Measuring Pharmacy Student Engagement in a Pharmacotherapy Course with Required Attendance.

OBJECTIVE: The purpose of this study was to evaluate student engagement in a pharmacotherapy course with required attendance, identify intervals where students were most and least likely to be engaged, and assess student perceptions of the importance of engagement. METHODS: In 2022, pharmacotherapy course faculty implemented a graded attendance policy. A survey instrument was developed to gauge student engagement throughout in-class sessions and included three questions regarding engagement to determine whether students were on-task, off-task-related, or off-task-unrelated. Each week throughout the semester, students were randomly surveyed for a beginning, middle and end time point. A second survey was utilized to collect perception data from students regarding attendance and engagement. The perception survey was released during the midpoint of the semester and at the end of the semester. RESULTS: The overall attendance rate was 91.1% (SD 4.64%) for the semester. Generally, students reported being on-task when surveyed. The average weekly tasks rates were 77.7% on-task, 15.8% off-task-related, and 6.5% off-task-unrelated. For the perception survey, both time points had a high response rate (82.8%, mid-point survey, 77.1%, end of semester). Most students had positive perceptions regarding mandatory attendance, engagement, and pre-class preparation. CONCLUSION: The current study endorses high levels of student engagement in a pharmacotherapy course with required attendance. Additionally, student perceptions were generally positive regarding required attendance. Future investigations need to be completed on the non-performance benefits of attending classes.

A Pharmacist's Role in a Case of Allergy Labeling and Acute Bacterial Rhinosinusitis Treatment.

This case report describes a pharmacist's intervention with a 58-year-old female who presented with recurrent rhinosinusitis symptoms and limited treatment options due to a complicated allergy history. Using guidelines for treatment of acute bacterial rhinosinusitis coupled with a thorough antibiotic allergy assessment, the pharmacist developed a treatment plan that was acceptable to both the patient and the provider. Pharmacists can play an essential role in verification of allergies to both medications and non-pharmaceutical products, which further ensures patient safety as well as optimization of appropriate treatment methods.

A Case of Clostridioides difficile: Update on Practice Guidelines.

This report describes a case of recurrent Clostridioides difficile infection (CDI) and illustrates that pharmacist's role in selecting appropriate treatment. The report discusses CDI risk factors and reviews the guidelines for the pharmacological management of CDI.

Adjuvant ß-Lactam Therapy Combined with Vancomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: Does ß-Lactam Class Matter?

We analyzed the impact of vancomycin (VAN) combined with adjuvant ß-lactam therapy (Combo) on persistent (≥5 days) methicillin-resistant Staphylococcus aureus bacteremia versus VAN alone by using pooled data from two previously published observational studies (n = 156). Combo was inversely associated with persistent bacteremia (adjusted odds ratio, 0.460; 95% confidence interval, 0.229 to 0.923). Acute kidney injury was more common with Combo than with VAN (18.9% and 7.6%, respectively; P = 0.062).

Outcomes of empiric aminoglycoside monotherapy for Pseudomonas aeruginosa bacteremia.

We evaluated 30-day mortality in patients with Pseudomonas aeruginosa bacteremia. There was no significant difference in mortality among patients who received functional aminoglycoside monotherapy versus inappropriate empiric therapy. Among patients given appropriate empiric therapy, functional aminoglycoside monotherapy was associated with less favorable outcomes compared to beta-lactam monotherapy.

Overtreatment of Asymptomatic Candiduria among Hospitalized Patients: a Multi-institutional Study.

Candiduria is common in hospitalized patients, and asymptomatic candiduria contributes to antifungal overuse. The guidelines for management of asymptomatic candiduria do not recommend antifungal use, but rather the elimination of predisposing factors. It is unknown whether these recommendations are being followed. The primary objective of this study was to characterize candiduria management among hospitalized patients. This was a retrospective cohort study of a random sample of 305 hospitalized patients with candiduria at four U.S. medical centers from January 2010 to December 2013. Patients were classified as asymptomatic or symptomatic based on established criteria, and data were collected by chart review. Infectious Diseases Society of America (IDSA) treatment guideline adherence and its association with clinical outcomes, including candiduria recurrence (short- and long-term) and 30-day readmission, were assessed. Eighty percent of patients were classified as having asymptomatic candiduria. Overall, 143 (47%) patients were not managed according to recommended guidelines, including 105/243 (43%) in the asymptomatic candiduria group and 38/62 (61%) in the symptomatic group (P = 0.01). Discordance among asymptomatic patients was driven by overtreatment with an antifungal (98/105 [93%]). Thirty-three percent of patients with asymptomatic candiduria not managed according to the guidelines were treated for over 7 days, and 5% received over 14 days of therapy. Fluconazole was the most commonly used empirical antifungal among asymptomatic candiduria patients (96%), followed by micafungin (4%). Asymptomatic candiduria patients not managed according to the guidelines had a trend toward higher 30-day readmission (35% versus 26%, P = 0.27). Inappropriate management of candiduria among hospitalized patients was high, leading to overtreatment with antifungal therapy.

Early Administration of Adjuvant ß-Lactam Therapy in Combination with Vancomycin among Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Infection: A Retrospective, Multicenter Analysis.

STUDY OBJECTIVE: To determine whether early administration of adjuvant ß-lactam in combination with vancomycin (COMBO) affects clinical outcomes compared to standard vancomycin therapy alone (STAN) among patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection. DESIGN: Retrospective, multicenter cohort study. SETTING: Five academic or community hospitals throughout the United States. PATIENTS: Adults with MRSA bloodstream infections treated with vancomycin (≥ 72 hrs) with or without an intravenous ß-lactam (≥ 48 hrs) initiated within 24 hours of initiating vancomycin. MEASUREMENTS AND MAIN RESULTS: The primary outcome was clinical failure, a composite endpoint including 30-day mortality, persistent bacteremia (≥ 7 days), bacteremia relapse, or change in antibiotic therapy during treatment due to clinical worsening. A multivariable logistic regression examined the impact of patient-, treatment-, and pathogen-level characteristics on clinical failure. A total of 201 patients were evaluated of whom 97 (48.3%) met the criteria for study inclusion; 40 (41.2%) in STAN and 57 (58.8%) in COMBO groups. Among patients in the STAN and COMBO groups, 30% and 24.6% experienced clinical failure, respectively (p=0.552). The median (interquartile range) duration of bacteremia in the STAN and COMBO groups was 4 days (2.5-6.5) and 3 days (2-5), respectively (p=0.048). In a multivariable analysis, receipt of COMBO therapy was inversely associated with clinical failure (adjusted odds ratio [aOR] 0.237, 95% confidence interval [CI] [0.057-0.982]; p=0.047). Other independent predictors of clinical failure included complicated bacteremia (aOR 6.856, 95% CI [1.641-28.649]; p=0.008) and antibiotic therapy not continued at discharge (aOR 45.404, 95% CI [9.383-219.714]; p<0.001). CONCLUSIONS: Receipt of COMBO therapy did not decrease the rate of clinical failure but was associated with expedited bacteremia clearance. Early adjuvant ß-lactam therapy deserves continued evaluation and clinical consideration.

Polymyxin B in Combination with Rifampin and Meropenem against Polymyxin B-Resistant KPC-Producing Klebsiella pneumoniae.

Safe and effective therapies are urgently needed to treat polymyxin-resistant KPC-producing Klebsiella pneumoniae infections and suppress the emergence of resistance. We investigated the pharmacodynamics of polymyxin B, rifampin, and meropenem alone and as polymyxin B-based double and triple combinations against KPC-producing K. pneumoniae isolates. The rates and extents of killing with polymyxin B (1 to 128 mg/liter), rifampin (2 to 16 mg/liter), and meropenem (10 to 120 mg/liter) were evaluated against polymyxin B-susceptible (PBs) and polymyxin B-resistant (PBr) clinical isolates using 48-h static time-kill studies. Additionally, humanized triple-drug regimens of polymyxin B (concentration at steady state [Css] values of 0.5, 1, and 2 mg/liter), 600 mg rifampin every 12 or 8 h, and 1 or 2 g meropenem every 8 h dosed as an extended 3-h infusion were simulated over 48 h by using a one-compartment in vitro dynamic infection model. Serial bacterial counts were performed to quantify the pharmacodynamic effect. Population analysis profiles (PAPs) were used to assess the emergence of polymyxin B resistance. Monotherapy was ineffective against both isolates. Polymyxin B with rifampin demonstrated early bactericidal activity against the PBs isolate, followed by regrowth by 48 h. Bactericidal activity was sustained at all polymyxin B concentrations of ≥2 mg/liter in combination with meropenem. No two-drug combinations were effective against the PBr isolate, but all simulated triple-drug regimens showed early bactericidal activity against both strains by 8 h that was sustained over 48 h. PAPs did not reveal the emergence of resistant subpopulations. The triple-drug combination of polymyxin B, rifampin, and meropenem may be a viable consideration for the treatment of PBr KPC-producing K. pneumoniae infections. Further investigation is warranted to optimize triple-combination therapy.

Emerging Issues and Treatment Strategies in Carbapenem-Resistant Enterobacteriaceae (CRE).

Carbapenems are the broadest spectrum antimicrobials utilized in the treatment of serious infections since the 1980s. Soon after their introduction, the discovery of carbapenem-resistant Enterobacteriaceae (CRE) was reported in the 1990s. Invasive CRE infections are associated with high mortality and limited treatment options making care for patients with these infections challenging for clinicians. Current practice has reverted back to the use of "older" antimicrobials, such as the polymyxins, tigecycline, and fosfomycin, to combat invasive CRE infections. However, recent approval of ceftazidime-avibactam has added another treatment option to the current antimicrobial armamentarium. Resistance among the "older" agents is still rare but has been reported. Currently, there are numerous agents that are under investigation as well as combination therapy that looks promising in the treatment of CRE infections.

Kidney injury associated with telavancin dosing regimen in an animal model.

The elevation of serum creatinine levels is a concern with telavancin therapy. We examined the onset of kidney injury associated with telavancin in an animal model. Urine samples were collected at baseline and daily to determine the concentrations of kidney injury molecule 1 (KIM-1), a marker for early kidney injury. When a clinically relevant exposure of telavancin was given daily to rats, some differences in kidney injury were attributed to the dosing regimen. Further investigations of alternative telavancin dosing regimens are warranted.

Assessment of minocycline and polymyxin B combination against Acinetobacter baumannii.

Antimicrobial resistance among Acinetobacter baumannii is increasing worldwide, often necessitating combination therapy. The clinical utility of using minocycline with polymyxin B is not well established. In this study, we investigated the activity of minocycline and polymyxin B against 1 laboratory isolate and 3 clinical isolates of A. baumannii. Minocycline susceptibility testing was performed with and without an efflux pump inhibitor, phenylalanine-arginine ß-naphthylamide (PAßN). The intracellular minocycline concentration was determined with and without polymyxin B (0.5 µg/ml). Time-kill studies were performed over 24 h using approximately 10(6) CFU/ml of each strain with clinically relevant minocycline concentrations (2 µg/ml and 8 µg/ml), with and without polymyxin B (0.5 µg/ml). The in vivo efficacy of the combination was assessed in a neutropenic murine pneumonia model. Infected animals were administered minocycline (50 mg/kg), polymyxin B (10 mg/kg), or both to achieve clinically equivalent exposures in humans. A reduction in the minocycline MIC (≥ 4×) was observed in the presence of PAßN. The intracellular concentration and in vitro bactericidal effect of minocycline were both enhanced by polymyxin B. With 2 minocycline-susceptible strains, the bacterial burden in lung tissue at 24 h was considerably reduced by the combination compared to monotherapy with minocycline or polymyxin B. In addition, the combination prolonged survival of animals infected with a minocycline-susceptible strain. Polymyxin B increased the intracellular concentration of minocycline in bacterial cells and enhanced the bactericidal activity of minocycline, presumably due to efflux pump disruption. The clinical utility of this combination should be further investigated.

Significant publications on infectious diseases pharmacotherapy in 2012.

PURPOSE: The most important articles pertaining to infectious diseases (ID) pharmacotherapy published in 2012, as nominated and ranked by panels of pharmacists and physicians with ID expertise, are summarized. SUMMARY: Members of the Houston Infectious Diseases Network were asked to nominate articles on ID research published in prominent peer-reviewed journals during the period January 1-December 31, 2012, with a major impact in the field of ID pharmacotherapy. A list of 42 nominated articles on general ID-related topics and 8 articles pertaining to human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) was compiled. In a survey conducted in January 2013, members of the Society of Infectious Diseases Pharmacists (SIDP) were asked to select from the list 10 general ID articles and 1 HIV/AIDS-related article that they considered to be the most important. Of the 180 SIDP members surveyed, 100 (55%) and 44 (24%) participated in ranking the general ID and HIV/AIDS-related articles, respectively. Summaries of the highest-ranked articles in both categories are presented here. CONCLUSION: With the volume of published ID-related research growing each year, both ID specialists and nonspecialists are challenged to stay current with the literature. Key ID-related publications in 2012 included updated recommendations on management of diabetic foot infections, articles on promising approaches to prevention and early treatment of HIV disease, and reports on developments in research on pharmacotherapies for methicillin-resistant Staphylococcus aureus bacteremia and Klebsiella pneumoniae infections.

Pseudomonas aeruginosa treatment and transmission reduction.

Infections caused by Pseudomonas aeruginosa can be difficult to treat and require a coordinated approach for their management. This involves quickly controlling the source of infection, establishing a correct etiologic diagnosis and administering appropriate empiric antimicrobial therapy. Once antimicrobial therapy has been initiated and susceptibilities are available, therapy should be tailored with optimized antibiotic doses for an appropriate duration in order to sufficiently treat the infection and minimize resistance emergence.

Outcomes of appropriate empiric combination versus monotherapy for Pseudomonas aeruginosa bacteremia.

Pseudomonas aeruginosa bacteremia is associated with high hospital mortality. Empirical combination therapy is commonly used to increase the likelihood of appropriate therapy, but the benefits of employing >1 active agent have yet to be established. The purpose of this study was to compare outcomes of patients receiving appropriate empirical combination versus monotherapy for P. aeruginosa bacteremia. This was a retrospective, multicenter, cohort study of hospitalized adult patients with P. aeruginosa bacteremia from 2002 to 2011. The primary endpoint (30-day mortality) was assessed using multivariate logistic regression, adjusting for underlying confounding variables. Secondary endpoints of hospital mortality and time to mortality were assessed by Fisher's exact test and the Cox proportional hazards model, respectively. A total of 384 patients were analyzed. Thirty-day mortality was higher for patients receiving inappropriate therapy than for those receiving appropriate empirical therapy (43.8% versus 21.5%; P = 0.03). However, there were no statistical differences in 30-day mortality following appropriate empirical combination versus monotherapy after adjusting for baseline APACHE II scores and lengths of hospital stay prior to the onset of bacteremia (P = 0.55). Observed hospital mortality was 36.6% for patients administered combination therapy, compared with 28.7% for monotherapy patients (P = 0.17). After adjusting for baseline APACHE II scores, the relationship between time to mortality and combination therapy was not statistically significant (P = 0.59). Overall, no significant differences were observed for 30-day mortality, hospital mortality, and time to mortality between combination and monotherapy for P. aeruginosa bacteremia. Empirical combination therapy did not appear to offer an additional benefit, as long as the isolate was susceptible to at least one antimicrobial agent.