Assessment of mortality stratified by meropenem minimum inhibitory concentration in patients with Enterobacteriaceae bacteraemia: A patient-level analysis of published data.

In 2010, the Clinical and Laboratory Standards Institute (CLSI) lowered carbapenem breakpoints to reduce the proportion of 'susceptible' organisms that produced carbapenemases. Few studies have evaluated the effect of this change on clinical outcomes. This systematic review aimed to evaluate the effect of carbapenem MICs on 30-day mortality from pooled patient-level data from studies of patients treated with carbapenems across a range of meropenem MICs. PubMed was searched to March 2019 with the terms 'carbapenem', 'meropenem', 'imipenem', 'doripenem', 'ertapenem', 'susceptibility' and 'outcomes'. Studies were included in the analysis if patients had Enterobacteriaceae bacteraemia treated with a carbapenem for ≥48 h and mortality was reported. Studies were excluded if all isolates were either susceptible or resistant to meropenem based on CLSI 2010 breakpoints or if only carbapenemase-producing isolates were included. Authors were contacted for patient-level data. The primary outcome was 30-day mortality, with planned subset analyses of patients treated with meropenem, receiving active combination therapy, treated in the ICU or infected with Klebsiella pneumoniae. Of 157 articles identified, 4 met the inclusion criteria (115 eligible patients). The odds of mortality increased with each increasing meropenem MIC dilution (OR = 1.51, 95% CI 1.06-2.15) as a continuous variable. A similar increase in odds was observed in patients treated with meropenem, treated in the ICU, infected with K. pneumoniae or receiving no other active antimicrobials. Increasing meropenem MICs in Enterobacteriaceae were associated with increased mortality; however, more work is needed to define optimal clinical decision rules for infections within the susceptible range.

Appropriateness of Beta-Lactam Allergy Record Updates After an Allergy Service Consult.

BACKGROUND: Many patients with a self-reported penicillin allergy go on to tolerate beta-lactam antibiotics. Allergy specialists may be consulted to determine the nature and extent of the allergy. However, electronic allergy records must be appropriately updated such that recommendations are carried forward. OBJECTIVE: To determine the percentage of patients who have their electronic allergy record updated after an allergy service consult (ASC). METHODS: This was a retrospective study of patients with at least 1 documented beta-lactam allergy and had an ASC during (inpatient) or prior to (outpatient) hospital admission at Northwestern Memorial Hospital and Prentice Women's Hospital in Chicago, Illinois. RESULTS: Within the study period, a total of 26 526 patients were identified as having a documented antibiotic allergy, with 21 657 patients (81.6% of patients with allergies) having a listed beta-lactam allergy. Of these patients, 1689 (7.8%) patients were identified as having an ASC during or prior to admission, with 598 patients meeting inclusion criteria. Changes in the allergy record were recommended by the ASC for 62% (n = 371) of patients; however, the allergy record was updated after the ASC in 74.9% (n = 278) of patients. CONCLUSION: ASC recommendations to delabel a patient as beta-lactam allergic must result in updating the allergy record in order to optimize future treatment. Given the low proportion of allergy-labeled patients tested, programs outside formal ASCs should be considered.

Traditional matriculation vs an early assurance program: Effect on elected student leadership positions and academic performance.

INTRODUCTION: The objective of this study was to compare leadership and academic performance among students admitted by traditional pathways vs. a dual acceptance program (DAP). METHODS: A list of students admitted to the Midwestern University Chicago College of Pharmacy (MWUCCP) DAP was cross-checked with students elected to serve in leadership positions and students on the MWUCCP Dean's List for their first professional year from 2010 to 2015. The proportion of students serving in leadership positions and those on the Dean's List were compared to students that matriculated via the traditional route. RESULTS: In total, 1069 students were analyzed (n = 937 traditional; n = 132 DAP). DAP students were more likely to have an elected leadership role (n = 61, 46.2% vs. n = 314, 33.5%, p < 0.01) and achieve Dean's List for their first professional year (n = 64, 48.5% vs. n = 292, 31.2%, p < 0.01) compared to traditional students. DISCUSSION AND CONCLUSIONS: DAP students were more likely to hold an elected leadership position than traditional students. Further study of DAP student motivation is needed to potentially assist in the success of other students.

Renal effects of non-tenofovir antiretroviral therapy in patients living with HIV.

A review of literature published regarding non-tenofovir antiretroviral agents causing renal adverse effects was conducted. The literature involving renal adverse effects and antiretroviral therapy is most robust with protease inhibitors, specifically atazanavir and indinavir, and includes reports of crystalluria, leukocyturia, nephritis, nephrolithiasis, nephropathy and urolithiasis. Several case reports describe potential nephropathy (including Fanconi syndrome) secondary to administration of abacavir, didanosine, lamivudine and stavudine. Case reports documented renal events such as acute renal failure, nephritis, proteinuria and renal stones with efavirenz administration. Regarding rilpivirine, a small increase of serum creatinine levels (SCr) was found in clinical trials; however, the clinical significance and impact on actual renal function is unknown. The integrase strand transfer inhibitors and enfuvirtide have a relatively safe renal profile, although studies have shown dolutegravir and raltegravir cause mild elevations in SCr without an impact on actual renal function. This is similar to the reaction observed with cobicistat, the pharmacokinetic enhancer frequently given with elvitegravir.

Effect of elevated imipenem/cilastatin minimum inhibitory concentrations on patient outcomes in Gram-negative bloodstream infections.

OBJECTIVES: Carbapenem minimum inhibitory concentration (MICs) are known to predict outcomes for patients with Gram-negative bacteraemia. However, limited data exist on how MICs influence such outcomes when organisms are classified as carbapenem-resistant. The purpose of this study was to evaluate the effect of increasing imipenem/cilastatin MICs on mortality in patients with Gram-negative bloodstream infection (BSI). METHODS: Patients with an imipenem/cilastatin-resistant (MIC>4mg/L) monomicrobial Gram-negative BSI were eligible for inclusion in the study and were assessed for baseline characteristics, organ function, microbiological data, timing and type of therapeutic treatment, and in-hospital mortality. RESULTS: A total of 62 patients with imipenem/cilastatin-resistant bacterial isolates (MIC>4mg/L) were retrospectively studied. Time to event analyses found no difference between patients who received carbapenem therapy and those who did not (P=0.10). After adjustment, patients receiving directed therapy were less likely to die (adjusted hazard ratio=0.35, 95% confidence interval 0.15-0.83; P<0.01), whereas higher modified Acute Physiology and Chronic Health Evaluation (APACHE) II score and days to positive culture were associated with non-survival. CONCLUSION: This study did not demonstrate a relationship between receipt of a carbapenem and mortality in patients with carbapenem-resistant Gram-negative BSI.

Improving patient access to hepatitis C virus treatment.

OBJECTIVES: To discuss the current barriers to hepatitis C virus (HCV) treatment; to provide information and resources to assist health care providers with the prior authorization process; to provide resources for potential access to medications if a patient's third-party payer may not be an option; and to discuss the pharmacist's vital role as a patient advocate and considerations once medications are approved. SUMMARY: Access to HCV medications is often restricted by third-party payers. Pharmacists are poised to fill an immediate need and assist with providing the necessary clinical evidence to gain access to HCV medications and advocate on the patient's behalf. Once approval for HCV treatment has been obtained, considerations must be given to procurement of therapy, refills, monitoring, and avoid interruptions in therapy. CONCLUSION: The assistance of a pharmacist should be sought to overcome barriers related to medication access. Once therapy has been obtained, the pharmacist can assist the entire patient care team to ensure timely refills, appropriate monitoring, tolerability of therapy, and continued medication access.

Analysis of PGY-1 Pharmacy Resident Candidate Letters of Recommendation at an Academically Affiliated Residency Program.

BACKGROUND: Letters of recommendation (LORs) are a critical component for differentiating among similarly qualified pharmacy residency candidates. These letters contain information that is difficult to ascertain from curricula vitae and pharmacy school transcripts. LOR writers may use any words or phrases appropriate for each candidate as there is no set framework for LORs. OBJECTIVE: The objective of this study was to characterize descriptive themes in postgraduate year 1 (PGY-1) pharmacy residency candidates' LORs and to examine which themes of PGY-1 pharmacy residency candidates' LORs are predictive of an interview invitation at an academically affiliated residency program. METHODS: LORs for candidates from the Pharmacy Online Residency Centralized Application System (PhORCAS) from 2013 and 2014 for the Midwestern University PGY-1 Pharmacy Residency were analyzed. LOR characteristics and descriptive themes were collected. All scores for candidate characteristics and overall PhORCAS recommendation were also recorded. RESULTS: A total of 351 LORs for 111 candidates from 2013 (n = 47 candidates) and 2014 (n = 64 candidates) were analyzed; 36 (32.4%) total candidates were offered an interview. Themes that were identified as predictors of an interview included a higher median (interquartile range) number of standout words (3 words [1.3-4] vs 3.8 words [2.5-5.5], P < .01) and teaching references (3.7 words [2.7-6] vs 5.7 words [3.7-7.8], P = .01). CONCLUSION: For this residency program, standout words and teaching references were important when offering interviews.

Effect of application score strategy on interviews offered to postgraduate year 1 pharmacy residency applicants.

OBJECTIVES: Residency programs may need to spend a large amount of time on the application review process in order to invite the best candidates for interviews. By using a different scoring strategy, this process could be made more efficient while still resulting in selection of the most appropriate candidates to interview. The objective of this study was to explore hypothetical scoring strategies for past residency applicants and to determine the percentage of these applicants that would have received an interview offer compared with the program's standard scoring strategy. METHODS: Two years of residency applications to a postgraduate year 1 (PGY1) program providing the majority of clinical experience in ambulatory care were analyzed. Four models were explored: 1) standard model (original method); 2) simplified model (derived from statistical methods); 3) intuition model (criteria thought to best exemplify program success); and 4) objective model (criteria easy to objectively record, e.g., grade point average). All 3 new models were compared with the standard model to determine the percentage of candidates who would have received an interview if their applications had been scored according to the new model. RESULTS: A total of 110 applications were reviewed (42 interviews offered). After a multivariable analysis, academics, leadership, interest in ambulatory care, and professionalism were included in the simplified model, which predicted 81% of the interviews offered through the standard model. The intuition and objective models predicted 71% and 48% of interviews offered through the standard model, respectively. CONCLUSION: Models scoring only 4 of the initial 12 criteria would have likely predicted 71% to 81% of original interview offers. Residency programs should consider periodically reviewing their application review processes to determine areas for improved efficiency.

Implementation of a pharmacy research committee to enhance the pharmacy resident research experience.

BACKGROUND AND PURPOSE: Most postgraduate year 1 (PGY1) pharmacy residents complete at least one research project as part of their graduation requirements. The research skills learned prepare residents to address research questions and generate evidence-based recommendations for patient care. However, there are multiple steps involved in a research project, and streamlining this process can be difficult. EDUCATIONAL ACTIVITY AND SETTING: Northwestern Memorial Hospital (NMH), a large academic center located in Chicago, IL, developed a research committee (RC) to facilitate research within the department of pharmacy for residents and to maintain residency research support materials. These materials included a charter to help guide the organizational structure and operations of the RC, research timelines, and a seminar series. FINDINGS: The RC works to ensure that the residents overcome any challenges that they may incur during their research projects by setting clear expectations and milestones. Feedback is provided by the residents and incorporated into the research process and support materials. DISCUSSION: The RC allows for individualized attention and personalization of the research experience for each resident. The program endeavors each year to provide the message that publication should be the final goal of a research project and not presentation at a conference. SUMMARY: Pharmacy residents receive support from the RC from throughout the year, not only when issues surround their project arise. Institutions may implement or modify existing programs based upon the resources provided.

Switch to atovaquone and subsequent re-challenge with trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis in a kidney transplant population.

Kidney transplant recipients who are switched to atovaquone (ATO) from trimethoprim-sulfamethoxazole (TMP/SMX) for Pneumocystis jirovecii pneumonia (PJP) prophylaxis because of adverse events or complications may miss opportunities to be re-challenged with TMP/SMX, the first-line agent. This single-site, retrospective study assessed kidney transplant recipients for documented reasons for switching from TMP/SMX to alternate PJP prophylaxis and outcomes of TMP/SMX re-challenge. Out of 166 patients, 155 initially received TMP/SMX; of these, 31 were switched to ATO for various reasons. Fourteen patients receiving ATO were re-challenged with TMP/SMX; all were successfully re-initiated on TMP/SMX therapy. Most patients switched to ATO post kidney transplant secondary to non-hypersensitivity reasons should be re-challenged with TMP/SMX because of the advantages it provides over other agents.

Use of organism identification by 16S ribosomal RNA polymerase chain reaction to shorten antimicrobial length of therapy.

BACKGROUND: Organism detection by 16S ribosomal RNA (rRNA) PCR followed by amplicon sequencing identification may help guide antimicrobial treatment in culture-negative patients. The objectives of this study were to assess the effect of a positive versus negative 16S rRNA PCR on antibiotic length of therapy (LOT) and rate of antibiotic discontinuation. METHODS: Patients with a sterile site, direct-specimen 16S rRNA PCR negative, and suspected active infection were matched 1:1 with 16S rRNA PCR positive patients based on specimen site and retrospectively evaluated. RESULTS: Ninety patients were included (n=45 positive and negative). 16S rRNA PCR negative patients had shorter median LOT (33days [IQR 8-46] versus 43days [IQR 29-51], P=0.02). Antibiotics were discontinued more frequently in 16S rRNA PCR negative patients (38% versus 4%, P<0.01). CONCLUSIONS: For culture-negative patients with suspected sterile site infection, a negative, direct-specimen 16S rRNA PCR may help discontinue antibiotics and decrease LOT.

Use of High-Dose Oral Valacyclovir During an Intravenous Acyclovir Shortage: A Retrospective Analysis of Tolerability and Drug Shortage Management.

INTRODUCTION: In late 2011, a shortage of IV acyclovir led to the need to empirically substitute high-dose oral valacyclovir (HDVA) to conserve IV acyclovir for patients with confirmed herpes simplex virus (HSV) meningitis or encephalitis. This report describes the management of the most recent national IV acyclovir shortage by the Antimicrobial Stewardship Program (ASP) at Northwestern Memorial Hospital (NMH), Chicago, IL, USA, and the use of HDVA. Secondarily, we assessed the safety and tolerability of HDVA as an alternate to IV acyclovir during this shortage. METHODS: We report the step-wise management, restrictions, and guidelines implemented at NMH during a protracted IV acyclovir shortage. The assessment of HDVA was a retrospective, observational cohort study of hospitalized patients receiving HDVA between 1 January 2012 and 31 December 2013. Appropriate demographic and treatment variables were collected. The primary outcome was percentage of patients experiencing an adverse event. RESULTS: There were 15 adult patients included in the study on a median daily dose of HDVA of 3 g (IQR 2-8). There were four patients with microbiologically confirmed viral CNS infections (n = 1 HSV-1, n = 2 HSV-2, n = 1 VZV encephalitis) and eleven patients with unknown causative pathogens. Six (40%) patients experienced at least one adverse drug reaction (ADR) to HDVA (thrombocytopenia, 33.3%, n = 5; headache, 6.7%, n = 1; nausea, 6.7%, n = 1; rash, 6.7%, n = 1). One patient (6.7%) was readmitted within 30 days with a suspected non-CNS infection. There were no treatment discontinuations or symptomatic therapy necessary to treat any of the ADRs. CONCLUSIONS: The shortage of IV acyclovir was successfully managed by the ASP and HDVA appeared to be well tolerated when used as an alternative to IV acyclovir.

Engaging Pharmacy Students in Research Through Near-Peer Training.

Objective. To describe the implementation of a near-peer training model within a student research program. Methods. A near-peer training model was implemented in a pharmacy student research program to promote development of effective teaching skills and research competencies. Under the supervision of a research mentor, senior learners precepted junior learners in various aspects of translational research. A three-step teaching process was employed throughout the experience in which junior learners performed an assigned task, senior learners provided guidance and mentorship, and research mentors provided feedback for improvement. Results. A total of 43 pharmacy trainees have participated in the student research program; each year of involvement now averages 15 to 18 students. The program has been responsible for almost 100 poster presentations at national meetings and more than 20 manuscripts in peer-reviewed journals. Funding through intramural grants and scholarships to compensate for conference expenses and other functions has also been awarded. Conclusion. Near-peer teaching supports a tiered-research model under the supervision of a research mentor. For health care systems and colleges of pharmacy with established research programs or those seeking to implement new programs, near-peer teaching appears to be a promising strategy to promote the development of research competencies in pharmacist trainees.

Analysis of an Infectious Diseases Pharmacist on Call Pager Program to Inform Educational Efforts.

Background: An on call infectious diseases (ID) pharmacist may be used as a resource for physicians, pharmacists, and other health care providers to help answer questions regarding anti-infective agents. Objective: To assess type, requestor, resources dedicated, and temporal trends of questions received through an ID pharmacist on call pager program. A secondary objective was to gather insight as to how this information was utilized to inform educational initiatives. Methods: This was a retrospective study of questions received by the ID pharmacist on call via pager at a large academic medical center. Question data were documented in a central database and analyzed to assess temporal trends and question type, and qualitatively analyzed to determine areas for targeted educational efforts. Results: The ID pharmacist on call recorded 545 questions during the 1-year study period; questions were composed of various antimicrobial agent-related queries, including antibiotic spectrum and selection (n = 251, 46.1%), dosing of antimicrobials (n = 195, 35.8%), and drug monitoring (n = 26, 4.8%). Targeted educational initiatives secondary to questions received included pharmacist education regarding the use of polymyxin antibiotics and antibiotic dosing protocol updates. Conclusions: An ID pharmacist on call pager program was utilized to inquire about antibiotic spectrum and selection for the majority of questions. Records of questions received may be utilized to direct educational efforts and create or revise targeted resources for pharmacists and other clinicians.

Evaluation of nucleoside reverse transcriptase inhibitor dosing during continuous veno-venous hemofiltration.

Background Unpredictable drug concentrations may lead to suboptimal exposure to nucleoside reverse transcriptase inhibitors (NRTIs) due to inadequate doses administered during continuous veno-venous hemofiltration (CVVH), which in turn may lead to decreased antiretroviral efficacy and possibly further HIV disease progression. Objective To compare administered doses of NRTIs to calculated doses of NRTIs to evaluate if patients were expected to have a favorable pharmacokinetic exposure profile while receiving CVVH. Methods The NRTI dose was compared to a table of recommendations based on a mathematical formula that estimates the amount of drug expected to be removed during CVVH. Results Twelve patients were on 27 NRTIs. Eleven (41%) NRTI doses were expected to provide a favorable pharmacokinetic profile based on pharmacokinetic mathematical calculations. Conclusion The majority of NRTIs were potentially not optimally dosed based on proposed pharmacokinetic calculations.

Student Characteristics Associated with Successful Matching to a PGY1 Residency Program.

Objective. To identify predictors for postgraduate matching success. Methods. In April 2014, a survey was distributed to students at five schools of pharmacy in the United States assessing organizational involvement, research and work experience, postgraduation plans, match status, and demographics. Results. Five hundred seventy-seven students (82%) completed the survey. Applicants who matched had a higher median number of interview offers compared to those who did not match. Significantly more females than males applied for a residency program. Those who matched had a higher median pharmacy school grade point average (GPA) compared to those who did not. No differences were observed in the rates of matching when leadership positions, student organizational membership, or previous work experience were considered. Conclusion. For pharmacy students in this study, number of applications and interviews, pharmacy school GPA, and female gender were associated with a higher likelihood of matching.

Prediction of inventory sustainability during a drug shortage.

PURPOSE: A methodology for predicting how long the on-hand inventory of a given medication will last during a supply shortage is described; a practical example of application of the methodology is provided. METHODS: Single-site data on consumption of i.v. tobramycin over an eight-month evaluation period were collected using commercial software that tabulates barcode-assisted medication administration (BCMA) events; administered doses were standardized as 1200-mg "vial-equivalents" and summed over the review period. The total number of vial-equivalents consumed was divided by the number of "non-zero weeks of consumption" (i.e., weeks during which any tobramycin use occurred) to obtain a mean ± S.D. weekly consumption rate; this rate was multiplied by the total i.v. tobramycin on-hand supply (in vial-equivalents) to determine the mean number of potentially sustainable weeks of therapy in the event a shortage were to restrict the future supply of the drug. RESULTS: Overall, 99.6 vial-equivalents of i.v. tobramycin were used during the evaluation period. The mean ± S.D. number of vial-equivalents used per non-zero week of consumption was 3.11 ± 1.26. A manual count of pharmacy inventory revealed that 102.9 vial-equivalents were available at the time of analysis. The mean predicted duration of supply was 33 weeks (95% confidence interval, -126 to 192 weeks). CONCLUSION: Available BCMA data on tobramycin consumption over eight months were used to calculate the mean number of weeks the on-hand supply of the drug could be expected to last during a persistent drug shortage.