Failure modes and effects analysis to improve transitions of care in patients discharged on outpatient parenteral antimicrobial therapy.

PURPOSE: To identify barriers to safe and effective completion of outpatient parenteral antimicrobial therapy (OPAT) in patients discharged from an academic medical center and to develop targeted solutions to potentially resolve or improve the identified barriers. SUMMARY: A failure modes and effects analysis (FMEA) was conducted by a multidisciplinary OPAT task force to evaluate the processes for patients discharged on OPAT to 2 postdischarge dispositions: (1) home and (2) skilled nursing facility (SNF). The task force created 2 process maps and identified potential failure modes, or barriers, to the successful completion of each step. Thirteen and 10 barriers were identified in the home and SNF process maps, respectively. Task force members created 5 subgroups, each developing solutions for a group of related barriers. The 5 areas of focus included (1) the OPAT electronic order set, (2) critical tasks to be performed before patient discharge, (3) patient education, (4) patient follow-up and laboratory monitoring, and (5) SNF communication. Interventions involved working with information technology to update the electronic order set, bridging communication and ensuring completion of critical tasks by creating an inpatient electronic discharge checklist, developing patient education resources, planning a central OPAT outpatient database within the electronic medical record, and creating a pharmacist on-call pager for SNFs. CONCLUSION: The FMEA approach was helpful in identifying perceived barriers to successful transitions of care in patients discharged on OPAT and in developing targeted interventions. Healthcare organizations may reproduce this strategy when completing quality improvement planning for this high-risk process.

Development of an antimicrobial stewardship module in an electronic health record: Options to enhance daily antimicrobial stewardship activities.

PURPOSE: The purpose of this manuscript is to describe our experience developing an antimicrobial stewardship (AS) module as a clinical decision support tool in the Epic electronic health record (EHR). SUMMARY: Clinical decision support systems within the EHR can be used to decrease use of broad-spectrum antibiotics, improve antibiotic selection and dosing, decrease adverse effects, reduce antibiotic costs, and reduce the development of antibiotic resistance. The Johns Hopkins Hospital constructed an AS module within Epic. Customized stewardship alerts and scoring systems were developed to triage patients requiring stewardship intervention. This required a multidisciplinary approach with a team comprising AS physicians and pharmacists and Epic information technology personnel, with assistance from clinical microbiology and infection control when necessary. In addition, an intervention database was enhanced with stewardship-specific interventions, and workbench reports were developed specific to AS needs. We herein review the process, advantages, and challenges associated with the development of the Epic AS module. CONCLUSION: Customizing an AS module in an EHR requires significant time and expertise in antimicrobials; however, AS modules have the potential to improve the efficiency of AS personnel in performing daily stewardship activities and reporting through a single system.

Modifiable Risk Factors for the Emergence of Ceftolozane-tazobactam Resistance.

BACKGROUND: Ceftolozane-tazobactam (TOL-TAZ) affords broad coverage against Pseudomonas aeruginosa. Regrettably, TOL-TAZ resistance has been reported. We sought to identify modifiable risk factors that may reduce the emergence of TOL-TAZ resistance. METHODS: Twenty-eight consecutive patients infected with carbapenem-resistant P. aeruginosa isolates susceptible to TOL-TAZ, treated with ≥72 hours of TOL-TAZ , and with P. aeruginosa isolates available both before and after TOL-TAZ exposure between January 2018 and December 2019 in Baltimore, Maryland, were included. Cases were defined as patients with at least a 4-fold increase in P. aeruginosa TOL-TAZ MICs after exposure to TOL-TAZ. Independent risk factors for the emergence of TOL-TAZ resistance comparing cases and controls were investigated using logistic regression. Whole genome sequencing of paired isolates was used to identify mechanisms of resistance that emerged during TOL-TAZ therapy. RESULTS: Fourteen patients (50%) had P. aeruginosa isolates which developed at least a 4-fold increase in TOL-TAZ MICs(ie, cases). Cases were more likely to have inadequate source control (29% vs 0%, P = .04) and were less likely to receive TOL-TAZ as an extended 3-hour infusion (0% vs 29%; P = .04). Eighty-six percent of index isolates susceptible to ceftazidime-avibactam (CAZ-AVI) had subsequent P. aeruginosa isolates with high-level resistance to CAZ-AVI, after TOL-TAZ exposure and without any CAZ-AVI exposure. Common mutations identified in TOL-TAZ resistant isolates involved AmpC, a known binding site for both ceftolozane and ceftazidime, and DNA polymerase. CONCLUSIONS: Due to our small sample size, our results remain exploratory but forewarn of the potential emergence of TOL-TAZ resistance during therapy and suggest extending TOL-TAZ infusions may be protective. Larger studies are needed to investigate this association.

Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report.

The novel coronavirus disease 2019 (COVID-19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID-19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID-19 pneumonia, and despite completing a 5-day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off-label, single-dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID-19. Future investigation of the effects of immunomodulators among transplant recipients with COVID-19 infection will be important.

Association of 30-Day Mortality With Oral Step-Down vs Continued Intravenous Therapy in Patients Hospitalized With Enterobacteriaceae Bacteremia.

Importance: Conversion to oral therapy for Enterobacteriaceae bacteremia has the potential to improve the quality of life of patients by improving mobility, eliminating catheter-associated discomfort, decreasing the risk for noninfectious and infectious catheter-associated adverse events, and decreasing health care costs. Objective: To compare the association of 30-day mortality with early oral step-down therapy vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. Design, Setting, and Participants: This retrospective multicenter cohort study included a 1:1 propensity score-matched cohort of 4967 unique patients hospitalized with monomicrobial Enterobacteriaceae bloodstream infection at 3 academic medical centers from January 1, 2008, through December 31, 2014. Eligibility criteria included appropriate source control measures, appropriate clinical response by day 5, active antibiotic therapy from day 1 until discontinuation of therapy, availability of an active oral antibiotic option, and ability to consume other oral medications or feeding. Statistical analysis was performed from March 2, 2018, to June 2, 2018. Exposures: Oral step-down therapy within the first 5 days of treatment of Enterobacteriaceae bacteremia. Main Outcomes and Measures: The main outcome was 30-day all-cause mortality. Results: Of the 2161 eligible patients, 1185 (54.8%) were male and 1075 (49.7%) were white; the median (interquartile range [IQR]) age was 59 (48-68) years. One-to-one propensity-score matching yielded 1478 patients, with 739 in each study arm. Sources of bacteremia included urine (594 patients [40.2%]), gastrointestinal tract (297 [20.1%]), central line-associated (272 [18.4%]), pulmonary (58 [3.9%]), and skin and soft tissue (41 [2.8%]). There were 97 (13.1%) deaths in the oral step-down group and 99 (13.4%) in the intravenous (IV) group within 30 days (hazard ratio [HR], 1.03; 95% CI, 0.82-1.30). There were no differences in recurrence of bacteremia within 30 days between the groups (IV, 6 [0.8%]; oral, 4 [0.5%]; HR, 0.82 [0.33-2.01]). Patients transitioned to oral step-down therapy were discharged from the hospital an average of 2 days (IQR, 1-6) sooner than patients who continued to receive IV therapy (5 days [IQR, 3-8 days] vs 7 days [IQR, 4-14 days]; P < .001). Conclusions and Relevance: In this study, 30-day mortality was not different among hospitalized patients who received oral step-down vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. The findings suggest that transitioning to oral step-down therapy may be an effective treatment approach for patients with Enterobacteriaceae bacteremia who have received source control and demonstrated an appropriate clinical response. Early transition to oral step-down therapy may be associated with a decrease in the duration of hospital stay for patients with Enterobacteriaceae bloodstream infections.

The Role of Ertapenem for the Treatment of Complicated Intra-abdominal Infections With a Positive Culture for Enterococcus faecalis.

Controversy remains as to whether Enterococcus faecalis recovered from intra-abdominal infections (IAIs) requires targeted therapy. In a multicenter study comparing patients with IAIs from which E. faecalis was identified in intra-abdominal cultures, no difference in clinical outcomes was observed between patients receiving ertapenem vs those receiving piperacillin/tazobactam.

Impact of a Prescriber-driven Antibiotic Time-out on Antibiotic Use in Hospitalized Patients.

A multicenter quasi-experimental study of a provider-driven antibiotic "time-out" in 3470 antibiotic courses showed no difference in antibiotic use before and after implementation, but did show a decrease in inappropriate therapy (45% vs 31%, P < .05). Single time-outs without input from antibiotic stewardship teams are insufficient to optimize prescribing.

Voriconazole Autoinduction and Saturable Metabolism After Cessation of Rifampin in a Patient With Invasive Central Nervous System Aspergillus: Importance of Therapeutic Drug Monitoring.

PURPOSE: Optimization of antifungal therapy with voriconazole can be challenging due to inter- and intrapatient variability in voriconazole pharmacokinetics (PK). In this case, we introduce challenges in voriconazole therapy due to drug-drug interactions, autoinduction, and saturable metabolism. SUMMARY: A 32-year-old male on chronic prednisone developed central nervous system (CNS) aspergillosis. He was started on high-dose intravenous (IV) voriconazole 8.5 mg/kg every 12 hours due to concerns for lasting induction effects of recent rifampin therapy. The initial voriconazole trough was 2 µg/mL. Frequent dose adjustments were made to maintain the therapeutic trough goal. On day 24 of voriconazole therapy, his trough was undetectable on IV voriconazole 5.5 mg/kg every 12 hours. His dose was escalated to 8.5 mg/kg every 12 hours to avoid subtherapeutic levels and therapeutic failure. On day 48, his trough level was 1.1 µg/mL on the same dose. His regimen was changed to 6.5 mg/kg every 8 hours at this point. Sixteen days after this regimen on day 74 of voriconazole therapy, his trough was 27.2 µg/mL indicating saturable PK of voriconazole in the absence of interacting drugs. CONCLUSION: Our findings highlight the unpredictable PK of voriconazole and reinforce the importance of continuous therapeutic drug monitoring in critically ill patients.

Impact of Case-Specific Education and Face-to-Face Feedback to Prescribers and Nurses in the Management of Hospitalized Patients With a Positive Clostridium difficile Test.

BACKGROUND: Approaches to changing providers' behavior around Clostridium difficile (CD) management are needed. We hypothesized that case-specific teaching points and face-to-face discussions with prescribers and nurses would improve management of patients with a positive CD test. METHODS: Charts of patients age ≥18 years with positive CD tests hospitalized July 2016 to May 2017 were prospectively reviewed to assess CD practices and generate management recommendations. The study had 4 periods: baseline (pre-intervention), intervention #1, observation, and intervention #2. Both interventions consisted of an in-person, real-time, case-based discussion and education by a CD Action Team (CDAT). Assessment occurred within 24 hours of a positive CD test for all periods; during the intervention periods, management was also assessed within 48 hours after CDAT-delivered recommendations. Outcomes included proportion of patients receiving optimized treatment and incidence rate ratios of practice changes (both CDAT-prompted and CDAT-independent). RESULTS: Overall, the CDAT made recommendations to 84 of 96 CD cases during intervention periods, and providers accepted 43% of CDAT recommendations. The implementation of the CDAT led to significant improvement in bowel movement (BM) documentation, use of proton pump inhibitors, and antibiotic selection for non-CD infections. Selection of CD-specific therapy improved only in the first intervention period. Laxative use and treatment of CD colonization cases remained unchanged. Only BM documentation, a nurse-driven task, was sustained independent of CDAT prompting. CONCLUSIONS: A behavioral approach to changing the management of positive CD tests led to self-sustained practice changes among nurses but not physicians. Better understanding of prescribers' decision-making is needed to devise enduring interventions.

Higher versus Lower Dose of Cefotetan or Cefoxitin for Surgical Prophylaxis in Patients Weighing One Hundred Twenty Kilograms or More.

BACKGROUND: Clinical practice guidelines recommend a 2-g dose of cefotetan and cefoxitin for surgical prophylaxis. Pharmacokinetic data suggest benefit from higher cefotetan and cefoxitin dosing in obese patients. However, clinical studies examining higher dosing strategies in this at-risk population are lacking. The purpose of this study was to determine whether 3 g of cefotetan or cefoxitin administered pre-operatively for patients who weigh 120 kg or more is associated with a lower proportion of surgical site infection (SSI) compared with 2 g. PATIENTS AND METHODS: Medical records of patients weighing 120 kg or more who had received cefotetan or cefoxitin (2 or 3 g) as surgical prophylaxis for intra-abdominal procedures between July 2012 and August 2015 were reviewed for the development of an SSI (primary outcome), study drug-related adverse events, and re-admissions attributed to SSIs (secondary outcomes). Relative risk calculations were performed for analysis of the primary and secondary outcomes. RESULTS: One-hundred seventy-five procedures in 169 patients were included in the study. Cefotetan was used in 81% (141/175) of procedures. Three grams of cefotetan or cefoxitin was used in 20% (35/175) of procedures. The median body mass index (BMI) in both dosing groups was 42 kg/m2 and patients who received 3 g more often weighed more than 130 kg (relative risk [RR] 1.36, 1.01-1.76; p = 0.04). Surgical site infections occurred in 20.7% within the 2-g group and 22.9% in the 3-g group (RR 1.10, 0.55-2.20; p = 0.78). There was no difference in the number of study drug-related adverse effects in the 3-g compared with the 2-g group. Thirty-day re-admissions because of SSI also did not differ between the 2-g and 3-g groups (7.9% vs. 17.1%, respectively; p = 0.11). CONCLUSION: This small retrospective study did not find a difference in SSI rates between 3-g and 2-g surgical prophylaxis dosing for patients 120 kg or more with a median BMI >40 kg/m2.

Use and Effectiveness of Peri-Operative Cefotetan versus Cefazolin Plus Metronidazole for Prevention of Surgical Site Infection in Abdominal Surgery Patients.

BACKGROUND: Current practice guidelines for antimicrobial prophylaxis in surgery recommend a cephamycin or cefazolin plus metronidazole for various abdominal surgeries. In February 2016, cephamycin drug shortages resulted in a change in The Johns Hopkins Hospital's (JHH) recommendation for peri-operative antibiotic prophylaxis in abdominal surgeries from cefotetan to cefazolin plus metronidazole. The primary objective of this study was to quantify the percentage of abdominal surgeries adherent to JHH peri-operative antibiotic prophylaxis guidelines. A sub-group analysis investigated whether prophylaxis with cefazolin plus metronidazole was associated with a lower rate of surgical site infections (SSIs) versus cefotetan. PATIENTS AND METHODS: This retrospective cohort study included adult inpatients who underwent an abdominal surgery at JHH in September 2015 (Study Period I: cefotetan) or February to March 2016 (Study Period II: cefazolin plus metronidazole). RESULTS: Two hundred abdominal surgery cases were included in the primary analysis. A subset of 156 surgical cases were included in the sub-group analysis. The overall adherence rate to JHH guidelines was 75% in Study Period I versus 17% in Study Period II (p < 0.001). The largest difference in adherence was attributed to pre-operative administration time (87% vs. 23%, p < 0.001), primarily because of the longer infusion time required for metronidazole. Surgical site infections occurred in 14% (12/83) of surgeries with cefotetan versus 8.2% (6/73) with cefazolin plus metronidazole for prophylaxis (p = 0.19). CONCLUSIONS: Adherence to an institution-specific peri-operative antibiotic prophylaxis guideline for abdominal surgeries was limited primarily by the longer infusion time required for pre-operative metronidazole. A higher percentage of SSIs occurred among abdominal surgeries with cefotetan versus cefazolin plus metronidazole for prophylaxis.

Prolonged linezolid use is associated with the development of linezolid-resistant Enterococcus faecium.

We assessed risk factors for and outcomes of linezolid-resistant vancomycin-resistant Enterococcus faecium (LRVREF) bacteremia over 7 years. Thirty-four LRVREF cases were matched to 68 linezolid-susceptible VREF controls. The odds of bacteremia with LRVREF increased by 7% for each additional day of prior linezolid exposure.

Sustained impact of a rapid microarray-based assay with antimicrobial stewardship interventions on optimizing therapy in patients with Gram-positive bacteraemia.

OBJECTIVES: To compare antibiotic optimization and outcomes of patients before implementation of the Verigene Gram-Positive Blood Culture (Verigene BC-GP) nucleic acid microarray assay to after implementation with antimicrobial stewardship (AS) interventions and after discontinuation of AS interventions. METHODS: A retrospective pre-post-post quasi-experimental study was conducted to compare the three periods. AS interventions consisted of real-time guidance to clinicians on antibiotic selection. The primary outcome was median time from Gram stain to optimal therapy. Secondary outcomes included median time to effective therapy, median duration of therapy for contaminant organisms, median length of stay after blood cultures were collected, and all-cause in-hospital mortality. RESULTS: Out of a total of 923 patients, 390 (125 baseline, 134 intervention, 131 post-intervention) who were not on optimal therapy at the time of Gram stain or had contaminated blood cultures were assessed. Compared with baseline, only the median time to optimal therapy for MSSA bacteraemia was reduced in both the intervention and post-intervention periods (17 versus 17 versus 50 h; P < 0.001), respectively. In an analysis adjusted for baseline differences among the groups using quantile regression models, use of the Verigene BC-GP assay in both periods significantly reduced time to optimal therapy by 14-22 h in patients who would achieve optimal therapy at ≥ 26 h without the assay. There were no differences in in-hospital mortality or hospital length of stay between study periods. CONCLUSIONS: A real-time AS intervention implemented alongside introduction of the Verigene BC-GP assay led to improvements in antibiotic therapy for patients with bacteraemia due to Gram-positive cocci, even after the AS intervention was discontinued.

Association of Adverse Events With Antibiotic Use in Hospitalized Patients.

Importance: Estimates of the incidence of overall antibiotic-associated adverse drug events (ADEs) in hospitalized patients are generally unavailable. Objective: To describe the incidence of antibiotic-associated ADEs for adult inpatients receiving systemic antibiotic therapy. Design, Setting, and Participants: Retrospective cohort of adult inpatients admitted to general medicine wards at an academic medical center. Exposures: At least 24 hours of any parenteral or oral antibiotic therapy. Main Outcomes and Measures: Medical records of 1488 patients were examined for 30 days after antibiotic initiation for the development of the following antibiotic-associated ADEs: gastrointestinal, dermatologic, musculoskeletal, hematologic, hepatobiliary, renal, cardiac, and neurologic; and 90 days for the development of Clostridium difficile infection or incident multidrug-resistant organism infection, based on adjudication by 2 infectious diseases trained clinicians. Results: In 1488 patients, the median age was 59 years (interquartile range, 49-69 years), and 758 (51%) participants were female. A total of 298 (20%) patients experienced at least 1 antibiotic-associated ADE. Furthermore, 56 (20%) non-clinically indicated antibiotic regimens were associated with an ADE, including 7 cases of C difficile infection. Every additional 10 days of antibiotic therapy conferred a 3% increased risk of an ADE. The most common ADEs were gastrointestinal, renal, and hematologic abnormalities, accounting for 78 (42%), 45 (24%), and 28 (15%) 30-day ADEs, respectively. Notable differences were identified between the incidence of ADEs associated with specific antibiotics. Conclusions and Relevance: Although antibiotics may play a critical role when used appropriately, our findings underscore the importance of judicious antibiotic prescribing to reduce the harm that can result from antibiotic-associated ADEs.

What Is the More Effective Antibiotic Stewardship Intervention: Preprescription Authorization or Postprescription Review With Feedback?

Background: The optimal approach to conducting antibiotic stewardship interventions has not been defined. We compared days of antibiotic therapy (DOT) using preprescription authorization (PPA) vs postprescription review with feedback (PPRF) strategies. Methods: A quasi-experimental, crossover trial comparing PPA and PPRF for adult inpatients prescribed any antibiotic was conducted. For the first 4 months, 2 medicine teams were assigned to the PPA arm and the other 2 teams to the PPRF arm. The teams were then assigned to the alternate arm for an additional 4 months. Appropriateness of antibiotic use was adjudicated by at least 2 infectious diseases-trained clinicians and according to institutional guidelines. Results: There were 2686 and 2693 patients admitted to the PPA and PPRF groups, with 29% and 27% of patients prescribed antibiotics, respectively. Initially, antibiotic DOTs remained relatively unchanged in the PPA arm. When changed to the PPRF arm, antibiotic use decreased (-2.45 DOT per 1000 patient-days [PD]). In the initial PPRF arm, antibiotic use decreased (slope of -5.73 DOT per 1000 PD) but remained constant when changed to the PPA arm. Median patient DOTs in the PPA and PPRF arms were 8 and 6 DOT per 1000 PD, respectively (P = .03). Antibiotic therapy was guideline-noncompliant in 34% and 41% of patients on days 1 and 3 in the PPA group (P < .01) and in 57% and 36% of patients on days 1 and 3 in the PPRF group (P = .03). Conclusions: PPRF may have more of an impact on decreasing antibiotic DOTs compared with PPA. This information may be useful for institutions without sufficient resources to incorporate both stewardship approaches.

Sustained Impact of an Antibiotic Stewardship Intervention for Community-Acquired Pneumonia.

Antibiotic stewardship interventions targeting community-acquired pneumonia have been successful in reducing antibiotic overuse in the short term, but the sustainability of their effects has not been investigated. We report that improvements in antibiotic use due to a syndrome-focused intervention for community-acquired pneumonia were sustained 3 years later without additional intervention. Infect Control Hosp Epidemiol 2016;1-4.

Use of PNA FISH for blood cultures growing Gram-positive cocci in chains without a concomitant antibiotic stewardship intervention does not improve time to appropriate antibiotic therapy.

Peptide nucleic acid fluorescence in situ hybridization (PNA FISH) is a rapid diagnostic assay that can identify certain organisms growing in blood cultures 30-90 min from the time of positive Gram-stain. Existing studies have demonstrated a clinical utility with this assay when antibiotic stewardship programs assist clinicians with interpreting the results. However, the benefit of these rapid assays in the absence of concomitant antibiotic stewardship involvement is unclear. In this randomized study of 220 patients with enterococcal or streptococcal bacteremia, we found that PNA FISH, in the absence of concomitant input from an antibiotic stewardship program, had no impact on time to effective or optimal therapy, length of hospital stay, or in-hospital mortality. Our results suggest that in the absence of guidance from an antibiotic stewardship program, the clinical benefits of rapid diagnostic microbiological tools may be reduced.