Is the standardized antibiotic administration ratio (SAAR) ready for prime time?

The standardized antibiotic administration ratio (SAAR) enables comparison of antibiotic use (AU) within and between hospitals and identifies target locations and antimicrobials for stewardship interventions. Thousands of institutions have already been submitting AU to the National Healthcare Safety Network. We highlight the benefits and meaningful utilization of SAAR in conjunction with antimicrobial stewardship interventions to improve antimicrobial prescribing in the clinical setting.

Antibiotic Myths for the Infectious Diseases Clinician.

Antimicrobials are commonly prescribed and often misunderstood. With more than 50% of hospitalized patients receiving an antimicrobial agent at any point in time, judicious and optimal use of these drugs is paramount to advancing patient care. This narrative will focus on myths relevant to nuanced consultation from infectious diseases specialists, particularly surrounding specific considerations for a variety of antibiotics.

Thoughts and beliefs of healthcare workers regarding the coronavirus disease 2019 (COVID-19) vaccine and which messaging themes might affect vaccine confidence and recommendation of the vaccine.

We surveyed healthcare workers within the Duke Antimicrobial Stewardship Outreach Network (DASON) to describe beliefs regarding coronavirus disease 2019 (COVID-19) vaccination and their decision-making process behind vaccination recommendations. In contrast to the type of messaging that appealed most on a personal level to the healthcare workers, they preferred a more generic message emphasizing safety and efficacy when making vaccination recommendations.

Top Myths of Diagnosis and Management of Infectious Diseases in Hospital Medicine.

Antimicrobial agents are among the most frequently prescribed medications during hospitalization. However, approximately 30% to 50% or more of inpatient antimicrobial use is unnecessary or suboptimal. Herein, we describe 10 common myths of diagnosis and management that often occur in the hospital setting. Further, we discuss supporting data to dispel each of these myths. This analysis will provide hospitalists and other clinicians with a foundation for rational decision-making about antimicrobial use and support antimicrobial stewardship efforts at both the patient and institutional levels.

A modified Delphi approach to develop a trial protocol for antibiotic de-escalation in patients with suspected sepsis.

Background: Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown. Methods: We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health record review. The 48 unique criteria were rated by anonymous electronic survey tools, and the results were fed back to the expert panel participants. Consensus was achieved to either retain or remove each criterion. Results: After 3 rounds, 22 unique criteria remained as part of the opt-out safety checklist. These criteria included high-risk comorbidities, signs of severe illness, lack of cultures during sepsis work-up or antibiotic use prior to blood cultures, or ongoing signs and symptoms of infection. Conclusions: The modified Delphi approach is a useful method to achieve expert-level consensus in the absence of evidence suifficient to provide validated guidance. The Delphi approach allowed for flexibility in development of an opt-out trial protocol for sepsis antibiotic de-escalation. The utility of this protocol should be evaluated in a randomized controlled trial.

Leveraging Existing and Soon-to-Be-Available Novel Diagnostics for Optimizing Outpatient Antibiotic Stewardship in Patients With Respiratory Tract Infections.

Respiratory tract infections (RTIs) drive many outpatient encounters and, despite being predominantly viral, are associated with high rates of antibiotic prescriptions. With rising antibacterial resistance, optimization of prescribing of antibiotics in outpatients with RTIs is a critical need. Fortunately, this challenge arises at a time of increasing availability of novel RTI diagnostics to help discern which patients have bacterial infections warranting treatment. Effective implementation of antibiotic stewardship is needed, but optimal approaches for ambulatory settings are unknown. Future research needs are reviewed in this summary of a research summit convened by the Infectious Diseases Society of America in the fall of 2019.

Electronically Available Patient Claims Data Improve Models for Comparing Antibiotic Use Across Hospitals: Results From 576 US Facilities.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) uses standardized antimicrobial administration ratios (SAARs)-that is, observed-to-predicted ratios-to compare antibiotic use across facilities. CDC models adjust for facility characteristics when predicting antibiotic use but do not include patient diagnoses and comorbidities that may also affect utilization. This study aimed to identify comorbidities causally related to appropriate antibiotic use and to compare models that include these comorbidities and other patient-level claims variables to a facility model for risk-adjusting inpatient antibiotic utilization. METHODS: The study included adults discharged from Premier Database hospitals in 2016-2017. For each admission, we extracted facility, claims, and antibiotic data. We evaluated 7 models to predict an admission's antibiotic days of therapy (DOTs): a CDC facility model, models that added patient clinical constructs in varying layers of complexity, and an external validation of a published patient-variable model. We calculated hospital-specific SAARs to quantify effects on hospital rankings. Separately, we used Delphi Consensus methodology to identify Elixhauser comorbidities associated with appropriate antibiotic use. RESULTS: The study included 11 701 326 admissions across 576 hospitals. Compared to a CDC-facility model, a model that added Delphi-selected comorbidities and a bacterial infection indicator was more accurate for all antibiotic outcomes. For total antibiotic use, it was 24% more accurate (respective mean absolute errors: 3.11 vs 2.35 DOTs), resulting in 31-33% more hospitals moving into bottom or top usage quartiles postadjustment. CONCLUSIONS: Adding electronically available patient claims data to facility models consistently improved antibiotic utilization predictions and yielded substantial movement in hospitals' utilization rankings.

Antifungal Drugs: Special Problems Treating Central Nervous System Infections.

Treating fungal infections in the central nervous system (CNS) remains a challenge despite the availability of new antifungal agents. Therapy is limited by poor understanding of the kinetic properties of antifungal drugs in the CNS compounded by lack of data for many agents. In some cases, clinical response rates do not correspond to data on drug concentrations in the cerebral spinal fluid and/or brain parenchyma. In order to better characterize the use of antifungal agents in treating CNS infections, a review of the essential principles of neuroPK are reviewed. Specific data regarding antifungal drug concentrations in the cerebral spinal fluid and brain tissue are described from human data where available. Alternative dosing regimens and the role of antifungal drug concentration monitoring in treating fungal infections in the CNS are also discussed. Having a better understanding of these key concepts will help guide clinicians in determining the best treatment courses for patients with these devastating infections.

Identification of population at risk for future Clostridium difficile infection following hospital discharge to be targeted for vaccine trials.

BACKGROUND: Efforts to develop a Clostridium difficile vaccine are underway; identification of patients at risk for C. difficile infection (CDI) is critical to inform vaccine trials. We identified groups at high risk of CDI ≥ 2 8 days after hospital discharge. METHODS: Hospital discharge data and pharmacy data from two large academic centers, in New York and Connecticut, were linked to active population-based CDI surveillance data from the Emerging Infections Program (EIP). Adult residents of the EIP surveillance area were included if they had an inpatient stay at a study hospital without prior history of CDI. The primary outcome was CDI by either toxin or molecular assay ≥ 28 days after an index hospitalization. Important predictors of CDI ≥ 28 days post discharge were initially identified through a Cox proportional hazards model (stepwise backward selection) using a derivation cohort; final model parameters were used to develop a risk score evaluated in the validation cohort. RESULTS: Of the 35,186 index hospitalizations, 288 (0.82%) had CDI ≥ 28 days post discharge. After parameter selection, age, number of hospitalizations in the prior 90 days, admission diagnosis, and the use of 3rd/4th generation cephalosporin, clindamycin or fluoroquinolone antibiotic classes remained in the model. Using the validation cohort, the risk score was predictive (p<0.001) with a c-score of 0.75. Based on the distribution of scores in the derivation cohort, we divided the patients into low and high risk groups. In the high risk group, 1.6% experienced CDI ≥ 28 days post discharge compared to 0.3% among our low risk group. CONCLUSIONS: Our study identified specific parameters for a risk score that can be applied at discharge to identify a patient population whose risk of CDI ≥ 28 days following an acute care hospitalization was 5 times greater than other patients.

Antimicrobial stewardship: another focus for patient safety?

PURPOSE OF REVIEW: This review describes the overlapping aspects of antimicrobial stewardship and patient-safety initiatives and justifies why stewardship belongs under the umbrella of patient safety. RECENT FINDINGS: Addressing the continued emergence of antibiotic resistance through the discovery of new drugs is not a sustainable strategy, particularly as antibiotics are increasingly more difficult and costly to develop. Thus, it is essential that we preserve the utility of existing antibiotics. Antimicrobial stewardship programs can assist with achieving this goal. Currently, however, the term 'antimicrobial stewardship' is generally not easily understood by regulators, hospital administrators, or the public. Perhaps more clout would be given to antimicrobial stewardship if it is associated with safety. In this review, we present concrete examples of how antimicrobial stewardship programs can focus on achieving goals already recognized as essential for patient safety. SUMMARY: Patient safety is an integral component of antimicrobial stewardship. To make the concept of antimicrobial stewardship more palatable, the association between antimicrobial stewardship and safety needs to be emphasized.

Pharmacist-managed antimicrobial stewardship program for patients discharged from the emergency department.

Positive outcomes of antimicrobial stewardship programs in the inpatient setting are well documented, but the benefits for patients not admitted to the hospital remain less clear. This report describes a retrospective case-control study of patients discharged from the emergency department (ED) with subsequent positive cultures conducted to determine whether integrating antimicrobial stewardship responsibilities into practice of the emergency medicine clinical pharmacist (EPh) decreased times to positive culture follow-up, patient or primary care provider (PCP) notification, and appropriateness of antimicrobial therapy. Pre- and post-implementation groups of an EPh-managed antimicrobial stewardship program were compared. Positive cultures were identified in 177 patients, 104 and 73 in pre- and post-implementation groups, respectively. Median time to culture review in the pre-implementation group was 3 days (range 1-15) and 2 days (range 0-4) in the post-implementation group (P = .0001). There were 74 (71.2%) and 36 (49.3%) positive cultures that required notification in the pre- and post-implementation groups, respectively, and the median time to patient or PCP notification was 3 days (range 1-9) and 2 days (range 0-4) in the 2 groups (P = .01). No difference was seen in the appropriateness of therapy. In conclusion, EPh involvement reduced time to positive culture review and time to patient or PCP notification when indicated.

Predictors of agr dysfunction in methicillin-resistant Staphylococcus aureus (MRSA) isolates among patients with MRSA bloodstream infections.

Despite emerging evidence that dysfunction in the accessory gene regulator (agr) locus is associated with deleterious outcomes among patients treated with vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infections, factors predictive of agr dysfunction have not been evaluated. This study describes the epidemiology of agr dysfunction, identifies predictors of agr dysfunction in MRSA isolates among those with MRSA bloodstream infections, and describes the relationship between agr dysfunction and other microbiologic phenotypes. A cross-sectional study of patients with MRSA bloodstream infections at two institutions in upstate New York was performed. Clinical data on demographics, comorbidities, disease severity, hospitalization history, and antibiotic history were collected. Microbiologic phenotypes, including agr dysfunction, MIC values by broth microdilution (BMD) and Etest, and vancomycin heteroresistance (hVISA) were tested. Multivariable analyses were performed to identify factors predictive of agr dysfunction. Among 200 patients with an MRSA bloodstream infection, the proportion of strains with agr dysfunction was 31.5%. The distribution of MICs determined by both BMD and Etest were equivalent across agr groups, and there was no association between agr dysfunction and the presence of hVISA. Severity of illness, comorbidities, and hospitalization history were comparable between agr groups. In the multivariate analysis, prior antibiotic exposure was the only factor of variables studied found to be predictive of agr dysfunction. This relationship was predominantly driven by prior beta-lactam and fluoroquinolone administration in the bivariate analysis. Identifying these institution-specific risk factors can be used to develop a process to assess the risk of agr dysfunction and guide empirical antibiotic therapy decisions.

Effect of colistin on phospholipid-based activated partial thromboplastin time clotting assay results in patients receiving concomitant heparin therapy.

STUDY OBJECTIVE: To determine whether intravenous colistin therapy has an effect on the results of the phospholipid-based activated partial thromboplastin time (aPTT) clotting assays containing cephalin in patients receiving concomitant heparin therapy. DESIGN: Retrospective medical record review. SETTING: University-affiliated teaching institution. PATIENTS: Thirty-six patients treated with intravenous colistin for at least 48 hours between January 1, 2005, and January 1, 2010, who were receiving heparin for at least 48 hours before colistin was started, and had aPTT tests performed at least 2 days before, during, and at least 2 days after treatment with colistin. MEASUREMENTS AND MAIN RESULTS: Repeated-measures analysis of variance testing was performed to determine if significant differences in aPTT results before, during, and after colistin therapy existed. Of a total of 120 courses of colistin therapy, only 36 met the inclusion criteria. The mean ± SD aPTT was 52.3 ± 20.4 seconds before administration of colistin, 51.1 ± 16.6 seconds during colistin therapy, and 51.3 ± 13.6 seconds after administration of colistin (p=0.9). Heparin infusion rates were adjusted 12 times and heparin withheld twice at least 2 days before colistin therapy was started, infusion rates were changed 8 times and heparin withheld once during colistin therapy, and infusion rates were changed 10 times and heparin withheld once at least 2 days after colistin therapy. CONCLUSION: Colistin therapy had no significant effect on the cephalin-based aPTT testing results in patients receiving concomitant heparin therapy. Further analyses are required to confirm these findings.

Alternative therapies for Clostridium difficile infections.

Clostridium difficile infection is a serious condition responsible for significant morbidity and mortality, especially in patients being treated with antimicrobials. Increasing frequency of the infection and hypervirulent C. difficile strains have resulted in more severe disease as well as therapeutic failures with traditional treatment (metronidazole and vancomycin). To review the studies assessing nontraditional therapies for the prevention and treatment of primary or recurrent C. difficile infection, we conducted a literature search of the PubMed-MEDLINE databases (1984-2010). Of the 98 studies identified, 21 met our inclusion criteria. Five clinical trials and one retrospective medical record review evaluated probiotic or prebiotic formulations for the prevention of C. difficile infection. Only one of these studies, which included Lactobacillus casei and L. bulgaricus in the probiotic formulation, showed efficacy. Ten clinical trials evaluated treatment of an initial episode of C. difficile infection (primary treatment) with the anti-microbials fidaxomicin, fusidic acid, rifampin, teicoplanin, and nitazoxanide, as well as the toxin-binding polymer, tolevamer. Only nitazoxanide and teicoplanin demonstrated noninferiority when compared with vancomycin or metronidazole. Four prospective studies and one retrospective study evaluated treatment of relapsing C. difficile infection. Prebiotic formulations for the prevention and treatment of recurrent C. difficile infection have not proved to be clinically warranted. Nitazoxanide, teicoplanin, and fidaxomicin may be considered as alternatives to traditional treatment; however, clinical experience is limited with these agents for this indication. Bacteriotherapy with fecal instillation has demonstrated high clinical cure rates in case studies and in a retrospective study; however, to our knowledge, randomized clinical trials are lacking for this therapeutic approach. As C. difficile infection rates continue to increase and hypervirulent strains continue to emerge, it is important for future clinical studies to assess alternative therapies.

Consensus summary of aerosolized antimicrobial agents: application of guideline criteria. Insights from the Society of Infectious Diseases Pharmacists.

Aerosolized delivery of antimicrobial agents is an attractive option for management of pulmonary infections, as this is an ideal method of providing high local drug concentrations while minimizing systemic exposure. With the paucity of consensus regarding the safety, efficacy, and means with which to use aerosolized antimicrobials, a task force was created by the Society of Infectious Diseases Pharmacists to critically review and evaluate the literature on the use of aerosolized antiinfective agents. This article summarizes key findings and statements for preventing or treating a variety of infectious diseases, including cystic fibrosis, bronchiecstasis, hospital-acquired pneumonia, fungal infections, nontuberculosis mycobacterial infection, and Pneumocystis jiroveci pneumonia. Our intention was to provide guidance for clinicians on the use of aerosolized antibiotics through evidence-based pharmacotherapy. Further research with well-designed clinical trials is necessary to elucidate the optimal dosage and duration of therapy and, of equal importance, to appreciate the true risks associated with the use of aerosolized delivery systems.

Inhaled azithromycin therapy.

The treatment of pulmonary infectious diseases with pharmaceutical aerosols is an attractive option considering the accessibility of the lungs for topical drug delivery. Aerosols have been targeted to the lungs for the treatment of asthma with great success. Current therapies for other diseases, including Pseudomonas aeruginosa, Pneumocystis jirovecii (formerly Pneumocystis carinii), and mycobacterial infections, remain suboptimal due to the efficacy/safety profile. This may be improved by aerosol targeted pulmonary drug delivery. Azithromycin is a broad spectrum antibiotic that acts by inhibiting protein synthesis. It is associated with side effects that might be avoided by aerosol delivery to the lungs. In the present study three concentrations of azithromycin (10, 50, and 100 mg/mL) were delivered from three nebulizers (Acorn II, Updraft, and LC Plus) operated at 8 L/min. Particles size analyses were conducted by inertial impaction and laser diffraction. In addition, emitted doses were determined. A linear proportionality existed across the concentration range between nominal dose and both fine particle dose/fraction and emitted dose, with R2 > 0.999 in all cases. The mass median aerodynamic diameter increased from 1.4 to 1.9 microm between 10 and 100 mg/mL of azithromycin solution concentration for the Acorn II. The particle size distributions were not all log-normally distributed. The median particle size delivered from the devices was largest for the Updraft (2.8 microm) and smallest for the Acorn II (1.9 microm) for 100 mg/mL azithromycin solution concentrations. The efficiencies of small particle delivery (%<4.7 microm) were as follows, LC Plus = Acorn II (85%) > UpDraft (75%). However, the emitted dose from the LC Plus (55 mg/min) was higher than the Acorn II (31 mg/min) to maximize lung exposure to the aerosol, small median diameters and broad particle size distributions would be most effective. This study demonstrates that the dose delivered to the lungs will be maximized, under the current operating conditions by adopting the LC Plus, and high (100 mg/mL) azithromycin concentrations.

Cost savings with implementation of PNA FISH testing for identification of Candida albicans in blood cultures.

Antifungal expenditures are substantial for many hospitals. Using caspofungin for the treatment of candidemia accounts for a sizable proportion of the costs. A cost minimization study that used a decision analytic model was done to compare in-hospital diagnosis and treatment costs using the Candida albicans peptide nucleic acid fluorescence in situ hybridization (PNA FISH) test versus the C. albicans screen test for differentiating C. albicans from non-albicans Candida species bloodstream infections. Assuming physician notification of yeast identity concurrent with blood culture positivity, potential savings resulting from use of the C. albicans PNA FISH test compared with the C. albicans screen test averaged $1837 per patient treated, although laboratory costs for doing the C. albicans PNA FISH test ($82.72) exceeded those for the C. albicans screen test ($2.83). Savings were realized through a decrease in antifungal drug costs, particularly caspofungin. Incorporating the C. albicans PNA FISH test as part of the initial identification algorithm for yeasts recovered from blood can result in substantial savings for hospitals.

Aspergillus fumigatus empyema, arthritis, and calcaneal osteomyelitis in a lung transplant patient successfully treated with posaconazole.

A 64-year-old male with Aspergillus fumigatus infection that had disseminated from the lung to the ankle and adjacent bone was treated successfully with posaconazole after therapy with itraconazole and amphotericin B lipid complex failed. Marked clinical improvement occurred within 6 weeks of initiation of posaconazole therapy; after 6 months, infection had resolved at all sites. The patient has had no recurrence of infection.