The prevalence of gram-negative bacteria with difficult-to-treat resistance and utilization of novel ß-lactam antibiotics in the southeastern United States.

Objective: To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel ß-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design: Retrospective, multicenter, cohort. Setting: Ten hospitals in the southeastern United States. Methods: GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel ß-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel ß-lactams. Results: The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 (P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel ß-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden. Conclusions: The overall prevalence of GNB with DTR and the use of novel ß-lactams remain low. However, the uptrend in the use of novel ß-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR.

Antifungal resistance, combinations and pipeline: oh my!

Invasive fungal infections are a strong contributor to healthcare costs, morbidity and mortality, especially amongst hospitalized patients. Historically, Candida was responsible for approximately 15% of all nosocomial bloodstream infections. In the past 10 years, the epidemiology of Candida species has altered, with increasing prevalence of resistant species. With rising fungal resistance, especially in Candida spp., the demand for novel antifungal therapies has exponentially increased over the last decade. Newer antifungal agents have become an attractive option for patients needing long-term therapy for infections or those requiring antifungal prophylaxis. Despite advances in coverage of non-Candida pathogens with newer agents, clinical scenarios involving multidrug-resistant fungal pathogens continue to arise in practice. Combination antifungal therapy can lead to a host of side-effects, some of which can be drug limiting. Additional antifungal therapies with enhanced fungal spectrum of activity and decreased rates of adverse effects are warranted. Fosmanogepix, ibrexafungerp, olorofim and rezafungin may help fill some of these gaps in the antifungal armamentarium. This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections.

Antibiotic De-Escalation in Critically Ill Patients with Negative Clinical Cultures.

(1) Background: Antibiotics are received by a majority of adult intensive care unit (ICU) patients. Guidelines recommend antibiotic de-escalation (ADE) when culture results are available; however, there is less guidance for patients with negative cultures. The purpose of this study was in investigate ADE rates in an ICU population with negative clinical cultures. (2) Methods: This single-center, retrospective, cohort study evaluated ICU patients who received broad-spectrum antibiotics. The definition of de-escalation was antibiotic discontinuation or narrowing of the spectrum within 72 h of initiation. The outcomes evaluated included the rate of antibiotic de-escalation, mortality, rates of antimicrobial escalation, AKI incidence, new hospital acquired infections, and lengths of stay. (3) Results: Of the 173 patients included, 38 (22%) underwent pivotal ADE within 72 h, and 82 (47%) had companion antibiotics de-escalated. Notable differences in patient outcomes included shorter durations of therapy (p = 0.003), length of stay (p < 0.001), and incidence of AKI (p = 0.031) in those that underwent pivotal ADE; no difference in mortality was found. (4) Conclusions: The results from this study show the feasibility of ADE in patients with negative clinical cultures without a negative impact on the outcomes. However, further investigation is needed to determine its effect on the development of resistance and adverse effects.

Evaluation of a Pediatric Community-Acquired Pneumonia Antimicrobial Stewardship Intervention at an Academic Medical Center.

(1) Background: Pneumonia is the leading diagnosis associated with antibiotic use in hospitalized children. The Infectious Diseases Society of America published pediatric community-acquired pneumonia (CAP) guidelines in 2011, but adherence to recommendations varies across institutions. The purpose of this study was to evaluate the impact of an antimicrobial stewardship intervention on antibiotic prescribing in pediatric patients admitted to an academic medical center. (2) Methods: This single-center pre/post-intervention evaluation included children admitted for CAP during three time periods (pre-intervention and post-intervention groups 1 and 2). The primary outcomes were changes in inpatient antibiotic selection and duration following the interventions. Secondary outcomes included discharge antibiotic regimens, length of stay, and 30-day readmission rates. (3) Results: A total of 540 patients were included in this study. Most patients were under five years of age (69%). Antibiotic selection significantly improved, with prescriptions for ceftriaxone decreasing (p < 0.001) and ampicillin increasing (p < 0.001) following the interventions. Antibiotic duration decreased from a median of ten days in the pre-intervention group and post-intervention group 1 to eight days in post-intervention group 2. (4) Conclusions: Our antibiotic stewardship intervention directed at pediatric CAP treatment resulted in improved antibiotic prescriptions and provides data that can be used to further educate providers at our institution.

Risk Factors for Bloodstream Infections Due to ESBL-Producing Escherichia coli, Klebsiella spp., and Proteus mirabilis.

(1) Background: Risk factors for extended-spectrum beta-lactamase (ESBL) infections could vary geographically. The purpose of this study was to identify local risk factors for ESBL production in patients with Gram-negative bacteremia. (2) Methods: This retrospective observational study included adult patients admitted from January 2019 to July 2021 and had positive blood cultures for E. coli, K. pneumoniae, K. oxytoca, and P. mirabilis. Patients with ESBL infection were matched to a non-ESBL-producing infection with the same organism. (3) Results: A total of 150 patients were included: 50 in the ESBL group and 100 in the non-ESBL group. Patients in the ESBL group had a longer length of stay (11 vs. 7 days, p < 0.001), but not increased mortality (14% vs. 15%, p = 0.87) Multivariate analysis identified the receipt of >1 antibiotic in the last 90 days as a risk factor for ESBL infection (OR = 3.448, 95% CI = 1.494-7.957; p = 0.004); (4) Conclusions: Recent antimicrobial use was identified as an independent risk factors for ESBL-producing Enterobacterales infections. Knowledge of this risk may improve empirical therapy and reduce inappropriate use.

Evaluation of an Antifungal Stewardship Initiative Targeting Micafungin at an Academic Medical Center.

Delays in the treatment of proven invasive fungal disease have been shown to be harmful. However, empiric treatment for all patients at risk of infection has not demonstrated benefit. This study evaluates the effects of a micafungin stewardship initiative on the duration of therapy and clinical outcomes at the University of Mississippi Medical Center in Jackson, Mississippi. This single-center quasi-experiment evaluated patients who received micafungin. Adult inpatients who received at least one treatment dose of micafungin in the pre-intervention (1 October 2020 to 30 September 2021) or post-intervention (1 October 2021 to 30 April 2022) groups were included. Patients were placed on micafungin for prophylaxis and those who required definitive micafungin therapy were excluded. An algorithm was used to provide real-time recommendations in order to assess change in the treatment days of micafungin therapy. A total of 282 patients were included (141 pre-group versus 141 post-group). Over 80% of the patients included in the study were in an intensive care unit, and other baseline characteristics were similar. The median number of treatment days with micafungin was 4 [IQR 3-6] in the pre-group and 3 [IQR 2-6] in the post-group (p = 0.005). Other endpoints, such as time to discontinuation or de-escalation, hospital mortality, and hospital length of stay, were not significantly different between the groups. An antifungal stewardship initiative can be an effective way to decrease unnecessary empiric antifungal therapy for patients who are at risk of invasive fugal disease.

Approach to fever in patients with neutropenia: a review of diagnosis and management.

Febrile neutropenia (FN) is associated with mortality rates as high as 40%, highlighting the importance of appropriate clinical management in this patient population. The morbidity and mortality of FN can be attributed largely to infectious processes, with specific concern for infections caused by pathogens with antimicrobial resistance. Expeditious identification of responsible pathogens and subsequent initiation of empiric antimicrobial therapy is imperative. There are four commonly used guidelines, which have variable recommendations for empiric therapy in these populations. All agree that changes could be made once patients are stable and/or with an absolute neutrophil count (ANC) over 500 cells/mcL. Diagnostic advances have the potential to improve knowledge of pathogens responsible for FN and decrease time to results. In addition, more recent data show that rapid de-escalation or discontinuation of empiric therapy, regardless of ANC, may reduce days of therapy, adverse effects, and cost, without affecting clinical outcomes. Antimicrobial and diagnostic stewardship should be performed to identify, utilize, and respond to appropriate rapid diagnostic tests that will aid in the definitive management of this population.

Analysis of the Clinical Impact of the BioFire FilmArray Meningitis Encephalitis Panel on Antimicrobial Use and Duration of Therapy at an Academic Medical Center.

The purpose of this study was to assess the clinical impact of the BioFire FilmArray Meningitis/Encephalitis (ME) panel on antimicrobial use and clinical outcomes. This retrospective, quasi-experiment evaluated adult and pediatric patients with suspected ME, evidenced by cerebrospinal fluid (CSF) culture. Hospital-acquired meningitis patients and patients who received antimicrobials >48 h prior to lumbar puncture were excluded. The primary endpoint was days of antimicrobial therapy pre- and post-implementation of the ME panel. Secondary endpoints included total length of stay, 30-day readmission, and individual days of antimicrobial therapy. Two hundred and sixty-four total adult and pediatric patients were included. Antimicrobial days of therapy had a median of 3 days (IQR 0−5) in the pre vs. post group with a median of 2 days (2−5) (p = 0.099). Days of therapy for acyclovir were significantly decreased in the post group (median 2 days [IQR 1−3] vs. 3 days [IQR 2.5−4.5], p = 0.0002). There were no significant differences in the secondary endpoints. Overall, implementation of the ME panel impacted the duration of antimicrobials, particularly acyclovir; however, opportunities for further education regarding antimicrobial de-escalation and utilization of the panel were identified. Antimicrobial stewardship program intervention is critical to maximize benefit of this rapid diagnostic test.

Rethinking residency recruitment, application, and interview processes to benefit applicants and programs long-term.

Pharmacy residency recruitment and interviews have been significantly impacted by the COVID-19 pandemic. Many traditional recruitment events and interviews were transitioned from in-person to virtual, and new approaches to recruitment, such as virtual open houses, were developed. There are limited data on how these changes impacted pharmacy residency applicants and programs, and the future of virtual events is currently unknown. We highlight recommendations for virtual recruitment and interviews and provide suggestions for residency programs and national organizations to improve virtual processes in the future.

Evaluation of Pharmacy Residency Recruitment and Interview Processes during the COVID-19 Pandemic (2020-2021 Application Cycle).

Introduction: Due to the COVID-19 pandemic, most pharmacy residency programs changed to an all-virtual format for recruitment and interviews for the 2020-2021 application cycle. There are no data evaluating the experiences and perceptions of these changes from the perspective of pharmacy residency programs and applicants. Methods: An electronic cross-sectional survey was distributed via email to post-graduate year 1 (PGY1) and post-graduate year 2 (PGY2) pharmacy residency programs and applicants across the Southeastern United States. Results have been reported according to the Checklist for Reporting of Survey Studies (CROSS) guidelines (Enhancing the QUAlity and Transparency Of health Research [EQUATOR] Network). Results: 142 residency applicants and 104 residency programs responded to the survey. Most respondents participated in virtual recruitment and interviews. In 2020-2021, less residency programs participated in local/regional showcases and personal placement services, but social media engagement increased. Of the applicants who responded, over half felt the need to apply to more programs during this application cycle, and a corresponding increase in applications were seen by residency programs. Residency interviews appeared shorter than previous years, and less programs offered an informal time to get to know the applicants. Overall, applicants and residency programs preferred on-site interviews, but both parties reported feeling confident creating rank lists after virtual interviews. Conclusion: These results highlight the impact of COVID-19 on residency recruitment and the interview process. Residency programs should implement feedback for improving the virtual experience, as able. The ongoing pandemic may affect the 2022-2023 application cycle, and pharmacy leadership organizations should consider developing guidance for applicants and residency programs on navigating another year of virtual events.This article is protected by copyright. All rights reserved.

Diabetic foot infections: A microbiologic review.

Diabetes mellitus continues to be an increasingly common comorbidity. Diabetic foot infections are one of the most common causes of hospitalization in this population, and account for a significant portion of increased hospitalization and healthcare expenditure. Complications, such as osteomyelitis, can necessitate the use of multiple, prolonged antibiotic courses. These courses often consist of broad-spectrum, empiric therapy determined by organisms considered to be commonly associated with these types of infections. Extended periods of broad-spectrum antibiotic regimens can contribute to antibiotic resistance and ultimately limit future treatment options. Furthermore, patient specific risk factors can impact the microbiologic diversity found in these infections. As a result, it is difficult to determine if a single empiric regimen is appropriate for all instances of diabetic foot infections. OBJECTIVES AND METHODS: This review analyzes global literature relating to the culture methods, incidence, risk factors, resistance patterns, and geographic distribution of the microorganisms isolated from diabetic foot infections using the PRISMA statement for systematic review and meta-analysis reporting. RESULTS: Staphylococcus aureus remains a significant pathogen, with a growing incidence of Pseudomonas aeruginosa and MDR gram-negative bacilli. CONCLUSIONS: Though some individualized risk factors can be useful, local epidemiology and resistance patterns remain essential for antibiotic treatment considerations.

Intravenous versus Oral Step-Down for the Treatment of Staphylococcus aureus Bacteremia in a Pediatric Population.

Limited data are available regarding optimal antimicrobial therapy for Staphylococcus aureus bacteremia (SAB) in pediatric patients. The purpose of this study was to assess clinical characteristics and outcomes associated with intravenous (IV) versus oral step-down treatment of pediatric SAB. This study evaluated patients aged 3 months to 18 years that received at least 72 h of inpatient treatment for SAB. The primary endpoint was 30-day readmission. Secondary endpoints included hospital length of stay and inpatient mortality. One hundred and one patients were included in this study. The median age was 7.9 years. Patients who underwent oral step-down were less likely to be immunocompromised and more likely to have community-acquired SAB from osteomyelitis or skin and soft tissue infection (SSTI). More patients in the IV therapy group had a 30-day readmission (10 (25.6%) vs. 3 (5.3%), p = 0.006). Mortality was low (5 (5%)) and not statistically different between groups. Length of stay was greater in patients receiving IV therapy only (11 vs. 7 days, p = 0.001). In this study, over half of the patients received oral step-down therapy and 30-day readmission was low for this group. Oral therapy appears to be safe and effective for patients with SAB from osteomyelitis or SSTIs.

Increased rates of blood culture contamination during the coronavirus disease 2019 pandemic.

We observed a higher rate of blood-culture contamination during the COVID-19 pandemic at our institution compared to a prepandemic period. Given the potential implications of blood contamination in antibiotic and diagnostic test utilization as well as added cost, it is imperative to continue efforts to minimize these episodes during the pandemic.

An evaluation of antipseudomonal dosing on the incidence of treatment failure.

INTRODUCTION: Significant mortality is associated with delays in appropriate antibiotic therapy in Pseudomonas aeruginosa infections. The impact of empiric dosing on clinical outcomes has been largely unreported. METHODS: This retrospective cohort compared treatment failure in patients receiving guideline-concordant or guideline-discordant empiric therapy with cefepime, meropenem, or piperacillin/tazobactam. Patients with culture-positive P. aeruginosa between 1 July 2013 and 31 July 2019 were eligible for inclusion. Patients with cystic fibrosis, polymicrobial infection, and urinary or pulmonary colonization were excluded. The composite primary outcome was treatment failure, defined as (1) therapy modification due to resistance/perceived treatment failure, (2) increased/unchanged qSOFA, or (3) persistent fever 48 h after initiating appropriate therapy. Secondary outcomes included rate of infectious diseases consultation, all-cause inpatient mortality, mechanical ventilation requirement, and infection-related intensive care unit and hospital lengths of stay. RESULTS: In total, 198 patients were included: 90 guideline-concordant and 108 guideline-discordant. Baseline characteristics were balanced. Treatment failure was more common in the guideline-discordant than the guideline-concordant group (62% versus 48%; p = 0.04). This remained significant when adjusting for supratherapeutic dosing (p = 0.02). Infectious diseases consultation was higher in the guideline-discordant group (46% versus 29%, p = 0.01), while intensive care unit length of stay was longer in the guideline-concordant group (4.5 versus 3 days, p = 0.03). Additional secondary outcomes were similar. CONCLUSION: Treatment failure was significantly higher in patients receiving guideline-discordant empiric antipseudomonal dosing. Guideline-directed dosing, disease states, and patient-specific factors should be assessed when considering empiric antipseudomonal dosing.

Epidemiology, Clinical Features, and Outcomes of Hospitalized Adults with COVID-19: Early Experience from an Academic Medical Center in Mississippi.

OBJECTIVES: To describe the demographics, clinical characteristics, and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) in an academic medical center in the southern United States. METHODS: Retrospective, observational cohort study of all adult patients (18 years and older) consecutively admitted with laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 infection between March 13 and April 25, 2020 at the University of Mississippi Medical Center. All of the patients either survived to hospital discharge or died during hospitalization. Demographics, body mass index, comorbidities, clinical manifestations, and laboratory findings were collected. Patient outcomes (need for invasive mechanical ventilation and in-hospital death) were analyzed. RESULTS: One hundred patients were included, 53% of whom were women. Median age was 59 years (interquartile range 44-70) and 66% were younger than 65. Seventy-five percent identified themselves as Black, despite representing 58% of hospitalized patients at our institution in 2019. Common comorbid conditions included hypertension (68%), obesity (65%), and diabetes mellitus (31%). Frequent clinical manifestations included shortness of breath (76%), cough (75%), and fever (64%). Symptoms were present for a median of 7 days (interquartile range 4-7) on presentation. Twenty-four percent of patients required mechanical ventilation and, overall, 19% died (67% of those requiring mechanical ventilation). Eighty-four percent of those who died were Black. On multivariate analysis, ever smoking (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.6) and history of diabetes mellitus (OR 5.9, 95% CI 1.5-24.3) were associated with mortality, and those admitted from home were less likely to die (vs outside facility, OR 0.2, 95% CI 0.0-0.7). Neither age, sex, race, body mass index, insurance status, nor rural residence was independently associated with mortality. CONCLUSIONS: Our study adds evidence that Black patients appear to be overrepresented in those hospitalized with and those who die from COVID-19, likely a manifestation of adverse social determinants of health. These findings should help guide preventive interventions targeting groups at higher risk of acquiring and developing severe COVID-19 disease.

An Antimicrobial Stewardship Intervention Improves Adherence to Standard of Care for Staphylococcus aureus Bloodstream Infection.

INTRODUCTION: Staphylococcus aureus bloodstream infections (SABSI) are a major cause of morbidity and mortality in the United States, and proper management is important to effect cure and prevent metastatic foci of infection. We aimed to utilize our antimicrobial stewardship program (ASP) to improve practices at a large academic hospital system. METHODS: Our ASP implemented a SABSI educational campaign directed at the hospital medicine, cardiology, and infectious diseases divisions. A stewardship intervention was then begun for all patients with SABSI recommending infectious diseases consultation, transesophageal echocardiography (TEE), source control, and preliminary antibiotic changes. A retrospective review was performed for all SABSI cases 2 years before and after implementation of the SABSI intervention. RESULTS: Two hundred forty-three cases before intervention and 259 after intervention were included. An increase in obtaining follow-up negative blood cultures (79.8% vs. 89.6%), infectious diseases consultation (52.7% vs. 86.5%), TEE (25.5% vs. 54.8%), beta-lactam switch for methicillin-susceptible S. aureus (55.2% vs. 74.4%), and source control (41.2% vs. 57.9%) was demonstrated. We demonstrated similar durations of bacteremia, length of stay, relapse, mortality, and rates of infective endocarditis. CONCLUSIONS: Adherence to standard of care for patients with SABSI can be dramatically improved through provider education, leveraging antimicrobial stewardship resources, and infectious diseases consultation.

Is It Time to Rethink the Notion of Carbapenem-Sparing Therapy Against Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae Bloodstream Infections? A Critical Review.

OBJECTIVE: To present systematic recommendations for carbapenem-sparing therapy against extended-spectrum ß-lactamases (ESBLs) Enterobacteriaceae bloodstream infections (BSIs) derived from a critical review of clinical data. DATA SOURCES: A systematic literature search using PubMed and MEDLINE databases (January 1, 2012, to June 30, 2017) was performed using key MESH terms: ESBL or extended-spectrum ß-lactamases and bacteremia or bloodstream infection with piperacillin/tazobactam, ciprofloxacin, levofloxacin, cefepime, cephamycins, carbapenem, doripenem, meropenem, and ertapenem. References within articles of interest were also evaluated. STUDY SELECTION AND DATA EXTRACTION: All English language trials were considered, and results were limited to clinical efficacy trials. Articles were screened by title and abstract for inclusion. DATA SYNTHESIS: Studies comparing noncarbapenem versus carbapenem therapy for ESBL BSIs were critically analyzed to identify heterogeneity among studies. Data abstracted included empirical or definitive therapy, patient population, dosing, source of infection and severity, infectious etiology, and outcome. CONCLUSIONS: Completely sparing carbapenem therapy cannot be justified among patients with ESBL BSIs. Determining the source of infection is critical to identify patients for whom carbapenem-sparing therapy is appropriate.

Comparison of susceptibility patterns using commercially available susceptibility testing methods performed on prevalent Candida spp.

The rising rates of invasive fungal infections caused by non-albicans Candida and the increasing emergence of antifungal resistance complicate the management of invasive candidiasis. Accurate and timely antifungal susceptibility testing is critical to targeting antifungal therapy. The purpose of this study was to compare commercially available susceptibility testing methods using prospectively collected Candida isolates. Susceptibility testing was performed on 74 Candida isolates collected from July 2014 to March 2015 using broth microdilution according to the Clinical and Laboratory Standards Institute method, Etest, Vitek 2 (YS-05) and Sensititre. Essential agreement and categorical agreement (CA) were assessed using the reference method. Of the 34 total blood isolates collected, Candida albicans comprised only 38 % (13) of the Candida spp. with Candidaglabrata being nearly as prevalent (29 %, 10). CA using Etest was 86 % for fluconazole, 72 % for caspofungin, 98 % for micafungin and 97 % for anidulafungin. Vitek 2 CA was 90 % for fluconazole and 98 % for caspofungin. Sensititre CA was 93 % for fluconazole, 98 % for caspofungin, 98 % for micafungin and 100 % for anidulafungin. Although our study tested a small population of Candida isolates, our results were variable by method. When implementing antifungal susceptibility testing, clinicians should be aware of the strengths and limitations of each testing method.