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Background. We assessed the impact of infectious disease (ID) consultation on management and outcome in patients with Staphylococcus aureus bacteremia (SAB). Methods. A retrospective cohort study examined consecutive SAB patients from 6 academic and community hospitals between 2007 and 2010. Quality measures of management including echocardiography, repeat blood culture, removal of infectious foci, and antibiotic therapy were compared between ID consultation (IDC) and no ID consultation (NIDC) groups. A competing risk model with propensity score adjustment was used to compare in-hospital mortality and time to discharge. Results. Of 847 SAB patients, 506 (60%) patients received an ID consultation and 341 (40%) patients did not. Echocardiography was done for 371 (73%) IDC and 191 (56%) NIDC patients (P < .0001) in hospital. Blood cultures were repeated within 2–4 days of bacteremia in 207 (41%) IDC and 107 (31%) NIDC patients (P = .0058). The infectious foci removal rate was not statistically different between the 2 groups. For empiric therapy, 474 (94%) IDC and 297 (87%) NIDC patients received appropriate antibiotics (P = .0013). For patients who finished the planned course of antibiotics, 285 of 422 (68%) IDC and 141 of 262 (54%) NIDC patients received the appropriate duration of antibiotic therapy (P = .0004). In hospital, 204 (24%) patients died: 104 of 506 (21%) IDC and 100 of 341 (29%) NIDC patients. Matched by propensity score, ID consultation had a subdistribution hazard ratio of 0.72 (95% confidence interval [CI], .52–.99; P = .0451) for in-hospital mortality and 1.28 (95% CI, 1.06–1.56; P = .0109) for being discharged alive. Conclusions. ID consultation is associated with better adherence to quality measures, reduced in-hospital mortality, and earlier discharge in patients with SAB.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is an important infection. Methicillin‐resistant S aureus (MRSA) screening is performed on hospitalized patients for infection control purposes. OBJECTIVE: To assess the usefulness of past MRSA screening for guiding empirical antibiotic therapy for SAB. METHODS: A retrospective cohort study examined consecutive patients with confirmed SAB and previous MRSA screening swab from six academic and community hospitals between 2007 and 2010. Diagnostic test properties were calculated for MRSA screening swab for predicting methicillin resistance of SAB. RESULTS: A total of 799 patients underwent MRSA screening swabs before SAB. Of the 799 patients, 95 (12%) had a positive and 704 (88%) had a negative previous MRSA screening swab. There were 150 (19%) patients with MRSA bacteremia. Overall, previous MRSA screening swabs had a positive likelihood ratio of 33 (95% CI 18 to 60) and a negative likelihood ratio of 0.45 (95% CI 0.37 to 0.54). Diagnostic accuracy differed depending on mode of acquisition (ie, community‐acquired, nosocomial or health care‐associated infection) (P<0.0001) and hospital (P=0.0002). At best, for health care‐associated infection, prior MRSA screening swab had a positive likelihood ratio of 16 (95% CI 9 to 28) and a negative likelihood ratio of 0.27 (95% CI 0.17 to 0.41). CONCLUSIONS: A negative prior MRSA screening swab cannot reliably rule out MRSA bacteremia and should not be used to guide empirical antibiotic therapy for SAB. A positive prior MRSA screening swab greatly increases likelihood of MRSA, necessitating MRSA coverage in empirical antibiotic therapy for SAB.

Tocilizumab is one of few treatments that have been shown to improve mortality in patients with coronavirus disease 2019 (COVID-19), but increased demand has led to relative global shortages. Recently, it has been suggested that lower doses, or fixed doses, of tocilizumab could be a potential solution to conserve the limited global supply while conferring equivalent therapeutic benefit to the dosing regimens studied in major trials. The relationship between tocilizumab dose, exposure, and response in COVID-19 has not been adequately characterized. There are a number of pharmacokinetic (PK) parameters that likely differ between patients with severe COVID-19 and patients in whom tocilizumab was studied during the US FDA approval process. Likewise, it is unclear whether a threshold exposure is necessary for tocilizumab efficacy. The safety and efficacy of fixed versus weight-based dosing of tocilizumab has been evaluated outside of COVID-19, but it is uncertain if these observations are generalizable to severe or critical COVID-19. In the current review, we consider the potential advantages and limitations of alternative tocilizumab dosing strategies. Leveraging PK models and simulation analyses, we demonstrate that a fixed single dose of tocilizumab 400 mg is unlikely to produce PK exposures equivalent to those achieved in the REMAP-CAP trial, although weight-stratified dosing appears to produce more uniform exposure distribution. Data from current and future trials could provide PK/pharmacodynamic insight to better inform dosing strategies at the bedside. Ultimately, rational dosing strategies that balance available limited supply with patient needs are required.

Background. β-lactam allergy skin testing (BLAST) is recommended by antimicrobial stewardship program (ASP) guidelines, yet few studies have systematically evaluated its impact when delivered at point of care. Methods. We conducted a pragmatic multicenter prospective evaluation of the use of point-of-care BLAST by ASPs. In staggered 3-month intervals, ASP teams at 3 hospitals received training by allergists to offer BLAST for eligible patients with infectious diseases receiving nonpreferred therapy due to severity of their reported allergy. The primary outcome was the proportion of patients receiving the preferred β-lactam therapy. Results. Of 827 patients with reported β-lactam allergy over 15 months, β-lactam therapy was preferred among 632 (76%). During baseline periods, 50% (124/246) received preferred β-lactam therapy based on history, compared with 60% (232/386) during the intervention periods (P = .02), which improved further to 81% (313/386) upon provision of BLAST (P < .001) without any increase in incidence of adverse drug reactions (4% vs 3%; P = .4). After adjusting for patient variables and the correlation between hospitals, the intervention period was associated with a 4.5-fold greater odds of receiving preferred β-lactam therapy (95% confidence interval, 2.4-8.2; P < .0001). Conclusions. The use of BLAST at the point of care across 3 hospital ASPs resulted in greater use of preferred β-lactam therapy without increasing the risk of adverse drug reactions. Longer-term studies are needed to better assess the safety and clinical impact of this ASP intervention.

Abstract Background Audit-and-feedback (A&F) is a core strategy for antimicrobial stewardship programs (ASPs). However, it is resource-intensive, and may not be practical in every setting. Recent guidelines support the non-ASP-led review of antimicrobials by prescribers (AM-REV) on a routine basis. A sustainable strategy for AM-REV in a critical care unit (CrCU) may improve antimicrobial utilization without additional ASP resources. Methods Using a quality improvement framework, a prompt for AM-REV strategy was created. The primary outcome was antimicrobial utilization defined by days of therapy/1000 patient-days (AM-DOT). A secondary process outcome was the proportion of relevant cases for which an antimicrobial prompt was provided to the prescriber (AM-PRT). Balancing measures included CrCU mortality rates, length of stay, and 48-hours re-admission rates. Utilization data of a control class of medications (proton-pump inhibitors) was also collected. AM-DOT was collected for 34 months pre- and 14 months post-intervention. AM-PRT was collected for 3 months pre- and 12 months post-intervention. Segmented regression analysis was used for the primary outcome, with a descriptive analysis of secondary outcomes. Results CrCU nurses were recruited to prompt AM-REV during CrCU rounds. A standardized script was developed to insert day of antimicrobial therapy into rounds; prescribers were primed to respond with affirmation, rationale, and clinical decisions. Plan-Do-Study-Act (PDSA) cycles further refined the intervention to include nursing reminders from CrCU pharmacists and increased engagement of nurses during formal A&F rounds. Prior to the intervention, monthly AM-DOT was 804 with a positive trend (7.3 DOT/1000PD, P < 0.05). Post-intervention resulted in an immediate reduction of 217 DOT/1000 PD (P < 0.05) with a non-significant negative AM-DOT trend, representing a 20% (95% CI –15%, -25%) reduction in AM-DOT per month. There was no significant change in utilization of the control class of medications. The ABX-PRT increased from 17% to 50% during the intervention period. Balancing measures were comparable pre and post-intervention. Conclusion Nurse prompting of AM-REV can lead to significant reductions in antimicrobial utilization, providing a non-ASP mechanism of sustaining antimicrobial awareness. Disclosures All authors: No reported disclosures.

Ivermectin, an antiparasitic agent, is not recommended for prophylaxis or treatment of coronavirus disease 2019 (COVID-19). Inappropriate use of ivermectin for treatment of COVID-19 may make it less available for patients with serious parasitic infections who could benefit from its use and worsen the current shortage of ivermectin in Canada. However, patients with COVID-19 who are candidates to receive immunomodulatory therapies (e.g. corticosteroids and interleukin-6 inhibitors) may be at risk of hyperinfection syndrome and disseminated disease from Strongyloides stercoralis. These complications can be severe and even fatal. It is important to recognize and screen patients who may be at risk of strongyloidiasis, as these patients may require treatment with ivermectin to avoid the potential for a hyperinfection syndrome and disseminated disease, which is frequently deadly. Clinicians should follow evidence-based recommendations to screen and treat for Strongyloides infection in patients with COVID-19 who are under consideration to receive specific COVID-19 therapies that alter immune response and may lead to hyperinfection syndrome or disseminated disease.

Background. There is no consensus on a universal dosing method for calculating high-dose chemotherapy in allogeneic Stem Cell Transplant (SCT) patients. The Metropolitan Life (Met-Life) Insurance Company’s weight—height tables have been used to determine body weight for chemotherapy dosing for SCT, however no formal study has been done to determine if the Met-Life weight— height tables can be used for chemotherapy dosing in SCT. We retrospectively studied the use of Met-Life weight—height tables for chemotherapy dosing in SCT. Our goal is to determine if patients with extremes of body size who had undergone an SCT and were dosed according to the Met-Life weight— height tables had an increase of Treatment Related Morbidity (TRM) or mortality or relapse. Patients and Methods. Patients were grouped into three different treatment regimens, cyclophosphamide/TBI, busulphan/cyclophosphamide, and AraC/cyclophosphamide/TBI. Patients in each treatment regimen were further divided into five equal groups based on weight. Treatment related morbidity and mortality was evaluated by comparing the lowest and highest quintiles to the middle quintiles within each treatment regimen. Result. Data from 262 patients was evaluated in this study. Overall, there was not an increase in TRM or mortality or in relapse in patients with extremes of body size. Conclusion. The Met-Life weight—height tables could be used to dose patients undergoing allogeneic SCTs. Additional prospective studies would need to be done comparing other chemotherapy dosing methods with the Met-Life weight—height tables to further validate this conclusion.