Analysis of infections among patients with historical culture positive for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae: Is ESBL-targeted therapy always needed?

Objective: Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions. Methods: A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP. Results: In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3. Conclusions: History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted.

Clinical impact of a multiplex rapid diagnostic pneumonia panel in critically ill patients.

Objective: To evaluate the clinical impact of the BioFire FilmArray Pneumonia Panel (PNA panel) in critically ill patients. Design: Single-center, preintervention and postintervention retrospective cohort study. Setting: Tertiary-care academic medical center. Patients: Adult ICU patients. Methods: Patients with quantitative bacterial cultures obtained by bronchoalveolar lavage or tracheal aspirate either before (January-March 2021, preintervention period) or after (January-March 2022, postintervention period) implementation of the PNA panel were randomly screened until 25 patients per study month (75 in each cohort) who met the study criteria were included. Antibiotic use from the day of culture collection through day 5 was compared. Results: The primary outcome of median time to first antibiotic change based on microbiologic data was 50 hours before the intervention versus 21 hours after the intervention (P = .0006). Also, 56 postintervention regimens (75%) were eligible for change based on PNA panel results; actual change occurred in 30 regimens (54%). Median antibiotic days of therapy (DOTs) were 8 before the intervention versus 6 after the intervention (P = .07). For the patients with antibiotic changes made based on PNA panel results, the median time to first antibiotic change was 10 hours. For patients who were initially on inadequate therapy, time to adequate therapy was 67 hours before the intervention versus 37 hours after the intervention (P = .27). Conclusions: The PNA panel was associated with decreased time to first antibiotic change and fewer antibiotic DOTs. Its impact may have been larger if a higher percentage of potential antibiotic changes had been implemented. The PNA panel is a promising tool to enhance antibiotic stewardship.

A comparison of active versus passive methods of responding to rapid diagnostic blood culture results.

Objective: To compare 2 methods of communicating polymerase chain reaction (PCR) blood-culture results: active approach utilizing on-call personnel versus passive approach utilizing notifications in the electronic health record (EHR). Design: Retrospective observational study. Setting: A tertiary-care academic medical center. Patients: Adult patients hospitalized with ≥1 positive blood culture containing a gram-positive organism identified by PCR between October 2014 and January 2018. Methods: The standard protocol for reporting PCR results at baseline included a laboratory technician calling the patient's nurse, who would report the critical result to the medical provider. The active intervention group consisted of an on-call pager system utilizing trained pharmacy residents, whereas the passive intervention group combined standard protocol with real-time in-basket notifications to pharmacists in the EHR. Results: Of 209 patients, 105, 61, and 43 patients were in the control, active, and passive groups, respectively. Median time to optimal therapy was shorter in the active group compared to the passive group and control (23.4 hours vs 42.2 hours vs 45.9 hours, respectively; P = .028). De-escalation occurred 12 hours sooner in the active group. In the contaminant group, empiric antibiotics were discontinued faster in the active group (0 hours) than in the control group and the passive group (17.7 vs 7.2 hours; P = .007). Time to active therapy and days of therapy were similar. Conclusions: A passive, electronic method of reporting PCR results to pharmacists was not as effective in optimizing stewardship metrics as an active, real-time method utilizing pharmacy residents. Further studies are needed to determine the optimal method of communicating time-sensitive information.

Inpatient Antibiotic Costs Associated With Switching From Vancomycin to Daptomycin for Outpatient Parenteral Antibiotic Therapy.

Purpose: The common practice of changing patients to daptomycin for outpatient parenteral antibiotic therapy (OPAT) can increase inpatient daptomycin use and impact inpatient pharmacy expenses. The purpose of this study was to quantify the additional inpatient antibiotic expenditures associated with changing patients from vancomycin to daptomycin for OPAT. Methods: This study examined patients who were discharged from January 1, 2018 to June 30, 2019. Patients were included if they were ≥18 years old, transitioned from vancomycin to daptomycin prior to discharge, and were cared for by the Infectious Diseases OPAT program. Patients switched to daptomycin for therapeutic reasons were excluded. A cost analysis evaluating the vancomycin regimen prior to changing to daptomycin and the daptomycin doses given prior to discharge and during readmissions for the first 6 weeks after discharge was performed using Wholesale Acquisition Costs. The primary outcome was the inpatient antibiotic expense associated with changing to daptomycin for OPAT. Results: Sixty-eight patients met study criteria. The mean number of inpatient doses of daptomycin administered prior to discharge was 4.3. Twelve patients were readmitted and received a mean of 5.3 additional doses. The estimated cost difference between the inpatient daptomycin doses and equivalent vancomycin therapy was $2647 per patient. Limiting patients to only 1 pre-discharge dose of daptomycin would reduce this cost difference to $926 per patient. Conclusion: Switching from vancomycin to daptomycin for OPAT can be associated with substantial inpatient pharmacy costs. These excessive costs can be mitigated if only 1 dose of daptomycin is given before discharge.

Evaluation of the Potential Impact of a Multiplex Rapid Diagnostic Panel in Critically Ill Patients With Hospital-Acquired Pneumonia.

Background Rapid diagnostic tools have emerged as valuable assets assisting clinicians in decision-making regarding patient management in the hospital setting. Our study sought to identify the potential impact of the BioFire® FilmArray® Pneumonia Panel (FP Panel) (BioFire Diagnostics, Salt Lake City, UT, USA) in patients with hospital-acquired pneumonia (HAP). Methods Respiratory samples obtained by bronchoalveolar lavage (BAL) or tracheal aspiration (TA) from ICU patients with a diagnosis of HAP were tested by the FP panel in addition to routine bacterial cultures. In addition, the electronic health records of these patients were reviewed to determine what potential changes in antimicrobial therapy could have been implemented if the panel results were known to the treatment team in real-time. A cost analysis was also performed incorporating the cost of the pneumonia panel and the savings associated with the potential decrease of antibiotic use and avoidance of the rapid viral diagnostic panel.  Results Fifty-six patients met the study criteria. The FP panel results could have prompted a change in therapy in 36 (64.3%) patients, with an anticipated mean reduction in time to optimized therapy of approximately 51 hours. In addition, the panel identified three cases where antimicrobials should have been altered because patients were not receiving empiric therapy with activity against the causative pathogen and 34 opportunities for antibiotic de-escalation. The cost analysis calculated an additional cost of $10 per patient associated with using the FP panel.  Conclusions The FP panel could have prompted a change in therapy in about two-thirds of patients studied. Its potential benefits include a more rapid time to optimized therapy, reduced exposure to and cost of broad-spectrum antimicrobials, and reduced cost of other rapid diagnostic tests.

Evaluation of the Infectious Diseases Society of America's Core Antimicrobial Stewardship Curriculum for Infectious Diseases Fellows.

BACKGROUND: Antimicrobial stewardship (AS) programs are required by Centers for Medicare and Medicaid Services and should ideally have infectious diseases (ID) physician involvement; however, only 50% of ID fellowship programs have formal AS curricula. The Infectious Diseases Society of America (IDSA) formed a workgroup to develop a core AS curriculum for ID fellows. Here we study its impact. METHODS: ID program directors and fellows in 56 fellowship programs were surveyed regarding the content and effectiveness of their AS training before and after implementation of the IDSA curriculum. Fellows' knowledge was assessed using multiple-choice questions. Fellows completing their first year of fellowship were surveyed before curriculum implementation ("pre-curriculum") and compared to first-year fellows who complete the curriculum the following year ("post-curriculum"). RESULTS: Forty-nine (88%) program directors and 105 (67%) fellows completed the pre-curriculum surveys; 35 (64%) program directors and 79 (50%) fellows completed the post-curriculum surveys. Prior to IDSA curriculum implementation, only 51% of programs had a "formal" curriculum. After implementation, satisfaction with AS training increased among program directors (16% to 68%) and fellows (51% to 68%). Fellows' confidence increased in 7/10 AS content areas. Knowledge scores improved from a mean of 4.6 to 5.1 correct answers of 9 questions (P = .028). The major hurdle to curriculum implementation was time, both for formal teaching and for e-learning. CONCLUSIONS: Effective AS training is a critical component of ID fellowship training. The IDSA Core AS Curriculum can enhance AS training, increase fellow confidence, and improve overall satisfaction of fellows and program directors.

Investing in the Future: A Role for Professional Societies to Prepare the Next Generation of Healthcare Leaders Through Curriculum Development and Dissemination.

Professional societies serve many functions that benefit constituents; however, few professional societies have undertaken the development and dissemination of formal, national curricula to train the future workforce while simultaneously addressing significant healthcare needs. The Infectious Diseases Society of America (IDSA) has developed 2 curricula for the specific purpose of training the next generation of clinicians to ensure the future infectious diseases (ID) workforce is optimally trained to lead antimicrobial stewardship programs and equipped to meet the challenges of multidrug resistance, patient safety, and healthcare quality improvement. A core curriculum was developed to provide a foundation in antimicrobial stewardship for all ID fellows, regardless of career path. An advanced curriculum was developed for ID fellows specifically pursuing a career in antimicrobial stewardship. Both curricula will be broadly available in the summer of 2021 through the IDSA website.

Accuracy of and prescriber perceptions related to documenting antibiotic indications during order entry at an academic medical center.

PURPOSE: To assess the accuracy of antibiotic indication documentation provided during order entry and prescriber perceptions of the requirement to specify indications. METHODS: Patients who received 1 of 6 selected antibiotics from May 1 through June 30, 2017, were identified. Records of 30 randomly selected patients who received each study antibiotic were retrospectively reviewed. The primary endpoint was indication accuracy, defined as agreement of the indication entered during order entry with that documented in progress notes at the time of order entry. Secondary endpoints included correlation of entered indication and final diagnosis for empiric antibiotics. A brief survey was emailed to prescribers to assess the burden and perceptions of requiring an indication during order entry. RESULTS: Four thousand five hundred twenty-four patients received 1 or more doses of a study antibiotic. For the 180 patients selected for evaluation, 89.4% of indications were accurate. Indications for antibiotics ordered for prophylaxis were more likely to be inaccurate than those for empiric or definitive antibiotics (accuracy rates of 46%, 94%, and 92%, respectively, p < 0.05). For empiric antibiotics, 78.5% of indications documented at order entry matched the final diagnosis. Two hundred fifty-four of 863 prescribers (29%) responded to the survey request. Most respondents felt that documenting the indication took no more than 20 seconds, was a "minor nuisance" or "occasionally burdensome," and had no impact on their consideration of antibiotic appropriateness. CONCLUSION: With the exception of prophylaxis, the indications documented during order entry were sufficiently accurate to assist antimicrobial stewardship efforts. Although indication documentation was perceived as a minor burden, surveyed prescribers indicated it had only a minimal beneficial effect on antibiotic prescribing.

Collaborative Antimicrobial Stewardship: Working with Microbiology.

There have been tremendous advances in methodologies available for detection and identification of organisms causing infections. Providers can now obtain identification results and antimicrobial susceptibility results in a shorter period of time. However, declining health care resources highlight the importance of selecting the right test at the right time to maximize diagnostic benefits. Therefore, the role of the antimicrobial stewardship team in the clinical microbiology laboratory has expanded to include diagnostic stewardship and provision of guidance on test selection for diagnosis and management of infection. This review focuses on the experience of our group in collaborative stewardship, emphasizing successes and challenges.

Multidisciplinary Authorship Among Infectious Diseases Society of America Clinical Practice Guidelines: Examining the Contributions of Infectious Diseases Pharmacists.

We describe the proportion of pharmacist representation among current and corresponding prior editions of Infectious Diseases Society of America (IDSA) clinical practice guidelines (CPGs). Pharmacist representation was 13% and 21% in previous and current editions, respectively, increasing significantly since 2011. We advocate for continued collaborations between IDSA and pharmacy organizations to enhance multidisciplinary representation in CPGs.

Antimicrobial Stewardship Training for Infectious Diseases Fellows: Program Directors Identify a Curriculum Need.

A needs assessment survey of infectious diseases (ID) training program directors identified gaps in educational resources for training and evaluating ID fellows in antimicrobial stewardship. An Infectious Diseases Society of America-sponsored core curriculum was developed to address that need.

Extended infusion compared to standard infusion cefepime as empiric treatment of febrile neutropenia.

Background Extended infusion (EI) dosing provides a longer time above the minimum inhibitory concentration, which is important for the clinical success of ß-lactam antibiotics, especially for patients with impaired immunity. The aim of this study was to determine the feasibility and clinical impact of administering cefepime by EI as treatment of febrile neutropenia. Methods This was a prospective, randomized, comparative pilot study. All patients received cefepime 2 g IV every 8 h, with the first dose administered using a 30-min infusion. After the first dose, patients were randomized to receive cefepime over 30 min as a standard infusion (SI) or 3 h (EI). Patients were >18 years old with febrile neutropenia (neutrophil count <500 cells/mm3 and temperature >38.0ºC) and received chemotherapy or stem cell transplant as treatment for malignancy. Patients were excluded for the following: allergy to a cephalosporin, creatinine clearance (CrCl) < 50 mL/min, receipt of concurrent Gram-negative antimicrobial, sepsis, or solid tumor malignancy. The primary outcome was defervescence by 72 h. Secondary outcomes included time to defervescence, clinical success, in-hospital mortality, hospital length of stay, and need for additional antimicrobials. Main results Sixty-three patients were enrolled: 33 in the SI arm and 30 in the EI arm. The groups were similar with regard to age, gender, weight, estimated creatinine clearance, and duration of neutropenia. None of the patients in the EI arm withdrew due to practical complications of receiving EI cefepime. Twenty-three patients in the SI arm and 20 patients in the EI arm defervesced by 72 h ( p = 0.99). There were no differences in secondary outcome measures; however, patients in the EI arm appeared to have defervesced more rapidly (median 19 vs. 41 h, p = 0.305). Conclusion Administration of cefepime by EI for the treatment of febrile neutropenia is feasible. Larger clinical trials are necessary to determine if EI cefepime imparts a clinical benefit in the treatment of febrile neutropenia.

Frequency of empiric antibiotic de-escalation in an acute care hospital with an established Antimicrobial Stewardship Program.

BACKGROUND: Expanding antimicrobial resistance patterns in the face of stagnant growth in novel antibiotic production underscores the importance of antibiotic stewardship in which de-escalation remains an integral component. We measured the frequency of antibiotic de-escalation in a tertiary care medical center with an established antimicrobial stewardship program to provide a plausible benchmark for de-escalation. METHODS: A retrospective, observational study was performed by review of randomly selected electronic medical records of 240 patients who received simultaneous piperacillin/tazobactam and vancomycin from January to December 2011 at an 885-bed tertiary care medical center. Patient characteristics including antibiotic regimen, duration and indication, culture results, length of stay, and hospital mortality were evaluated. Antibiotic de-escalation was defined as the use of narrower spectrum antibiotics or the discontinuation of antibiotics after initiation of piperacillin/tazobactam and vancomycin therapy. Subjects dying within 72 h of antibiotic initiation were considered not de-escalated for subsequent analysis and were subtracted from the study population in determining a modified mortality rate. RESULTS: The most commonly documented indications for piperacillin/tazobactam and vancomycin therapy were pneumonia and sepsis. Of the 240 patients studied, 151 (63%) had their antibiotic regimens de-escalated by 72 h. The proportion of patients de-escalated by 96 h with positive vs. negative cultures was similar, 71 and 72%, respectively. Median length of stay was 4 days shorter in de-escalated patients, and the difference in adjusted mortality was not significant (p = 0.82). CONCLUSIONS: The empiric antibiotic regimens of approximately two-thirds of patients were de-escalated by 72 h in an institution with a well-established antimicrobial stewardship program. While this study provides one plausible benchmark for antibiotic de-escalation, further studies, including evaluations of antibiotic appropriateness and patient outcomes, are needed to inform decisions on potential benchmarks for antibiotic de-escalation.

Executive Summary: Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.

Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.

The Addition of Intravenous Metronidazole to Oral Vancomycin is Associated With Improved Mortality in Critically Ill Patients With Clostridium difficile Infection.

BACKGROUND: The optimal therapy for critically ill patients with Clostridium difficile infection (CDI) is not known. We aimed to evaluate mortality among critically ill patients with CDI who received oral vancomycin (monotherapy) vs oral vancomycin with intravenous (IV) metronidazole (combination therapy). METHODS: A single-center, retrospective, observational, comparative study was performed. Patients with a positive C. difficile assay who received oral vancomycin while bedded in an intensive care unit (ICU) between June 2007 and September 2012 were evaluated. Patients meeting ≥3 of the following criteria were included: albumin <2.5 g/dL, heart rate >90 bpm, mean arterial pressure <60 mmHg, white blood cell count ≥15 000 cells/mL, age >60 years, serum creatinine ≥1.5 times baseline, or temperature ≥100.4°F. Patients in the combination therapy group received IV metronidazole within 48 hours after initiating vancomycin. Patients <18 years or with unrelated gastrointestinal disease were excluded. The primary outcome was in-hospital mortality. Patients were matched using Acute Physiology and Chronic Health Evaluation II scores. RESULTS: Eighty-eight patients were included, 44 in each group. Patient characteristics were similar although more patients in the combination group had renal disease. Mortality was 36.4% and 15.9% in the monotherapy and combination therapy groups, respectively (P = .03). Secondary outcomes of clinical success, length of stay, and length of ICU stay did not differ between groups. CONCLUSIONS: Our data are supportive of the use of combination therapy with oral vancomycin and IV metronidazole in critically ill patients with CDI. However, prospective, randomized studies are required to define optimal treatment regimens in this limited population of CDI patients.

Health care provider education as a tool to enhance antibiotic stewardship practices.

Antibiotic stewardship education for health care providers provides a foundation of knowledge and an environment that facilitates and supports optimal antibiotic prescribing. There is a need to extend this education to medical students and health care trainees. Education using passive techniques is modestly effective for increasing prescriber knowledge, whereas education using active techniques is more effective for changing prescribing behavior. Such education has been shown to enhance other antibiotic stewardship interventions. In this review, the need and suggested audience for antibiotic stewardship education are highlighted, and effective education techniques are recommended for increasing knowledge of antibiotics and improving their use.

BK virus encephalitis: case report, review of the literature, and description of a novel treatment modality.

OBJECTIVE: To describe a case of BK virus encephalitis with attempted direct antiviral therapy, review the reported cases of BK virus in the central nervous system, and report the novel use of intravenous cimetidine in place of oral probenecid to minimize the toxicities of intravenous cidofovir. CASE SUMMARY: A 36-year-old male with acute myelomonocytic leukemia and subsequent myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplant. His course was complicated by severe graft-versus-host disease involving his skin and gastrointestinal tract. Five weeks after transplantation, he developed fever and confusion. Magnetic resonance imaging was suggestive of limbic encephalitis and cerebrospinal fluid tested positive for BK virus. Therapy with intravenous cidofovir was thought to be indicated. Although probenecid is commonly used to minimize the toxicities of cidofovir, the patient's severe graft-versus-host disease raised concerns about absorption of oral medications. Based on animal models and pharmacokinetic data, intravenous cimetidine was used in place of oral probenecid. Despite these therapies, the patient's mental status did not improve. He developed progressive organ system failure, and care was ultimately withdrawn. DISCUSSION: BK virus is increasingly described as a cause of encephalitis. The majority of reported cases have occurred in immunocompromised patients and have generally had a poor outcome. This case describes attempted antiviral therapy using cidofovir, the antiviral agent used most frequently in other syndromes due to BK virus. Intravenous cimetidine is a novel modality used to minimize ocular and renal toxicities frequently seen with cidofovir, and we believe this warrants further investigation. CONCLUSIONS: BK virus may be a cause of encephalitis in immunocompromised hosts, and cidofovir represents a possible treatment option. Intravenous cimetidine can be considered to minimize toxicities associated with cidofovir use in patients unable to tolerate or absorb oral probenecid.