an ABX-AE on other management decisions is as important as the direct harm of the ABX-AE when assessing severity. (4) Feedback must be curated to prevent clinicians from being overwhelmed with data. (5) Clinicians will be more receptive to feedback regarding ABX-AEs if feedback is contextualized (Fig.). Conclusions: The themes identified and assessment of ABX-AEs of greatest clinical concern may help inform the development of effective ABX-AE feedback methods to improve antibiotic safety.Disclosures: None

Risk Factors and outcomes associated with inappropriate empiric broad-spectrum antibiotic use in hospitalized patients with community-acquired pneumonia

Background: Inappropriate broad-spectrum antibiotic use targeting methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa can result in increased adverse events, antibiotic resistance, and Clostridioides difficile infection. In 2019, revised ATS/IDSA community-acquired pneumonia (CAP) guidelines removed healthcare-associated pneumonia (HCAP) as a clinical entity and modified patient factors warranting empiric broad-spectrum antibiotic (BSA) use. As a result, most patients hospitalized with CAP should receive empiric antibiotics targeting standard CAP pathogens. Based on revised guidelines, we evaluated predictors and outcomes associated with inappropriate BSA use among hospitalized patients with CAP. Methods: Between November 2019 and July 2022, trained abstractors collected data on non-ICU adult medical patients admitted with CAP at 67 Michigan hospitals who received either an inappropriate empiric BSA on hospital day 1 or 2 or a standard CAP regimen. Inappropriate empiric BSA use was defined as use of an anti-MRSA or anti-pseudomonal antibiotic in a patient eligible for standard CAP coverage per IDSA guidelines. Patients with immune compromise, moderate or severe chronic obstructive pulmonary disease (COPD), pulmonary complication, or guideline-concordant treatment with BSA were excluded. Data collected included comorbidities, antibiotic use and hospitalizations in the preceding 90 days, cultures in the preceding year, signs or symptoms of pneumonia, hospital characteristics, and 30-day postdischarge patient outcomes. Data were collected through chart review and patient phone calls. Predictors of inappropriate empiric BSA were evaluated using logistic general estimating equation (GEE) models, accounting for hospital-level clustering. We assessed the effect of inappropriate empiric BSA (vs standard CAP therapy) on 30-day patient outcomes using logistic GEE models controlling for predictors associated with the outcome and probability of treatment. Results: Of 8,286 included patients with CAP, 2,215 (26.7%) were empirically treated with inappropriate BSA. The median BSA treatment was 3 days (IQR, 2.5). After adjustments, factors associated with inappropriate empiric BSA treatment included hospitalization or treatment with high-risk antibiotics in preceding 90 days, transfer from a postacute care facility, hemodialysis, support with ≥3 L supplemental oxygen, severe sepsis, leukocytosis, and higher pneumonia severity index (Fig. 1). After adjustments, patients with inappropriate empiric BSA treatment had higher readmissions 30 days after discharge, more transfers to the intensive care unit, more antibiotic-associated adverse events, and longer hospitalizations (Fig. 2). Conclusions: Patients hospitalized with CAP often received inappropriate BSA as empiric coverage, and this inappropriate antibiotic selection was associated with worse patient outcomes. To improve patient outcomes, stewardship efforts should focus on reducing inappropriate BSA use in patients hospitalized for CAP with historic HCAP risk factors or severe CAP without other guideline-directed indications for BSA.Financial support. H.M.S. initiative is underwritten by Blue Cross and Blue Shield of Michigan.Disclosures: None

Defining a clinical prediction rule to diagnose bacterial gastroenteritis requiring empirical antibiotics in an emergency department setting: A retrospective review

BackgroundGastroenteritis (GE) is a non-specific term for various pathologic states of the gastrointestinal tract. Infectious agents usually cause acute GE. At present, there are no robust decision-making rules that predict bacterial GE and dictate when to start antibiotics for patients suffering from acute GE to the emergency department (ED). We aim to define a clinical prediction rule to aid in the diagnosis of bacterial GE, requiring empirical antibiotics in adult patients presenting to the emergency department with acute GE.MethodsA two-year retrospective case review was performed on all cases from July 2015 to June 2017 that included patients with acute GE symptoms referred to the ED, after which their stool cultures were performed. The clinical parameters analyzed included patient with comorbid conditions, physical examination findings, historical markers, point-of-care and radiographic tests and other laboratory work. We then used multi-variate logistic regression analysis on each group (bacterial culture–positive GE and bacterial culture–negative GE) to elucidate clinical criteria with the highest yield for predicting bacterial gastroenteritis (BGE).ResultsA total of 756 patients with a mean age of 52 years, 52% female and 48% male, respectively, were included in the study. On the basis of the data of these patients, we suggested using a scoring system to delineate the need for empirical antibiotics in patients with suspected bacterial GE based on six clinical and laboratory variables. We termed this the BGE score. A score 0 – 2 points suggests low risk (0.9%) of bacterial GE. A score of 3 – 4 points confers an intermediate risk of 12.0% and a score of 5 – 8 points confers a high risk of 85.7%. A cut-off of ≥ 5 points may be used to predict culture-positive BGE with a 75% sensitivity and 75% specificity. The area under the receiver operating characteristic (AUROC) for the scoring system (range 0 – 8) was 0.812 (95% CI: 0.780–0.843) p-value < 0.001.ConclusionWe suggest using the BGE scoring system (cut-off ≥ 5 points) to delineate the need for empirical antibiotics in patients diagnosed with gastroenteritis. While this is a pilot study, which will require further validation with a larger sample size, our proposed decision-making rule will potentially serve to improve the diagnosis of BGE and thus reduce unnecessary prescription of antibiotics, which will in turn reduce antibiotic-associated adverse events and save on costs worldwide.

Going local: Evaluating guideline adherence and appropriateness of antibiotic prescribing in patients with febrile neutropenia at an academic teaching hospital.

Febrile neutropenia (FN) is a medical emergency with significant morbidity and mortality for oncology patients, requiring comprehensive workup and timely antibiotic administration. We evaluated concordance with locally developed FN guidelines and outcomes of cancer patients admitted to general internal medicine at an academic teaching hospital. We conducted a retrospective observational cohort study of patients admitted between July 1, 2016, and June 30, 2017, for FN. Patients were classified as having low-risk or high-risk FN according to their malignancy and chemotherapy. Primary outcome was the proportion of patients receiving guideline-concordant antibiotics within 48 hours of admission to general internal medicine. Secondary outcomes were the proportion of patients in whom empirical antibiotics were active against pathogens isolated, rate of antibiotic-associated adverse events, and in-hospital mortality. We used logistic regression to model relationship between FN risk and guideline-concordant antibiotics. Among 100 patients included, 34 (34%) were low-risk FN and 66 (66%) were high-risk. Proportion of guideline-concordant empirical antibiotics was significantly lower among low-risk FN patients than high-risk patients: 12 (35%) of 34 versus 47 (71%) of 66 (P = .001). Empirical antibiotics were active against 17 (94%) of 18 isolated pathogens. The mortality rate was 3%, and 16% of patients experienced antibiotic-associated adverse events. Hematological malignancy and infectious diseases-trained physician involvement were associated with guideline-concordant prescribing, with adjusted odds ratios of 3.76 (95% CI, 1.46-9.70; P = .006) and 3.71 (95% CI, 1.49-9.23; P = .005), respectively. Guideline concordance was low compared to published reports. Factors influencing appropriate antimicrobial prescribing in patients with FN warrant further exploration.

Cancer is chronic but antimicrobial stewardship is iconic: A retrospective cohort of optimal antibiotic use in ambulatory oncology clinics.

To evaluate antibiotic prescribing in ambulatory oncology clinics and to identify opportunities to improve antibiotic use. Retrospective cohort of adult patients who received care at 4 ambulatory oncology clinics from May 2021 to December 2021. Patients were included if they actively followed with a hematologist-oncologist for a cancer diagnosis and received an antibiotic prescription for uncomplicated upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), urinary tract infection (UTI), or acute bacterial skin-skin structure infection (ABSSSI) at an oncology clinic. The primary outcome was receipt of optimal antibiotic therapy, defined as a composite of drug, dose, and duration according to local and national guidelines. Patient characteristics were described and compared; predictors of optimal antibiotic use were identified using multivariable logistic regression. In total, 200 patients were included in this study: 72 (36%) received optimal antibiotics and 128 (64%) received suboptimal antibiotics. The proportions of patients receiving optimal therapy by indication were ABSSSI (52%), UTI (35%), URTI (27%), and LRTI (15%). The most common suboptimal prescribing components were dose (54%), selection (53%) and duration (23%). After adjusting for female sex and LRTI, ABSSSI (adjusted odds ratio, 2.28; 95% confidence interval, 1.19-4.37) was associated with optimal antibiotic therapy. Antibiotic-associated adverse drug events occurred in 7 patients; 6 occurred patients who received prolonged durations and 1 occurred in a patient who received an optimal duration (P = .057). Suboptimal antibiotic prescribing in ambulatory oncology clinics is common and mostly driven by antibiotic selection and dosing. Duration of therapy may also be an area for improvement as national oncology guidelines have not adopted short-course therapy.

Consider this tool to reduce antibiotic-associated adverse events in patients with sepsis

Predictive biomarker procalcitonin can aid clinical decision-making on continued antibiotic treatment in this patient population.

1842. Intravenous to Oral Antibiotic Stepdown for Uncomplicated Streptococcal Bacteremia

Abstract Background Historically, intravenous (IV) antibiotics have been the standard of care for the treatment of bloodstream infections (BSIs). IV antibiotic use predisposes patients to line-related complications and is associated with increased length of stay (LOS) and treatment costs as compared to oral (PO) antibiotics. The purpose of this study was to compare the efficacy and safety of IV therapy versus PO stepdown for uncomplicated Streptococcal BSIs. Methods This single-center, retrospective, non-inferiority study included adults who had Streptoccoccus spp. in blood cultures with susceptibilities reported, &amp;lt; 48 hours of positive blood cultures, and were treated for the BSI. Patients were excluded if they had polymicrobial bacteremia, mortality prior to treatment completion, unattainable source control, or a complicated infection. The primary outcome was clinical success, defined as absence of infection recurrence, infection-related readmission, and infection-related mortality at 90 days. Secondary outcomes included individual components of composite endpoint, microbiological success, LOS, IV-line associated complications, and antibiotic-associated adverse events. Results Of 79 patients included, 36 patients (45.6%) received IV for the full course of therapy and 43 (54.4%) received PO stepdown. Baseline characteristics were similar between groups. The most common sources were skin and soft tissue (34.6%) and oropharyngeal (13.6%). The median duration of IV therapy in PO stepdown patients was 4.4 days (IQR 2.7 – 6.9). Amoxicillin/clavulanate (44%) and cefdinir (24%) were the most common PO agents. Clinical success occurred in 94% of IV only patients and 91% of PO stepdown patients (p = 0.573). No infection-related deaths or recurrences occurred. Line complications were more frequent in patients receiving IV compared to PO stepdown therapy (14% vs. 0%, p = 0.015). LOS was lower in the PO stepdown group (11 vs. 6 days, p &amp;lt; 0.001). Conclusion This study strengthens the hypothesis that PO stepdown therapy may be non-inferior to IV therapy for clinical success with a trend towards decreased LOS and line complications. However, this study was not powered to meet statistical significance. We are collaborating with several other centers to determine the true impact of this intervention. Disclosures All Authors: No reported disclosures.

159. Antibiotic and diagnostic stewardship surrounding pre-operative testing in patients undergoing cardiac surgery

Abstract Background Despite national guidelines from the US Preventative Services Task Force and the Infectious Diseases Society of America that recommend against screening for asymptomatic bacteriuria (ASB, defined as &amp;gt; 105 CFU of an organism) in most circumstances, pre-operative screening urine culture (UCx) continues. Detection and treatment of ASB leads to antibiotic exposure and risk of antibiotic-associated adverse events like drug reactions, Clostridioides difficile infection (CDI), and colonization by drug-resistant organisms. We describe the implementation of eliminating pre-operative screening for ASB in patients undergoing cardiac surgery. Figure 1Pre-operative checklist for cardiac surgery prior to intervention Methods This was a pre-post study of practice change involving removing ASB screening as part of the pre-cardiac surgery checklist (Figure 1). The pre-intervention period was 08/18/21 – 11/17/21, the post intervention period was 12/1/21 – 3/1/22. We identified all patients who underwent a cardiac arterial bypass graft procedure with or without vein harvesting. We reviewed pre-operative UCx, test indication, antibiotic administration pre-operatively due to culture growth, and post-operative CDI and CAUTI within 30 days post procedure identified through routine infection prevention and control surveillance. Results Pre-intervention, 117/128 (91.4%) patients undergoing cardiac surgery had a UCx collected. Of the UCx, 100% were ordered as part of the pre-operative checklist and not for symptoms. Five patients pre-intervention had ASB detected. Four patients received antibiotics to treat ASB. A fifth patient received antibiotics for bacteriuria which did not meet ASB count threshold. Post-intervention, 15/123 had a UCx (12.3%). Of these, 12/15 were ordered as part of the pre-operative checklist (80%), and the remaining three had symptoms documented. Post-intervention, one patient had ASB detected and did not receive antibiotics. Pre- and post-intervention there were 2 cases of CDI (2/128, 1.6% and 2/123, 1.6%, respectively). There were no CAUTIs either pre- or post-intervention. Conclusion Standard pre-operative UCx is known to be a low-value test and is not recommended by national guidelines. In this single-center diagnostic stewardship intervention, screening was reduced by 87.2%. There was no change in infectious outcomes. Disclosures All Authors: No reported disclosures.

905. Impact of a Real-Time Electronic Alert on Antibiotic Treatment Duration for Pneumonia in Hospitalized Patients

Abstract Background Limiting antibiotic prescribing to the shortest effective duration reduces antibiotic-associated adverse events and resistance. Up to two-thirds of patients receive excessive durations of therapy for pneumonia. This study evaluated the effect of a stewardship intervention to reduce excess antibiotic duration for inpatients with pneumonia. Methods A dashboard was developed to generate real-time alerts when inpatients at an academic medical center received antibiotics with an indication of community- or hospital-acquired pneumonia for more than 5 or 7 days, respectively. From November 2019 through April 2021, alerts were regularly reviewed by the antibiotic stewardship (AS) team and intervened upon when patients exceeded the guideline recommended duration of therapy for pneumonia without additional indications for continuing antibiotics. We compared inappropriate duration of therapy pre- and post-implementation of the dashboard by calculating the mean number of excess days of antibiotics beyond the recommended duration. Patients with SARS-CoV-2 infection and patients on hospital services that care for patients with cystic fibrosis, bronchiectasis, or immunocompromising conditions were excluded. Four other hospitals within the same health system that did not utilize the dashboard generated alerts served as a comparison group. Results During the intervention period, the AS team reviewed 834 patients with dashboard alerts and documented 115 interventions. For alerts reviewed without intervention, reasons for lack of intervention included active Infectious Diseases consult, additional infection diagnosis requiring a longer duration, and delayed clinical improvement. In the post-implementation period there was a mean of 1.28 excess days of antibiotics for pneumonia compared to the pre-implementation mean of 1.36 excess days. In comparison, aggregating data from the hospitals not utilizing the dashboard, there was a mean of 0.67 excess days post-intervention, compared to a mean 0.62 days pre-intervention. Conclusion The pneumonia dashboard is a potentially valuable stewardship tool which may reduce excess days of antibiotics for pneumonia. The dashboard’s impact may be improved by daily review and excluding patients with additional infection diagnoses. Disclosures Kathleen Degnan, MD, Gilead: Grant/Research Support.

Antibiotic-associated Adverse Drug Events in Hospitalized Children

Antibiotic-associated Adverse Drug Events in Hospitalized Children

Recommendations for antimicrobial stewardship during end-of-life patient care

Background: Antimicrobials are frequently used during end-of-life care and may be prescribed without a clear clinical indication. Overuse of antimicrobials is a major public health concern because of the development of multidrug resistant organisms (MDROs). Antimicrobial stewardship programs are associated with reductions in antibiotic resistance and antibiotic-associated adverse events. We sought to identify and describe opportunities to successfully incorporate stewardship strategies into end-of-life care. Methods: We completed semistructured interviews with 15 healthcare providers at 2 VA medical centers, 1 inpatient setting and 1 long-term care setting. Interviews were conducted via telephone between November 2020 and June 2021 and covered topics related to antibiotic prescribing for hospice and palliative-care patients, including how to improve antimicrobial stewardship during the end-of-life period. We targeted healthcare providers who are involved in prescribing antibiotics during the end-of-life period, including hospitalists, infectious disease physicians, palliative care and hospice physicians, and pharmacists. All interviews were recorded, transcribed, and analyzed using consensus-based inductive and deductive coding. Results: End-of-life care, particularly hospice care, was described as an underutilized resource for patients, who are often enrolled in their final days of life rather than earlier in the dying process. Even at facilities with established antimicrobial stewardship programs, healthcare providers interviewed believed that opportunities for antimicrobial stewardship in the hospice and palliative care settings were missed. Recommendations for how stewardship should be incorporated in end-of-life care included receiving feedback on antimicrobial prescribing, increasing pharmacist involvement in prescribing decisions, and targeted education for providers on end-of-life care, including the value of shared decision making with patients around antibiotic use. Conclusions: Improved antibiotic prescribing during end-of-life care is critical in the effort to combat antimicrobial resistance. Healthcare providers discussed antimicrobial stewardship activities during end-of-life patient care as a potential avenue to improve appropriate antibiotic prescribing. Future research should evaluate the feasibility and effectiveness of incorporating these strategies into end-of-life patient care.Funding: NoneDisclosures: None

Antimicrobial Stewardship Using Biomarkers: Accumulating Evidence for the Critically Ill.

This review aims to summarize current progress in the management of critically ill, using biomarkers as guidance for antimicrobial treatment with a focus on antimicrobial stewardship. Accumulated evidence from randomized clinical trials (RCTs) and observational studies in adults for the biomarker-guided antimicrobial treatment of critically ill (mainly sepsis and COVID-19 patients) has been extensively searched and is provided. Procalcitonin (PCT) is the best studied biomarker; in the majority of randomized clinical trials an algorithm of discontinuation of antibiotics with decreasing PCT over serial measurements has been proven safe and effective to reduce length of antimicrobial treatment, antibiotic-associated adverse events and long-term infectious complications like infections by multidrug-resistant organisms and Clostridioides difficile. Other biomarkers, such as C-reactive protein and presepsin, are already being tested as guidance for shorter antimicrobial treatment, but more research is needed. Current evidence suggests that biomarkers, mainly procalcitonin, should be implemented in antimicrobial stewardship programs even in the COVID-19 era, when, although bacterial coinfection rate is low, antimicrobial overconsumption remains high.