Variation in Clinical Practice and Attitudes on Antibacterial Management of Fever and Neutropenia in Patients With Hematologic Malignancy: A Survey of Cancer Centers Across the United States.

BACKGROUND: Contemporary information regarding fever and neutropenia (FN) management, including approaches to antibacterial prophylaxis, empiric therapy, and de-escalation across US cancer centers, is lacking. METHODS: This was a self-administered, electronic, cross-sectional survey of antimicrobial stewardship physicians and pharmacists at US cancer centers. The survey ascertained institutional practices and individual attitudes on FN management in high-risk cancer patients. A 5-point Likert scale assessed individual attitudes. RESULTS: Providers from 31 of 86 hospitals (36%) responded, and FN management guidelines existed in most (29/31, 94%) hospitals. Antibacterial prophylaxis was recommended in 27/31 (87%) hospitals, with levofloxacin as the preferred agent (23/27, 85%). Cefepime was the most recommended agent for empiric FN treatment (26/29, 90%). Most institutional guidelines (26/29, 90%) recommended against routine addition of empiric gram-positive agents except for specific scenarios. Eighteen of 29 (62%) hospitals explicitly provided guidance on de-escalation of empiric, systemic antibacterial therapy; however, timing of de-escalation was variable according to clinical scenario. Among 34 individual respondents, a majority agreed with use of antibiotic prophylaxis in high-risk patients (25, 74%). Interestingly, only 10 (29%) respondents indicated agreement with the statement that benefits of antibiotic prophylaxis outweigh potential harms. CONCLUSION: Most US cancer centers surveyed had institutional FN management guidelines. Antibiotic de-escalation guidance was lacking in nearly 40% of centers, with heterogeneity in approaches when recommendations existed. Further research is needed to inform FN guidelines on antibacterial prophylaxis and therapy de-escalation.

Antimicrobial Stewardship and the Infection Control Practitioner: A Natural Alliance.

Antibiotic overuse and misuse has contributed to rising rates of multidrug-resistant organisms and Clostridioides difficile. Decreasing antibiotic misuse has become a national public health priority. This review outlines the goals of antimicrobial stewardship, essential members of the program, implementation strategies, approaches to measuring the program's impact, and steps needed to build a program. Highlighted is the alliance between antimicrobial stewardship programs and infection prevention programs in their efforts to improve antibiotic use, improve diagnostic stewardship for C difficile and asymptomatic bacteriuria, and decrease health care-associated infections and the spread of multidrug-resistant organisms.

Monoclonal Antibodies for Early Treatment of COVID-19 in a World of Evolving SARS-CoV-2 Mutations and Variants.

Monoclonal antibodies targeting the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 spike protein are important outpatient treatment options in coronavirus disease 2019 to mitigate progression of disease and prevent hospitalization. The impact of different RBD mutations on the efficacy of the available monoclonal antibodies and processes for incorporating this impact into treatment algorithms are ill defined. Herein, we synthesize the data surrounding the impact of key RBD mutations on the efficacy of US Food and Drug Administration Emergency Use Authorized monoclonal antibodies and describe our approach at Michigan Medicine at monitoring mutation frequency in circulating virus and developing an algorithm that incorporates these data into outpatient treatment pathways.

The role of electronic health record and "add-on" clinical decision support systems to enhance antimicrobial stewardship programs.

Increasingly, demands are placed on healthcare systems to meet antimicrobial stewardship standards and reporting requirements. This trend, combined with reduced financial and personnel resources, has created a need to adopt information technology (IT) to help ease these burdens and facilitate action. The incorporation of IT into an antimicrobial stewardship program can help improve stewardship intervention efficiencies and facilitate the tracking and reporting of key metrics, including outcomes. This paper provides a review of the stewardship-related functionality within these IT systems, describes how these platforms can be used to improve antimicrobial use, and identifies how they can support current and potential future antimicrobial stewardship regulatory and accreditation standards. Finally, recommendations to help close the gaps in existing systems are provided and suggestions for future areas of development within these programs are delineated.

Institution-wide and Within-Patient Evolution of Daptomycin Susceptibility in Vancomycin-Resistant Enterococcus faecium Bloodstream Infections.

We report daptomycin minimum inhibitory concentrations (MICs) for vancomycin-resistant Enterococcus faecium isolated from bloodstream infections over a 4-year period. The daptomycin MIC increased over time hospital-wide for initial isolates and increased over time within patients, culminating in 40% of patients having daptomycin-nonsusceptible isolates in the final year of the study. Infect Control Hosp Epidemiol 2018;39:226-228.

Disease-based antimicrobial stewardship: a review of active and passive approaches to patient management.

Although new antimicrobial stewardship programmes (ASPs) often begin by targeting the reduction of antimicrobial use, an increasing focus of ASPs is to improve the management of specific infectious diseases. Disease-based antimicrobial stewardship emphasizes improving patient outcomes by optimizing antimicrobial use and increasing compliance with performance measures. Directing efforts towards the comprehensive management of specific infections allows ASPs to promote the shift in healthcare towards improving quality, safety and patient outcome metrics for specific diseases. This review evaluates published active and passive disease-based antimicrobial stewardship interventions and their impact on antimicrobial use and associated patient outcomes for patients with pneumonia, acute bacterial skin and skin structure infections, bloodstream infections, urinary tract infections, asymptomatic bacteriuria, Clostridium difficile infection and intra-abdominal infections. Current literature suggests that disease-based antimicrobial stewardship effects on medical management and patient outcomes vary based on infectious disease syndrome, resource availability and intervention type.

Risk factors for subtherapeutic levels of posaconazole tablet.

Background: Posaconazole is the prophylactic antifungal of choice for patients with haematological malignancies at high risk of invasive fungal infections (IFIs). Studies have demonstrated that subtherapeutic concentrations of posaconazole are associated with breakthrough fungal infections and specific risk factors for subtherapeutic troughs associated with the suspension formulation have been identified. However, these risk factors have not been evaluated in a large patient population with the recently approved tablet formulation. Objectives: To determine the risk factors for subtherapeutic posaconazole troughs associated with the tablet formulation in patients receiving posaconazole as IFI prophylaxis. Patients and methods: From 1 February 2013 to 31 March 2015 all posaconazole serum trough concentrations were evaluated. A total of 157 patients receiving posaconazole tablet for prophylaxis during induction therapy for haematological malignancies and allogeneic stem cell transplant recipients with graft-versus-host disease were included for analysis. Results: Overall, 28 patients (18%) had subtherapeutic troughs (<700 ng/mL). Patients were more likely to have subtherapeutic troughs if they had diarrhoea (n = 24; 83%) (P < 0.001), were receiving a proton pump inhibitor (n = 27; 93%) (P = 0.016) and weighed >90 kg (n = 14; 48%) (P = 0.047). Conclusions: While the posaconazole tablet has provided more consistent therapeutic concentrations when compared with the suspension there may still be a role for therapeutic drug monitoring (TDM). These results may guide us to a specific population in which TDM is necessary to identify subtherapeutic troughs.

Risk factors and impact of Clostridium difficile recurrence on haematology patients.

Objectives: The incidence of Clostridium difficile infection (CDI) in adults with malignancy is 7%-14% compared with 1%-2% in the general hospitalized population. Despite the increased incidence of CDI in this population, a major concern is the propensity of CDI to recur, leading to delays in therapy impacting outcomes. We conducted a retrospective case-control study to identify risk factors for recurrent CDI (rCDI) and to determine the impact of rCDI on adult patients with a haematological malignancy. Methods: Adult haematology patients with CDI from June 2010 to December 2014 were divided into two groups: rCDI and non-rCDI. Multivariable models using logistic regression were constructed to identify risk factors for rCDI. Results: A total of 100 patients in our study yielded a 41% recurrence rate. CDI impacted chemotherapy significantly more in the rCDI group (53.7% versus 11.9%, P <0.001), primarily due to interruptions in established treatment plans (46.3% versus 10.3%, P <0.001). Risk factors for rCDI identified at index included salvage lymphoma chemotherapy (OR 9.64, 95% CI 1.02-91.15, P = 0.048) and severe CDI (OR 4.82, 95% CI 1.31-17.66, P = 0.018). Longitudinal risk factors included exposure to fluoroquinolones (OR 3.96, 95% CI 1.04-15.15, P = 0.044), ceftriaxone (OR 18.93, 95% CI 1.27-281.95, P = 0.033) and piperacillin/tazobactam (OR 10.4, 95% CI 1.81-59.64, P = 0.009). Conclusions: Haematology patients exhibit a higher rate of rCDI than general hospitalized patients. Utilization of this multivariable model to guide index CDI therapy at index may help to decrease the rCDI and prevent delays or interruptions in chemotherapy.

Cost Analysis of Implementing Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Plus Real-Time Antimicrobial Stewardship Intervention for Bloodstream Infections.

Studies evaluating rapid diagnostic testing plus stewardship intervention have consistently demonstrated improved clinical outcomes for patients with bloodstream infections. However, the cost of implementing new rapid diagnostic testing can be significant, and such testing usually does not generate additional revenue. There are minimal data evaluating the impact of adding matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for rapid organism identification and dedicating pharmacy stewardship personnel time on the total hospital costs. A cost analysis was performed utilizing patient data generated from the hospital cost accounting system and included additional costs of MALDI-TOF equipment, supplies and personnel, and dedicated pharmacist time for blood culture review and of making interventions to antimicrobial therapy. The cost analysis was performed from a hospital perspective for 3-month blocks before and after implementation of MALDI-TOF plus stewardship intervention. A total of 480 patients with bloodstream infections were included in the analysis: 247 in the preintervention group and 233 in the intervention group. Thirty-day mortality was significantly improved in the intervention group (12% versus 21%, P < 0.01), and the mean length of stay was reduced, although the difference was not statistically significant (13.0 ± 16.5 days versus 14.2 ± 16.7 days, P = 0.44). The total hospital cost per bloodstream infection was lower in the intervention group ($42,580 versus $45,019). Intensive care unit cost per bloodstream infection accounted for the largest share of the total costs in each group and was also lower in the intervention group ($10,833 versus $13,727). Implementing MALDI-TOF plus stewardship review and intervention decreased mortality for patients with bloodstream infections. Despite the additional costs of implementing MALDI-TOF and of dedicating pharmacy stewardship personnel time to interventions, the total hospital costs decreased by $2,439 per bloodstream infection, for an approximate annual cost savings of $2.34 million.

Effect of an antimicrobial stewardship intervention on outcomes for patients with Clostridium difficile infection.

BACKGROUND: Although antimicrobial stewardship programs (ASPs) are uniquely positioned to improve treatment of Clostridium difficile infection (CDI) through targeted interventions, studies to date have not rigorously evaluated the influence of ASP involvement on clinical outcomes attributed to CDI. METHODS: We performed a quasiexperimental study of adult patients with CDI before (n = 307) and after (n = 285) a real-time ASP review was initiated. In the intervention group, an ASP pharmacist was notified of positive CDI results and consulted with the care team to initiate optimal therapy, minimize concomitant antibiotic and acid-suppressive therapy, and recommend surgical/infectious diseases consultation in complicated cases. The primary outcome was a composite of attributable 30-day mortality, intensive care unit admission, colectomy/ileostomy, and recurrence. RESULTS: A higher percentage of patients in the ASP intervention group had acid-suppressive therapy discontinued (30% vs 13%; P < .01). Among patients with severe CDI, more patients in the intervention group received an infectious diseases consultation (17% vs 10%; P = .04), received appropriate therapy with oral vancomycin (87% vs 59%; P <.01), and vancomycin was initiated earlier (mean, 1.1 vs 1.7 days; P <.01). Incidence of the composite outcome was not significantly different between the 2 groups (12.3% vs 14.7%; P = .40). CONCLUSIONS: ASP review and intervention improved CDI process measures. A decrease in composite outcomes was not found, which may be due to low baseline rates of attributable complications in our institution.

Antimicrobial Stewardship for the Infection Control Practitioner.

Antibiotic misuse is a serious patient safety concern and a national public health priority. Years of indiscriminant antibiotic use has promoted selection for antibiotic resistant bacteria and Clostridium difficile This crisis has led to clinicians being faced with managing untreatable infections, often in the most vulnerable patient populations. This review summarizes the goals of antimicrobial stewardship programs, the essential members needed to initiate a program, various antimicrobial stewardship strategies, the role of the infection control practitioner in stewardship, barriers to its implementation and maintenance, approaches to measure the impact of a program, and the steps needed to initiate a program.

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.

Recurrent Clostridium difficile infection in intensive care unit patients.

BACKGROUND: The purpose of this study was to assess the 12-week cumulative incidence of recurrent Clostridium difficile infection (rCDI) and identify risk factors for rCDI in patients that acquired index C difficile infection (CDI) while in the intensive care unit (ICU). METHODS: This retrospective single-center cohort study reviewed adult patients from 6 different ICUs who developed a CDI between February 2010 and September 2013. RESULTS: Out of 162 included ICU patients, 34 experienced rCDI. Risk of rCDI was higher in the ICU versus non-ICU group (21% vs 17%, P = .03). The incidence of rCDI was highest in the surgical intensive care unit (SICU) at 43.8%. A multivariable logistic regression model was constructed and identified 5 significant risk factors for rCDI: previous CDI (odds ratio [OR], 8.03; 95% confidence interval [CI], 1.90-34.02; P = .005), log10 ICU length of stay in days (OR, 3.67; 95% CI, 1.13-11.85; P = .03), acquisition of CDI in the medical intensive care unit (MICU) (OR, 5.35; 95% CI, 1.60-17.85; P = .006) or SICU (OR, 15.30; 95% CI, 4.09-57.23; P < .001), and chronic obstructive pulmonary disease (COPD) (OR, 3.55; 95% CI, 1.41-8.94; P = .007). CONCLUSION: ICU adults had a significantly higher 12-week incidence of rCDI than non-ICU patients. Risk factors for rCDI after acquisition of infection in an ICU include MICU and SICU patients, previous CDI, COPD, and length of stay.

Impact of an antimicrobial stewardship-led intervention for Staphylococcus aureus bacteraemia: a quasi-experimental study.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) carries high rates of morbidity and mortality. Antimicrobial stewardship programmes (ASPs) are well situated to promote adherence to quality performance measures in order to optimize the management of SAB and associated clinical outcomes. METHODS: This uncontrolled pre-post quasi-experimental study evaluated compliance with an ASP-driven comprehensive care bundle and associated clinical outcomes for patients with SAB. The ASP provided recommendations to prescribers to promote adherence with quality performance measures, which included: initiate effective antibiotics within 24 h of Gram's stain; achieve therapeutic vancomycin trough concentration; provide ß-lactam therapy if MSSA; obtain repeat blood cultures every 48 h until clearance; complete appropriate treatment duration; eliminate or debride foci of infection; and obtain an echocardiogram for complicated bacteraemia. RESULTS: One hundred and seventy patients with SAB were included: 82 patients in the pre-intervention group and 88 patients in the ASP-intervention group. Overall bundle adherence to quality performance measures improved from 56.1% (46/82) in the pre-intervention group to 84.1% (74/88) in the ASP-intervention group (P < 0.001), which was associated with a reduction in 30 day readmission with SAB [9 patients (11.0%) versus 1 patient (1.1%), P = 0.008]. The 30 day mortality was numerically lower in the ASP-intervention group, but the difference was not statistically significant [16 patients (19.5%) versus 10 patients (11.4%), P = 0.2]. CONCLUSIONS: Implementation of an ASP-driven comprehensive care bundle for SAB improved adherence with performance measures and was associated with a decrease in hospital readmission for SAB.

Risk factors for piperacillin/tazobactam-resistant Gram-negative infection in hematology/oncology patients with febrile neutropenia.

PURPOSE: Febrile neutropenia (FN) is a life-threatening complication of cancer therapy, and initial ineffective therapy is associated with poor outcomes. Piperacillin/tazobactam (PTZ) is a commonly used empiric antibiotic for the treatment of FN, but resistance among Gram-negative pathogens is well described. We conducted a retrospective case-control study to identify risk factors for PTZ-resistant (PTZ-R) Gram-negative isolates. METHODS: Hematology/oncology patients with FN from November 2007 to November 2013 with a positive culture for Gram-negative bacilli were divided into two groups: PTZ-sensitive (PTZ-S) and PTZ-R. A multivariable model using logistic regression was constructed to identify risk factors for PTZ-R. RESULTS: A total of 171 patients were included (25 PTZ-R, 146 PTZ-S), yielding a 14.6 % resistance rate. Thirty-day all-cause mortality was significantly higher in the PTZ-R group (29 vs 11 %, P = 0.024). Multivariable analysis yielded intensive care unit (ICU) status (odds ratio (OR) 20.18; 95 % confidence interval (CI) 1.03-397.35; P = 0.048), antibiotics for > 14 days in the previous 90 days (OR 6.02; CI 1.17-30.93; P = 0.032), and respiratory source (OR 13.65; CI 1.14-163.57; P = 0.039) as significant risk factors for PTZ-R, and the receiver operating characteristic area under the curve of the model was 0.894. Among PTZ-R isolates, 88 % were sensitive to meropenem and 100 % were sensitive to amikacin. CONCLUSIONS: Given the high mortality rates in the PTZ-R group, a risk-factor-guided approach driven by this multivariable model may help identify patients that could benefit from amikacin combination therapy to help optimize empiric therapy in this setting.

Clinical outcomes of Enterobacteriaceae infections stratified by carbapenem MICs.

The Clinical and Laboratory Standards Institute (CLSI) lowered the MIC breakpoints for meropenem and imipenem from 4 mg/liter to 1 mg/liter for Enterobacteriaceae in 2010. The breakpoint change improves the probability of pharmacodynamic target attainment and eliminates the need for microbiology labs to perform confirmatory testing for Klebsiella pneumoniae carbapenemase (KPC) production or other beta-lactamases that hydrolyze carbapenems. However, there are limited data evaluating clinical outcomes of the affected breakpoints, and it is unknown if patients infected with Enterobacteriaceae with reduced susceptibility are more likely to have poor outcomes when treated with a carbapenem. We conducted a single-center retrospective matched-cohort analysis in adult patients with Enterobacteriaceae infections treated with meropenem, imipenem, or doripenem. Patients with Enterobacteriaceae infection with a carbapenem MIC of 2 to 8 mg/liter were matched based on pathogen, source of infection, comorbidities, and disease severity (1:1 ratio) to those with a carbapenem MIC of ≤1 mg/liter. A total of 36 patients were included in the study. The group with carbapenem MICs of 2 to 8 mg/liter had a significantly higher 30-day mortality than the group with carbapenem MICs of ≤1 mg/liter (38.9% compared to 5.6%, P = 0.04). Total hospital length of stay (LOS) and intensive care unit (ICU) LOS were longer in the group with MICs of 2 to 8 mg/liter than in the group with MICs of ≤1 mg/liter (57.6 days compared to 34.4 days [P = 0.06] and 56.6 days compared to 21.7 days [P < 0.01], respectively). Patients infected with Enterobacteriaceae with a carbapenem MIC of 2, 4, or 8 mg/liter had higher mortality rates and longer ICU LOS than matched cohorts with carbapenem MICs of ≤1 mg/liter, which supports CLSI's recommendation to lower susceptibility breakpoints for carbapenems.

Demonstrating the value of antimicrobial stewardship programs to hospital administrators.

The movement away from fee-for-service models to those that emphasize quality of care and patient outcomes affords a unique opportunity for antimicrobial stewardship programs to expand their value for hospital administration. Antimicrobial stewardship participants must collaborate with administrators and key stakeholders to position themselves to improve economic, process, and outcomes measures. This will allow the establishment of antimicrobial stewardship programs as essential components of the present and future healthcare quality journey.