A Resident-Preceptor Collaboration to Encourage Wellness and Reduce Burnout Amongst Pharmacy Residents.

Pharmacy residents are especially vulnerable to burnout given the professional and personal stressors associated with postgraduate training. Residency programs need to prioritize burnout reduction strategies to support resident health and well-being. This commentary describes a resident-preceptor collaborative approach to encourage wellness and reduce burnout within a large residency program at an academic medical center. Strategies that have been utilized include (1) fostering collaboration among residents and preceptors; (2) assessing resident interests and needs to ensure alignment; (3) leveraging available institutional and community resources; and (4) integrating initiatives within the existing residency program structure. This commentary aims to provide suggestions that can be implemented to address resident burnout for other residency programs, regardless of resource availability.

Clinical Outcomes with Ertapenem for Pneumonia in Obese versus Nonobese Patients.

The objective of this study was to compare the rate of pneumonia resolution in obese (body mass index [BMI], ≥30 kg/m2) and nonobese (BMI, <30 kg/m2) patients treated with 1 gram ertapenem daily. In this retrospective cohort study, we evaluated patients treated at The Ohio State University Wexner Medical Center between 1 January 2015 and 31 August 2020. Patients were included if they were between 18 and 89 years old and received ertapenem for at least 48 hours for pneumonia treatment. Patients were excluded if they were pregnant, were incarcerated, had renal impairment, received antibiotics with Gram-negative activity for a significant period prior to or in addition to ertapenem, and had other concomitant deep-seated infections. The primary outcome of clinical resolution was defined as meeting any of the following three criteria in order of evaluations: discontinuation of antibiotics by day 8 of therapy, afebrile while on ertapenem in addition to a decrease in white blood cell count, or improvement on chest radiograph at day 7 of therapy. A multivariable logistic regression analysis was performed to examine the association between obesity and clinical resolution, while adjusting for proven confounders. There were 76 nonobese and 65 obese patients included. The median patient BMI was 23.7 kg/m2 (21.0 to 26.9) and 35.0 kg/m2 (32.8 to 39.8) for the nonobese and obese cohorts, respectively. Clinical resolution was achieved in 78% (59/76) of nonobese and 75% (49/65) of obese patients (P = 0.75) without an observed difference in the regression model. Outcomes were similar in obese and nonobese patients treated with 1 gram of ertapenem daily for pneumonia.

Clinical Outcomes With Definitive Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia With Retained Daptomycin and Ceftaroline Combination Therapy vs De-escalation to Monotherapy With Vancomycin, Daptomycin, or Ceftaroline.

BACKGROUND: Lower mortality has been observed with combination therapy compared to monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia; however, there is a lack of evidence for continued combination therapy over de-escalation to monotherapy following bacteremia clearance. METHODS: This was a single-center, retrospective study evaluating patients with MRSA bacteremia hospitalized from November 1, 2011, through July 31, 2019. Patients who received three to ten days of combination therapy followed by de-escalation to monotherapy were directly compared to patients retained on combination therapy. The primary composite outcome included inpatient infection-related mortality, 60-day readmission, and 60-day bacteremia recurrence. RESULTS: A total of 286 patients with MRSA bacteremia were identified, with 146 patients omitted based on exclusion criteria. The study population included 66 in the combination therapy group and 74 in the monotherapy group. Study population was 51% female (n = 71) and 78% white (n = 109) with median age of 46 years (IQR 34.5-61). No significant difference was observed in the primary composite outcome (21% combination therapy group vs 24% monotherapy group; P =.66), with retained observations after controlling for confounders. Within this outcome, there was no significant difference in 60-day readmission (20% combination therapy group vs 18% monotherapy group; P =.75), bacteremia recurrence (3% combination therapy group vs 7% monotherapy group; P =.45), or inpatient infection-related mortality (2% combination therapy group vs 5% monotherapy group; P = 1.00). CONCLUSIONS: No difference was found in the composite outcome of 60-day bacteremia recurrence, readmission, or inpatient infection-related mortality for patients with MRSA bacteremia retained on combination therapy versus those de-escalated to monotherapy.

Clinical Impact of an Antibiotic Time Out Initiative at an Academic Medical Center.

Background: Various strategies aimed at limiting inappropriate antimicrobial use including antibiotic time out (ATO) have been proposed to combat the development of antimicrobial resistance, yet there are limited studies that have assessed the impact of ATO on clinical outcomes. Methods: This single-center retrospective study reviewed the effect of a passive ATO strategy by comparing 100 adult patients with an ATO matched by infection type to 100 antibiotic-treated adult patients lacking an ATO note. Results: No difference in clinical outcomes was observed, however, ATO did result in improved optimization of antibiotic selection and duration, and reduction of piperacillin/tazobactam and vancomycin use. Conclusion: Further studies are warranted to evaluate the impact of ATO on clinical outcomes of a larger homogenous population with specified infectious diagnoses and clinical characteristics.

Clinical outcomes of combination versus monotherapy for gram negative non-HACEK infective endocarditis.

The objective of this single-center, retrospective cohort study was to identify whether combination therapy is associated with a lower rate of adverse outcomes for the treatment of Gram negative non-HACEK IE. The primary endpoint was a composite of 60-day all-cause mortality, readmission, or recurrence of bacteremia. Of the 60 patients included, 56.7% met the primary composite outcome, with 20% overall mortality at 60 days. There was no difference in the primary composite outcome of 60-day readmission, infection recurrence or mortality between groups, with 62% of patients in the monotherapy group and 50% of patients in the combination therapy group experiencing the composite outcome (P = 0.36). Despite the high mortality and complicated nature of non-HACEK Gram negative IE, this study showed no difference in 60-day bacteremia recurrence, readmission or mortality among patients treated with combination therapy or monotherapy, suggesting that monotherapy may lead to similar clinical outcomes.

Clinical Outcomes of Daptomycin Versus Anti-Staphylococcal Beta-Lactams in Definitive Treatment of Methicillin-susceptible Staphylococcus aureus Bloodstream Infections.

OBJECTIVES: Staphylococcus aureus (S. aureus) is the leading cause of bacteraemia and infective endocarditis worldwide. The preferred management of patients with methicillin-susceptible S. aureus (MSSA) bacteraemia includes definitive therapy with intravenous anti-staphylococcal beta-lactam (ASBL) antibiotics. Daptomycin (DAP) has been targeted as a viable substitute for beta-lactam allergic or intolerant patients. METHODS: This single-center retrospective cohort study assessed clinical outcomes of DAP compared with ASBL antibiotics [nafcillin (NAF) or cefazolin (CFZ)] for the treatment of MSSA bacteraemia in patients hospitalised from 01 November 2011 to 31 October 2018. The primary outcome was a composite of the following: clinical failure, MSSA recurrence and MSSA persistence or inpatient infection-related mortality. Secondary outcomes included duration of MSSA bacteraemia, infection-related length of stay, infection-related 90-day readmission, 30-day all-cause mortality, and adverse events necessitating a change in therapy. RESULTS: Of 89 patients with MSSA bacteraemia who were included: 29 received DAP, 30 received NAF and 30 received CFZ. There was no difference in the composite primary outcome in patients treated with DAP compared with ASBL (10% vs. 5%, P = 0.39). The DAP cohort had a longer hospital length of stay compared with the ASBL group (20 days vs. 11.5 days, P = 0.0007). No differences were detected between other secondary outcomes. CONCLUSION: This study suggests that DAP may serve as a comparable alternative to ASBLs for treatment of MSSA bacteraemia, as no differences in clinical outcomes were identified. Larger studies are needed to confirm these findings.

Oral fluoroquinolones for definitive treatment of gram-negative bacteremia in cancer patients.

PURPOSE: Bloodstream infections (BSI) are significant causes of morbidity and mortality in cancer patients. These patients often receive 10 to 14 days of intravenous (IV) antibiotics. The objective of this study was to compare the outcomes of cancer patients transitioned from IV to oral (PO) therapy compared to continuation of IV treatment. METHODS: This was a single-center, retrospective cohort study of hospitalized adult cancer patients with gram-negative bacteremia. Patients transitioned to a PO fluoroquinolone (FQ) within 5 days were allocated to the IV-to-PO group, while the remaining patients comprised the IV group. The primary outcome was the composite of treatment failure, defined as infection-related readmission, infection recurrence, or inpatient mortality. A multivariable logistic regression model was constructed to account for confounding variables. Secondary outcomes assessed included infection-related length of stay (LOS), hospital LOS, and adverse events, such as Clostridioides difficile infection and catheter-related complications. RESULTS: The IV-to-PO group included 78 patients, while the remaining 133 patients were allocated to the IV group. Differences at baseline included more hematologic malignancy, neutropenia, ICU admissions, and higher Pitt bacteremia scores in the IV group. The rate of treatment failure was significantly higher in the IV group (24% vs 9%; p < 0.01), which persisted in the logistic regression (aOR 3.5, 95% CI 1.3-9.1). The IV-to-PO group had decreased infection-related and hospital length of stay, as well as fewer catheter-related complications. CONCLUSIONS: The use of PO FQ may be considered for the definitive treatment of uncomplicated Enterobacterales BSI in cancer patients.

Safety outcomes with high-dose daptomycin in patients with acute kidney injury and/or end-stage renal disease.

WHAT IS KNOWN: Daptomycin is associated with a number of adverse effects including eosinophilic pneumonia, hypersensitivity reaction, myopathy, rhabdomyolysis, headache and transaminitis. The adverse effects of high-dose daptomycin have not been fully evaluated in patients with end-stage renal disease (ESRD). OBJECTIVE: To determine the incidence and characteristics of significant adverse effects in patients receiving high-dose daptomycin with severe renal dysfunction. METHODS: A single-centre, retrospective study was conducted to assess safety outcomes of high-dose daptomycin in patients with an estimated creatinine clearance less than 30 mL/min. Adult patients aged 18 to 89 years admitted between 1 July 2015 and 1 July 2019 were eligible for inclusion. Patients must have received definitive daptomycin therapy with doses greater than or equal to 7.5 mg/kg based on actual body weight. The primary outcome was overall incidence of creatine phosphokinase (CK) elevation, myopathy and rhabdomyolysis. RESULTS AND DISCUSSION: A total of 74 patients who received daptomycin therapy were screened with 50 included in the study. The population was well distributed in terms of gender (48% male, n = 24) with a median age of 61 (IQR, 48-67) years. The primary indication for daptomycin use was Gram-positive bacteremia. The median daptomycin dose was 750 (IQR, 600-875) mg, or 8.46 (IQR, 7.92-9.96) mg/kg based on actual body weight, with a median patient weight of 81 (IQR, 65-113) kg. The median duration of therapy was 27 (IQR, 14-42) days. One patient experienced significant CK elevation while on daptomycin therapy with rhabdomyolysis; however, daptomycin was continued as there was an alternative explanation for an elevated CK. One patient experienced daptomycin discontinuation due to CK elevation without meeting the definition for significant CK elevation. WHAT IS NEW AND CONCLUSION: In a cohort of patients with severe renal dysfunction treated with daptomycin 7.5 mg/kg or greater, significant CK elevation on daptomycin therapy was infrequently observed. Future research should confirm these findings, with special consideration for higher mg/kg dosages and/or obese populations.

Clinical outcomes following treatment of Enterobacter species pneumonia with piperacillin/tazobactam compared to cefepime or ertapenem.

BACKGROUND: Enterobacter spp. are a common cause of nosocomial pneumonia and treatment can be complicated by AmpC resistance. Carbapenems are the treatment of choice; however, alternatives are needed. Cefepime has been shown to be non-inferior to carbapenems. There are limited data to support the use of piperacillin/tazobactam. The objective of this study was to determine if piperacillin/tazobactam is non-inferior to cefepime or ertapenem for Enterobacter pneumonia treatment. OBJECTIVES: To compare the rate of clinical cure in patients with Enterobacter pneumonia receiving definitive treatment with piperacillin/tazobactam, cefepime, or ertapenem. Secondary outcomes included hospital mortality, infection-related length of stay, duration of mechanical ventilation, recurrent pneumonia, and resistance. METHODS: Retrospective, single-center study. RESULTS: Of 114 patients included, 59 received definitive treatment with piperacillin/tazobactam and 55 received cefepime or ertapenem. There was no difference in the proportion of patients who achieved clinical cure in the piperacillin/tazobactam group compared to the cefepime or ertapenem group (76.3% vs. 87.3%, P = 0.13). Treatment group was not associated with clinical cure when controlling for confounders in multivariable logistic regression (adjusted odds ratio [OR] 0.59, 95% confidence interval [CI] 0.15-2.37). The rate of recurrent pneumonia was 11.4% in the piperacillin/tazobactam group and 6.7% in the cefepime or ertapenem group (P = 0.48). Other secondary outcomes did not differ between the groups. CONCLUSIONS: In this retrospective study of patients with Enterobacter pneumonia, clinical cure with piperacillin/tazobactam was comparable to that with cefepime or ertapenem; however, a prospective trial with a larger population is needed to determine if definitive treatment with piperacillin/tazobactam is non-inferior to definitive treatment with cefepime or ertapenem.

Efficacy of combination therapy versus monotherapy in the treatment of Stenotrophomonas maltophilia pneumonia.

BACKGROUND: Stenotrophomonas maltophilia is intrinsically resistant to several antibiotics, making it potentially challenging to treat. Studies have demonstrated treatment failures and resistance development with monotherapy (MT); however, clinical data are limited with combination therapy (CT). OBJECTIVES: To compare clinical outcomes with CT versus MT for S. maltophilia pneumonia. METHODS: This was a retrospective cohort study of patients admitted between November 2011 and October 2017 with S. maltophilia pneumonia who received at least 48 h of effective therapy. The primary outcome was clinical response after 7 days of effective therapy with CT versus MT. Secondary outcomes included development of a non-susceptible isolate, 30 day microbiological cure, infection recurrence, infection-related mortality and all-cause mortality. The Wilcoxon rank sum test, the Pearson χ2 test and Fisher's exact test were utilized for univariate analyses. A multivariable logistic regression model was used to assess clinical response while adjusting for confounding variables. RESULTS: Of 252 patients with S. maltophilia pneumonia included, 38 received CT and 214 received MT. There was no difference in 7 day clinical response with CT versus MT (47.4% versus 39.7%, P = 0.38), even after controlling for immune status, APACHE II score and polymicrobial pneumonia (adjusted OR 1.51, 95% CI 0.63-3.65). Thirty day microbiological cure (P = 0.44), recurrence (P = 0.53), infection-related mortality (P = 0.19) and isolation of a non-susceptible isolate during or after therapy (P = 1.00 each) were also similar between both groups; however, 30 day all-cause mortality was greater with CT (P = 0.03). CONCLUSIONS: CT had similar rates of clinical efficacy and resistance development compared with MT for S. maltophilia pneumonia.

Clinical Outcomes with Penicillin Versus Alternative ß-Lactams in the Treatment of Penicillin-Susceptible Staphylococcus aureus Bacteremia.

OBJECTIVES: To identify the impact of penicillin versus alternative ß-lactams on clinical outcomes in patients with penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Adult patients with PSSA bacteremia treated with a ß-lactam as definitive therapy. MEASUREMENTS: The primary outcome was a composite end point of 30-day clinical failure (change in PSSA therapy due to persistent or worsening signs and symptoms, PSSA bacteremia recurrence or persistence, and/or infection-related mortality) in patients treated with penicillin versus alternative ß-lactams. Secondary outcomes included infection-related and hospital length of stay (LOS), 90-day recurrence, 90-day infection-related readmission, 30-day all-cause mortality, adverse drug events (ADEs), and 30-day change in PSSA therapy due to ADEs. A subgroup analysis comparing penicillin, nafcillin, and cefazolin was also conducted. MAIN RESULTS: For the 122 patients who were included, the most common definitive therapies were nafcillin (37%), cefazolin (29%), and penicillin (21%). No difference was found in 30-day clinical failure (4% vs 11%, p=0.46), infection-related LOS (12 days vs 11 days, p=0.39), hospital LOS (12.5 days vs 12 days, p=0.69), 90-day recurrence (p=1.00), 90-day infection-related readmission (p=1.00), or 30-day all-cause mortality (p=0.45) between penicillin and other ß-lactams. The prevalence of ADEs was different among penicillin, nafcillin, and cefazolin (p=0.049), with nafcillin requiring more changes in therapy (p=0.005). CONCLUSIONS: Definitive therapy with penicillin had similar efficacy compared with alternative ß-lactams for the treatment of PSSA bacteremia. However, nafcillin was associated with more ADEs requiring a change in therapy.