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.

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.

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.

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.

Optimizing empiric antibiotic therapy in patients with severe ß-lactam allergy.

Antibiotic selection is challenging in patients with severe ß-lactam allergy due to declining reliability of alternate antibiotics. Organisms isolated from these patients may exhibit unique resistance phenotypes. The objective of this study was to determine which alternate antibiotics or combinations provide adequate empirical therapy for patients with ß-lactam allergy who develop Gram-negative infections at our institution. We further sought to determine the effects of risk factors for drug resistance on empirical adequacy. A retrospective analysis was conducted for adult patients hospitalized from September 2009 to May 2010 who had a severe ß-lactam allergy and a urine, blood, or respiratory culture positive for a Gram-negative organism and who met predefined criteria for infection. Patient characteristics, culture and susceptibility data, and predefined risk factors for antibiotic resistance were collected. Adequacies of ß-lactam and alternate antibiotics were compared for all infections and selected subsets. The primary outcome was adequacy of each alternate antibiotic or combination for all infections. One hundred sixteen infections (40 pneumonias, 67 urinary tract infections, and 9 bacteremias) were identified. Single alternate agents were adequate less frequently than ß-lactams and combination regimens. Only in cases without risk factors for resistance did single-agent regimens demonstrate acceptable adequacy rates; each factor conferred a doubling of risk for resistance. Resistance risk factors should be considered in selecting empirical antibiotics for Gram-negative pathogens in patients unable to take ß-lactams due to severe allergy.

Antimicrobial stewardship programs in community hospitals: the evidence base and case studies.

By controlling and changing how antimicrobial agents are selected and administered, antimicrobial stewardship programs (ASPs) aim to prevent or slow the emergence of antimicrobial resistance; optimize the selection, dosing, and duration of antimicrobial therapy; reduce the incidence of drug-related adverse events; and lower rates of morbidity and mortality, length of hospitalization, and costs. There is an abundant and growing body of evidence demonstrating that ASPs change the quantity and quality of antimicrobial prescriptions; however, measuring whether, when, and how ASPs improve patient outcomes and change patterns of antimicrobial resistance--which is the ultimate goals of ASPs--has been difficult, but the totality of evidence indicates that ASPs are capable of achieving these goals. In this article, we review the existing data on ASPs and their effects on patient care and antimicrobial resistance, as well as strategies for establishing ASPs in different types of hospitals.

Antimicrobial stewardship for inpatient facilities.

Antibiotic stewardship aims to improve patient care and reduce unwanted consequences of antimicrobial overuse or misuse, including lowered efficacy, emergence of antimicrobial resistance, development of secondary infections, adverse drug reactions, increased length of hospital stay, and additional healthcare costs. Recent guidelines make specific recommendations for the development of institutional programs to enhance antimicrobial stewardship. Optimally, such programs should be comprehensive, multidisciplinary, supported by hospital and medical staff leadership, and should employ evidence-based strategies that best fit local needs and resources. An infectious diseases physician and clinical pharmacist with infectious diseases training are recommended as core members of the multidisciplinary team, although a hospitalist with interest (and perhaps additional training) in antimicrobial therapy may be able to fill the void. Program directors and core members should be compensated for their time. Principal proactive strategies--with evidence supporting their consideration--include prospective audits, with intervention and feedback, formulary restriction, and preauthorization. Other strategies include persistent one-on-one education, guidelines adapted to local needs, and informatics to support clinical decision making. Intervention goals are to prevent unnecessary antimicrobial starts, to streamline or de-escalate therapy early in its course, and to convert from parenteral to oral therapy, optimize dosing, and ensure the appropriate length of therapy. Most community hospitals, if sufficiently resourced, should be able to implement a successful antimicrobial stewardship program. Evidence suggests that good antimicrobial stewardship can lead to less overall and inappropriate antimicrobial use, lower drug-related costs, reductions in Clostridium difficile-associated disease, and, in some studies, less emergence of antimicrobial resistance.

Corticosteroids in the treatment of hepatic tuberculosis: case report and review of the literature.

The role of corticosteroid therapy in addition to anti-tuberculous agents in the treatment of hepatic tuberculosis is unclear. We describe a 54-y-old female with hepatic tuberculosis and worsening hepatitis after initiation of anti-tuberculosis therapy. She experienced considerable clinical improvement and ultimately a complete recovery upon the receipt of adjunctive corticosteroids.

Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever.

BACKGROUND: Rickettsia parkeri rickettsiosis, a recently identified spotted fever transmitted by the Gulf Coast tick (Amblyomma maculatum), was first described in 2004. We summarize the clinical and epidemiological features of 12 patients in the United States with confirmed or probable disease attributable to R. parkeri and comment on distinctions between R. parkeri rickettsiosis and other United States rickettsioses. METHODS: Clinical specimens from patients in the United States who reside within the range of A. maculatum for whom an eschar or vesicular rash was described were evaluated by > or =1 laboratory assays at the Centers for Disease Control and Prevention (Atlanta, GA) to identify probable or confirmed infection with R. parkeri. RESULTS: During 1998-2007, clinical samples from 12 patients with illnesses epidemiologically and clinically compatible with R. parkeri rickettsiosis were submitted for diagnostic evaluation. Using indirect immunofluorescence antibody assays, immunohistochemistry, polymerase chain reaction assays, and cell culture isolation, we identified 6 confirmed and 6 probable cases of infection with R. parkeri. The aggregate clinical characteristics of these patients revealed a disease similar to but less severe than classically described Rocky Mountain spotted fever. CONCLUSIONS: Closer attention to the distinct clinical features of the various spotted fever syndromes that exist in the United States and other countries of the Western hemisphere, coupled with more frequent use of specific confirmatory assays, may unveil several unique diseases that have been identified collectively as Rocky Mountain spotted fever during the past century. Accurate assessments of these distinct infections will ultimately provide a more valid description of the currently recognized distribution, incidence, and case-fatality rate of Rocky Mountain spotted fever.

Controlling prescription drug expenditures: a report of success.

OBJECTIVE: To determine whether a multi-interventional program can limit increases in prescription drug expenditures while maintaining utilization of needed medications. STUDY DESIGN: Quasi-experimental, pre-post design. METHODS: The program included formulary changes, quantity limits, and mandatory pill splitting for select drugs implemented in phases. We assessed the short-term effects of each intervention by comparing class-specific drug spending and generic medication use before and after benefit changes. Long-term effects were determined by comparing overall spending with projected spending estimates, and by examining changes in the planwide use of generic medications over time. Effects on medication utilization were assessed by examining members' use of selected classes of chronic medications before and after the policy changes. RESULTS: Over 3 years, the plan and members saved $6.6 million attributed to the interventions. Most of the savings were due to the reclassification of select brand-name drugs to nonpreferred status (estimated annual savings, $941,000), followed by the removal of nonsedating antihistamines from the formulary (annual savings, $565,000), and the introduction of pill splitting (annual savings, $342,000). Limiting quantities of select medications had the smallest impact (annual savings, $135,000). Members' use of generic medications steadily increased from 40% to 57%. Although 17.5% of members stopped using at least 1 class of selected medications, members' total use of chronic medications remained constant. CONCLUSIONS: A combination of interventions can successfully manage prescription drug spending while preserving utilization of chronic medications. Additional studies are needed to determine the effect of these cost-control interventions on other health outcomes.