Impact of a pharmacy-driven MRSA nares screening protocol on vancomycin discontinuation in a tele-antimicrobial stewardship model.

A pharmacist-driven protocol for methicillin-resistant Staphylococcus aureus nares screening and empiric vancomycin discontinuation was instituted in a community healthcare system utilizing a tele-antimicrobial stewardship program to reduce inappropriate use of vancomycin. The protocol and associated intervention resulted in a significant decrease in both vancomycin utilization and the rate of acute kidney injury.

Impact of Rapid Identification and Stewardship Intervention on Coagulase-Negative Staphylococcus Bloodstream Infection.

We investigated the impact of rapid diagnostic testing with and without algorithm-based stewardship recommendations on antibiotic use for bloodstream infection with coagulase-negative staphylococci. A significant reduction in antibiotic days of therapy was achieved in the stewardship intervention group that was not seen with rapid diagnostic testing alone.

Evaluation of fidaxomicin use in community hospitals after a clinical guideline change at a large health system and opportunities for stewardship.

After updating our health system's Clostridioides difficile treatment protocols in 2018, we reviewed 104 unique hospital encounters involving fidaxomicin at 10 community hospitals. Half (50%) of regimens were adherent to our guidelines, with infectious diseases (ID) providers were frequently nonadherent. Antimicrobial stewardship programs are important for facilitating best practices, even among ID specialists.

Impact of Clinical Decision Support System Implementation at a Community Hospital With an Existing Tele-Antimicrobial Stewardship Program.

Background: Lack of on-site antimicrobial stewardship expertise is a barrier to establishing successful programs. Tele-antimicrobial stewardship programs (TASPs) utilizing a clinical decision support system (CDSS) can address these challenges. Methods: This interrupted time series study reports the impact of CDSS implementation (February 2020) within an existing TASP on antimicrobial usage in a community hospital. Segmented regression analysis was used to assess differences in antimicrobial usage from January 2018 through December 2021. Pre- and post-CDSS frequencies of intravenous vs oral antimicrobials, time to optimal therapy (TTOT), pharmacist efficiency (number of documented interventions per month), and percentage of hospitalized patients receiving antimicrobials were compared with descriptive statistics. Results: Implementation of a CDSS into an existing TASP was associated with an immediate 11% reduction in antimicrobial usage (level change, P < .0001). Antimicrobial usage was already trending down by 0.25% per month (pre-CDSS slope, P < .0001) and continued to trend down at a similar rate after implementation (post-CDSS slope, P = .0129). Frequency of use of select oral agents increased from 38% to 57%. Median TTOT was 1 day faster (2.9 days pre-CDSS vs 1.9 days post-CDSS). On average, pharmacists documented 2.2-fold more interventions per month (198 vs 90) and patients received 1.03 fewer days of antimicrobials per admission post-CDSS. Conclusions: Implementation of a CDSS within an established TASP at a community hospital resulted in decreased antimicrobial usage, higher rates of oral usage, faster TTOT, and improved pharmacist efficiency.

Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge: A Cohort Study and Randomized Comparative Effectiveness Trial.

Importance: The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant. Objective: To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab. Design, Setting, and Participants: This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria. Exposure: For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy. Main Outcomes and Measures: For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound. Results: A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence. Conclusions and Relevance: In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant. Trial Registration: ClinicalTrials.gov Identifier: NCT04790786.

The comparative effectiveness of COVID-19 monoclonal antibodies: A learning health system randomized clinical trial.

BACKGROUND: Monoclonal antibodies (mAb) that neutralize SARS-CoV-2 decrease hospitalization and death compared to placebo in patients with mild to moderate COVID-19; however, comparative effectiveness is unknown. We report the comparative effectiveness of bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab. METHODS: A learning health system platform trial in a U.S. health system enrolled patients meeting mAb Emergency Use Authorization criteria. An electronic health record-embedded application linked local mAb inventory to patient encounters and provided random mAb allocation. Primary outcome was hospital-free days to day 28. Primary analysis was a Bayesian model adjusting for treatment location, age, sex, and time. Inferiority was defined as 99% posterior probability of an odds ratio < 1. Equivalence was defined as 95% posterior probability the odds ratio is within a given bound. FINDINGS: Between March 10 and June 25, 2021, 1935 patients received treatment. Median hospital-free days were 28 (IQR 28, 28) for each mAb. Mortality was 0.8% (1/128), 0.8% (7/885), and 0.7% (6/922) for bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab, respectively. Relative to casirivimab-imdevimab (n = 922), median adjusted odds ratios were 0.58 (95% credible interval [CI] 0.30-1.16) and 0.94 (95% CI 0.72-1.24) for bamlanivimab (n = 128) and bamlanivimab-etesevimab (n = 885), respectively. These odds ratios yielded 91% and 94% probabilities of inferiority of bamlanivimab versus bamlanivimab-etesevimab and casirivimab-imdevimab, and an 86% probability of equivalence between bamlanivimab-etesevimab and casirivimab-imdevimab. INTERPRETATION: Among patients with mild to moderate COVID-19, bamlanivimab-etesevimab or casirivimab-imdevimab treatment resulted in 86% probability of equivalence. No treatment met prespecified criteria for statistical equivalence. Median hospital-free days to day 28 were 28 (IQR 28, 28) for each mAb. FUNDING AND REGISTRATION: This work received no external funding. The U.S. government provided the reported mAb. This trial is registered at ClinicalTrials.gov, NCT04790786.

Development of a Centralized Antimicrobial Stewardship Program Across a Diverse Health System and Early Antimicrobial Usage Trends.

Background: Expanding antimicrobial stewardship to community hospitals is vital and now required by regulatory agencies. UPMC instituted the Centralized Health system Antimicrobial Stewardship Efforts (CHASE) Program to expand antimicrobial stewardship to all UPMC hospitals regardless of local resources. For hospitals with few local stewardship resources, we used a model integrating local non-Infectious Diseases (ID) trained pharmacists with centralized ID experts. Methods: Thirteen hospitals were included. Eleven were classified as robust (4) or nonrobust (7) depending on local stewardship resources and fulfillment of Centers for Disease Control and Prevention core elements of hospital antimicrobial stewardship. In addition to general stewardship oversight at all UPMC hospitals, the centralized team interacted regularly with nonrobust hospitals for individual patient reviews and local projects. We compared inpatient antimicrobial usage rates at nonrobust versus robust hospitals and at 2 UPMC academic medical centers. Results: The CHASE Program expanded in scope between 2018 and 2020. During this period, antimicrobial usage at these 13 hospitals decreased by 16% with a monthly change of -4.7 days of therapy (DOT)/1000 patient days (PD) (95% confidence interval [CI], -5.5 to -3.9; P < .0001). Monthly decrease at nonrobust hospitals was -3.3 DOT/1000 PD per month (-4.5 to -2.0, P < .0001), similar to rates of decline at both robust hospitals (-3.3 DOT/1000 PD) and academic medical centers (-4.8 DOT/1000 PD) (P = .167). Conclusions: Coordinated antimicrobial stewardship can be implemented across a large and diverse health system. Our hybrid model incorporating a central team of experts with local community hospital pharmacists led to usage decreases over 3 years at a rate comparable to that seen in larger hospitals with more established stewardship programs.

Launching a comparative effectiveness adaptive platform trial of monoclonal antibodies for COVID-19 in 21 days.

Outpatient treatments that limit progression to severe coronavirus disease 2019 (COVID-19) are of vital importance to optimise patient outcomes and public health. Monoclonal antibodies (mAb) demonstrated ability to decrease hospitalizations in randomized, clinical trials. However, there are many barriers to mAb treatment such as patient access and clinician education. There are no data comparing efficacy or safety of available mAbs. We sought to rapidly launch an adaptive platform trial with the goals of enhancing access to treatment, regardless of geography and socioeconomic status, and evaluating comparative efficacy and safety of available mAbs. Within 21 days from idea genesis, we allocated mAb treatment to all patients within the context of this clinical trial. Within 2 months, we closed the gap of the likelihood of receiving mAb, conditional on background positivity rate, between Black and White patients (Black patients 0.238; White patients 0.241). We describe trial infrastructure, lessons learned, and future directions for a culture of learning while doing.

Impact of Bamlanivimab Monoclonal Antibody Treatment on Hospitalization and Mortality Among Nonhospitalized Adults With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Monoclonal antibody treatment may prevent complications of coronavirus disease 2019 (COVID-19). We sought to quantify the impact of bamlanivimab monoclonal antibody monotherapy on hospitalization and mortality among outpatients at high risk of COVID-19 complications. METHODS: In this observational study we compared outpatients who received bamlanivimab monoclonal antibody from December 9, 2020 to March 3, 2021 to nontreated patients with a positive polymerase chain reaction or antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the same period who were eligible for monoclonal antibody treatment. The primary outcome was 28-day hospitalization or all-cause mortality, and the secondary outcome was hospitalization or emergency department visit without hospitalization. The risk-adjusted odds of study outcomes comparing bamlanivimab treated and untreated patients was determined using 1:5 propensity matching and multivariable logistic regression. RESULTS: Among 232 patients receiving bamlanivimab matched with 1160 comparator patients, the mean age was 67 years, 56% were female, and 196 (14%) of patients experienced hospitalization or mortality. After adjustment for propensity to receive treatment, bamlanivimab treatment was associated with a significantly reduced risk-adjusted odds of hospitalization or mortality within 28 days (odds ratio [OR], 0.40; 95% confidence interval [95% CI], 0.24-0.69; P < .001). Bamlanivimab treatment was also associated with a significantly lower risk adjusted odds of hospitalization or emergency department visit without hospitalization (OR, 0.54; 95% CI, 0.35-0.82; P = .004). The results were most strongly associated with patients age 65 years and older. CONCLUSIONS: Bamlanivimab monoclonal antibody monotherapy was associated with reduced hospitalizations and mortality within 28 days among outpatients with mild to moderate COVID-19.Use of bamlanivimab monotherapy for outpatients with mild to moderate COVID-19 infection was associated with reductions in hospitalizations and mortality within 28 days. Benefit was strongest in those age 65 years or older.

Establishing a Distribution Network for COVID-19 Monoclonal Antibody Therapy Across a Large Health System During a Global Pandemic.

Emergency authorized coronavirus disease 2019 (COVID-19)-neutralizing monoclonal antibodies can aid outpatients with mild to moderate COVID-19 infection. Many report barriers to adequate distribution and uptake. We present our model for distribution in a large health system as well as early lessons learned.

The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization.

OBJECTIVES: The primary objective is to evaluate the comparative effectiveness of COVID-19 specific monoclonal antibodies (mABs) with US Food and Drug Administration (FDA) Emergency Use Authorization (EUA), alongside UPMC Health System efforts to increase patient access to these mABs. TRIAL DESIGN: Open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization PARTICIPANTS: We will evaluate patients who meet the eligibility criteria stipulated by the COVID-19 mAB EUAs who receive mABs within the UPMC Health System, including infusion centers and emergency departments. EUA eligibility criteria include patients with mild to moderate COVID-19, <10 days of symptoms, and who are at high risk for progressing to severe COVID-19 and/or hospitalization (elderly, obese, and/or with specific comorbidities). The EUA criteria exclude patients who require oxygen for the treatment of COVID-19 and patients already hospitalized for the treatment of COVID-19. We will use data collected for routine clinical care, including data entered into the electronic medical record and from follow-up calls. INTERVENTION AND COMPARATOR: The interventions are the COVID-19 specific mABs authorized by the EUAs. All aspects of mAB treatment, including eligibility criteria, dosing, and post-infusion monitoring, are as per the EUAs. As a comparative effectiveness trial, all patients receive mAB treatment, and the interventions are compared against each other. When U.S. government mAB policies change (e.g., FDA grants or revokes EUAs), UPMC Health System policies and the evaluated mAB interventions will accordingly change. From November 2020 to February 2021, FDA issued EUAs for three mAB treatments (bamlanivimab; bamlanivimab and etesevimab; and casirivimab and imdevimab), and at trial launch on March 10, 2021 we evaluated all three. Due to a sustained increase in SARS-CoV-2 variants in the United States resistant to bamlanivimab administered alone, on March 24, 2021 the U.S. Government halted distribution of bamlanivimab alone, and UPMC accordingly halted bamlanivimab monotherapy on March 31, 2021. On April 16, 2021, FDA revoked the EUA for bamlanivimab monotherapy. At the time of manuscript submission, we are therefore evaluating the two mAB treatments authorized by EUAs (bamlanivimab and etesevimab; and casirivimab and imdevimab). MAIN OUTCOMES: The primary outcome is total hospital free days (HFD) at 28 days after mAB administration, calculated as 28 minus the number of days during the index stay (if applicable - e.g., for patients admitted to hospital after mAB administration in the emergency department) minus the number of days readmitted during the 28 days after treatment. This composite endpoint captures the number of days from the day of mAB administration to the 28 days thereafter, during which the patient is alive and free of hospitalization. Death within 28 days is recorded as -1 HFD, as the worst outcome. RANDOMISATION: We will start with equal allocation. Due to uncertainty in sample size, we will use a Bayesian adaptive design and response adaptive randomization to ensure ability to provide statistical inference despite variable sample size. When mABs are ordered by UPMC physicians as a generic referral order, the order is filled by UPMC pharmacy via therapeutic interchange. OPTIMISE-C19 provides the therapeutic interchange via random allocation. Infusion center operations teams and pharmacists use a mAB assignment application embedded in the electronic medical record to determine the random allocation. BLINDING (MASKING): This trial is open-label. However, outcome assessors conducting follow-up calls at day 28 are blinded to mAB assignment, and investigators are blinded to by-mAB aggregate outcome data until a statistical platform trial conclusion is reached. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size will be determined by case volume throughout the course of the pandemic, supply of FDA authorized mABs, and by that needed to reach a platform trial conclusion of inferiority, superiority, or futility of a given mAB. The trial will continue as long as more than one mAB type is available under EUA, and their comparative effectiveness is uncertain. TRIAL STATUS: Protocol Version 1.0, February 24, 2021. Recruitment began March 10, 2021 and is ongoing at the time of manuscript submission. The estimated recruitment end date is February 22, 2022, though the final end date is dependent on how the pandemic evolves, mAB availability, and when final platform trial conclusions are reached. As noted above, due to U.S. Government decisions, UPMC Health System halted bamlanivimab monotherapy on March 31, 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04790786 . Registered March 10, 2021 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Current practices and safety of medication use during rapid sequence intubation.

PURPOSE: Characterize medication practices during and immediately after rapid sequence intubation (RSI) by provider/location and evaluate adverse drug events. MATERIALS AND METHODS: This was a multicenter, observational, cross-sectional study of adult and pediatric intensive care unit and emergency department patients over a 24-h period surrounding first intubation. RESULTS: A total of 404 patients from 34 geographically diverse institutions were included (mean age 58 ±â€¯22 years, males 59%, pediatric 8%). During RSI, 21%, 87%, and 77% received pre-induction, induction, and paralysis, respectively. Significant differences in medication use by provider type were seen. Etomidate was administered to 58% with sepsis, but was not associated with adrenal insufficiency. Ketamine was associated with hypotension post-RSI [RR = 1.78 (1.36-2.35)] and use was low with traumatic brain injury/stroke (1.5%). Succinylcholine was given to 67% of patients with baseline bradycardia and was significantly associated with bradycardia post-RSI [RR = 1.81 (1.11-2.94)]. An additional 13% given succinylcholine had contraindications. Sedation practices post-RSI were not consistent with current practice guidelines and most receiving a non-depolarizing paralytic did not receive adequate sedation post-RSI. CONCLUSIONS: Medication practices during RSI vary amongst provider and medications are often used inappropriately. There is opportunity for optimization of medication use during RSI.

Risk factors for carbapenem-nonsusceptible Pseudomonas aeruginosa: Case-control study.

The objective of this case case-control study was to identify risk factors for carbapenem-nonsusceptible Pseudomonas aeruginosa in adult acute care hospitalized patient at 2 large academic medical centers. Risk factors were evaluated using logistic regression within a generalized estimating equations framework to account for clustering of patients within study site. Of 1161 total isolates, 271 (23.3%) were carbapenem-nonsusceptible of which respiratory was the most common source (54.3%). In the multivariable model, intra-abdominal (P < 0.0001) and respiratory (P = 0.0014) sources were associated with a higher odds for carbapenem nonsusceptibility when compared to urine source. Prior positive culture (P < 0.0001), use of an antipseudomonal carbapenem in the prior 30 days (P < 0.0001) and culture collection in the intensive care unit (P < 0.0001) were also associated with increased odds for carbapenem-nonsusceptibility. Further studies to validate these findings are warranted.

Evaluation of a Hepatitis C Patient Management Program at a University Specialty Pharmacy.

BACKGROUND: The University of Rochester (UR) Specialty Pharmacy hepatitis C patient management program offers a unique advantage of being integrated within the same health system as the University of Rochester Medical Center (URMC) Gastroenterology and Hepatology division. OBJECTIVE: The primary purpose of this study was to assess treatment success through the incidence of achieving a sustained virological response (SVR) in patients served by the UR Specialty Pharmacy versus other nonintegrated pharmacies. METHODS: This was a single-center retrospective cohort study in adult patients of URMC Gastroenterology and Hepatology prescribed hepatitis C treatment between January 1, 2014, and July 15, 2015. The incidence of SVR, adherence, delay in therapy initiation, early treatment discontinuation, rate of attainment of viral load measurement post-therapy completion, and predictors associated with treatment outcome were assessed. RESULTS: A total of 414 patients were prescribed hepatitis C virus treatment during the study period; 137 did not initiate therapy. The rate of SVR was 93% among patients at the UR Specialty Pharmacy and 89% at nonintegrated pharmacies ( P = 0.357). Adherence to therapy was 100% and 97% at the UR Specialty Pharmacy and nonintegrated pharmacies, respectively ( P = 0.046). CONCLUSIONS: The UR Specialty Pharmacy was associated with a 93% SVR rate and significantly greater adherence compared with nonintegrated pharmacies. Larger studies are needed to determine if a significant difference in SVR exists between integrated and nonintegrated pharmacies. This study provides a framework for other institutions to justify developing integrated hepatitis C specialty pharmacy services and evaluate their success.

Methadone and Corrected QT Prolongation in Pain and Palliative Care Patients: A Case-Control Study.

BACKGROUND: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. OBJECTIVE: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool. DESIGN: We performed a case-control study of adult inpatients receiving ME for pain management. Settings/Subjects: Adult inpatients receiving ME with a QTc >470 msec (males) and >480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation. RESULTS: Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7-38.2; p < 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4-28.9; p < 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5-28.2; p < 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6-13.9; p < 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8-10.7; p < 0.01), malignancy (OR: 3.3; 95% CI: 1.2-9.3; p < 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9-4.8; p < 0.07), and ME doses >45 mg per day (OR: 1.9; 95% CI: 0.8-4.8; p < 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0-0.46; p < 0.01). CONCLUSIONS: Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses >45 mg per day.

New thoughts on the "forgotten" aspect of antimicrobial stewardship: adverse event reporting.

Antimicrobial stewardship is an activity that optimizes patient care through selection of the most appropriate antimicrobial therapy. Antimicrobial stewardship programs strive to enhance patient care and reduce preventable consequences of antimicrobial use. They are also vital in monitoring for the development of adverse events occurring as a result of antimicrobial therapy, although literature reviews of this activity are scarce. Although randomized controlled trials are considered the gold standard to study the efficacy of a medication, these trials are not designed to test safety end points and often are only able to identify the most commonly occurring and acute adverse events. In addition, prior to a drug going to market, it is difficult to detect rare adverse events because the associated costs are economically untenable given the limited pipeline of novel agents. These limitations in some ways may be resolved with the use of postmarketing surveillance and spontaneous reporting systems such as the United States Food and Drug Administration Adverse Event Reporting System. The focus of this commentary is to highlight the importance of adverse event reporting by antimicrobial stewardship programs to spontaneous reporting systems as a means to improve patient care.

How safe are recently FDA-approved antimicrobials? A review of the FDA adverse event reporting system database.

STUDY OBJECTIVE: To review quantitatively and qualitatively the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database to provide clinicians with a general understanding of the comparative occurrence of clinically meaningful adverse events associated with 15 antimicrobial new molecular entities approved by the FDA since 2006: anidulafungin, darunavir, maraviroc, raltegravir, doripenem, telavancin, ceftaroline, boceprevir, telaprevir, fidaxomicin, bedaquiline, dolutegravir, simeprevir, sofosbuvir, and dalbavancin. DESIGN: Retrospective analysis. DATA SOURCE: FDA AERS database. MEASUREMENTS AND MAIN RESULTS: Empirica Signal software was used to query the AERS database from November 1968 to December 2012. Using disproportionality analyses, we calculated a relative reporting ratio (RRR) estimate for reports of antimicrobial adverse events. The RRR estimate compares the occurrence of a specific adverse event with an index drug of interest to the occurrence of the same adverse event with similar agents or with all other FDA-approved prescription drugs. Common industry practice considers an RRR meaningful if the 5th percentile of the distribution is at least 2 (RRR05 of 2.0 or higher). Antimicrobials were compared with agents within their respective antimicrobial therapeutic class as well as with all agents in the AERS database. Seventeen adverse signals with an RRR05 of 2.0 or higher were identified from the database for six agents. Ten of the 17 signals were not included in the most up-to-date manufacturers' package inserts for four of the six agents: doripenem-associated hepatic dysfunction (RRR05 3.7) and hyperchloremia (RRR05 2.6); boceprevir-associated weight loss (RRR05 2.2); darunavir-associated premature labor (RRR05 3.1), sudden infant death syndrome (RRR05 2.9), ventricular hypertrophy (RRR05 2.7), acute coronary syndrome (RRR05 2.4), and congenital anomaly in offspring (RRR05 2.4); and raltegravir-associated congenital heart valve disorders (RRR05 2.5) and SIDS (RRR05 2.3). CONCLUSION: Clinically meaningful adverse event signals appeared to be associated with antimicrobial new molecular entities approved since 2006 including many not yet identified in package inserts. Although a disproportionality analysis suggests a quantitative signal for these associations, causality cannot be inferred from the data. Due to several key limitations in this type of analysis, investigative studies are needed to further explore these adverse event signals and the potential mechanisms by which they occur.

Information literacy skills retention over the first professional year of pharmacy school.

The authors aimed to determine if first-professional-year pharmacy students retain library literature search skills throughout the school year. Students (n = 61 consented) were given an identical seven-item quiz on basic library search skills prior to library instruction in the fall semester and at the end of the spring semester. There was no significant difference between median scores on the two quizzes, nor were any significant differences noted in subgroup analyses. Search competency may be retained to a higher degree if library instruction is moved later in the pharmacy curriculum when literature search skills are used more often.

A review of tuberculosis: Focus on bedaquiline.

PURPOSE: The history and prevalence of tuberculosis and the role of bedaquiline in multidrug-resistant (MDR) tuberculosis are reviewed. SUMMARY: Tuberculosis continues to cause significant morbidity and mortality worldwide. Increasing rates of drug-resistant tuberculosis are a significant concern and pose serious implications for current and future treatment of the disease. In December 2012, the Food and Drug Administration approved bedaquiline as part of the treatment regimen for pulmonary MDR tuberculosis. Bedaquiline's unique mechanism of action presents an alternative approach to current antimycobacterial killing. By directly inhibiting adenosine triphosphate (ATP) synthase, bedaquiline is effective against both replicating and dormant mycobacteria. Pulmonary cavitary lesions can contain heterogeneous populations. This potential mix of semireplicating and hypometabolic mycobacteria is more difficult to eliminate with conventional antitubercular drugs, thus increasing the risk of resistance. No in vitro cross-resistance between bedaquiline and currently available antitubercular agents has been observed thus far. Because bedaquiline targets a completely different enzyme, cross-resistance with other conventional agents remains unlikely. Enhanced sterilizing capacity via synergistic depletion of ATP further exhibits the promising potential of bedaquiline with pyrazinamide. A course of bedaquiline requires 24 weeks of therapy in combination with other antitubercular drugs. CONCLUSION: The approval of bedaquiline represents a major milestone in MDR tuberculosis therapy. Bedaquiline should be considered in patients who have not responded to a regimen containing four second-line drugs and pyrazinamide and patients with documented evidence of MDR tuberculosis resistant to fluoroquinolones. The exact role of bedaquiline cannot be determined until further efficacy and safety data are obtained through ongoing Phase III trials.

Therapeutic options for the treatment of postherpetic neuralgia: a systematic review.

Postherpetic neuralgia (PHN) is a chronic and painful condition that may result in significant disturbances to normal activities and decreases in the quality of life for those affected. Despite the availability of several first- and second-line treatment options, many patients may experience refractory pain. The objectives of this review were to summarize evidence for Food and Drug Administration (FDA)-approved and off-label therapies for the treatment of PHN and to present gaps in the current literature for future research focus. Several agents, including pregabalin, gabapentin, and opioids, have been shown to significantly improve pain when compared with placebo. However, evidence regarding the comparative effectiveness of these treatment alternatives is lacking. In order to choose the optimal treatment, providers should consider issues related to efficacy, safety, and tolerability in conjunction with patient goals, preferences, and adherence issues. Evidence from randomized or observational studies that directly compare agents with each other should help to inform treatment choices.