Impact of Pharmacist Intervention in Response to Automated Molecular Diagnostic Tests of Blood Culture Results.

BACKGROUND: Rapid molecular diagnostic tests can aid in deescalating antimicrobial therapy prior to final culture and susceptibility reports. OBJECTIVE: The purpose of this study was to determine whether a new workflow that incorporated pharmacist review of these results reduced time to change in antimicrobial therapy. METHODS: This retrospective study analyzed pre- and post-implementation of pharmacist review of positive blood cultures analyzed by rapid diagnostics with clinical recommendations paged to providers. Patients 18 years of age or older initiated on empiric antibiotics were included. The primary outcome was the time to change to targeted antimicrobials. Other outcomes evaluated were rates of Clostridioides difficile (C difficile) infection, inpatient mortality, and intensive care unit and hospital lengths of stay. RESULTS: A total of 199 patients were included, with 98 and 101 patients in the pre- and post-implementation groups, respectively. The median time to change to targeted antimicrobials was significantly reduced with pharmacist intervention from 18.35 to 8.43 hours (P = 0.042). The groups had similar rates of C difficile infection (1% vs 0%, P = 0.492) and mortality (7.1% vs 5%, P = 0.564). The post-group also had significant reductions in antibiotic days of therapy (10.5 vs 9 days, P = 0.014) and intensive care unit length of stay (3.04 vs 1.44 days, P = 0.046). Median hospital length of stay was similar between the pre- and post-groups (8.5 vs 8 days, P = 0.106), respectively. CONCLUSION: Incorporating pharmacist review of rapid molecular results of blood cultures decreased time to change to targeted antimicrobials and reduced inpatient antibiotic days of therapy.

Impact of antimicrobial selection for prophylaxis of left ventricular assist device surgical infections.

BACKGROUND: Surgical site infections (SSIs) after left ventricular assist device (LVAD) implantation are associated with high mortality, while surgical prophylaxis is variable. METHODS: This retrospective study included adult patients who underwent LVAD implantation at a single center. We compared outcomes in patients who received narrow antimicrobial prophylaxis (cefazolin, vancomycin, or both) to those who received broad antimicrobial prophylaxis (any antimicrobial combination targeting gram-positive and gram-negative organisms not included in the narrow group) at 30-day and 1-year postimplantation. Cox-proportional hazards models and log-rank tests were used for survival analysis. RESULTS: Among the 39 and 65 patients comprising narrow and broad groups respectively, there was no difference in rate of SSI at 30 days (6.2% vs. 12.8%, p = .290) and 1 year (16.9% vs. 25.6%, p = .435). Comparing narrow to broad prophylaxis, the risk of mortality (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.15-1.35, logrank p = .14), and composite of mortality and infection was reduced (HR = 0.92, 95% CI = 0.45-1.88, logrank p = .83), but did not reach statistical significance. Most culture positive infections were due to gram-positive bacteria (70%) and the most common organisms were the Staphylococcus spp (47%). There were no significant differences in the rate of SSI at 1-year (p = 1.00) and mortality (p = .33) by device type. CONCLUSIONS: The rates of infection and all-cause mortality were not different between patients who received narrow or broad prophylaxis. This highlights an opportunity for institutions to narrow their surgical infection prophylaxis protocols to primarily cover gram-positive organisms.

The dynamic treatment of SARS-CoV-2 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or novel coronavirus disease 2019 (COVID-19) emerged from China in December 2019 and progressed to become a global pandemic. Our understanding of its pathophysiology and potential management was initially extrapolated from previous epidemics of coronaviruses like SARS and MERS. SARS-CoV-2 is asymptomatic or minimally symptomatic in more than 80% of patients and requires no additional management; however, the remaining patients progress to pneumonia and hypoxemia with ranging severity, including a smaller group that requires intensive care unit admission. To date, there are no approved treatments for SARS-CoV-2, and current management is focused on supplemental oxygen and supportive care. The antiviral medication remdesivir recently received emergency use authorization by the US Food and Drug Administration for patients with severe disease. Multiple clinical trials evaluating different treatment modalities such as antivirals, immunomodulators, convalescent plasma, and monoclonal antibodies, among others, are still ongoing. We believe that patients present with clinical phenotypes that correlate with the spectrum of disease. Each phenotype may benefit from one or multiple interventions. We discuss treatments under evaluation in clinical trials and their potential application based on clinical phenotype presentation.

Outcomes analysis in patients with extended-spectrum beta-lactamase bacteremia empirically treated with piperacillin/tazobactam versus carbapenems.

Infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria are associated with worse outcomes and have limited treatment options. Carbapenems remain the drug of choice for these infections due to evidence of a mortality benefit and the mixed clinical efficacy associated with piperacillin/tazobactam (PTZ). Though definitive treatment for ESBL infections is well defined, evidence for appropriate empiric therapy remains inconclusive, and the role of rapid molecular assays that identify ESBL has not been evaluated. This multicenter retrospective study at nine Baylor Scott & White Health sites included patients who had positive blood cultures with ESBL-producing bacteria identified by rapid molecular assay and were empirically prescribed PTZ or carbapenems. A total of 117 patients were included in the study; 66 received empiric PTZ and 51 received carbapenems. Results showed no difference in hospital mortality (3% vs 7.8%, P = 0.4), hospital length of stay (6.1% vs 5.9%, P = 0.88), intensive care unit length of stay (4.7% vs 3.3%, P = 0.39), or recurrent ESBL bacteremia (7.6% vs 7.8%, P = 0.99) between the PTZ and carbapenem empiric treatment groups, respectively. In the era of rapid molecular assays, these results suggest that empiric PTZ use and avoidance of empiric carbapenem therapy in the first 24 hours of infection can be considered until a microbiological diagnosis is confirmed.

Evaluating predictors of invasive candidiasis in patients with and without candidemia on micafungin.

Numerous risk factors have been linked to invasive candidiasis; however, they are nonspecific and often trigger empiric antifungal therapy in a large number of patients. Identification of more precise predictors could promote judicious use of empiric echinocandins. In this retrospective review, 127 patients with blood cultures positive for Candida spp. were compared to a randomly selected cohort of 134 patients on empiric micafungin for ≥3 days and with blood cultures negative for Candida spp. Factors associated with candidemia included total parenteral nutrition (TPN; 26.0% vs 15.7%, P = 0.040), multifocal Candida colonization (23.6% vs 3.0%, P < 0.001), and positive 1,3-ß-d-glucan assay (95.0% vs 35.0%, P < 0.001). Patients without candidemia on empiric micafungin were more likely to receive antibiotic therapy in the previous 10 days (55.9% vs 79.9%, P < 0.001) and to be taking immunosuppressive medications (11.0% vs 30.6%, P < 0.001). Receipt of TPN (odds ratio [OR] = 2.07, 95% confidence interval [CI], 1.02-4.21), severe sepsis (OR = 2.20, 95% CI, 1.00-4.83), and multifocal Candida colonization (OR = 13.87, 95% CI, 4.43-43.37) were independently associated with candidemia in the multivariable logistic regression model. Therefore, the absence of these risk factors, especially in conjunction with a negative 1,3-ß-d-glucan assay, may be used to recommend de-escalation of empiric micafungin therapy.

Clinical uptake of antimicrobial stewardship recommendations following Nanosphere Verigene Blood Culture Gram-negative reporting.

We performed a retrospective chart review of patients to determine if the Verigene Gram-negative blood culture (BC-GN) results would lead to earlier deescalation of empiric therapy for inpatients with GN bacteremia with Citrobacter spp., Enterobacter spp., Klebsiella spp., and Escherichia coli to appropriate targeted coverage. A total of 899 records were reviewed from April 2014 to February 2016 from three institutions within the Baylor Scott & White Health network. The cases were reviewed for initial antibiotic coverage, timing of Verigene results, change in antibiotic coverage, and how these changes related to the timing of Verigene results. The lab reported the BC-GN results and final conventional susceptibility results within 2.5 ± 1.3 and 73.6 ± 40.0 hours from the Gram stain, respectively. Overall, 29.1% of patients were transitioned from empiric to targeted therapy at 12.2 ± 13.5 hours in response to BC-GN results, which was significantly earlier (P < 0.001) than results by conventional methods. After accounting for patients already on targeted therapy, polymicrobial infections, and patients deceased or lost to follow-up, we identified antibiotic stewardship opportunities in ∼28% of GN infections. Further subanalysis demonstrated site-specific differences in the uptake of stewardship recommendations, whereby 32.4%, 50.5%, and 15.0% of cases at different hospitals demonstrated the expected change in antibiotics. These results suggest that Verigene had the expected impact in a third of the cases and the results reporting algorithm minimized the real-time involvement of the pharmacist while maintaining optimal patient management. However, this impact varied substantially by clinical site and was tempered by variable initial antibiotic coverage and clinician response.

Palliative Radiotherapy in the Presence of Well-Controlled Metastatic Disease after Initial Chemotherapy May Prolong Survival in Patients with Metastatic Esophageal and Gastric Cancer.

PURPOSE: We report the outcomes of patients treated with palliative radiotherapy (pRT) to the primary tumour in the context of well-controlled metastatic disease after initial chemotherapy. MATERIALS AND METHODS: Clinical records of 132 patients with metastatic esophago-gastric (OG) cancer treated with palliative chemotherapy (pCT) between January 2009 and June 2013 were reviewed. Ninetyseven patients had responding or stable disease after 3 months of chemotherapy, of whom 53 patients received pRT to the primary tumour after initial chemotherapy in the presence of well-controlled metastatic disease (group A, pCT-RT). The remaining 44 patients were treated with pCT alone (group B, pCT). Treatment-related outcomes were assessed in above groups including time to local progression (TTLP), progression-free and overall survival. RESULTS: The median overall survival for patients treated with pRT after initial chemotherapy (group A) was 23.3 months (95% confidence interval [CI], 17.70 to 28.89 months) and significantly higher than the 14 months (95% CI, 10.91 to 17.08 months) in patients treated with pCT alone (group B) (p < 0.001). The use of pCT-RT was an independent predictor of OS in multivariate analysis. Local recurrence was observed in 12/53 of patients (23%) in group A compared to 16/44 (36%) in group B. The median TTLP was significantly higher in patients after pCT-RT at 17.3 months (5.23 months to 44.50 months) compared to 8.3 months (range, 4.10 to 25.23 months) in patients treated with pCT alone (p=0.006). CONCLUSION: The possibility of pRT influencing systemic disease in advanced OG cancer has not been reported, and results from the present study present strong arguments for investigation of this therapeutic strategy in a randomized trial.