Evaluation of Gram Stain-Guided Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus Pneumonia in Intensive Care Unit Patients.

Background: Despite high negative predictive values (NPVs) seen with methicillin-resistant Staphylococcus aureus (MRSA) nares polymerase chain reaction (PCR) assays, utilization of both respiratory sample Gram stain and MRSA nares PCR in patients with pneumonia may contribute to overuse of laboratory resources. The purpose of this study was to evaluate if a Gram stain demonstrating no Gram-positive organisms from a respiratory sample is sufficient to allow for de-escalation of vancomycin therapy. Methods: This single center study retrospectively identified intensive care unit (ICU) patients started on vancomycin for presumed pneumonia at University of Wisconsin (UW) Health in Madison, WI between August 2022 and March 2023. Patients with respiratory sample demonstrating no Gram-positives on Gram stain met inclusion criteria if the sample was ordered within 24 h of vancomycin initiation. The primary outcome was NPV of respiratory sample Gram stain demonstrating no Gram-positive organisms with respect to MRSA detection of the respiratory culture. Secondary outcomes included the NPV of combined MRSA nares PCR plus respiratory sample Gram stain, and difference in time to event in patients that had both a respiratory sample and MRSA nares PCR ordered. Results: A total of 370 patients were screened for study eligibility; of which 99 patients met inclusion criteria. NPV of respiratory sample Gram stain was 99% for MRSA culture. The combined NPV of respiratory sample Gram stain plus MRSA nares PCR was 98.9% for MRSA culture (n = 88). Respiratory sample was ordered 2.3 h faster compared to MRSA nares PCR (4.3 vs 6.6 h, P = .036). Respiratory sample Gram stain resulted 4.5 h faster compared to MRSA nares PCR (10.7 vs 15.2 h, P = .002). Conclusion: Respiratory sample Gram stains demonstrating no Gram-positive organisms may be used to de-escalate vancomycin and deprioritize the use of MRSA nares PCR.

Maribavir for the Management of Cytomegalovirus in Adult Transplant Recipients: A Review of the Literature and Practical Considerations.

OBJECTIVE: To review the efficacy and safety of maribavir for management of cytomegalovirus (CMV) in solid organ transplant recipients. DATA SOURCES: A literature search of PubMed and the Cochrane Controlled Trials Register (1960 to early July 2022) was performed using the following search terms: maribavir, 1263W94, and cytomegalovirus. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language studies were reviewed and considered, with a focus on phase 3 trials. DATA SYNTHESIS: Maribavir, an orally available benzimidazole riboside with minimal adverse effects, was originally studied for universal prophylaxis in phase 3 trials but failed to demonstrate noninferiority over placebo and oral ganciclovir. It was effective for preemptive treatment in a dose-finding Phase 2 study. Maribavir is FDA approved for treatment of refractory/resistant CMV infection based on improved response rate at 8 weeks compared with investigator-assigned therapy (IAT) when initiated at median viral loads less than approximately 10 000 IU/mL (55.7% vs 23.9%, P < 0.001). Recurrence after 8-week treatment for refractory/resistant CMV was high (maribavir 50% vs IAT 39%). Significant drug interactions exist and must be managed by a pharmacotherapy expert to prevent harm. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The addition of maribavir to the antiviral armamentarium should improve the management of refractory/resistant CMV, allowing early transition from toxic, high-cost, intravenous agents such as foscarnet and outpatient management. Optimal timing of initiation, duration, and potential alternative uses are unclear. CONCLUSION: Future studies are needed to fully elucidate the role of maribavir in the management of CMV after transplant.

CMV antiviral stewardship: navigating obstacles to facilitate target attainment.

PURPOSE OF REVIEW: Despite the availability of potent antivirals, consensus guidelines and decades of research, cytomegalovirus (CMV) continues to be associated with negative outcomes after solid organ transplant. This has been attributed to postprophylaxis CMV infection and a lack of development of CMV-specific cell mediated immunity (CMI). A shift from a focus on antiviral prevention to a focus on CMI target attainment is needed to improve CMV outcomes after transplantation. RECENT FINDINGS: There are many obstacles to CMI target attainment. Antiviral stewardship programs (AVS) have been employed to improve patient outcomes through appropriate antiviral use, reduction of unnecessary exposure and resistance mitigation. By focusing on the patient's unique substrate of conglomerate risk factors and addressing these factors specifically with evidenced based methodology, the AVS can address these obstacles, increasing rates of CMI and subsequently reducing risk of future CMV infection and negative outcomes. SUMMARY: With its multidisciplinary composition utilizing decades of experience from antimicrobial stewardship principles and practices, the AVS is uniquely poised to facilitate the shift from a focus on prevention to CMI target attainment and be the supporting pillar for the frontline transplant clinician caring for transplant patients with CMV.

Cytomegalovirus antiviral stewardship in solid organ transplant recipients: A new gold standard.

PURPOSE: Antimicrobial stewardship programs (ASPs) are essential entities that promote the appropriate use of antimicrobials, leading to improved patient outcomes and reduced resistance. Application to the immunocompromised host is a natural progression for expansion. Cytomegalovirus (CMV) infection is a common complication following solid organ transplant with significant implications on graft survival, making it an attractive ASP target. The aim of this piece is to review our center-specific experience with the development, implementation, and maintenance of a CMV stewardship initiative at a large transplant center. METHODS: Our CMV stewardship initiative began in 2018. Herein, we review 3 years' experience and quality-related improvement that occurred from initiation to present state and share our stewardship algorithms. Special attention is paid to the impact of the program as well as our increased understanding of the complex interplay between prevention, treatment, and host development of CMV-specific cell-mediated immunity (CMI). RESULTS: We found our stewardship initiative not only reduced the incidence of ganciclovir resistance but also streamlined care via a centralized and structured approach. This objective, protocolized program has resulted in a significant shift away from a reactive to a proactive state and in turn, reduced CMV treatment rates (26% at initiation to 12% in the current state, p = .012). CONCLUSION: A dedicated multidisciplinary team focused on CMV stewardship is imperative in providing a patient-centered approach focused on development of CMV-specific CMI, and as a result prevention of CMV disease. We believe these programs will be the new gold standard for CMV management.

Vancomycin Advanced Therapeutic Drug Monitoring: Exercise in Futility or Virtuous Endeavor to Improve Drug Efficacy and Safety?

Vancomycin is commonly prescribed to hospitalized patients. Decades of pharmacokinetic/pharmacodynamic research culminated in recommendations to monitor the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration in order to optimize vancomycin exposure and minimize toxicity in the revised 2020 guidelines. These guideline recommendations are based on limited data without high-quality evidence and limitations in strength. Despite considerable effort placed on vancomycin therapeutic drug monitoring (TDM), clinicians should recognize that the majority of vancomycin use is empiric. Most patients prescribed empiric vancomycin do not require it beyond a few days. For these patients, AUC determinations during the initial days of vancomycin exposure are futile. This added workload may detract from high-level patient care activities. Loading doses likely achieve AUC targets, so AUC monitoring after a loading dose is largely unnecessary for broad application. The excessive vancomycin TDM for decades has been propagated with limitations in evidence, and it should raise caution on contemporary vancomycin TDM recommendations.

Association of ß-Lactam Allergy Documentation and Prophylactic Antibiotic Use in Surgery: A National Cross-Sectional Study of Hospitalized Patients.

Alternative antibiotics for surgical prophylaxis are associated with increased adverse events and surgical site infection compared to cefazolin. In a sample of perioperative inpatients from 100 hospitals in the United States, cefazolin was 9-fold less likely to be used in patients with a documented ß-lactam allergy whereas clindamycin was 45-fold more likely.

Effectiveness of oritavancin for management of skin and soft tissue infections in the emergency department: A case series.

Skin and soft tissue infections, such as cellulitis, are commonly diagnosed in the emergency department and these patients are often admitted to the hospital for intravenous antibiotic therapy. Oritavancin is a novel antibiotic approved for the treatment of skin and soft tissue infections that is administered as a one-time infusion. While oritavancin has demonstrated comparable efficacy with multi-dose parenteral antibiotics in clinical trials and has been proposed as an alternative to admission for emergency department patients, there is a paucity of available real world effectiveness data. In this case series, we describe the characteristics and outcomes of ten patients with high-risk skin and soft tissue infections who received oritavancin and were discharged from the emergency department.

Penicillin Allergy Evaluation Access: A National Survey.

In a study of 121 hospitals from 38 US states, 44% had access to an allergist for inpatient consultations and 39% had access to inpatient penicillin skin testing, indicating that the majority of US hospitals lack sufficient resources to address inpatient penicillin allergies.

Finding the niche: An interprofessional approach to defining oritavancin use criteria in the emergency department.

INTRODUCTION: Cellulitis is commonly treated in the emergency department (ED). Oritavancin is a novel, broad-spectrum antibiotic which provides an entire treatment course for cellulitis with one dose. However, optimal ED prescribing scenarios for oritavancin have not been well defined. The purpose of this study was to identify a population of ED patients with cellulitis who would be most appropriate to receive oritavancin. METHODS: This was a descriptive, retrospective study conducted at a Midwest healthcare system with two EDs. Over a 1 year period, all adult patients admitted from the ED to an inpatient ward with an ICD-10 diagnosis for cellulitis were reviewed using a priori defined criteria to identify potentially avoidable admissions (PAA). Potentially avoidable admissions were further characterized and compared to the non-avoidable admission population. Identified patient-specific criteria for PAAs were used to develop oritavancin inclusion/exclusion criteria and a case selection flowchart. RESULTS: Eighty-six patients were identified during the study period. Nine patients (10.5%) were deemed a PAA. A majority of the PAA population had at least one risk factor for treatment failure (55% with diabetes mellitus) and this group was significantly younger than the non-PAA group (42.2 vs 58.6 years; P = 0.01). There were no differences between the PAA group and the non-PAA group in regard to non-age demographics, other risk factors for outpatient treatment failure, comorbidities, or length of stay. CONCLUSION: Oritavancin is an outpatient treatment alternative for cellulitis patients whose only justification for planned admission is the presence of one or more risk factors for treatment failure.

Impact of Triazole Therapeutic Drug Monitoring Availability and Timing.

Therapeutic drug monitoring (TDM) is an established strategy to optimize antifungal therapy with certain triazoles. While established relationships exist between concentration and safety or efficacy, the impact of TDM timing on outcomes is unknown. We report clinical outcomes, including antifungal exposure and mortality, in patients receiving institutional versus reference laboratory TDM. The availability of in-house triazole assays reduced the time to drug concentration result (12 versus 68 h; P < 0.001) and time to achieve therapeutic serum concentrations (10 versus 31 days; P < 0.001). Subtherapeutic concentrations were associated with higher patient mortality (32% versus 13.3%; P = 0.036).

Top 10 Myths Regarding the Diagnosis and Treatment of Cellulitis.

BACKGROUND: Cellulitis is commonly treated in the emergency department (ED). Patients who present with cellulitis incur significant health care costs and may be overtreated with antibiotics. The accurate diagnosis and treatment of cellulitis plays an important role in cost-effective, high-quality medical care, as well as appropriate antibiotic utilization. OBJECTIVE: We aim to describe common fallacies regarding cellulitis. We present 10 myths that result in misdiagnosis, overtreatment, or inappropriate empiric management of cellulitis. Clinical presentation, including swelling and redness, is explored in depth, along with incidence of community-acquired methicillin-resistance Staphylococcus aureus, management of tick bites, and effective antibiotic therapy for cellulitis. DISCUSSION: Patients are often treated for cellulitis unnecessarily or inappropriately. Awareness of these myths will help guide providers in clinical decision making in order to effectively tailor treatment for these infections. CONCLUSIONS: Cellulitis is not as simple as it might seem, and is commonly misdiagnosed in the ED. Noninfectious causes of local symptoms, including lymphedema, venous stasis, and deep vein thrombosis need to be considered. Cellulitis should be treated with empiric antimicrobial therapy based on patient risk factors and regional susceptibility patterns. This review will assist providers in managing cellulitis and avoiding treatment errors that lead to high costs, unwanted side effects for patients, and overuse of antibiotics.

Engaging in Collaborative Research: Focus on the Pharmacy Practitioner.

Research offers an opportunity for investigators to explore unanswered questions, highlight best practices, and engage in collaboration. Clinical research can engage health care professionals to identify treatments or procedures to enhance patient care, quality of life, and outcomes. Research may also include experiences in a unique practice site or teaching methodology of trainees, staff, or patients. The goal of research is to improve individual patient care via dissemination of knowledge through publications. This article aims to highlight the importance of pharmacist-led research in the academic or community medical center and the need for resident-based research and mentorship for the integration of collaborative research and achievement of organizational goals.

Top Ten Myths Regarding the Diagnosis and Treatment of Urinary Tract Infections.

BACKGROUND: Urinary tract infections (UTI) are the most common type of infection in the United States. A Centers for Disease Control and Prevention report in March 2014 regarding antibiotic use in hospitals reported "UTI" treatment was avoidable at least 39% of the time. The accurate diagnosis and treatment of UTI plays an important role in cost-effective medical care and appropriate antimicrobial utilization. OBJECTIVE: We summarize the most common misperceptions of UTI that result in extraneous testing and excessive antimicrobial treatment. We present 10 myths associated with the diagnosis and treatment of UTI and succinctly review the literature pertaining to each myth. We explore the myths associated with pyuria, asymptomatic bacteriuria, candiduria, and the elderly and catheterized patients. We attempt to give guidance for clinicians facing these clinical scenarios. DISCUSSION: From our ambulatory, emergency department, and hospital experiences, patients often have urine cultures ordered without an appropriate indication, or receive unnecessary antibiotic therapy due to over-interpretation of the urinalysis. CONCLUSIONS: Asymptomatic bacteriuria is common in all age groups and is frequently over-treated. A UTI diagnosis should be based on a combination of clinical symptoms with supportive laboratory information. This review will assist providers in navigating common pitfalls in the diagnosis of UTI.

Use of electronic health records and clinical decision support systems for antimicrobial stewardship.

Electronic health records (EHRs) and clinical decision support systems (CDSSs) have the potential to enhance antimicrobial stewardship. Numerous EHRs and CDSSs are available and have the potential to enable all clinicians and antimicrobial stewardship programs (ASPs) to more efficiently review pharmacy, microbiology, and clinical data. Literature evaluating the impact of EHRs and CDSSs on patient outcomes is lacking, although EHRs with integrated CDSSs have demonstrated improvements in clinical and economic outcomes. Both technologies can be used to enhance existing ASPs and their implementation of core ASP strategies. Resolution of administrative, legal, and technical issues will enhance the acceptance and impact of these systems. EHR systems will increase in value when manufacturers include integrated ASP tools and CDSSs that do not require extensive commitment of information technology resources. Further research is needed to determine the true impact of current systems on ASP and the ultimate goal of improved patient outcomes through optimized antimicrobial use.

Daptomycin dosing based on ideal body weight versus actual body weight: comparison of clinical outcomes.

Daptomycin use at our institution changed to ideal body weight dosing based on a published analysis of pharmacokinetic-pharmacodynamic efficacy target attainment, bacterial ecology, and a desire to reduce drug toxicity. The current study compared outcomes between actual body weight and ideal body weight dosing of daptomycin before and after this intervention. In the evaluable group, 69 patients received doses based on actual body weight and 48 patients received doses based on ideal body weight. Patients were treated for documented Enterococcus species, Staphylococcus aureus, or coagulase-negative Staphylococcus infections, including bloodstream, intraabdominal, skin and soft tissue, urinary, and bone. There was no statistically significant difference in clinical success between the groups (88.9% for actual body weight compared to 89.1% for ideal body weight, P = 0.97). After we adjusted for gender, age, body mass index, concomitant 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, infection type, and organism type, clinical success rates remained similar between groups (adjusted odds ratio of 0.68 in favor of actual body weight, 95% confidence interval [CI] of 0.13 to 3.55). Microbiological outcomes, length of stay, mortality, and adverse effects were also similar between groups. Further studies are warranted to confirm that ideal body weight dosing provides similar outcomes to actual body weight dosing for all patients and types of infections and organisms.

Finding value in novel antibiotics: How can infectious diseases adopt incremental cost-effectiveness to improve new antibiotic utilization?

Research and development of innovative antimicrobials is paramount to addressing the antimicrobial resistance threat. Although antimicrobial discovery and development has increased, difficulties have emerged in the pharmaceutical industry after market approval. In this minireview, we summarize clinical trial data on recently approved antibiotics, calculate incremental cost-effectiveness ratio (ICER) values, and explore ways to adapt ICER calculations to the limitations of antimicrobial clinical trial design. We provide a systematic review and analysis of randomized, controlled studies of antibiotics approved from 2014 - 2022 and extracted the relevant clinical data. Adapted-ICER (aICER) calculations were conducted using the primary condition-specific outcome that was reported in each study (percent mortality or percent cure rate). The literature search identified 18 studies for the 8 total antibiotics which met inclusion criteria and contained data required for aICER calculation. aICER values ranged from -$17,374 to $4,966 per percent mortality and -$43,931 to $2,529 per percent cure rate. With regards to mortality, ceftolozane/tazobactam and imipenem/cilastatin/relebactam proved cost efficacious, with aICER values of $4,965 per percent mortality and $1,955 per percent mortality respectively. Finding value in novel antibiotic agents is imperative to further justifying their development, and aICER values are the most common method of determining value in healthcare. The current outcomes of clinical trials are difficult to translate to aICER, which most effectively use Quality-Adjusted Life Years (QALY) as the quality standard in other fields such as oncology. Future antimicrobial trials should consider introducing methods of assessing measures of health gain such as QALY to better translate the value of novel antimicrobials in healthcare.