Cost evaluation of continuation of therapy with dalbavancin compared to standard-of-care antibiotics alone in hospitalized persons who inject drugs with severe gram-positive infections.

PURPOSE: Persons who inject drugs (PWID) are at risk for severe gram-positive infections and may require prolonged hospitalization and intravenous (IV) antibiotic therapy. Dalbavancin (DBV) is a long-acting lipoglycopeptide that may reduce costs and provide effective treatment in this population. METHODS: This was a retrospective review of PWID with severe gram-positive infections. Patients admitted from January 1, 2017, to November 1, 2019 (standard-of-care [SOC] group) and from November 15, 2019, to March 31, 2022 (DBV group) were included. The primary outcome was the total cost to the healthcare system. Secondary outcomes included hospital days saved and treatment failure. RESULTS: A total of 87 patients were included (37 in the DBV group and 50 in the SOC group). Patients were a median of 34 years old and were predominantly Caucasian (82%). Staphylococcus aureus (82%) was the most common organism, and bacteremia (71%) was the most common type of infection. Compared to the SOC group, the DBV group would have had a median of 14 additional days of hospitalization if they had stayed to complete their therapy (P = 0.014). The median total cost to the healthcare system was significantly lower in the DBV group than in the SOC group ($31,698.00 vs $45,093.50; P = 0.035). The rate of treatment failure was similar between the groups (32.4% in the DBV group vs 36% in the SOC group; P = 0.729). CONCLUSION: DBV is a cost-saving alternative to SOC IV antibiotics for severe gram-positive infections in PWID, with similar treatment outcomes. Larger prospective studies, including other patient populations, may demonstrate additional benefit.

Antibiotic Use and Associated Risk Factors for Antibiotic Prescribing in COVID-19 Hospitalized Patients.

BACKGROUND: Literature suggests that antibiotic prescribing in COVID-19 patients is high. Currently, there are insufficient data on what drives antibiotic prescribing practices throughout the COVID-19 pandemic. OBJECTIVE: This study sought to determine antibiotic use rates and identify risk factors for antibiotic prescribing in hospitalized patients. It was the first study to assess risk factors for receiving more than 1 course of antibiotics. METHODS: This was a retrospective, multi-center, observational study. Patients admitted from March 1, 2020, to May 31, 2020, and treated for COVID-19 were included. The primary endpoint was the rate of antibiotic use during hospitalization. Secondary endpoints included risk factors associated with antibiotic use, risk factors associated with receiving more than 1 antibiotic course, and rate of microbiologically confirmed infections. RESULTS: A total of 208 encounters (198 patients) were included in the final analysis. Eighty-three percent of patients received at least 1 course of antibiotics, despite low rates of microbiologically confirmed infection (12%). Almost one-third of patients (30%) received more than 1 course of antibiotics. Risk factors identified for both antibiotic prescribing and receiving more than 1 course of antibiotics included increased hospital length of stay (median 12 days), intensive care unit admission, and the necessity for mechanical ventilation. CONCLUSION AND RELEVANCE: There were high rates of antibiotic prescribing with low rates of microbiologically confirmed bacterial co-infection. Many patients received more than 1 course of antibiotics during hospitalization. This study highlights the importance and demand for appropriate antibiotic stewardship practices in COVID-19 patients.

Clinical Outcomes and Treatment Strategies in Patients With Non-Carbapenemase-producing Carbapenem-Resistant Versus Carbapenem-Susceptible Enterobacterales Infections.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are difficult to treat and can cause significant morbidity and mortality, however most data reflect carbapenemase-producing infections. OBJECTIVE: Our objective was to evaluate clinical outcomes of non-carbapenemase-producing CRE (nCP-CRE) compared with carbapenem-susceptible Enterobacterales (CSE) infections. METHODS: This was a retrospective, multicenter, observational study (January 1, 2018 to December 31, 2020). The primary outcome was clinical success at 30 days with secondary outcomes, including clinical success at 90 days, clinical success based on treatment for nCP-CRE, persistent bacteremia, intensive care unit (ICU) admission, length of stay, and rate of Clostridioides difficile or multidrug resistant infections. RESULTS: The final analysis included 211 patients: 142 (67%) with CSE and 69 (33%) with nCP-CRE infections. Prior carbapenem exposure was more common with nCP-CRE (15% vs 4%, P = 0.01). Clinical success at 30 days was similar between groups (77% vs 74%, P = 0.73). There were no differences in secondary outcomes. There was an overall low use of carbapenems (empiric 6%, definitive 7%). Most nCP-CRE infections were treated with a monotherapy carbapenem-sparing regimen (empiric 88%, definitive 90%). Limitations include the retrospective design and the high rate of urinary infections. CONCLUSION AND RELEVANCE: Our study found no difference in clinical outcomes between nCP-CRE and CSE infections. Application of this study with future studies would help in determining optimal regimens for these infections.

Development and implementation of pharmacy department and pharmacy resident well-being programs.

PURPOSE: Burnout in healthcare can have serious consequences, as it decreases patient care quality. Recent studies have found pharmacy employees have high rates of burnout, but formalized pharmacy well-being programs are not reported in the literature. METHODS: We developed a departmental pharmacy well-being program and focused residency well-being program in October and July 2020, respectively. The program committees sent anonymous surveys to all pharmacy employees to identify opportunities to improve well-being. The feasibility and impact of ideas were assessed by committee members and presented to pharmacy leadership who endorsed and supported all proposed initiatives prior to implementation. Pharmacist distress scores were measured using the Well-Being Index (WBI). RESULTS: The WBI was completed by 49% of invited pharmacists (137 of 278) in November 2020 and 41% (116 of 283) in June 2021. There was a numerical improvement in mean (SD) WBI scores from 2.06 (2.47) in November 2020 to 1.52 (2.49) in June 2021 (P = 0.09). Pharmacy residents had significantly higher distress scores than nonresident pharmacists (P = 0.01). However, pharmacy resident scores improved by almost 50% between the 2 time points, from 4.43 (2.13) to 2.40 (2.42); P = 0.03. CONCLUSION: The development of a system-wide pharmacy well-being program creates a structure to collect ideas from employees, implement well-being initiatives, measure burnout using a validated tool such as the WBI, and continue to build, evaluate, and adapt new interventions. Importantly, the program went beyond addressing individual needs and addressed institutional opportunities that impact well-being. This can serve as a model for other pharmacy departments looking to implement similar programs.

Empiric aztreonam is associated with increased mortality compared to beta-lactams in septic shock.

PURPOSE: To determine if aztreonam as initial empiric treatment of adult septic shock is associated with increased mortality compared to the use of anti-pseudomonal beta-lactam agents. METHODS: This was a multicenter, retrospective cohort study of 582 adult emergency department patients admitted to 12 acute care facilities within a single health system from January 2014 to December 2017 with septic shock receiving either aztreonam or an anti-pseudomonal beta-lactam for empiric treatment and discharged with an infection-related ICD-9 or ICD-10 code. The primary endpoint was in-hospital mortality. RESULTS: Initial exposure to aztreonam was associated with increased hospital mortality compared to treatment with an anti-pseudomonal beta-lactam agent (22.7% vs. 12.9%, OR = 1.98, 95% CI: 1.27-3.11). When adjusted for APACHE II score, the treatment group effect on mortality remained statistically significant (OR = 1.74, 95% CI: 1.08-2.80). Aztreonam use was also associated with increased utilization of aminoglycosides (28.9% vs. 12.4%, p < 0.0001) and fluoroquinolones (50.5% vs. 25.8%, p < 0.01). There was no difference in hospital or intensive care unit length of stay in surviving patients between the two groups. CONCLUSIONS: Compared to anti-pseudomonal beta-lactams, empiric treatment with aztreonam is associated with increased mortality and greater antibiotic exposure among patients with acute septic shock. These findings suggest that treatment with anti-pseudomonal beta-lactams should be prioritized over allergy avoidance whenever feasible.

Antibiotic Stewardship Interventions Improve Choice of Antibiotic Prophylaxis in Total Joint Arthroplasty in Patients with Reported Penicillin Allergies.

BACKGROUND: Most patients who report a penicillin allergy can tolerate cefazolin, the preferred prophylaxis in a total joint arthroplasty (TJA). Regardless, patients with a reported penicillin allergy are less likely to receive first-line perioperative antibiotics as a result of inaccurate penicillin allergy documentation and misconceptions regarding cross-reactivity between penicillin and cephalosporins. The over-reporting of penicillin allergies and the safety of cephalosporins in patients with reported penicillin allergies have been well established throughout the evidence [13]. QUESTIONS/PURPOSES: The study sought to answer two questions: (1) Do antibiotic stewardship interventions improve adherence to appropriate prophylactic antibiotic usage in patients with a documented penicillin allergy undergoing primary TJA? (2) What is the risk of allergic or adverse reactions secondary to cefazolin use in patients with a documented penicillin allergy? METHODS: This was a single-center, retrospective study of orthopaedic patients older than 18 years who underwent a primary elective TJA at a 261-bed community hospital. The study had two periods: the preintervention period ran from March 1, 2017 to August 30, 2017 and the postintervention period was from March 1, 2019 to August 30, 2019. A total of 396 patients with a history of a documented penicillin allergy underwent a THA or TKA during the study periods. After reviewing every fourth patient with a history of a documented penicillin allergy who met study inclusion criteria and excluding those patients who had a codocumented cephalosporin allergy, a total of 180 patients with a documented penicillin allergy were evaluated (90 patients in the preintervention group and 90 patients in the postintervention group). To answer our first study question, regarding whether antibiotic stewardship interventions improve adherence to appropriate prophylactic antibiotic usage in patients with a documented penicillin allergy undergoing primary TJA, we evaluated appropriate antibiotic usage pre- and postintervention. To answer our second study question, concerning the risk of allergic or adverse reactions secondary to cefazolin use in patients with a documented penicillin allergy, we reviewed signs of allergic reactions in patients who received cefazolin for a primary TJA and had a documented penicillin allergy. RESULTS: Postintervention antibiotic use was more appropriate (91% [82 of 90] versus 54% [49 of 90], risk ratio 1.67 [95% confidence interval 1.37 to 2.04]; p < 0.01), particularly in patients with nonsevere allergy (preintervention: 47% [36 of 76] versus postintervention: 96% [76 of 79]; p < 0.01). No patients had signs of an allergic reaction related to cefazolin, including eight patients with severe penicillin allergy. CONCLUSION: A multifaceted antibiotic stewardship intervention increased the appropriateness of antibiotic prophylaxis in elective primary TJA. Patients with nonsevere penicillin allergies, even those reporting hives or local swelling, tolerated cefazolin. Antibiotic stewardship interventions can be implemented across institutions to expand cephalosporin use in patients with a reported penicillin allergy within orthopaedic TJA patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Rate of broad-spectrum antibiotic overuse in patients receiving outpatient parenteral antibiotic therapy (OPAT).

Broad-spectrum antibiotics with once-daily dosing are often chosen for outpatient parenteral antibiotic therapy (OPAT) due to convenience even when narrower-spectrum antibiotics are appropriate. At our institution, up to 50% of select broad-spectrum OPAT regimens had potential to be narrowed, highlighting the need to re-evaluate regimens for de-escalation prior to discharge.

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species.

OBJECTIVES: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. METHODS: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. RESULTS: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis. CONCLUSIONS: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

Antimicrobial de-escalation in adult hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin.

BACKGROUND: The optimal duration of empiric antimicrobial therapy in febrile neutropenia of unknown origin is unclear. This study evaluated outcomes in autologous and allogeneic hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin who received early de-escalation of broad-spectrum antimicrobials prior to hematopoietic recovery versus those who continued broad-spectrum antimicrobials until hematopoietic recovery. METHODS: A single-center, retrospective study assessed hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin. Patients were categorized into either cohort 1, representing early de-escalation prior to hematopoietic recovery, or cohort 2, representing continuation of broad-spectrum antimicrobials until hematopoietic recovery. RESULTS: A total of 107 patients were included (22.4% in cohort 1 and 77.6% in cohort 2). Most patients (87.5%) in cohort 1 underwent haploidentical hematopoietic cell transplantation, whereas 84.3% of patients in cohort 2 received autologous hematopoietic cell transplantation. There were no significant differences in rates of recurrent fever (4.2% versus 7.2%, in cohorts 1 and 2, respectively, adjusted odds ratio = 0.84, P = 0.85), re-escalation (4.2% versus 4.8%, adjusted odds ratio = 1.57, P = 0.64), and Clostridioides difficile-associated infections (4.2% versus 2.4%, adjusted odds ratio = 2.27, P = 0.43). No patient experienced in-hospital mortality, intensive care unit admission, or bacteremia. CONCLUSION: Hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin in which broad-spectrum antimicrobials were de-escalated prior to hematopoietic recovery did not experience adverse outcomes. These results concur with recently published studies and the Fourth European Conference on Infections in Leukemia guidelines. An early de-escalation approach in haploidentical hematopoietic cell transplantation recipients specifically appears safe and may result in a reduction in antimicrobial utilization.

Inpatient Antibiotic Stewardship Interventions in the Adult Oncology and Hematopoietic Stem Cell Transplant Population: A Review of the Literature.

Objective: To review the use of antibiotic stewardship interventions in the adult oncology and hematopoietic cell transplantation (HCT) populations. Data Sources: A literature search of PubMed was performed from inception to October 31, 2019. The general search terms used were oncology, cancer, hematologic malignancy, antimicrobial stewardship, antibiotic stewardship, febrile neutropenia, neutropenic fever, de-escalation, discontinuation, prophylaxis, practice guidelines, clinical pathway, rapid diagnostics, Filmarray, Verigene, MALDI-TOF, antibiotic allergy, and antimicrobial resistance. Study Selection and Data Extraction: Relevant English-language studies describing interventions supported by the Infectious Diseases Society of America guidelines on "Implementing an Antibiotic Stewardship Program" were included. Data Synthesis: Antibiotic stewardship publications in the oncology population have increased in recent years. Studies have described the impact of stewardship interventions, including preauthorization, prospective audit and feedback, implementation of clinical pathways, de-escalation of empirical antibiotics for febrile neutropenia (FN) prior to neutrophil recovery, allergy assessments, and use of rapid diagnostic testing. Many of these interventions have been shown to decrease antibiotic use without increased negative consequences, such as affecting length of stay or mortality. Relevance to Patient Care and Clinical Practice: This review synthesizes available evidence for implementing antibiotic stewardship interventions, particularly de-escalation of antibiotics for FN and implementation of clinical pathways for FN and sepsis, in oncology patients and HCT recipients. Summary tables highlight studies and specific research needs for clinicians. Conclusions: Immunocompromised populations, including oncology patients, have often been excluded from stewardship studies. Antibiotic stewardship is effective in reducing antibiotic consumption and improving outcomes in this patient population, although more quality data are needed.

Novel developments in the treatment of acute bacterial skin and skin structure infections.

Introduction: Acute bacterial skin and skin structure infection (ABSSSI) represents a major burden for healthcare systems. The increased prevalence of Methicillin-resistant Staphylococcus aureus, combined with the limited availability of microbiologic data when treating ABSSSI, has led to a need for more convenient, less toxic anti-MRSA agents. Recent approvals have added several agents to the antibiotic armamentarium that provide an expanded spectrum of activity and ease of administration compared to older agents. Areas covered: In this review, the authors discuss updated approaches to the management of ABSSSI. They also provide a review of recent FDA approved antibiotics and emerging investigational agents for treatment of ABSSSI. Expert opinion: Several new antibiotic agents have received FDA approval through the revised guidance on ABSSSI clinical trials with advantages of activity against MRSA and ease of administration. In theory, this may translate to reducing the utilization of healthcare resources by allowing for earlier discharge and reducing the need for outpatient parenteral therapy. While the approval of new agents offers the opportunity to improve and simplify treatment of ABSSSI, it is more important now than ever to use these agents in a responsible manner.

Effect of a multifaceted stewardship intervention on antibiotic prescribing and outcomes for acute bacterial skin and skin structure infections.

BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI) are a leading cause of hospitalization, but are often treated inappropriately in the inpatient setting. A multifaceted stewardship intervention was implemented to encourage prescribing of guideline-concordant therapy (GCT). OBJECTIVE: To examine the impact of this initiative on antimicrobial prescribing practices and patient outcomes. METHODS: This was a single-center, retrospective study of adult inpatients admitted with a primary or secondary diagnosis of ABSSSI, classified by type and severity based on signs of systemic infection. Patients treated during the pre-intervention period (pre-IP) were compared with patients treated during the post-intervention period (post-IP). The primary endpoint was receipt of GCT. Secondary endpoints included receipt of anti-anaerobic antibiotic (AAA) or broad-spectrum antibiotics (BSA). RESULTS: A total of 125 patients were included, 64 in the pre-IP and 61 in the post-IP. There was a statistically significant increase in prescribing of GCT during the post-IP compared with the pre-IP (14% versus 56%, p < 0.0001) and a decrease in use of AAA (56% versus 34%, p = 0.01). No difference was observed with use of BSA (16% versus 15%, p = 0.89). Use of the computerized order set during the post-IP was low (18%). There was a numerical, but non-significant reduction in 30-day readmission (14.1% versus 6.6%, p = 0.17). CONCLUSION: The multifaceted intervention was effective for improving prescribing of GCT for ABSSSI. Given low use of the computerized order set, improved prescribing seemed to be driven by provider education. Strategies around ongoing education may be key to sustain positive results of stewardship interventions.