Search

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.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.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. more...

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. more...

Purpose Small community hospitals often lack the human, financial, and technological resources necessary to implement and maintain successful antimicrobial stewardship programs now required by national regulatory and accrediting bodies. Creative solutions are needed to address this problem. Summary A 3-stage, quasi-experimental study including patients receiving antibiotics for pneumonia, skin and soft tissue infections, and urinary tract infections at a community hospital in Wisconsin from June 2013 to December 2015 was conducted. Remote telehealth prospective audit and feedback, guideline and order set management, and staff education targeting pharmacists, nurses, and physicians were provided during the 7-month intervention phase; these services were then removed for the postintervention period. Antimicrobial utilization (days of therapy [DOT] per 1,000 patient-days), hospital length of stay, and readmission and 30-day mortality rates were assessed to determine the impact of telehealth services on these outcomes. During the preintervention (baseline), intervention, and postintervention periods, 1,037 patients received antibiotics for the targeted infectious disease conditions. Patient demographics and rates of infectious disease conditions were similar among the different periods. Telehealth antimicrobial stewardship reduced broad-spectrum antibiotic use, including use of imipenem (from 83 to 31 DOT, P < 0.001), levofloxacin (from 123 to 99 DOT, P < 0.001), and vancomycin (from 104 to 85 DOT, P < 0.001), compared to utilization during the baseline period; mean (SD) length of stay also decreased (from 4.6 [2.8] days to 4.2 [2.6] days, P = 0.02). After nonrenewal of telehealth stewardship, vancomycin and piperacillin/tazobactam usage returned to or exceeded baseline levels. Conclusion The partnership between an academic medical center and a small community hospital improved antimicrobial utilization and clinical outcomes. Successful telehealth antimicrobial stewardship models should be explored further as a means to provide optimal patient care. more...

Purpose A systematic review was performed to determine if remote stewardship (telestewardship) provides clinical and fiscal benefit and is a feasible alternative to local stewardship programs. Summary Antibiotic resistance is an increasingly important national and global threat. US regulators have made antimicrobial stewardship programs a condition of participation in federally funded healthcare programs, and stewardship programs are surveyed during accreditation visits. Small and rural hospitals are at risk for stewardship noncompliance because lack of resources limits comprehensive stewardship program implementation. Remote stewardship programs are established to remedy this area of partial compliance. To characterize the impact of remote stewardship on selected clinical and fiscal outcomes, PubMed was searched for studies involving telestewardship that reported data on antimicrobial utilization, patient length of stay, mortality, bacterial susceptibility, hospital-acquired Clostridioides difficile infection (HA-CDI), and/or antimicrobial costs. A systematic approach was used to screen study titles, abstracts, and content and data extracted. Study quality was analyzed using Cochrane risk-of-bias assessment tools. Fourteen studies were included in the final review. Collectively, the antimicrobial utilization data was positive, with utilization of targeted antimicrobials decreasing after telestewardship implementation. Mixed (both positive and neutral) results were found for patient length of stay, mortality, and HA-CDI rates. Fiscal outcomes were consistently positive. Conclusion Based on the reviewed evidence, remote antimicrobial stewardship programs may aid in the more judicious use of antimicrobials by decreasing utilization rates. More studies are needed to clarify patient-oriented outcomes. Telestewardship has positive effects in terms of cost savings, although savings may be offset by the structure of the program. more...

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. more...

Classical stewardship efforts have targeted immunocompetent patients; however, appropriate use of antimicrobials in the immunocompromised host has become a target of interest. Cytomegalovirus (CMV) infection is one of the most common and significant complications after solid-organ transplant (SOT). The treatment of CMV requires a dual approach of antiviral drug therapy and reduction of immunosuppression for optimal outcomes. This dual approach to CMV management increases complexity and requires individualization of therapy to balance antiviral efficacy with the risk of allograft rejection. In this review, we focus on the development and implementation of CMV stewardship initiatives, as a component of antimicrobial stewardship in the immunocompromised host, to optimize the management of prevention and treatment of CMV in SOT recipients. These initiatives have the potential not only to improve judicious use of antivirals and prevent resistance but also to improve patient and graft survival given the interconnection between CMV infection and allograft function. more...

This cohort study examines the rates of neutropenic fever–associated admissions and outpatient antibiotic use among patients with cancer receiving chemotherapy before and during the COVID-19 pandemic. more...

PurposeThe objective of this study was to implement a standardized process across health systems to determine the prevalence and clinical relevance of prescribing errors intercepted by pharmacists.MethodsThis prospective, multicenter, observational study was conducted across 11 hospitals. Pharmacist-intercepted prescribing errors were collected during inpatient order verification over 6 consecutive weeks utilizing a standardized documentation process. The potential harm of each error was evaluated using a modified National Coordinating Council for Medication Error Reporting and Prevention (NCC-MERP) index with physician validation, and errors were stratified into those with potentially low, serious, or life-threatening harm. Endpoints included the median error rate per 1,000 patient days, error type, and potential harm with correlating cost avoidance.ResultsPharmacists intervened on 7,187 errors, resulting in a mean error rate of 39 errors per 1,000 patient days. Among the errors, 46.6% (n = 3,349) were determined to have potentially serious consequences and 2.4% (n = 175) could have been life-threatening if not intercepted. This equates to $874,000 in avoided cost. The top 3 error types occurring with the highest frequency were “wrong dose/rate/frequency” (n = 2,298, 32.0%), “duplicate therapy” (n = 1,431, 19.9%), and “wrong timing” (n = 960, 13.4%). “Wrong dose/rate/frequency” (n = 49, 28%), “duplicate therapy” (n = 26, 14.9%), and “drug-disease interaction” (n = 24, 13.7%) errors occurred with the highest frequency among errors with potential for life-threatening harm. “Wrong dose/rate/frequency” (n = 1,028, 30.7%), “wrong timing” (n = 573, 17.1%), and “duplicate therapy” (n = 482, 14.4%) errors occurred with the highest frequency among errors with potentially serious harm.ConclusionDocumentation of pharmacist intervention on prescribing errors via a standardized process creates a platform for multicenter analysis of prescribing error trends and an opportunity for development of system-wide solutions to reduce potential harm from prescribing errors. more...

This pre-post study examines the association between respiratory virus incidence and ambulatory antibiotic orders and the COVID-19 pandemic.

Key points In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients. Purpose There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. Methods We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19–targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). Results A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19–directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028). Conclusion While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments. more...

Objective:Evaluate the difference in antibiotic prescribing between various levels of resident training or attending types.Design:Observational, retrospective study.Setting:Tertiary-care, academic medical center in Madison, Wisconsin.Methods:We measured antibiotic utilization from January 1, 2016, through December 31, 2018, in our general medicine (GM) and hospitalist services. The GM1 service is staffed by outpatient internal medicine physicians, the GM2 service is staffed by geriatricians and hospitalists, and the GM3 service is staffed by only hospitalists. The GMA service is led by junior resident physicians, and the GMB service is led by senior resident physicians. We measured utilization using days of therapy (DOT) per 1,000 patient days (PD). In a secondary analysis based on antibiotic spectrum, we used average DOT per 1,000 PD.Results:Teaching services prescribed more antibiotics than nonteaching services (671.6 vs 575.2 DOT per 1,000 PD; P < .0001). Junior resident–led services used more antibiotics than senior resident–led services (740.9 vs 510.0 DOT per 1,000 PD; P < .0001). Overall, antibiotic prescribing was numerically similar between various attending physician backgrounds. A secondary analysis showed that GM services prescribed more broad-spectrum, anti-MRSA, and anti-pseudomonal antibiotics than the hospitalist services. GM junior resident–led services prescribed more broad-spectrum, anti-MRSA, and antipseudomonal therapy compared to their senior counterparts.Conclusions:Antibiotics were prescribed at a significantly higher rate in services associated with trainees than those without. Services led by a junior resident physician prescribed antibiotics at a significantly higher rate than services led by a senior resident. Interventions to reduce unnecessary antibiotic exposure should be targeted toward resident physicians, especially junior trainees. more...

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. more...

Background The majority of antimicrobial use occurs in the ambulatory setting. Antimicrobial stewardship programs (ASPs) are effective in improving appropriate prescribing and are now required by accreditation bodies. Methods This was a cross-sectional, multicenter survey describing the current state of ambulatory ASPs in a national cohort of Vizient member hospitals with ambulatory healthcare settings and serves as a benchmark for stewardship strategies related to program effectiveness. Results One hundred twenty-nine survey responses from a variety of institution types across 44 states were received. Survey respondents reported a fully functioning ASP in 7% (9 of 129) of ambulatory practices compared with 88% (114 of 129) of inpatient institutions. Effectiveness in at least 1 antibiotic use-related outcome (ie, utilization, resistance, Clostridioides difficile infection, or cost) in the past 2 years was reported in 18% (18 of 100) of ambulatory and 84% (103 of 123) of inpatient ASPs. Characteristics of ambulatory ASPs demonstrating effectiveness were institution guidelines (89%, 16 of 18), rapid diagnostic testing for respiratory viruses or group A Streptococcus (89% 16 of 18), outpatient antibiograms (78% 14 of 18), and dedicated pharmacist support (72%, 13 of 18). Ambulatory ASP effectiveness was shown to increase as programs met more of the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antimicrobial Stewardship (P, A national cohort of ambulatory stewardship program characteristics and activities compared with inpatient stewardship programs. Ambulatory ASP effectiveness was shown to increase as programs met more of the Centers of Disease Control and Prevention Core Elements of Outpatient Antimicrobial Stewardship. more...

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 β-lactam allergy whereas clindamycin was 45-fold more likely. more...

While current research efforts focus primarily on identifying patient level interventions that mitigate the direct impact of COVID-19, it is important to consider the collateral effects of COVID-19 on antimicrobial resistance. Early reports suggest high rates of antibiotic utilization in COVID-19 patients despite their lack of direct activity against viral pathogens. The ongoing pandemic is exacerbating known barriers to optimal antibiotic stewardship in the ED, representing an additional direct threat to patient safety and public health. There is an urgent need for research analyzing overall and COVID-19 specific antibiotic prescribing trends in the ED. Optimizing ED stewardship during COVID-19 will likely require a combination of traditional stewardship approaches (e.g. academic detailing, provider education, care pathways) and effective implementation of host response biomarkers and rapid COVID-19 diagnostics. Antibiotic stewardship interventions with demonstrated efficacy in mitigating the impact of COVID-19 on ED prescribing should be widely disseminated and inform the ongoing pandemic response. more...

In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients.There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period.We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19-targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs).A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19-directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028).While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments. more...

ObjectiveWe conducted a quality improvement initiative to restrict fluoroquinolone prescribing on two inpatient units housing high-risk patients and applied a human factors approach to understanding the barriers and facilitators to success of this intervention by front-line providers.MethodsThis was a mixed-methods, quasi-experimental study. This study was conducted on two inpatient units at a tertiary care academic medical center: the medical-surgical intensive care and abdominal solid organ transplant units. Unit-level data were collected retrospectively for 24 months pre- and post- fluoroquinolone restriction intervention, implemented in July 2016, for all admissions to the study units. Our restriction intervention required antimicrobial stewardship pre-approval for fluoroquinolone prescribing. We explored barriers and facilitators to optimal fluoroquinolone prescribing using semi-structured interviews attending, fellow and resident physicians, advanced practice providers and pharmacists on these units.ResultsHospital-onset C. difficile infection did not decrease significantly, but fluoroquinolone use declined significantly from 111.6 to 19.8 days of therapy per 1000 patient-days without negatively impacting length of stay, readmissions or mortality. Third generation cephalosporin and aminoglycoside use increased post-restriction. Providers identified our institution's strong antimicrobial stewardship program and pharmacy involvement in antimicrobial decision making as key facilitators of fluoroquinolone optimization and patient complexity, lack of provider education and organizational culture as barriers to optimal prescribing.ConclusionsFluoroquinolones can be safely restricted even among high-risk patients without negatively impacting length of stay, readmissions or mortality. Our study provides a framework for successful antimicrobial stewardship interventions informed by perceptions of front line providers. more...

To summarize literature describing the antimicrobial timeout, its rationale for use as an antimicrobial stewardship program (ASP) strategy, and its potential role in overall ASP strategy. Studies have correlated a formal antimicrobial timeout process with increased rates of therapy modification and reductions in use of select broad-spectrum antibiotics. There remains a need for further guidance on how to best implement a system-wide antimicrobial timeout. The antimicrobial timeout is a stewardship tool that protocolizes review of objective clinical data and encourages stewardship practices, such as antimicrobial de-escalation, parenteral-to-enteral route interchange, dose optimization, and appropriate duration. Logically, the timeout encourages thoughtful reassessment of antimicrobial therapy and should produce positive antimicrobial utilization outcomes; however, clinical effectiveness data is conflicting, with more research necessary. Institutions should implement standardized processes by which their clinical services evaluate and thoughtfully assess use of antimicrobials among their patients whether they are being treated in the hospital or possibly, at home. Implementation of a formal timeout may allow a greater sharing of responsibility for antimicrobial stewardship among formal members of stewardship programs and front-line clinicians. more...

Objective Oritavancin is a lipoglycopeptide antibiotic approved for use in acute bacterial skin and skin structure infections as a single 1200-mg parenteral dose. Because of oritavancin's long half-life and broad gram-positive activity, interest in its use for other infections is high. Methods This study is a retrospective cohort evaluation of patients receiving oritavancin at a single academic medical center. All patients receiving more than one dose of oritavancin were included. Patients were excluded if therapy was interrupted by more than 14 days. Efficacy, defined a priori as clinical success, improvement, or failure, and adverse drug effect outcomes were collected. Results Seventeen patients received multiple oritavancin doses (range 2–18 doses) for the treatment of complicated infections including osteomyelitis, surgical site infection, intravascular infections, and pneumonia. All patients achieved clinical success or improvement with oritavancin. Four patients (24%) had an adverse event requiring oritavancin discontinuation that reversed rapidly. Conclusions Off-label oritavancin use may be a safe and effective alternative to daily antibiotic infusions to treat complicated infectious disease processes. This study is limited by small sample size and retrospective design, but it provides information on using oritavancin in these complex gram-positive infections. more...

The new triazole antifungal, isavuconazole, gained approval in 2015 for the treatment of invasive aspergillosis (IA) and mucormycosis in adult patients. Predictable pharmacokinetics, a favorable safety profile, and demonstrated clinical efficacy against a wide spectrum of yeasts and molds result in expansion of the antifungal armamentarium. The place in therapy for this medication has yet to be defined. This review aims to place isavuconazole’s role in therapy in perspective. Three studies evaluate isavuconazole activity in the treatment of IA, mucormycosis, and candidiasis. Isavuconazole was non-inferior to voriconazole in the treatment of IA and had similar outcomes to liposomal amphotericin (L-AMB) and posaconazole in the treatment of mucormycosis. Isavuconazole did not meet a priori non-inferiority margins for superior clinical outcome response in the treatment of candidemia. Cost-effectiveness analyses compare isavuconazole to other treatment options with favorable outcomes regarding isavuconazole use. Considering the potential for substantial cost savings, non-inferiority to L-AMB and other triazoles in terms of efficacy, a more favorable safety profile, and an oral formulation, isavuconazole has advantages over current standard of care for the treatment of IA and mucormycosis. For other invasive fungal infections including candidiasis, clinical outcome data and cost-effectiveness analysis are needed. Isavuconazole is a safe, effective, and fiscally responsible treatment option for the treatment of IA and mucormycosis. more...

Background PSA with MDR and XDR are a growing threat, and appropriate initial treatment of this organism is critical. C/T is a novel antibiotic with broad gram-negative in vitro susceptibility among surveillance studies. However comprehensive susceptibility analyses of C/T among PSA clinical isolates in comparison with other anti-PSA antibiotics remain limited, since routine clinical C/T susceptibility testing is not typically performed. Methods This study assessed all adult inpatient cultures positive for PSA from 32 months at an academic health system. Antimicrobial susceptibility was prospectively performed using Kirby Bower disk diffusion and interpreted by BIOMIC V3 during routine clinical care. Initial susceptibility testing included C/T along with amikacin, aztreonam, cefepime, ciprofloxacin, doripenem, gentamicin, imipenem, meropenem, piperacillin/tazobactam, and tobramycin. MDR and XDR isolates were identified using established definitions. The primary outcome was to quantify C/T resistant PSA (includes intermediate and resistant strains). Secondary outcomes were to determine resistance to other anti-PSA antibiotics and to identify C/T activity among isolates with MDR, XDR and pan-β-lactam resistance (PBLR = all β-lactams except C/T). Results A total of 2990 PSA isolates from 2339 cultures in 1311 individual patients were collected. Most cultures were from the lung (45%), followed by urine (30%), and body fluids (10%). For the primary outcome, 121/2990 (4%) of PSA isolates were C/T resistant. All PSA blood cultures were susceptible to C/T. Table 1 summarizes in vitro activity of all anti-PSA agents evaluated. C/T had the greatest percent susceptibility across all culture locations including MDR/XDR PSA isolates with median MICs of 8 µg/mL. For PBLR strains 35/66 (53%) were susceptible to C/T with a median MIC of 8 µg/mL. Table 1 Conclusion C/T susceptibility testing during routine care over a 2.5-year period revealed 96% susceptibility among PSA. C/T showed the highest susceptibility among all anti-PSA antibiotics for all culture locations and for MDR and XDR isolates. Given the high rates of resistance to traditional anti-PSA agents, the value of new agents with high rates of in vitro susceptibility in the gram-negative armamentarium is high. Disclosures Warren Rose, PharmD, MPH, Merck (Grant/Research Support)Paratek (Grant/Research Support) Janet Radaatz, PharmD, Merck (Employee) Laura A. Puzniak, PhD, Merck (Employee) Ryan J. Dillon, MSc, Merck & Co., Inc., (Employee) more...

The in vitro activity of meropenem-vaborbactam was examined against clinical carbapenem-resistant Enterobacteriaceae isolates collected over 3 years at our medical center. Only 3 KPC-producers were identified. Susceptibility to meropenem-vaborbactam was noted in 15/16 (94%) isolates (MIC90 2 mg/L) that were nonsusceptible to meropenem. Meropenem-vaborbactam may have utility at centers where non–KPC-producers are more frequent. more...

Background Daptomycin and ceftaroline (DAP-CPT) have been used for persistent methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), but have rarely been compared with other therapies. This study provides an exploratory analysis of patients placed on DAP-CPT vs standard of care (SOC) for MRSAB. Methods This is a retrospective, matched cohort study MRSAB patients at 4 hospitals in the United States. Patients receiving DAP-CPT for ≥72 hours at any point in therapy were matched 2:1 when possible, 1:1 otherwise, to SOC, first by infection source, then age and renal function. SOC was empiric treatment with vancomycin or daptomycin and any subsequent combination antibiotic(s), except for DAP-CPT. Results Fifty-eight patients received DAP-CPT with 113 matched SOC. Ninety-six percent of SOC received vancomycin, and 56% (63/113) escalated therapy at least once in the treatment course. Twenty-four patients received DAP-CPT within 72 hours of index culture; 2 (8.3%) died within 30 days vs 14.2% (16/113) with SOC (P > .05). Subgroup analysis identified numerically lower mortality in DAP-CPT patients with a Charlson comorbidity index ≥3, endovascular source, and receipt of DAP-CPT within 72 hours of index culture. The median MRSAB duration was 9.3 vs 4.8 days for DAP-CPT and SOC, respectively. DAP-CPT was initiated on day 6 on average; after receipt of DAP-CPT, MRSAB duration was 3.3 days. Conclusions DAP-CPT treatment is often delayed in MRSAB. Combination therapy may be more beneficial if initiated earlier, particularly in patients at higher risk for mortality. Blinded, randomized, prospective studies are needed to eliminate selection bias inherent in retrospective analyses when examining DAP-CPT vs SOC., This multicenter, retrospective, exploratory, matched study compares demographics and clinical outcomes of patients receiving daptomycin plus ceftaroline at any time in treatment course versus other therapy for MRSA bacteremia. This combination used within 72 hours of index culture may be more beneficial for survival than as salvage therapy. more...

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). more...

Background Treatment guidelines for pneumonia recommend beta-lactam antibiotic-based therapy. Although reported penicillin allergy is common, more than 90% of patients with reported penicillin allergy are not allergic. Objective We evaluated the association of a documented penicillin and/or cephalosporin (P/C) allergy to antibiotic use for the treatment of inpatient pneumonia. Methods This was a national cross-sectional study conducted among Vizient, Inc., network hospitals that voluntarily contributed data. Among hospitalized patients with pneumonia, we examined the relation of a documented P/C allergy in the electronic health record to prevalence of first-line beta-lactam antibiotic administration and alternative antibiotics using multivariable log-binomial regression with generalized estimating equations. Results Of 2,276 inpatients receiving antibiotics for pneumonia at 95 U.S. hospitals, 450 (20%) had a documented P/C allergy. Compared with pneumonia patients without a documented P/C allergy, patients with a documented P/C allergy had reduced prevalence of first-line beta-lactam antibiotic use (adjusted prevalence ratio [aPR] 0.79; 95% confidence interval [95% CI] 0.69-0.89]). Patients with high-risk P/C reactions (n = 91) had even lower prevalence of first-line beta-lactam antibiotic use (aPR 0.47; 95% CI 0.35-0.64). Alternative antibiotics associated with a higher use in pneumonia patients with a documented P/C allergy included carbapenems (aPR 1.61; 95% CI 1.22-2.13) and fluoroquinolones (aPR 1.52; 95% CI 1.21-1.91). Conclusions Inpatients with documented P/C allergy and pneumonia were less likely to receive recommended beta-lactams and more likely to receive carbapenems and fluoroquinolones. Inpatient allergy assessment may improve optimal antibiotic therapy for the 20% of inpatients with pneumonia and a documented P/C allergy. more...

IntroductionClostridioides difficileinfection (CDI) is one of the most common healthcare-associated infections in the USA, having high incidence in intensive care units (ICU). Antibiotic use increases risk of CDI, with fluoroquinolones (FQs) particularly implicated. In healthcare settings, antibiotic stewardship (AS) and infection control interventions are effective in CDI control, but there is little evidence regarding the most effective AS interventions. Preprescription authorisation (PPA) restricting FQs is a potentially promising AS intervention to reduce CDI. The FQ Restriction for the Prevention of CDI (FIRST) trial will evaluate the effectiveness of an FQ PPA intervention in reducing CDI rates in adult ICUs compared with preintervention care, and evaluate implementation effectiveness using a human-factors and systems engineering model.Methods and analysisThis is a multisite, stepped-wedge, cluster, effectiveness-implementation clinical trial. The trial will take place in 12 adult medical-surgical ICUs with ≥10 beds, using Epic as electronic health record (EHR) and pre-existing AS programmes. Sites will receive facilitated implementation support over the 15-month trial period, succeeded by 9 months of follow-up. The intervention comprises a clinical decision support system for FQ PPA, integrated into the site EHRs. Each ICU will be considered a single site and all ICU admissions included in the analysis. Clinical data will be extracted from EHRs throughout the trial and compared with the corresponding pretrial period, which will constitute the baseline for statistical analysis. Outcomes will include ICU-onset CDI rates, FQ days of therapy (DOT), alternative antibiotic DOT, average length of stay and hospital mortality. The study team will also collect implementation data to assess implementation effectiveness using the Systems Engineering Initiative for Patient Safety model.Ethics and disseminationThe trial was approved by the Institutional Review Board at the University of Wisconsin-Madison (2018-0852-CP015). Results will be made available to participating sites, funders, infectious disease societies, critical care societies and other researchers.Trial registration numberNCT03848689. more...

tudy Objective As patients with abdominal solid organ transplants (SOT) are at increased risk of polymicrobial intraabdominal infections (IAIs) following transplantation, the objective of this study was to compare the effectiveness and adverse event profile of tigecycline with those of other broad-spectrum therapies for polymicrobial IAIs in this population. Design Retrospective cohort study. Setting Large academic medical center with multiple outpatient clinics. Patients A total of 81 adult SOT recipients were included who were treated for confirmed or suspected polymicrobial IAIs from 2007–2012; of these patients, 27 received tigecycline and 54 received comparator therapy with a broad-spectrum β-lactam (e.g., piperacillin-tazobactam, cefepime, or meropenem) with or without glycopeptide or lipopeptide gram-positive therapy (vancomycin or daptomycin) (comparator group). Patients in the comparator group were matched to tigecycline-treated patients based on transplant type (kidney, combined kidney-pancreas, combined kidney-liver, or solitary pancreas) in a 1:2 ratio (tigecycline:other broad-spectrum antibiotics). Measurements And Main Results Data on patient demographics, comorbidities, and clinical variables were collected and compared by using bivariate analyses. Clinical outcomes—clinical cure, improvement, or failure, and disease recurrence—as well as death within 1 year were analyzed by bivariate analyses and logistic regression. Clinical cure was lower in the tigecycline group versus the comparator group (40.7% vs 72.2%, p=0.008), but cure combined with improvement was similar between the two groups (85.2% vs 88.9%, p=0.724). Multiple logistic regression analysis showed that treatment with comparator antibiotics increased the odds of cure (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.15–12.27) and reduced the odds of treatment failure (OR 0.59, 95% CI 0.07-4.55) and death within 1 year (OR 0.79, 95% CI 0.22–2.86); however, patients receiving comparator antibiotics were more likely to have disease recurrence (OR 1.45, 95% CI 0.33–6.36). Patients receiving tigecycline experienced a higher rate of adverse events than those receiving comparator antibiotics (29.6% vs 9.3%, p=0.026). Conclusion Patients receiving tigecycline were less likely to achieve optimal clinical outcomes and had more adverse events. Alternative regimens should be selected over tigecycline for treatment of polymicrobial IAIs in abdominal SOT recipients until additional studies are completed to examine its role in this population. This article is protected by copyright. All rights reserved. more...

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. more...

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. more...

Procalcitonin is a sensitive and specific marker of bacterial infection; low results allow clinicians to safely de-escalate antibiotics. This retrospective cohort study aimed to determine the effect of low procalcitonin results on withholding, discontinuing, or de-escalating antibiotics in hospitalized patients at a tertiary care center. Antibiotics were initiated or continued without de-escalation in 55% of patients with low procalcitonin results. Among patients with low procalcitonin results, the primary service, but not measures of patient complexity, disease severity, or underlying disease process (lower respiratory tract infection evaluation versus systemic inflammatory response syndrome/possible sepsis) was associated with initiation or continued broad-spectrum antibiotic use. Provider-level factors may be an important variable in the initiation or continued use of broad-spectrum antibiotics for patients with low procalcitonin levels. more...

Background As the number of joint replacement surgeries continues to rise, so does the number of joint infections. Many patients end up needing the implantation of antibiotic loaded bone cement (ALBC) to treat their infection. The use of localized high dose vancomycin, tobramycin, and gentamicin may be linked to acute kidney injury (AKI) in certain patients. Our hypothesis is that patients who developed AKI after receiving a joint spacer had a predisposition to AKI due to other comorbidities, high antibiotic doses in ALBC, immunosuppression, or the use of other nephrotoxic drugs pre-op. These patients may need close monitoring of their renal function and serum antibiotic levels after surgery. Methods We performed a chart review of 428 patients who underwent an orthopedic surgery that involved insertion of ALBC at our institution between 2015 and 2018. We excluded patients under age 18, those who had antibiotic irrigation only, trauma patients, non-arthroplasty surgeries (such as fractures and debridement of deep wounds), and patients with missing data for 30 days after the surgery. We identified 57 patients who fit our inclusion criteria and received a bone cement spacer or beads to treat an infection of the hip, knee, shoulder, or ankle. We matched patients who had AKI to 2 patients who did not have AKI. Matching was based on age (± 5 years), joint operated on, and antibiotics used. Results 15 patients showed an elevated serum creatinine level of over 1.2 within 30 days of surgery. 86.7% of these patients were male, their average age was 64.1 ± 6.2 years old, 40% had hip surgery, 46.7% knee surgery, 6.7% ankle, and 6.7% shoulder. All received vancomycin and tobramycin in Palacos bone cement. Compared to their case-control matches, these patients had more frequent use of immunosuppressive medication, a history of malignancy, a history of previous kidney disease, and obesity. The use of combined intravenous vancomycin and piperacillin-tazobactam post-operatively may also be linked to higher rates of AKI. Conclusion Immunosuppression, obesity, male gender, and history of kidney injury and cancer are factors associated with AKI after ALBC spacer implantation. Further analysis and study are needed to identify potential causation between ALBC use and AKI. Disclosures All Authors: No reported disclosures more...

Antimicrobial resistance is recognized as a global health crisis.[1][1] In the United States alone, more than 2 million patients contract antibiotic-resistant infections that result in 23,000 deaths annually.[2][2] One factor contributing to antimicrobial resistance is antimicrobial misuse or more...

Purpose The physical and chemical compatibility of cefepime and vancomycin at concentrations typically used in prolonged-infusion cefepime infusions was assessed. Methods Samples from a typical Y-site configuration of standard-infusion vancomycin and prolonged-infusion cefepime were collected at various time points during the simulated 4-hour infusion. Samples were analyzed by visual inspection, spectrophotometry, and high-performance liquid chromatography (HPLC). Infusion antibiotics were reconstituted in pairwise combinations of 0.9% sodium chloride injection and 5% dextrose injection to determine the effects of solvent selection on stability. Infusion simulations were performed in triplicate without light protection under fluorescent lighting at room temperature (22.5 °C). Experimental replicates were not run simultaneously but on sequential days due to the considerable time (~12 hours) required to analyze samples obtained from a single infusion simulation and the known time-dependent instability of reconstituted cefepime beyond 24 hours. Physical stability was assessed visually for evidence of particulate formation, haze, precipitation, color change, and gas evolution. Samples were also assessed spectrophotometrically at 600 nm at the time of collection and 24 hours after collection. Results Cefepime was compatible with vancomycin at the concentrations tested. The solvent selected (0.9% sodium chloride or 5% dextrose) to reconstitute either antibiotic had no impact on compatibility. Solutions were indistinguishable from positive and negative controls (heat-degraded cefepime and freshly reconstituted cefepime, respectively) at all time points assessed in terms of visual clarity, spectrophotometric absorbance, and HPLC recovery. Conclusion Cefepime and vancomycin were physically and chemically compatible during simulated Y-site administration of prolonged-infusion cefepime. more...

The Society for Healthcare Epidemiology of America and the Infectious Disease Society of America (SHEA/IDSA) released guidelines outlining the strategies of antimicrobial stewardship program (ASP) activities in 2006. These strategies have been supported by advances in technology, beginning with the novel use of clinical decision support systems (CDSS) at LDS Hospital in Salt Lake City, UT. This sophisticated home-grown program allowed for timely and tailored information to be exchanged between the electronic medical record (EMR) and physicians, resulting in reduced drug costs and improved patient outcomes. This CDSS technology became the basis of many third-party vendors that emerged to offer support and improve clinical and fiscal outcomes. However, third-party programs are expensive, require double documentation of interventions within the third-party platform and the EMR, and lack prescriber interaction at the time of prescribing; although they are more customizable and allow for real-time alerts between the microbiology lab and ASP team members. The advancement of the electronic health records (EHR) has expanded the capability for ASPs to use the EHR for clinical stewardship activities rather than outsource it to a third-party vendor. Epic and Cerner currently lead the market in EMR technology and are expected to continue expanding ASP functionality in their foundation systems. more...