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.

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.

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.

Evaluation of Meropenem Extended Versus Intermittent Infusion Dosing Protocol in Critically Ill Patients.

Extended infusion (EI) administration of ß-lactams can improve target attainment in critically ill patients with altered pharmacokinetics/pharmacodynamics. To optimize meropenem dosing in patients with severe sepsis/septic shock, our Antimicrobial Stewardship Program implemented a EI meropenem (EIM) protocol in an 18-bed Medical Intensive Care Unit in March 2014. In this retrospective study, we compared intensive care unit (ICU) mortality and clinical response in patients who received meropenem for ≥72 hours administered per EIM protocol of 1 g over 3 hours every 8 hours versus intermittent infusion (IIM) protocol of 500 mg over 30 minutes every 6 hours. Age, weight, comorbidities, severity of illness, and vasopressor use were comparable between groups (EIM protocol n = 52, IIM protocol n = 96). The IIM protocol group had higher rates of renal dose adjustment at meropenem initiation. Among 56 identified gram-negative (GN) pathogens, 94% had meropenem minimal inhibitory concentration ≤0.25 mg/L. The ICU mortality was lower (19 vs 37%; P = .032) and clinical response was higher (83% vs 46%; P < .01) in the EIM protocol versus IIM protocol group. Total vasopressor days were shorter (2 vs 3 days; P = .038), and white blood cell normalization rate was higher (87% vs 51%; P < .01) in the EIM protocol versus IIM protocol group. There was no difference in days of mechanical ventilation, duration of therapy, and ICU stay. The IIM protocol was also identified as an independent risk factor associated with ICU mortality (hazard ratio: 3.653, 95% confidence interval: 1.689-7.981; P = .001) after adjusting for Sequential Organ Failure Assessment score. In this cohort of patients with severe sepsis/septic shock and highly susceptible GN pathogens, there was improved mortality and clinical response in the EIM protocol group.

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.

Impact of Stewardship Interventions on Antiretroviral Medication Errors in an Urban Medical Center: A 3-Year, Multiphase Study.

BACKGROUND: There is a high prevalence of HIV infection in Newark, New Jersey, with University Hospital admitting approximately 600 HIV-infected patients per year. Medication errors involving antiretroviral therapy (ART) could significantly affect treatment outcomes. The goal of this study was to evaluate the effectiveness of various stewardship interventions in reducing the prevalence of prescribing errors involving ART. METHODS: This was a retrospective review of all inpatients receiving ART for HIV treatment during three distinct 6-month intervals over a 3-year period. During the first year, the baseline prevalence of medication errors was determined. During the second year, physician and pharmacist education was provided, and a computerized order entry system with drug information resources and prescribing recommendations was implemented. Prospective audit of ART orders with feedback was conducted in the third year. Analyses and comparisons were made across the three phases of this study. RESULTS: Of the 334 patients with HIV admitted in the first year, 45% had at least one antiretroviral medication error and 38% had uncorrected errors at the time of discharge. After education and computerized order entry, significant reductions in medication error rates were observed compared to baseline rates; 36% of 315 admissions had at least one error and 31% had uncorrected errors at discharge. While the prevalence of antiretroviral errors in year 3 was similar to that of year 2 (37% of 276 admissions), there was a significant decrease in the prevalence of uncorrected errors at discharge (12%) with the use of prospective review and intervention. CONCLUSIONS: Interventions, such as education and guideline development, can aid in reducing ART medication errors, but a committed stewardship program is necessary to elicit the greatest impact.

Probable acyclovir-induced angioedema in a patient with HIV infection and suspected varicella-zoster virus encephalitis.

PURPOSE: A probable acyclovir-associated hypersensitivity reaction resulting in severe facial angioedema and respiratory distress is reported. SUMMARY: A 51-year-old woman with human immunodeficiency virus (HIV) infection and end-stage renal disease arrived at the emergency department (ED) with a diffuse rash on the chest and back; she was diagnosed with varicella-zoster virus infection, received one dose of i.v. acyclovir, and was discharged home with a prescription for valacyclovir. After taking one dose of the drug, she became confused and agitated. The next day the patient returned to the ED; she was confused and unresponsive, with signs and symptoms suggesting viral encephalitis. After a workup including lumbar puncture fluid, she was treated empirically with i.v. acyclovir for viral encephalitis. Within one hour of receiving the acyclovir infusion, the patient developed angioedema of the lips, tongue, and periorbital areas requiring intubation and transfer to the intensive care unit. Further acyclovir therapy was withheld, and foscarnet therapy was initiated for the presumptive treatment of viral encephalitis. Over the next few days, the patient's angioedema completely resolved; her mental status gradually improved while she completed a 14-day course of foscarnet therapy. The application of the Naranjo scale indicated a probable adverse reaction to acyclovir, likely mediated by acyclovir-specific immunoglobulin E, highlighting the need to consider alternative antiviral agents without cross-reactivity to acyclovir in patients with confirmed or suspected viral encephalitis. CONCLUSION: A 51-year-old woman with HIV infection developed probable acyclovir-induced angioedema after receiving i.v. acyclovir therapy for suspected viral encephalitis.

Pseudomonas aeruginosa bacteremia secondary to fingerstick glucose monitoring.

Routine fingersticks for blood glucose monitoring are essential for the management of diabetic patients. However, the development of infections following fingersticks is a potential complication of blood glucose monitoring that has been reported in the literature. We describe a case of Pseudomonas aeruginosa bacteremia introduced during a routine fingerstick for blood glucose monitoring in a febrile neutropenic patient.