What Is Left to Tackle in Inpatient Antimicrobial Stewardship Practice and Research.

Despite widespread uptake of antimicrobial stewardship in acute care hospitals, there is ongoing need for innovation and optimization of ASPs. This article discusses current antimicrobial stewardship practice challenges and ways to improve current antimicrobial stewardship workflows. Additionally, we propose new workflows that further engage front line clinicians in optimizing their own antibiotic decision making.

Infectious Diseases Consultation Associated With Reduced Mortality in Gram-Negative Bacteremia.

Gram-negative bacteremia (GN-BSI) can cause significant morbidity and mortality, but the benefit of infectious diseases consultation (IDC) is not well defined. A 24-site observational cohort study of unique hospitalized patients with 4861 GN-BSI episodes demonstrated a 40% decreased risk of 30-day mortality in patients with IDC compared to those without IDC.

Evaluating the Follow-up of Post-discharge Positive Sterile Site Cultures and the Impact on Infection-Related Complications.

INTRODUCTION: Numerous patients have cultures pending at discharge which, if not addressed, may delay diagnosis and initiation of appropriate antimicrobials. The purpose of the study is to evaluate the appropriateness of discharge antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge. METHODS: This was a cross-sectional cohort study of patients admitted from July 1 to December 31, 2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission ≥ 48 h and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial changes based on finalized cultures. Secondary objectives included prevalence and timeliness of result documentation and rates of 30-day readmission, among intervention warranted versus not warranted. Chi-squared or Fisher's exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day readmission stratified by infectious disease (ID) involvement due to the potential for effect modification. RESULTS: A total of 208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7%); deep tissue and blood were the most common culture sites (29.3%). Change in discharge antimicrobial was warranted in 36.5% of patients (n = 76). Result documentation was overall low (35.5%). Time to documentation was significantly shorter in patients warranting antimicrobial intervention (4 days vs. 9 days, P = 0.039), although rates of hospital readmission were higher in this group (32.9% vs. 22.7%, P = 0.109). Finally, in patients not being followed by ID, documentation of finalized results was associated with decreased odds of 30-day readmission (aOR 0.19; 95% CI 0.07-0.53). CONCLUSIONS: A significant number of patients with cultures finalized post-discharge warranted antimicrobial intervention. Acknowledgment of finalized culture results may decrease the risk of 30-day hospital readmission, particularly in patients not followed by ID. Quality improvement efforts should focus on methods to improve documentation and action on pending cultures to positively impact patient outcomes.

Is diagnostic stewardship possible in solid organ transplantation?

BACKGROUND: Diagnostic stewardship in solid organ transplant (SOT) recipients has the potential to help these vulnerable patients at risk for over-testing and overtreatment. METHODS: Herein, we review potential targets for diagnostic stewardship in SOT, such as Clostridioides difficile testing, urine cultures, molecular diagnostics, as well as novel areas of diagnostic stewardship. RESULTS: Bundled interventions focused on appropriate C. difficile testing can result in a significant decrease in testing and clinical diagnosis of C. difficile infection without any harms related to delay in diagnosis. In otherwise stable renal transplant recipients after the first month of transplant, screening urine cultures have not been shown to improve outcomes. Novel targets that require additional study in the SOT population include noninvasive fungal diagnostics and cytomegalovirus testing strategies CONCLUSIONS: Diagnostic stewardship is an innovative approach to improve diagnosis and limit unnecessary antimicrobial use. While there has been little direct exploration of diagnostic stewardship in the SOT population, there is great potential for benefit given frequent testing with diagnostics that have imperfect sensitivity and specificity, and sometimes great cost. Diagnostic stewardship in the SOT population is indeed possible but will require a multidisciplinary effort to ensure that appropriates tests and benefits are realized.

Real-world Antimicrobial Stewardship Experience in a Large Academic Medical Center: Using Statistical and Machine Learning Approaches to Identify Intervention "Hotspots" in an Antibiotic Audit and Feedback Program.

Background: Prospective audit with feedback (PAF) is an impactful strategy for antimicrobial stewardship program (ASP) activities. However, because PAF requires reviewing large numbers of antimicrobial orders on a case-by-case basis, PAF programs are highly resource intensive. The current study aimed to identify predictors of ASP intervention (ie, feedback) and to build models to identify orders that can be safely bypassed from review, to make PAF programs more efficient. Methods: We performed a retrospective cross-sectional study of inpatient antimicrobial orders reviewed by the University of Maryland Medical Center's PAF program between 2017 and 2019. We evaluated the relationship between antimicrobial and patient characteristics with ASP intervention using multivariable logistic regression models. Separately, we built prediction models for ASP intervention using statistical and machine learning approaches and evaluated performance on held-out data. Results: Across 17 503 PAF reviews, 4219 (24%) resulted in intervention. In adjusted analyses, a clinical pharmacist on the ordering unit or receipt of an infectious disease consult were associated with 17% and 56% lower intervention odds, respectively (adjusted odds ratios [aORs], 0.83 and 0.44; P ≤ .001 for both). Fluoroquinolones had the highest adjusted intervention odds (aOR, 3.22 [95% confidence interval, 2.63-3.96]). A machine learning classifier (C-statistic 0.76) reduced reviews by 49% while achieving 78% sensitivity. A "workflow simplified" regression model that restricted to antimicrobial class and clinical indication variables, 2 strong machine learning-identified predictors, reduced reviews by one-third while achieving 81% sensitivity. Conclusions: Prediction models substantially reduced PAF review caseloads while maintaining high sensitivities. Our results and approach may offer a blueprint for other ASPs.

Follow-up Blood Culture Practices for Gram-Negative Bloodstream Infections in Immunocompromised Hosts at a Large Academic Medical Center.

The role of follow-up blood cultures (FUBCs) in gram-negative bloodstream infections to improve clinical outcomes remains controversial, especially among immunocompromised patients. Among 139 patients, FUBCs were common (117, 84.2%); however, positive FUBCs were rare (3, 2.6%). Only presence of fever was associated with a positive FUBC.

Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process.

BACKGROUND: Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions. METHODS: Panelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds. RESULTS: Thirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable. CONCLUSIONS: In the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario.

HHV-6 Encephalitis After Chimeric Antigen Receptor T-cell Therapy (CAR-T): 2 Case Reports and a Brief Review of the Literature.

Human herpesvirus 6 (HHV-6) reactivation can occur in patients who are highly immunosuppressed, including those who have undergone hematopoietic stem cell transplantation (HSCT). HHV-6 encephalitis is a severe manifestation that is well described in the HSCT population. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel cancer-directed immunotherapy that results in severe immunosuppression. Patients undergoing CAR-T therapy may be at risk for HHV-6 encephalitis, which can be difficult to distinguish from a common adverse effect of CAR-T therapy, neurotoxicity. Herein, we describe 2 patients diagnosed with HHV-6 encephalitis after CAR-T therapy and discuss the diagnostic approach and differential diagnosis for altered mental status after CAR-T therapy. Diagnosing HHV-6 encephalitis can be difficult in this patient population as altered mental status is common after CAR-T therapy and may be attributed to CAR-T-associated neurotoxicity.

Effectiveness and Safety of Biodegradable Calcium Sulfate Antibiotic Beads as Adjuvant Therapy in Vascular Graft Infections.

This is a retrospective cohort study evaluating the safety and effectiveness of biodegradable calcium sulfate antibiotic beads in vascular graft infections compared with standard of care. No differences in acute kidney injury or hypercalcemia were observed between the cohorts. Recurrence of infection did not occur in the 13-patient bead cohort compared with 14 patients who had recurrence in the 45-patient nonbead cohort with a number needed to treat of 4.0.

Change in hospital antibiotic use and acquisition of multidrug-resistant gram-negative organisms after the onset of coronavirus disease 2019.

Interrupted time series segmented regression was conducted to trend antibiotic use and multidrug-resistant gram-negative (MDRGN) acquisition relative to COVID-19 in an academic hospital. Total antibiotic use and antibiotic use related to pneumonia was higher in the period after the onset of COVID-19 compared to the similar calendar period in 2019. Furthermore, MDRGN acquisition increased 3% for every increase in positive COVID-19 tests per week.

Multicenter retrospective cohort study of the clinical significance of Staphylococcus lugdunensis isolated from a single blood culture set.

BACKGROUND: Staphylococcus lugdunensis is a coagulase negative Staphylococcus species and frequent human skin commensal with the potential for aggressive infection. Guidance surrounding S. lugdunensis bacteremia (SLB) from a single set of blood cultures is lacking. METHODS: A multicenter, retrospective cohort of patients with SLB from at least one blood culture set within the University of Maryland Medical System from 2015 to 2019 is presented. Objectives are to describe baseline characteristics, compare the clinical status and treatment course, and to evaluate the clinical outcomes among patients with SLB in single versus multiple sets. RESULTS: Thirty-six patients were included, 24 with one set of blood cultures positive for S lugdunensis and 12 with multiple sets. Baseline characteristics were similar between the groups, though patients with SLB in multiple sets were more commonly on hemodialysis (P = 0.029). Central lines were the most common source (17%). Most (97%) fulfilled systemic inflammatory response syndrome or Souvenir criteria, had an infectious focus on imaging, or had a second positive culture site. Most (78%) were treated as clinically significant. Patients with multiple positive sets were more commonly treated with antibiotics for >2 weeks (P = 0.02). CONCLUSIONS: SLB was rare and occurred more frequently as a single set of positive cultures. Patient characteristics and clinical courses were similar between single and multiple set groups. Given the potential severity of S. lugdunensis bacteremia it seems prudent to treat S. lugdunensis in a single blood culture as true bacteremia, pending larger studies and guidelines.

Diabetic Foot Infections: Local Prevalence of and Case-Control Study of Risk Factors for Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa.

We identified deep diabetic foot infections by culture and conducted a case-control study examining the risk factors for moderate to severe methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PsA) diabetic foot infections. Our MRSA prevalence was lower than literature values; PsA was higher. Gangrene may be predictive of Pseudomonas infection.

Effect of urine reflex culturing on rates of cultures and infections in acute and long-term care.

BACKGROUND: Urine cultures are often positive in the absence of a urinary tract infection (UTI). Pyuria is generally considered necessary to diagnose a UTI. PROBLEM: Urine cultures are often positive in the absence of UTI leading to unnecessary antibiotics. METHODS: Quasi-experimental pre-post study of all patient urine cultures ordered in a VA acute care hospital, emergency department (ED), and two long-term care (LTC) facilities from August 2016 to August 2018. Urine cultures performed per 100 days were compared pre- (August 2016 to July 2017) versus post-intervention (August 2017 to August 2018) using interrupted time series negative binomial regression. INTERVENTION: We examined whether reflexing to urine culture only if a urinalysis (UA) found greater than 10 WBC/hpf decreased urine culturing. RESULTS: In acute-care, reflex culturing resulted in a 39% time series regression analysis adjusted decrease in the rate of cultures performed (pre-intervention, 3.6 cultures/100 days vs. Post-intervention, 1.8 cultures/100 days, p < 0.001). Pre-intervention, 29% (4/14) of Catheter-associated UTI (CAUTI) would not have been reported if reflex culturing was employed. In the ED, reflex culturing was associated with a 38% (p = 0.0015) regression analysis adjusted decrease in cultures, from 5.4/100 visits to 3.3/100 visits. In LTC, there was a small absolute, but regression analysis adjusted increase of 89% (p = 0.0018) in rates from (0.4/100 days to 0.5/100 days). CONCLUSION: In acute care and ED, urine reflex culturing decreased the number of urine cultures performed. A small absolute increase was seen between pre-post time periods in LTC. Reflex testing generally decreases cultures and may lead to more accurate diagnoses of CAUTI.

A Propensity Score Matched Study of the Positive Impact of Infectious Diseases Consultation on Antimicrobial Appropriateness in Hospitalized Patients with Antimicrobial Stewardship Oversight.

Hospital-based antibiotic stewardship (AS) programs provide oversight and guidance for appropriate antimicrobial use in acute care settings. Infectious disease expertise is beneficial in the care of hospitalized patients with infections. The impact of infectious diseases consultation (IDC) on antimicrobial appropriateness in a large tertiary hospital with an established AS program was investigated. This was a cross-sectional study from October 2017 to March 2019 at a large academic hospital with an AS-directed prospective audit and feedback process and multiple IDC services. Antimicrobial appropriateness was adjudicated by an AS team member after antimicrobial start. Antimicrobial appropriateness was compared among antimicrobial orders with and without IDC using propensity score matching and multivariable logistic regression. Analyses were stratified by primary services caring for the patients. There were 10,508 antimicrobial orders from 6,165 unique patient encounters. Overall appropriateness was 92%, with higher appropriateness among patients with IDC versus without IDC (94% versus 84%; P < 0.0001). After propensity score matching and adjustment for certain antibiotics, organisms, syndromes, and locations, IDC was associated with a greater antimicrobial appropriateness odds ratio (OR) of 2.4 (95% confidence interval [CI], 1.9 to 3.0). Stratification by primary service showed an OR of 2.9 (95% CI, 2.1 to 3.8) for surgical specialties and an OR of 1.6 (95% CI, 1.1 to 2.2) for medical specialties. Even with a high overall antimicrobial appropriateness, patients with IDC had greater odds of antimicrobial appropriateness than those without IDC, and this impact was greater in surgical specialties. Infectious diseases consultation can be synergistic with antimicrobial stewardship programs.

Dalbavancin Use in Vulnerable Patients Receiving Outpatient Parenteral Antibiotic Therapy for Invasive Gram-Positive Infections.

INTRODUCTION: Dalbavancin is approved for acute bacterial skin and skin structure infections (ABSSSIs) but offers a potential treatment option for complicated invasive gram-positive infections. Importantly, dalbavancin's real benefits may be in treating complicated infections in vulnerable patient populations, such as persons who inject drugs (PWID). METHODS: A multicenter retrospective analysis was performed from March 2014 to April 2017 to assess 30- and 90-day clinical cure and adverse drug events (ADEs) in adult patients who received ≥ 1 dose of dalbavancin for a non-ABSSSI indication. RESULTS: During the study period, 45 patients received dalbavancin, 28 for a non-ABSSSI indication. The predominant infections treated included osteomyelitis (46%), endovascular infection (25%) and uncomplicated bacteremia (14%). Half of the patients had positive Staphylococcus aureus in cultures, 29% methicillin resistant and 21% methicillin susceptible. Most patients were prescribed dalbavancin as sequential treatment with a median of 13.5 days of prior antibiotic therapy. The most common reason for choosing dalbavancin over standard therapy use was PWID (54%). Seven patients were lost to follow-up at day 30. Of the remaining evaluable patients, 30-day clinical cure was achieved in 15/21 (71%) patients. The most common reason for failure was lack of source control (4/6, 67%). At day 90, relapse occurred in two patients. Three patients had a potential dalbavancin-associated ADE: two patients with renal dysfunction and one patient with pruritus. CONCLUSIONS: This study demonstrates a possible role for dalbavancin in the treatment of non-ABSSSI invasive gram-positive infections in select vulnerable OPAT patients.

Peer Comparison of Anti-MRSA Agent Prescription in the Inpatient Setting.

Peer comparison has potential as an effective antimicrobial stewardship intervention in the inpatient setting. We report a new metric, days of therapy per 100 service days, for comparing antibiotic utilization. Among 14 prescribers on the primary infectious diseases service during a 6-month period, we identified 1 outlier for each anti-MRSA agent. Infect Control Hosp Epidemiol 2017;38:1506-1508.

Impact of CLSI and EUCAST Cefepime breakpoint changes on the susceptibility reporting for Enterobacteriaceae.

OBJECTIVE: We analyzed the effects of different cefepime MIC breakpoints on Enterobacteriaceae cefepime susceptibility and the presence of AmpC and extended-spectrum ß-lactamase (ESBL) genes within the cefepime MIC interpretative categories. METHODS: Using Enterobacteriaceae susceptibility data from 2013 comparisons of MIC breakpoints were performed using Pearson's chi-squared test. Molecular testing on a subset of isolates was done. RESULTS: Among 3784 non-duplicate clinical isolates, cefepime susceptibility decreased from 97.6% to 96.1% to 93.7% for CLSI 2013, CLSI 2014, and EUCAST 2011, respectively. In ceftriaxone non-susceptible isolates, cefepime susceptibility decreased from 79% to 66% (P<0.0001) using CLSI 2013 and 2014, respectively, which was greater and statistically significant for Escherichia coli and Klebsiella spp. but not for Enterobacter spp. (P=0.06). Isolates with MIC ≤1µg/mL more often harbored AmpC (77%) than ESBL (18%) genes. CONCLUSIONS: Lower cefepime MIC breakpoints decrease cefepime susceptibility for isolates harboring ESBLs, while sparing the majority of those with AmpCs.

Implementation of an Infectious Disease Fellow-Managed Penicillin Allergy Skin Testing Service.

Background. A large percentage of patients presenting to acute care facilities report penicillin allergies that are associated with suboptimal antibiotic therapy. Penicillin skin testing (PST) can clarify allergy histories but is often limited by access to testing. We aimed to implement an infectious diseases (ID) fellow-managed PST program and to assess the need for PST via national survey. Methods. We conducted a prospective observational study of the implementation of an ID fellow-managed penicillin allergy skin testing service. The primary outcome of the study was to assess the feasibility and acceptability of an ID fellow-managed PST service and its impact on the optimization of antibiotic selection. In addition, a survey of PST practices was sent out to all ID fellowship program directors in the United States. Results. In the first 11 months of the program, 90 patients were assessed for PST and 76 patients were tested. Of the valid tests, 96% were negative, and 84% with a negative test had antibiotic changes; 63% received a narrower spectrum antibiotic, 80% received more effective therapy, and 61% received more cost-effective therapy. The majority of survey of respondents (n = 50) indicated that overreporting of penicillin allergy is a problem in their practice that affects antibiotic selection but listed inadequate personnel and time as the main barriers to PST. Conclusions. Inpatient PST can be successfully managed by ID fellows, thereby promoting optimal antibiotic use in patients reporting penicillin allergies. This model can increase access to PST at institutions without adequate access to allergists while also providing an important educational experience to ID trainees.

Treatment options for extended-spectrum beta-lactamase (ESBL) and AmpC-producing bacteria.

INTRODUCTION: Extended spectrum ß-lactamases (ESBL) and AmpC ß-lactamases are increasing causes of resistance in many Gram-negative pathogens of common infections. This has led to a growing utilization of broad spectrum antibiotics, most predominately the carbapenem agents. As the prevalence of ESBL and AmpC-producing isolates and carbapenem resistance has increased, interest in effective alternatives for the management of these infections has also developed. AREAS COVERED: This article summarizes clinical literature evaluating the utility of carbapenem-sparing regimens for the treatment of ESBL and AmpC-producing Enterobacteriaceae, mainly ß-lactam-ß-lactamase inhibitor combinations and cefepime (FEP). EXPERT OPINION: Based on available data, the use of piperacillin-tazobactam (PTZ) and FEP in the treatment of ESBL-producing Enterobacteriaceae cannot be widely recommended. However, certain infections and patient characteristics may support for effective use of these alternative agents. In the treatment of infections caused by AmpC-producing Enterobacteriaceae, FEP has been shown to be a clinically useful carbapenem-sparing alternative. Carbapenems and FEP share many structurally similar characteristics in regards to susceptibility to AmpC ß-lactamases, which further create confidence in the use FEP in these situations. Patient and infection specific characteristics should be used to employ FEP optimally.