Diagnostic stewardship: what impacts antibiotics use?

PURPOSE OF REVIEW: The aim of this study was to review recently published diagnostic stewardship studies of common clinical infectious syndromes and the impact on antibiotic prescribing. RECENT FINDINGS: Diagnostic stewardship can be implemented within healthcare systems and tailored to infectious syndromes, including urinary tract, gastrointestinal, respiratory and bloodstream infections. In urinary syndromes, diagnostic stewardship can decrease unnecessary urine culturing and associated antibiotic prescribing. Diagnostic stewardship of Clostridium difficile testing can decrease antibiotics and test ordering with a reduction in healthcare-associated C. difficile infections. Respiratory syndrome multiplex arrays can decrease time to results and increase detection of clinically relevant pathogens but may not decrease antibiotics use, or worse, could increase over-prescribing if diagnostic stewardship of ordering practices is not exercised. Lastly, blood culturing practices can be improved by clinical decision support to safely decrease collection and broad-spectrum antibiotic use. SUMMARY: Diagnostic stewardship decreases unnecessary antibiotic use in a way that is different from and complementary to antibiotic stewardship. Further studies are needed to quantify the full impact on antibiotic use and resistance. Future considerations should be to institutionalize diagnostic stewardship in patient care activities to leverage integration into systems-based interventions.

Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients.

OBJECTIVES: We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. MATERIALS AND METHODS: Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. RESULTS: Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. CONCLUSIONS: Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.

Optimal Urine Culture Diagnostic Stewardship Practice-Results from an Expert Modified-Delphi Procedure.

BACKGROUND: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship. METHODS: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen experts ranked recommendations on a 9-point Likert scale. Recommendations on which the panel did not reach agreement were discussed during a virtual meeting, then a second round of ranking by email was completed. After secondary review of results and panel discussion, a series of guidance statements was developed. RESULTS: One hundred and sixty-five questions were reviewed. The panel reaching agreement on 104, leading to 18 overarching guidance statements. The following strategies were recommended to optimize ordering urine cultures: requiring documentation of symptoms, sending alerts to discourage ordering in the absence of symptoms, and cancelling repeat cultures. For urine culture processing, conditional urine cultures and urine white blood cell count as criteria were supported. For urine culture reporting, appropriate practices included nudges to discourage treatment under specific conditions and selective reporting of antibiotics to guide therapy decisions. CONCLUSIONS: These 18 guidance statements can optimize use of urine cultures for better patient outcomes.

Does calculation method matter for targeting vancomycin area under the curve?

OBJECTIVES: To assess differences in vancomycin AUC estimates from two common, clinically applied first-order pharmacokinetic equation methods compared with Bayesian estimates. METHODS: A cohort of patients who received vancomycin and therapeutic drug monitoring was studied. First-order population pharmacokinetic equations were used to guide initial empirical dosing. After receipt of the first dose, patients had peak and trough serum levels drawn and steady-state AUC was estimated using first-order pharmacokinetic equations as standard care. We subsequently created a Bayesian model and used individual Empirical Bayes Estimates to precisely calculate vancomycin AUC24-48, AUC48-72 and AUC72-96 in this cohort. AUC at steady state (AUCSS) differences from the first-order methods were compared numerically and categorically (i.e. below, within or above 400-600 mg·h/L) to Bayesian AUCs, which served as the gold standard. RESULTS: A total of 65 adult inpatients with 409 plasma samples were included in this analysis. A two-compartment intravenous infusion model with first-order elimination fit the data well. The mean of Bayesian AUC24-48 was not significantly different from AUC estimates from the two first-order pharmacokinetic equation methods (P = 0.68); however, Bayesian AUC48-72 and Bayesian AUC72-96 were both significantly different when compared with both first-order pharmacokinetic equation methods (P < 0.01 for each). At the patient level, categorical classifications of AUC estimates from the two first-order pharmacokinetic equation methods differed from categorizations derived from the Bayesian calculations. Categorical agreement was ∼50% between first-order and Bayesian calculations, with declining categorical agreement observed with longer treatment courses. Differences in categorical agreement between calculation methods could potentially result in different dose recommendations for the patient. CONCLUSIONS: Bayesian-calculated AUCs between 48-72 and 72-96 h intervals were significantly different from first-order pharmacokinetic method-estimated AUCs at steady state. The various calculation methods resulted in different categorical classification, which could potentially lead to erroneous dosing adjustments in approximately half of the patients.

Day at the Races: Comparing BioFire FilmArray Blood Culture ID Panels With Verigene Blood Culture Panel in Gram-Negative Bloodstream Infections Using DOOR-MAT Analysis.

Three rapid diagnostic test panels (Verigene BC-GN, BioFire BCID, and BCID 2 [RUO]) were compared using the Desirability of Outcome Ranking Management of Antimicrobial Therapy (DOOR-MAT) to evaluate potential downstream antimicrobial prescribing decisions resulting from the panels' different organism and resistance detection. BioFire BCID 2 (RUO) had the best mean DOOR-MAT scores.

Comparing the Clinical Utility of Rapid Diagnostics for Treatment of Bloodstream Infections Using Desirability of Outcome Ranking Approach for the Management of Antibiotic Therapy (DOOR-MAT).

Decisions regarding which rapid diagnostic test (RDT) for bloodstream infections to implement remain challenging given the diversity of organisms detected by different platforms. We used the desirability of outcome ranking management of antimicrobial therapy (DOOR-MAT) as a framework to compare two RDT platforms on potential desirability of antimicrobial therapy decisions. An observational study was performed at University of Maryland Medical System comparing Verigene blood culture (BC) to GenMark Dx ePlex blood culture ID (BCID) (research use only) panels on blood cultures from adult patients. Positive percent agreement (PPA) between each RDT platform and Vitek MS was calculated for comparison of on-panel targets. Theoretical antimicrobial decisions were made based on RDT results, taking into consideration patient parameters, antimicrobial stewardship practices, and local infectious diseases epidemiology. DOOR-MAT with a partial credit scoring system was applied to these decisions, and mean scores were compared across platforms using a paired t test. The study consisted of 160 unique patients. The Verigene BC PPA was 98.6% (95% confidence interval [CI], 95.1 to 99.8), and ePlex BCID PPA was 98% (95% CI, 94.3 to 99.6). Among the 31 organisms not on the Verigene BC panels, 61% were identified by the ePlex BCID panels. The mean (standard deviation [SD]) DOOR-MAT score for Verigene BC was 86.8 (28.5), while that for ePlex BCID was 91.9 (23.1) (P = 0.01). Both RDT platforms had high PPA for on-panel targets. The ePlex BCID was able to identify more organisms than Verigene, resulting in higher mean DOOR-MAT scores.

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.

Identifying and Bridging the Gaps in Antimicrobial Stewardship in Post-Acute and Long-Term Care.

National organizations have developed guidelines and tools for antimicrobial stewardship (AMS) in post-acute and long-term care (PALTC), but there is a need to effectively translate these into actionable, measurable, and impactful programs. An electronic needs assessment survey was developed and distributed to health care providers and administrators involved with AMS activities in PALTC facilities in Maryland. The results of this survey were used to develop a statewide initiative to improve AMS in nursing facilities. The survey revealed that barriers to implementing AMS include limited access or poor utilization of experts in AMS and infectious disease, adverse event data collection tools, and locally developed protocols and guidelines. Strategies to improve AMS included the provision of free continuing education to a multidisciplinary audience and improved access to individuals with expertise in infectious disease and the development of an adverse drug event tool. Continuing to provide meaningful tools and resources that address the specific needs of nursing facilities should lead to improved compliance with regulations and ultimately improved resident outcomes. [Journal of Gerontological Nursing, 46(1), 8-13.].

An Antibiotic Stewardship Program Blueprint for Optimizing Verigene BC-GN within an Institution: a Tale of Two Cities.

Rapid diagnostic tests (RDTs) have revolutionized the management of Gram-negative bacteremia by allowing antimicrobial stewardship teams the ability to escalate therapy and improve patient outcomes through timely organism identification and detection of certain resistance determinants. However, given the complex nature of Gram-negative resistance, stewardship teams are left without clear direction for how to respond when resistance determinants are absent, as the safety of de-escalation in this setting is unknown. The primary purpose of this analysis was to determine the negative predictive values (NPVs) of resistance marker absence for predicting susceptibility in target bug-drug scenarios at two geographically distinct institutions. A total of 1,046 Gram-negative bloodstream isolates that were analyzed with the Verigene BC-GN platform were assessed. Except for Pseudomonas aeruginosa, the absence of resistance determinants as reported by the RDT largely predicted susceptibility to target antibiotics at both institutions. NPVs for ceftriaxone susceptibility in Escherichia coli and Klebsiella pneumoniae in the absence of either CTX-M or a carbapenemase gene were 98% and 93 to 94%, respectively. Similar results were seen with other target bug-drug scenarios, with NPVs of 94 to 100% demonstrated at both institutions, with the exception of P. aeruginosa, for which NPVs were poor, likely due to the more complex nature of resistance in this pathogen. The results of this study show that clinicians at both institutions should have confidence in de-escalation in the absence of resistance determinant detection by Verigene BC-GN testing, and the methodology described within this article can serve as a blueprint for other stewardship programs to employ at their institutions to optimize management of Gram-negative bacteremia.

Multicenter Observational Study of Ceftaroline Fosamil for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections.

Novel therapies for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) are needed in the setting of reduced antibiotic susceptibilities and therapeutic failure. Ceftaroline is a cephalosporin antibiotic with MRSA activity. Although not FDA approved for MRSA BSI, ceftaroline has generated much interest as a potential treatment option. However, detailed descriptions of its use in this setting remain limited. To address this, we conducted a retrospective, multicenter, observational study of adult patients with MRSA BSI treated with at least 72 h of ceftaroline from 2011 to 2015. Safety outcomes were examined in the overall cohort, while efficacy outcomes were examined among patients who had not cleared their BSI prior to ceftaroline initiation. Data were also stratified by ceftaroline monotherapy or combination therapy. Predictors of clinical failure on ceftaroline treatment were also sought. Overall, 211 patients were included in the safety population; Clostridium difficile infection, rash, and neutropenia occurred in 6 patients (2.8%), 7 patients (3.3%), and 3 patients (1.4%), respectively. Clinical success was observed in 86 (68.3%) of the 126 patients included in the efficacy population. The monotherapy and combination therapy subgroups had similar proportions of patients experiencing success (69.7 and 64.9%, respectively). The median BSI durations post-ceftaroline treatment were 2 days (interquartile range, 1 to 4 days) for monotherapy and 3 days (interquartile range, 1.5 to 5 days) for combination therapy. Higher acute physiology and chronic health evaluation II scores and comorbid malignancy independently predicted treatment failure. Ceftaroline appears effective for MRSA BSI as both monotherapy and combination therapy. However, comparative studies are needed to further delineate the role of ceftaroline in MRSA BSI treatment.

Time Is of the Essence: The Impact of Delayed Antibiotic Therapy on Patient Outcomes in Hospital-Onset Enterococcal Bloodstream Infections.

BACKGROUND: With increasing prevalence of vancomycin-resistant enterococci (VRE), appropriate antibiotic therapy for enterococcal bloodstream infections (EBSI) can be delayed. Data regarding the impact of delayed therapy on EBSI outcomes are conflicting, and the time delay most strongly associated with poor outcomes has not been defined. METHODS: This was a single-center, retrospective cohort study of adult, nonneutropenic patients with hospital-onset EBSI from 2010 to 2014. Classification and regression tree (CART) analysis was used to determine the delay in appropriate therapy most predictive of 30-day mortality. Appropriate therapy was defined as antibiotic therapy to which the enterococci and copathogen, where applicable, were susceptible. Outcomes and clinical characteristics were compared between patients receiving early or delayed therapy, defined by CART timepoint. Poisson regression was employed to determine the independent association of delayed therapy on 30-day mortality and predictors of delayed therapy. RESULTS: Overall, 190 patients were included. A breakpoint in time to appropriate therapy was identified at 48.1 hours, where 30-day mortality was substantially increased (14.6% vs 45.3%; P < .001). Patients receiving appropriate therapy after 48.1 hours also experienced higher in-hospital mortality and longer EBSI duration. After adjustment for severity of illness and comorbidity, delayed therapy ≥48.1 hours was associated with a 3-fold increase in 30-day mortality (risk ratio, 3.16 [95% confidence interval, 1.96-5.09]). Vancomycin resistance was the only independent predictor of delayed therapy. CONCLUSIONS: In patients with hospital-onset EBSI, receipt of appropriate therapy within the first 48 hours was associated with reduced mortality, underscoring the potential role of rapid diagnostic testing for early identification of VRE.

Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus: Does Vancomycin Heteroresistance Matter?

Vancomycin remains the mainstay treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections, including pneumonia. There is concern regarding the emergence of vancomycin tolerance, caused by heterogeneous vancomycin-intermediate S. aureus (hVISA), and subsequent vancomycin treatment failure. Pneumonia is associated with high morbidity and mortality, especially with delays in appropriate therapy. This study evaluated the clinical outcomes of patients with hVISA pneumonia compared to those with vancomycin-susceptible S. aureus (VSSA) pneumonia. A retrospective cohort of patients with MRSA pneumonia from 2005 to 2014 was matched at a ratio of 2:1 VSSA to hVISA infections to compare patient characteristics, treatments, and outcomes. hVISA was determined by the 48-h population analysis profile area under the curve. Characteristics between VSSA and hVISA infections were compared by univariate analysis and multivariable logistic regression analysis to determine independent risk factors of inpatient mortality. Eighty-seven patients were included, representing 29 hVISA and 58 VSSA cases of pneumonia. There were no significant differences in demographics or baseline characteristics. Sequential organ failure assessment (SOFA) scores were a median of 7 (interquartile ratio [IQR], 5 to 8) in hVISA patients and 5 (IQR, 3 to 8) in VSSA (P = 0.092) patients. Inpatient mortality was significantly higher in hVISA patients (44.8% versus 24.1%; P = 0.049). Predictors of inpatient mortality upon multivariable regression were SOFA score (adjusted odds ratio [aOR], 1.36; 95% confidence interval [CI], 1.08 to 1.70), Panton-Valentine leukocidin (PVL) positivity (aOR, 6.63; 95% CI, 1.79 to 24.64), and hVISA phenotype (aOR, 3.95; 95% CI, 1.18 to 13.21). Patients with hVISA pneumonia experienced significantly higher inpatient mortality than those with VSSA pneumonia. There is a need to consider the presence of vancomycin heteroresistance in pneumonia caused by MRSA in order to potentially improve clinical outcomes.

Daptomycin Improves Outcomes Regardless of Vancomycin MIC in a Propensity-Matched Analysis of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections.

Vancomycin remains the mainstay treatment for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) despite increased treatment failures. Daptomycin has been shown to improve clinical outcomes in patients with BSIs caused by MRSA isolates with vancomycin MICs of >1 mg/liter, but these studies relied on automated testing systems. We evaluated the outcomes of BSIs caused by MRSA isolates for which vancomycin MICs were determined by standard broth microdilution (BMD). A retrospective, matched cohort of patients with MRSA BSIs treated with vancomycin or daptomycin from January 2010 to March 2015 was completed. Patients were matched using propensity-adjusted logistic regression, which included age, Pitt bacteremia score, primary BSI source, and hospital of care. The primary endpoint was clinical failure, which was a composite endpoint of the following metrics: 30-day mortality, bacteremia with a duration of ≥7 days, or a change in anti-MRSA therapy due to persistent or worsening signs or symptoms. Secondary endpoints included MRSA-attributable mortality and the number of days of MRSA bacteremia. Independent predictors of failure were determined through conditional backwards-stepwise logistic regression with vancomycin BMD MIC forced into the model. A total of 262 patients were matched. Clinical failure was significantly higher in the vancomycin cohort than in the daptomycin cohort (45.0% versus 29.0%; P = 0.007). All-cause 30-day mortality was significantly higher in the vancomycin cohort (15.3% versus 6.1%; P = 0.024). These outcomes remained significant when stratified by vancomycin BMD MIC. There was no significant difference in the length of MRSA bacteremia. Variables independently associated with treatment failure included vancomycin therapy (adjusted odds ratio [aOR] = 2.16, 95% confidence interval [CI] = 1.24 to 3.76), intensive care unit admission (aOR = 2.46, 95% CI = 1.34 to 4.54), and infective endocarditis as the primary source (aOR = 2.33, 95% CI = 1.16 to 4.68). Treatment of MRSA BSIs with daptomycin was associated with reduced clinical failure and 30-day mortality; these findings were independent of vancomycin BMD MIC.

Association between vancomycin day 1 exposure profile and outcomes among patients with methicillin-resistant Staphylococcus aureus infective endocarditis.

Given the critical importance of early appropriate therapy, a retrospective cohort (2002 to 2013) was performed at the Detroit Medical Center to evaluate the association between the day 1 vancomycin exposure profile and outcomes among patients with MRSA infective endocarditis (IE). The day 1 vancomycin area under the concentration-time curve (AUC0-24) and the minimum concentration at 24 h (Cmin 24) was estimated for each patient using the Bayesian procedure in ADAPT 5, an approach shown to accurately predict the vancomycin exposure with low bias and high precision with limited pharmacokinetic sampling. Initial MRSA isolates were collected and vancomycin MIC was determined by broth microdilution (BMD) and Etest. The primary outcome was failure, defined as persistent bacteremia (≥7 days) or 30-day attributable mortality. Classification and regression tree analysis (CART) was used to determine the vancomycin exposure variables associated with an increased probability of failure. In total, 139 patients met study criteria; 76.3% had right-sided IE, 16.5% had left-sided IE, and 7.2% had both left and right-sided IE. A total of 89/139 (64%) experienced failure by composite definition. In the CART analysis, failure was more pronounced in patients with an AUC0-24/MIC as determined by BMD of ≤600 relative to those with AUC0-24/MIC as determined by BMD of >600 (69.8% versus 54.7%, respectively, P = 0.073). In the logistic regression analysis, an AUC/MIC as determined by BMD of ≤600 (adjusted odds ratio, 2.3; 95% confidence interval, 1.01 to 5.37; P = 0.047) was independently associated with failure. Given the retrospective nature of the present study, further prospective studies are required but these data suggest that patients with an AUC0-24/MIC as determined by BMD of ≤600 present an increased risk of failure.

Impact of the combination of daptomycin and trimethoprim-sulfamethoxazole on clinical outcomes in methicillin-resistant Staphylococcus aureus infections.

Complicated Staphylococcus aureus infections, including bacteremia, are often associated with treatment failures, prolonged hospital stays, and the emergence of resistance to primary and even secondary therapies. Daptomycin is commonly used as salvage therapy after vancomycin failure for the treatment of methicillin-resistant S. aureus (MRSA) infections. Unfortunately, the emergence of daptomycin resistance, especially in deep-seated infections, has been reported, prompting the need for alternative or combination therapy. Numerous antibiotic combinations with daptomycin have been investigated clinically and in vitro. Of interest, the combination of daptomycin and trimethoprim-sulfamethoxazole (TMP-SMX) has proved to be rapidly bactericidal in vitro to strains that are both susceptible and nonsusceptible to daptomycin. However, to date, there is limited clinical evidence supporting the use of this combination. This was a multicenter, retrospective case series of patients treated with the combination of daptomycin and TMP-SMX for at least 72 h. The objective of this study was to describe the safety and effectiveness of this regimen in clinical practice. The most commonly stated reason that TMP-SMX was added to daptomycin was persistent bacteremia and/or progressive signs and symptoms of infection. After the initiation of combination therapy, the median time to clearance of bacteremia was 2.5 days. Microbiological eradication was demonstrated in 24 out of 28 patients, and in vitro synergy was demonstrated in 17 of the 17 recovered isolates. Further research with this combination is necessary to describe the optimal role and its impact on patient outcomes.

The Diagnosis and Treatment of Adult Urinary Tract Infections in the Emergency Department.

Emergency medicine has been called the art of "making complicated clinical decisions with limited information." This description is particularly relevant in the case of diagnosis and treatment of urinary tract infections (UTIs). Although common, UTIs are often challenging to diagnose given the presence of non-specific signs and symptoms and over-reliance on laboratory findings. This review provides an interdisciplinary interpretation of the primary literature and practice guidelines, with a focus on diagnostic and antimicrobial stewardship in the emergency department.

The importance of pharmacist engagement in diagnostic stewardship.

Diagnostic stewardship is increasingly recognized as a powerful tool to improve patient safety. Given the close relationship between diagnostic testing and antimicrobial misuse, antimicrobial stewardship (AMS) pharmacists should be key members of the diagnostic team. Pharmacists practicing in AMS already frequently engage with clinicians to improve the diagnostic process and have many skills needed for the implementation of diagnostic stewardship initiatives. As diagnostic stewardship becomes more broadly used, all infectious disease clinicians, including pharmacists, must collaborate to optimize patient care.

Diagnostic stewardship to improve patient outcomes and healthcare-associated infection (HAI) metrics.

Diagnostic stewardship seeks to improve ordering, collection, performance, and reporting of tests. Test results play an important role in reportable HAIs. The inclusion of HAIs in public reporting and pay for performance programs has highlighted the value of diagnostic stewardship as part of infection prevention initiatives. Inappropriate testing should be discouraged, and approaches that seek to alter testing solely to impact a reportable metric should be avoided. HAI definitions should be further adapted to new testing technologies, with focus on actionable and clinically relevant test results that will improve patient care.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.