Outpatient parenteral antimicrobial therapy (OPAT) is a widely used, safe, and cost-effective treatment. Most public and private insurance providers require prior authorization (PA) for OPAT, yet the ...impact of the inpatient PA process is not known. Our aim was to characterize discharge barriers and PA delays associated with high-priced OPAT antibiotics.
This was an institutional review board-approved study of adult patients discharged with daptomycin, ceftaroline, ertapenem, and novel beta-lactam-beta-lactamase inhibitor combinations from January 2017 to December 2017. Patients with an OPAT PA delay were compared with patients without a delay. The primary endpoint was total direct hospital costs from the start of treatment.
Two-hundred patients were included: 141 (71%) no OPAT delay vs 59 (30%) OPAT delay. More patients with a PA delay were discharged to a subacute care facility compared with an outpatient setting: 37 (63%) vs 52 (37%), P = .001. Discharge delays and median total direct hospital costs were higher for patients with OPAT delays: 31 (53%) vs 21 (15%), P < .001 and $19 576 (interquartile range IQR, 10 056-37 038) vs $7770 (IQR, 3031-13 974), P < .001. In multiple variable regression, discharge to a subacute care facility was associated with an increased odds of discharge delay, age >64 years was associated with a decreased odds of discharge delay.
OPAT with high-priced antibiotics requires significant care coordination. PA delays are common and contribute to discharge delays. OPAT transitions of care represent an opportunity to improve patient care and address access barriers.
Coronavirus disease 2019 (COVID-19) can progress to cytokine storm that is associated with organ dysfunction and death. The purpose of the present study is to determine clinical characteristics ...associated with 28 day in-hospital survival in patients with coronavirus disease 2019 (COVID-19) that received tocilizumab. This was a retrospective observational cohort study conducted at a five hospital health system in Michigan, United States. Adult patients with confirmed COVID-19 that were admitted to the hospital and received tocilizumab for cytokine storm from March 1, 2020 through April 3, 2020 were included. Patients were grouped into survivors and non-survivors based on 28 day in-hospital mortality. Study day 0 was defined as the day tocilizumab was administered. Factors independently associated with in-hospital survival at 28 days after tocilizumab administration were assessed. Epidemiologic, demographic, laboratory, prognostic scores, treatment, and outcome data were collected and analyzed. Clinical response was collected and defined as a decline of two levels on a six-point ordinal scale of clinical status or discharged alive from the hospital. Of the 81 patients included, the median age was 64 (58–71) years and 56 (69.1%) were male. The 28 day in-hospital mortality was 43.2%. There were 46 (56.8%) patients in the survivors and 35 (43.2%) in the non-survivors group. On study day 0 no differences were noted in demographics, clinical characteristics, severity of illness scores, or treatments received between survivors and non-survivors. C-reactive protein was significantly higher in the non-survivors compared to survivors. Compared to non-survivors, recipients of tocilizumab within 12 days of symptom onset was independently associated with survival (adjusted OR: 0.296, 95% CI: 0.098–0.889). SOFA score ≥8 on day 0 was independently associated with mortality (adjusted OR: 2.842, 95% CI: 1.042–7.753). Clinical response occurred more commonly in survivors than non-survivors (80.4% vs. 5.7%; p < 0.001). Improvements in the six-point ordinal scale and SOFA score were observed in survivors after tocilizumab. Early receipt of tocilizumab in patients with severe COVID-19 was an independent predictor for in-hospital survival at 28 days.
•Patients receiving tocilizumab within 12 days of COVID-19 symptom onset had an increase in 28 day in-hospital survival.•A higher severity of illness prior to tocilizumab administration was associated with increased mortality.•Secondary infections occurred in 22.2% receiving tocilizumab, but infection was not associated with increased mortality.
Background: The prevalence of exposure to pharmacogenomic medications is well established but little is known about how long patients are exposed to these medications. Aim: Our objective was to ...describe the amount of exposure to actionable pharmacogenomic medications using patient-level measures among a large nationally representative population using an insurance claims database. Methods: Our retrospective cohort study included adults (18+ years) from the IQVIA PharMetrics® Plus for Academics claims database with incident fills of 72 Clinical Pharmacogenetics Implementation Consortium level A, A/B, or B medications from January 2012 through September 2018. Patient-level outcomes included the proportion of days covered (PDC), number of fills, and average days supplied per fill over a 12-month period. Results: Over 1 million fills of pharmacogenetic medications were identified for 605,355 unique patients. The mean PDC for all medications was 0.21 (SD 0.3), suggesting patients were exposed 21% (77 days) of the year. Medications with the highest PDC (0.55–0.89) included ivacaftor, tamoxifen, clopidogrel, HIV medications, transplant medications, and statins; with the exception of statins, these medications were initiated by fewer patients. Pharmacogenomic medications were filled an average of 2.8 times (SD 3.0, range 1–81) during the year following the medication’s initiation, and the average days supplied for each fill was 22.3 days (SD 22.4, range 1–180 days). Conclusion: Patient characteristics associated with more medication exposure were male sex, older age, and comorbid chronic conditions. Prescription fill data provide patient-level exposure metrics that can further our understanding of pharmacogenomic medication utilization and help inform opportunities for pharmacogenomic testing.
Introduction: Carbapenem-resistant organisms (CROs) present a serious public health problem. Limited treatment options has led to increased use of colistin and polymyxin. Since 2014, the US Food and ...Drug Administration approved 4 new beta-lactam beta-lactamase inhibitor (BLBLI) combination antibiotics with activity against CROs. These new antibiotics have been shown to be more effective and less toxic than colistin and polymyxin but are considerably more expensive. This study evaluated the cost-effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Methods: A decision-tree microsimulation model was used to evaluate the cost effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Treatment groups differed in risk of mortality and risk of an acute kidney injury (AKI). The relative risk of mortality was determined by creating a meta-analysis comparing new BLBLIs to colistin. Cost inputs included medication costs and the cost to treat an AKI. The primary outcomes include quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). Model inputs included: clinical outcomes and adverse events (30-day mortality and AKI); cost of treatment and adverse drug events; and health utilities. A 3% discount was applied for outcomes. A lifetime horizon was used from the perspective of the US healthcare system with a willingness-to-pay (WTP) threshold of $100 000. A sensitivity analysis was done to incorporate uncertainty. Results: The meta-analysis found the treatment with a new BLBLI was associated with a 50% decrease in the relative risk of 30-day mortality compared to colistin (RR 0.47, 95% CI 0.25-0.88). Treatment with a new BLBLI cost $16 200 and produced 11.5 QALYs, on average. The average colistin based regimen cost $3500 and produced 8.3 QALYs. The new BLBLIs were determined to be cost-effective with an ICER of $3900 per QALY gained. Treatment with a BLBLI remained cost-effective under all uncertainty scenarios tested. Conclusion: New BLBLIs are cost-effective compared to colistin for the treatment of CROs and are associated with improved mortality and fewer AKI events. The use of colistin should be reserved for cases where new BLBLIs are not available or there is documented resistance to these new antibiotics.
Abstract
Purpose
The purpose of this study was to improve antimicrobial management and outcomes of critically ill patients with community-acquired pneumonia (CAP) through implementation of a ...pharmacist-driven bundle for ordering evidence-based diagnostic tests in a medical intensive care unit (MICU).
Methods
An inpatient collaborative practice agreement (CPA) was established for MICU pharmacists to order criteria-driven diagnostic testing for CAP from November 2017–March 2018. Adults admitted to the MICU and started on empiric antibiotics for CAP were included. The intervention arm was compared with a standard of care (SOC) group from November 2016–March 2017.
Results
Ninety-one patients were included in each group. There was no difference in the median antibiotic duration between SOC and CPA, at 7 days (interquartile range IQR, 6–10) versus 7 days (IQR, 6–8), respectively. The overall use of evidence-based diagnostic tests increased in the CPA group. Patients in the CPA group had more frequent pathogen identification (SOC and CPA, respectively: 31 34% versus 46 51%, p = 0.035) and antimicrobial deescalation (24 26% versus 53 58%, p < 0.001). There was no significant difference in length of intensive care unit stay, at 4 days for SOC (IQR, 2–10) versus 6 days for CPA (IQR, 3–10), and no significant difference in inpatient all-cause mortality (13 14% versus 7 8%), retreatment 14 15% versus 11 12%), or 30-day readmission 16 (18% versus 13 14%) for SOC and CPA, respectively. The CPA was the only variable that was independently associated with antimicrobial deescalation (odds ratio, 4.030; 95% confidence interval, 2.101–7.731) in a multiple logistic regression.
Conclusion
Implementation of a pharmacy-driven pneumonia diagnostic stewardship bundle improved the use of evidence-based diagnostics and increased the frequency of pathogen identification. This intervention was associated with increased antimicrobial deescalation without a negative impact on patient safety outcomes.
Objectives
Several recent studies have suggested that the physiopathology of bipolar disorder (BD) is related to immune system alterations and inflammation. Lithium (Li) is a mood stabilizer that is ...considered the first‐line treatment for this mood disorder. The goal of the present study was to investigate the effects of Li administration on behavior and cytokine levels interleukin (IL)‐1β, IL‐4, IL‐6, IL‐10, and tumor necrosis factor‐alpha (TNF‐α) in the periphery and brains of rats subjected to an animal model of mania induced by amphetamine (d‐AMPH).
Methods
Male Wistar rats were treated with d‐AMPH or saline (Sal) for 14 days; on Day 8 of treatment, the rats were administered Li or Sal for the final seven days. Cytokine (IL‐1β, IL‐4, IL‐6, IL‐10, and TNF‐α) levels were evaluated in the cerebrospinal fluid (CSF), serum, frontal cortex, striatum, and hippocampus.
Results
The present study showed that d‐AMPH induced hyperactivity in rats (p < 0.001), and Li treatment reversed this behavioral alteration (p < 0.001). In addition, d‐AMPH increased the levels of IL‐4, IL‐6, IL‐10, and TNF‐α in the frontal cortex (p < 0.001), striatum (p < 0.001), and serum (p < 0.001), and treatment with Li reversed these cytokine alterations (p < 0.001).
Conclusions
Li modulates peripheral and cerebral cytokine production in an animal model of mania induced by d‐AMPH, suggesting that its action on the inflammatory system may contribute to its therapeutic efficacy.
Abstract
Background
Outpatient parenteral antimicrobial therapy (OPAT) allows patients to receive prolonged antimicrobial therapy while reducing the length of hospitalization and healthcare costs. In ...the United States, most public and private insurance companies require prior authorization (PA) for OPAT. The impact of OPAT PA delays is not known. This study aimed to characterize discharge barriers and authorization delays associated with high-cost OPAT antibiotics.
Methods
IRB-approved study of adult patients discharged with high-cost OPAT antibiotics from January to December 2017. Antibiotics were included based on the frequency of OPAT use and average sales price (ASP) greater than $100 per day, including: daptomycin, ceftaroline, ertapenem, and the novel β-lactam β-lactam inhibitor combinations. Patients with an OPAT authorization delay >24 hours were compared with patients without an OPAT authorization delay. Primary endpoint: total direct hospital costs, starting from the start of treatment with the OPAT antibiotic, from the institutional perspective using Healthcare Cost and Utilization Project and Center for Medicare and Medicaid Services 2019 ASP Drug Pricing data. Secondary outcomes: discharge delay and 30-day readmission or mortality.
Results
Two-hundred patients included: 151 (76%) no OPAT delay vs. 49 (25%) OPAT delay. The use of antibiotics was similar between groups, except ertapenem was more common in the no OPAT delay group: 60 (43%) vs. 15 (25%), P = 0.022. Patients with no OPAT delay were more commonly discharged with home infusion and less commonly to a facility: 75 (53%) vs. 19 (32%), P = 0.007, and 52 (37%) vs. 37 (63%), P = 0.001, respectively. Discharge delays were more common in patients with OPAT delays: 21 (15%) vs. 31 (53%), P < 0.001. The median total direct hospital costs were higher in patients with OPAT delays: $7,770 (3,031–13,974) vs. $19,576 vs. (10,056–37,038), P < 0.001. Table 1 compares the total direct hospital costs of patients with and without an authorization delay.
Conclusion
OPAT with high-cost antibiotics requires significant care coordination. Authorization delays for these antibiotics are common and may contribute to a delay in discharge. OPAT transitions of care represent an important opportunity for Infectious Diseases providers to improve care and address access barriers.
Disclosures
All authors: No reported disclosures.
Abstract
Background
The overuse of broad-spectrum antibiotics drives antimicrobial resistance (AMR), and the prevalence of highly-resistant Gram-negative infections is increasing across the world, ...especially in low- and middle-income countries (LMIC). Carbapenem resistance is of particular concern since these are often the last line agents. Antimicrobial restriction is an antimicrobial stewardship intervention (AMS) that aims to reduce the use of broad-spectrum antibiotics to preserve antimicrobial susceptibility.
Methods
This is retrospective, observational study of antibiotic consumption and prevalence of antibiotic resistance of bacterial isolates from inpatients at Jigme Dorji Wangchuck National Referral Hospital, a 350-bed multi-specialty hospital in Thimphu, Bhutan. Antibiotic consumption and antimicrobial susceptibility were monitored from January 2015 to December 2017 by the pharmacy department and the microbiology lab, respectively. Antibiotic consumption was measured using defined daily doses (DDD) and expressed as DDDs per 1,000 persons per day. The antibiotic susceptibility was determined using the Clinical Laboratory Standards Institute (CLSI) guideline. A hospital AMS program with multidisciplinary team and good hospital managerial/ leadership support were initiated in 2016 and interventions included antimicrobial restrictions, educations, guidelines for use, post prescription review, de-escalation, audit and feedback.
Results
From 2015 to 2016, the DDDs of carbapenems and piperacillin–tazobactam (PTZ) increased while ceftriaxone decreased (Figure 1). After the AMS program was implemented in 2016, the annual DDDs of carbapenems decreased while PTZ and ceftriaxone increased. Antimicrobial susceptibility of Klebsiella pneumoniae and Escheriachia coli blood isolates to carbapenems and ceftriaxone increased from 2016 to 2017: 50/61 (82%) vs. 45/49 (92%) and 24/91 (26%) vs. 31/92 (34%), respectively.
Conclusion
Implementing an AMS program that restricted the use of carbapenems resulted in a decrease in carbapenem use and increased antimicrobial susceptibility for carbapenems and ceftriaxone. AMS interventions can be successful to decrease carbapenem-resistance in LMIC.
mutations are associated with resistance to HER2-targeted therapies. We previously showed that
transgenic mammary tumors are resistant to the HER2 antibodies trastuzumab and pertuzumab but respond to ...PI3K inhibitor buparlisib (TPB). In this study, we identified mechanisms of resistance to combined inhibition of HER2 and PI3K. TPB-resistant tumors were generated by treating
tumor-bearing mice long term with the drug combination. RNA sequencing of TPB-resistant tumors revealed that extracellular matrix and cell adhesion genes, including collagen II (
), were markedly upregulated, accompanied by activation of integrin β1/Src. Cells derived from drug-resistant tumors were sensitive to TBP when grown
, but exhibited resistance when plated on collagen or when reintroduced into mice. Drug resistance was partially reversed by the collagen synthesis inhibitor ethyl-3,4-dihydroxybenzoate. Inhibition of integrin β1/Src blocked collagen-induced resistance to TPB and inhibited growth of drug-resistant tumors. High collagen II expression was associated with significantly lower clinical response to neoadjuvant anti-HER2 therapy in HER2
breast cancer patients. Overall, these data suggest that upregulation of collagen/integrin/Src signaling contributes to resistance to combinatorial HER2 and PI3K inhibition.
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Contamination of blubber tissues by organochlorine pesticides (OC) and PCBs was assessed in female and male pups and juveniles, as well as in adult females and subdominant adult males of the Southern ...elephant seal, Mirounga leonina, from Elephant Island in the Antarctic Peninsula. All residues of persistent organochlorine contaminants analyzed were found in blubber samples, except for β-HCH, endosulfan II, endrin, heptachlor, and aldrin. The relative concentrations of the analytes detected were ΣDDT > ΣPCB > Σchlordane > mirex > dieldrin > HCB> Σendosulfan > methoxychlor > ΣHCHs > other OC pesticides. OC and PCBs concentrations were 1 or 2 orders of magnitude lower than those found in pinnipeds from northern hemisphere. The ratio ΣDDT/ΣPCB was higher in southern elephant seals. The relative importance of some OC residues indicates that pesticides used either currently or in the recent past in countries in the southern hemisphere are the sources of contamination in the Antarctic region. Data showed that concentrations of contaminants generally increased from pups < juveniles < adults and suggested that pups accumulated contaminants through transfer from the mother seals via transplacental and lactational routes.
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