Utility of incorporation of beta-D-glucan and T2Candida testing for diagnosis and treatment of candidemia.

The additive role of non-culture-based methods for the diagnosis of candidemia remains unknown. We evaluated 2 clinical practices followed in our hospitals for the diagnosis of candidemia, namely practice#1 including a combination of blood cultures and T2Candida, and practice#2 that also included Beta-D-glucan (BDG). Three out of 96 patients testing positive with practice#1 received a complete antifungal course. Of the 120 patients evaluated with practice#2, 29 were positive. Only 55.2% of those received a complete course. We observed significant differences in antifungal utilization, with 268.5 antifungal days/1000 patient-days for practice#1, as opposed to 371.9 days for practice#2, a nearly 40% difference. However, we found similar rates of antifungal discontinuation among negative patients at 3 days of testing (36.8% and 37.0% respectively). No differences were detected in death and/or subsequent diagnosis of candidemia. In summary, addition of BDG was interpreted variably by clinicians, was associated with an increase in antifungal utilization, and did not correlate with measurable clinical benefits for patients.

Treatment of Piperacillin-Tazobactam-Nonsusceptible/Ceftriaxone-Susceptible Infections With Carbapenem Versus Carbapenem-Sparing Antimicrobials.

Background: Escherichia coli and Klebsiella pneumoniae with a piperacillin-tazobactam-nonsusceptible/ceftriaxone-susceptible (TZP-NS/CRO-S) phenotype have been increasingly identified, with limited available literature evaluating treatment strategies. Methods: This was a retrospective study of noncritically ill adults hospitalized between 2013 and 2021 and treated at least 48 hours for TZP-NS/CRO-S E coli or K pneumoniae infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy. Results: Of 1062 patients screened, 200 were included (CG, n = 51; CSG, n = 149). Baseline characteristics, including Charlson Comorbidity Index (CCI; median [interquartile range], 6 [3-9] vs 6 [4-9]; P = .704), were similar between groups, except for more immunocompromised CG patients (29% vs 11%, P = .001). The most common infection sources were urinary (31% vs 57%, P = .002) and bloodstream (18% vs 17%, P = .887). Eighty-eight percent of the CG received meropenem, while 58% of the CSG received ceftriaxone as targeted therapy. There was no statistical difference in the primary endpoint between overall groups (27% vs 17%, P = .123), nor when stratified by infection source. More patients in the CSG switched to oral therapy (15 [29%] vs 100 [67%], P < .001). In multivariate analysis, CCI was an independent predictor of the primary outcome (odds ratio [OR], 1.199 [95% confidence interval, 1.074-1.340]; P = .001), while treatment with carbapenem-sparing therapy was not. Conclusions: Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort.

Novel Multidisciplinary Approach for Outpatient Antimicrobial Stewardship Using an Emergency Department Follow-Up Program.

Purpose: Outpatient antimicrobial stewardship programs (ASPs) are becoming increasingly prevalent in healthcare. Many programs have demonstrated the effectiveness of pharmacist-driven outpatient consultations or follow-up programs to ensure appropriate antimicrobial prescribing. However, there is a paucity of literature describing multidisciplinary approaches in large healthcare systems for patients discharged from the emergency department (ED). The objective of this study was to describe the feasibility and impact of a combined effort between ASP pharmacotherapy specialists and nurse practitioners (NPs) in managing an ED follow-up center. Methods: A retrospective analysis was conducted for patients discharged from the ED between January 2018 and June 2019. Patients were identified for inclusion based on documentation by ASP pharmacotherapy specialists in the electronic health record for patient-specific inquiries from ED follow-up center NPs. The primary outcome of this study was to describe the number and types of interventions made by ASP pharmacotherapy specialists. Results: A total of 1088 patients were included in the study, for 1114 documented ASP calls. The urinary tract was the most common source of positive culture (79%), and third-generation cephalosporins were the most frequent antibiotic associated with calls (20%). Out of total calls, 60% lead to ASP interventions. Among total calls, the most frequent interventions were to correct drug-bug mismatches (20%), initiate new therapy (10%), and discontinue therapy (7%). Conclusion: This report describes a novel initiative that combines the efforts of ED NPs and ASP pharmacotherapy specialists in managing an ED follow-up center at a large healthcare system.

Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients With Community-Acquired Pneumonia Admitted Within a Large Academic Health System.

BACKGROUND: Limited data support use of pneumococcal urinary antigen testing (PUAT) for patients with community-acquired pneumonia (CAP) as an antimicrobial stewardship tool. At our institution, CAP guidelines and admission order set were standardized to include universal PUAT. METHODS: This was a retrospective study of adults hospitalized in 2019 who had PUAT performed. We compared incidence and timing of de-escalation in PUAT- positive vs -negative groups and described patients' outcomes. RESULTS: We evaluated 910 patients, 121 (13.3%) of whom were PUAT positive. No difference in baseline characteristics, including severity of illness, was observed between groups. Initial de-escalation occurred in 82.9% and 81.2% of PUAT-positive and -negative patients, respectively (P = .749). Median time to de-escalation was shorter in the PUAT-positive group (1 [interquartile range {IQR}, 0-2] day vs 1 [IQR, 1-2] day, P = .01). Within 24 hours of PUAT, more patients in the PUAT-positive group had atypical coverage discontinued (61.3% vs 47.2%, P = .026) without difference in methicillin-resistant Staphylococcus aureus (MRSA) agent discontinuation (or antipseudomonal de-escalation). Among the PUAT-positive group, unadjusted analysis demonstrated shorter median length of stay in patients who were de-escalated compared to those who were not (6 [IQR, 4-10] vs 8 [IQR, 7-12] days, P = .0005), without difference in the incidence of Clostridioides difficile, in-hospital mortality, or 30-day infection-related readmission. CONCLUSIONS: We observed earlier de-escalation in the PUAT-positive group. This seems to be due to discontinuation of atypical rather than anti-MRSA or antipseudomonal coverage. Further antimicrobial stewardship interventions are warranted.

Oral Vancomycin as Secondary Prophylaxis for Clostridioides difficile Infection.

OBJECTIVES: Secondary oral vancomycin prophylaxis (OVP) has been used in adults with a history of Clostridioides difficile infection (CDI) while receiving systemic antibiotics to prevent CDI recurrence. However, this practice has not been studied in pediatric patients. The objective of this study was to assess the utility of secondary OVP in pediatric patients with previous CDI who received subsequent antibiotic exposure. METHODS: A multicampus, retrospective cohort evaluation was conducted among patients aged ≤18 years with any history of clinical CDI and receiving systemic antibiotics in a subsequent encounter from 2013-2019. Patients who received concomitant OVP with antibiotics were compared with unexposed patients. The primary outcome was CDI recurrence within 8 weeks after antibiotic exposure. Infection with vancomycin-resistant enterococci and risk factors for CDI recurrence were assessed. RESULTS: A total of 148 patients were screened, of which 30 and 44 patients received OVP and no OVP, respectively. Patients who received OVP had greater antibiotic use and hospital lengths of stay. The incidence of CDI recurrence within 8 weeks of antibiotic exposure was significantly lower in patients who received OVP (3% vs 25%; P = .02) despite this group having notably more risk factors for recurrence. There were no vancomycin-resistant enterococci infections in any patients within either group. After adjustment in a multivariable analysis, secondary OVP was associated with less risk of recurrence (odds ratio, 0.10; 95% confidence interval, 0.01-0.86; P = .04). CONCLUSIONS: Secondary OVP while receiving systemic antibiotics reduces the risk of recurrent CDI in pediatric patients with a history of CDI.

Outcomes of COVID-19 Patients Hospitalized at Acute Care Services: Real-World Experience in the New York Metropolitan Area During the Early Pandemic Before Initiation of Clinical Trials.

As New York became the epicenter of the COVID-19 pandemic early on, clinicians were challenged to provide optimal medical and pharmaceutical care, despite the paucity of supporting literature and guidance. We sought to describe prescribing patterns and outcomes of physician response to the urgent need to treat COVID-19 patients before initiation of randomized clinical trials. METHODS: This was a retrospective cohort study of adult patients with COVID-19 initially admitted to acute care services during March 2020. Critically ill patients requiring intensive care unit level of care on admission were excluded. RESULTS: A total of 639 consecutive patients (supportive care, n = 247; treatment n = 392) were included in the analysis. Overall, the 28-day mortality rate was 12.2%. The mortality was 8.7% higher in the treatment group (15.6% vs 6.9% in the supportive care group, P < 0.001). Treatment was not protective against progression to severe disease (18.4% vs 3.6% with supportive care, P < 0.0001). Time to defervescence, duration of oxygen support, and hospital and intensive care unit (ICU) length of stay were also higher in the treatment group. In multivariate analysis, 60 years or older, presence of severe disease, and need for ICU admission were identified as independent predictors of 28-day mortality. There were 41 (10.5%) adverse event in the treatment group, with the majority being QT prolongation and gastrointestinal effects. CONCLUSIONS: In this cohort of hospitalized patients admitted to acute care services, treatment with hydroxychloroquine, lopinavir/ritonavir or both could not be shown to improve mortality, progression to severe disease, or clinical response.

Clinical Outcomes of Ceftriaxone vs Penicillin G for Complicated Viridans Group Streptococci Bacteremia.

BACKGROUND: Ceftriaxone (CTX) and penicillin G (PCN G) are considered reasonable treatment options for viridans group streptococci (VGS) bloodstream infections, but comparisons between these agents are limited. We evaluated clinical outcomes among patients treated with these agents for complicated VGS bacteremia. METHODS: This was a single-center retrospective study of adult patients with ≥1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in the PCN arm) between January 2013 and June 2019. The primary outcome was a composite of safety end points, including hospital readmission due to VGS bacteremia or adverse events (AEs) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to AEs from therapy, and development of extended-spectrum beta-lactamase resistance. Secondary outcomes included individual safety end points, VGS bacteremia recurrence, hospital readmission, and all-cause mortality. RESULTS: Of 328 patients screened, 94 met eligibility criteria (CTX n = 64, PCN n = 30). Streptococcus mitis was the most common isolate, and infective endocarditis was the predominant source of infection. CTX was not significantly associated with increased risk of the primary composite safety outcome (CTX 14% vs PCN 27%; P = .139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. No secondary end points differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary composite safety outcome. CONCLUSIONS: Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate higher rates of treatment failure, adverse events, or resistance.

Intravenous push versus intravenous piggyback beta-lactams for the empiric management of gram-negative bacteremia.

WHAT IS KNOWN AND OBJECTIVE: Nationwide shortages of small-volume parenteral solutions (SVPS) compelled hospitals to develop strategies including the use of intravenous push (IVP) administration of antibiotics to reserve SVPS for absolute necessities. It is unknown if administration of beta-lactam antibiotics (BL) via IVP results in worse clinical outcomes compared to intravenous piggyback (IVPB) due to the potential inability to achieve pharmacodynamic targets. METHODS: Our health-system implemented a mandatory IVP action plan for BL from October 2017 to September 2018. This was a retrospective study of adult patients with GNB who received empiric therapy with IVPB (30 minutes) or IVP (5 minutes) cefepime (FEP) or meropenem (MEM) for at least 2 days. Endpoints included clinical response, microbiological clearance and mortality. All data are presented as n (%) or median (interquartile range). RESULTS: The final cohort included 213 patients (IVPB n = 105, IVP n = 108). The primary source of bacteremia was urinary, with Escherichia coli being the primary pathogen. Escalation of therapy was similar between groups (15 [14%] vs 11 [10%], P = .36) at a median of 3 days (P = .68). No significant differences were observed in any secondary endpoints including microbiological clearance, bacteremia recurrence, time to defervescence, WBC normalization, vasopressor duration or in-hospital mortality. WHAT IS NEW AND CONCLUSION: Our findings suggest no differences in clinical response with the use of IVP compared to IVPB FEP and MEM for treatment of GNB. This form of administration may be considered as a fluid conservation strategy in times of shortage.

Safety of intravenous push administration of beta-lactams within a healthcare system.

PURPOSE: A critical shortage of small-volume parenteral solutions in late 2017 led hospitals to develop strategies to ensure availability for critical patients, including administration of antibiotics as intravenous push (IVP). Minimal literature has been published to date that assesses the safety of administration of beta-lactams via this route. Therefore, the purpose of this study was to evaluate the safety of IVP administration of select beta-lactam antibiotics. METHODS: We performed a retrospective review of IVP administrations of aztreonam, ceftriaxone, cefepime, and meropenem at two campuses of the New York University Langone Health system after October 2017. Patients receiving surgical prophylaxis or more than one IVP antibiotic simultaneously were excluded. The primary endpoint was adverse events (ADE) following IVP administration of antibiotics. RESULTS: We evaluated 1000 patients who received IVP aztreonam (n = 43), ceftriaxone (n = 544), cefepime (n = 368) or meropenem (n = 45). There were 10 (1%) ADE observed, 5 of which were allergic reactions. Four ADE were neurotoxicity related to IVP cefepime. Based on the Naranjo score, 1 adverse event was "probably" and 3 were "possibly" related to cefepime IVP administration. Lastly, only 1 report of phlebitis was observed with the use of IVP ceftriaxone. CONCLUSIONS: The use of IVP as an alternative to intravenous piggyback (IVPB) during times of drug shortage for select beta-lactam antibiotics appears to be safe, and ADE are similar to those previously described for IVPB administration. Future studies evaluating clinical outcomes between IVP and IVPB administration may be of benefit.

Dalbavancin Use in the Emergency Department Setting.

Background: Although dalbavancin's (DBV's) long half-life and one-time dosing strategy confer ideal administration in the ambulatory setting, the optimal role of DBV in the management of acute bacterial skin and skin structure infections (ABSSSIs) remains to be elucidated. Objectives: The primary objective of this study was to compare treatment outcomes of ABSSSI between patients who received DBV in the emergency department (ED) as part of standard care versus patients who received DBV as part of a telehealth program. Methods: This was a retrospective cohort study evaluating patients who received DBV at 3 urban EDs. The primary end point was the incidence of ABSSSI recurrence. Secondary outcomes included need for hospital admission and ED length of stay (LOS; in hours). Results: A total of 65 ABSSSI treatment courses were included; 42 were included in the telehealth criteria (TC) cohort and 23 in the initial criteria (IC) cohort. There were 14% (6/42) infection recurrences in the TC cohort and 22% (5/23) in the IC cohort, with median time to recurrence being 4 and 14 days, respectively. Median ED LOS was significantly shorter in the TC (5 vs 25 hours, P < 0.05). Numerically fewer individuals in the TC cohort required inpatient admission (0 vs n = 2, 9%). Conclusion and Relevance: Our results suggest that patients may be safely administered DBV in an ED setting, with telehealth follow-up. Providing structured patient selection criteria is an effective method of assisting ED providers in selecting appropriate DBV candidates to limit potential recurrences and readmissions.

Posaconazole versus voriconazole as antifungal prophylaxis during induction therapy for acute myelogenous leukemia or myelodysplastic syndrome.

OBJECTIVE: Patients with acute myelogenous leukemia or myelodysplastic syndrome undergoing induction chemotherapy are at increased risk of invasive fungal infection due to prolonged, severe neutropenia. Due to this risk, national guidelines recommend invasive fungal infection prophylaxis in this population until the resolution of neutropenia. Although posaconazole has demonstrated superiority over fluconazole and itraconazole, there is limited evidence for voriconazole for invasive fungal infection prophylaxis in this population. Even less data are available comparing posaconazole and voriconazole directly. The study objective was to investigate the efficacy and safety of delayed-release posaconazole tablets versus voriconazole for primary invasive fungal infection prophylaxis. The primary outcome was rate of discontinuation of either agent. Secondary outcomes included specific rates of discontinuation due to adverse events and drug-drug interactions, rates of breakthrough invasive fungal infection, and 30-day and 100-day mortality rates. METHODS: This was a retrospective cohort study of adult patients admitted to NYU Langone Health between 1 January 2014 and 31 August 2017 and initiated on invasive fungal infection prophylaxis during induction or reinduction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. RESULTS: In total, 77 patients were included in the study: 43 using posaconazole delayed-release tablets and 34 using oral voriconazole. In the posaconazole group, 30% of patients (n = 13) discontinued therapy for any reason compared with 35% (n = 12) of patients in the voriconazole group (p = 0.64). A higher percentage of patients in the voriconazole group discontinued due to adverse events (6 patients, 18% vs. 1 patient, 2%, p = 0.04). Mortality rates at 30 and 100 days were similar between both groups. No breakthrough invasive fungal infections was noted in either group. CONCLUSION: Overall, discontinuations for any reason were similar in patients taking both posaconazole delayed-release and oral voriconazole. Both posaconazole delayed-release tablets and oral voriconazole appear to be effective at preventing invasive fungal infection in acute myelogenous leukemia and myelodysplastic syndrome patients undergoing induction chemotherapy, although posaconazole may be more tolerable.

Multilayer Model of Pharmacy Participation in the Antimicrobial Stewardship Program at a Large Academic Medical Center.

Purpose: Leveraging pharmacy personnel resources for the purpose of antimicrobial stewardship program (ASP) operations presents a challenging task. We describe our experience integrating all pharmacists into an ASP, and evaluate the impact on ASP interventions, antimicrobial utilization, rate of selected hospital-onset infections and readmission. Summary: During a study period (January 1 to December 31, 2015), a total of 14 552 ASP-related pharmacy interventions were performed (ASP clinical pharmacotherapy specialists [CPS] n = 4025; non-ASP CPS n = 4888; hospital pharmacists n = 5639). Sixty percent of interventions by ASP CPS were initiated utilizing the dedicated ASP phone, and 40% through prospective audit and feedback. Non-ASP CPS performed interventions during bedside rounds (dose adjustment 23%, initiate new or alternative anti-infective 21%, discontinue antibiotic(s) 12%, therapeutic drug monitoring 11%, de-escalation 4%), whereas hospital pharmacists participated at the point of verification (dose adjustment 75%, restricted antibiotic verification 15%, and reporting major drug-drug interactions 4%). The acceptance rate of interventions by providers and clinicians was >90% for all groups. Annual aggregate antimicrobial use decreased by 6.4 days of therapy/1000 patient-days (DOT/1000 PD; P = 1.0). Ceftriaxone use increased by 8.4 DOT/1000 PD (P = .029) without a significant compensatory increase in the use of antipseudomonal agents. Sustained low rates of hospital-onset Clostridium difficile (CDI) and carbapenem-resistant Enterobacteriaceae (CRE) infections were observed in 2015 compared with the prior year (1.1 and 1.2 cases/1000 PD, 0.2 and 0.1 cases/1000 PD, respectively). Thirty-day readmission rate decreased by 0.6% (P = .019). Conclusions: Integration of all pharmacists into ASP activities based on the level of patient care and responsibilities is an effective strategy to expand clinical services provided by ASP.

Role of postgraduate year 2 pharmacy residents in providing weekend antimicrobial stewardship coverage in an academic medical center.

PURPOSE: The integration of pharmacy residents into an antimicrobial stewardship program (ASP) is described, and data on the residents' ASP interventions and outcomes are reported. SUMMARY: ASP coverage of nighttime, holiday, and weekend shifts is often provided by infectious diseases (ID) medical fellows and staff pharmacists, potentially leading to inconsistent stewardship practices. As part of an initiative by a large urban hospital to provide around-the-clock, comprehensive ASP services 7 days a week, postgraduate year 2 (PGY2) pharmacy residents in ID or critical care were assigned to provide ASP coverage on weekends. Over a 12-month period, residents providing ASP weekend coverage documented a total of 1,443 interventions, of which 1,000 (69%) were pursuant to 72-hour prospective audit and feedback review and 443 (31%) occurred during ASP phone coverage. A comparison of overall antimicrobial utilization (mean ± S.D. days of therapy [DOT] per 1,000 patient-days [PD]) before and after implementation of resident ASP coverage on weekends showed a decrease in aggregate antimicrobial use from 799.3 ± 46.8 to 740.7 ± 17.3 DOT/1,000 PD (a difference of 58.6 DOT/1,000 PD, p = 0.08), with a corresponding decline in the incidence of hospital-onset Clostridium difficile infection (from 1.18 cases to 0.9 case per 1,000 PD). CONCLUSION: By expanding the hospital's ASP services by assigning PGY2 pharmacy residents to weekend coverage, the institution was able to provide high-level clinical care 7 days per week, which benefited both patients and PGY2 pharmacy residents while meeting national ASP regulatory requirements.

Multidrug-Resistant Bacteroides fragilis Bacteremia in a US Resident: An Emerging Challenge.

We describe a case of Bacteroides fragilis bacteremia associated with paraspinal and psoas abscesses in the United States. Resistance to b-lactam/b-lactamase inhibitors, carbapenems, and metronidazole was encountered despite having a recent travel history to India as the only possible risk factor for multidrug resistance. Microbiological cure was achieved with linezolid, moxifloxacin, and cefoxitin.