Elise M. Gilbert

Antiretroviral Pharmacokinetics in Pregnant Women.

For women infected with the human immunodeficiency virus (HIV) who become pregnant, the use of combination antiretroviral therapy (ART) significantly reduces transmission of HIV from mother to child. Selection of an appropriate ART regimen for use among pregnant women requires consideration of numerous factors including maternal and fetal safety, antiretroviral pharmacokinetics, and regimen efficacy. Optimization of antiretroviral pharmacokinetics during pregnancy requires special consideration because pregnancy‐associated changes in drug absorption, distribution, metabolism, and excretion are known to occur throughout pregnancy and postpartum. Understanding antiretroviral placental transfer may offer additional insight into each drugs potential role in preventing HIV transmission in utero and may also have implications regarding viral resistance in cases where transmission does occur. In this review, we summarize key published data describing antiretroviral pharmacokinetics in pregnant women, providing suggestions for clinical application of these data where appropriate.

Integration of outpatient infectious diseases clinic pharmacy services and specialty pharmacy services for patients with HIV infection

PURPOSE The integration of specialty pharmacy services and existing outpatient clinical pharmacy services within an infectious diseases (ID) clinic to optimize the care of patients with human immunodeficiency virus (HIV) infection is described. SUMMARY The management of HIV-infected patients is a highly specialized area of practice, often requiring use of complex medication regimens for reduction of HIV-associated morbidity and mortality prophylaxis and treatment of opportunistic infections, and prevention of HIV transmission. To maximize the effectiveness and safety of treatment with antiretroviral agents and associated pharmacotherapies, an interdisciplinary team is often involved in patient care. At Chicago-based Northwestern Medicine (NM), the outpatient ID clinic has long worked with an interdisciplinary care team including physicians, clinical pharmacists, nurses, and social workers to care for patients with HIV infection. In April 2014, specialty pharmacy services for patients with HIV infection were added to the NM ID clinics care model to help maintain continuity of care and enhance patient follow-up. The care model includes well-defined roles for clinical pharmacists, pharmacy residents and students on rotation, and licensed pharmacy technicians. Specialty pharmacy services, including medication education, prescription fulfillment, assistance with medication access (e.g., navigation of financial assistance programs, completion of prior-authorization requests), and treatment monitoring, allow for closed-loop medication management of the HIV-infected patient population. CONCLUSION Integration of specialty pharmacy services with the interdisciplinary care provided in the outpatient NM ID clinic has enhanced continuity of care for patients with HIV infection in terms of prescription filling, medication counseling, and adherence monitoring.

Investigating the Extremes of Antibiotic Use with an Epidemiologic Framework

ABSTRACT Benchmarks for judicious use of antimicrobials are needed. Metrics such as defined daily doses (DDDs) and days of therapy (DOTs) quantify antimicrobial consumption. However, benchmarking with these metrics is complicated by interhospital variability. Thus, it is important for each hospital to monitor its own temporal consumption trends. Time series analyses allow trends to be detected; however, many of these methods are complex. We present simple regressive methods and caveats in using them to define potential antibiotic over- and underutilizations.

Implementation of a cefazolin-based stewardship pathway for methicillin-susceptible Staphylococcus aureus bloodstream infections paired with infectious diseases consultation

Methicillin-susceptible Staphylococcus aureus (MSSA) infections have been successfully treated both with cefazolin and antistaphylococcal penicillins; cefazolin appears effective in MSSA bloodstream infections (BSIs). Thus, our antimicrobial stewardship programme (ASP) implemented a clinical pathway supporting cefazolin use in MSSA-BSIs and restricting oxacillin use to infectious diseases (ID) consultation due to cefazolins lower cost and more convenient dosing. This before and after quasi-experimental study was conducted to describe the impact on outcomes and process of care measures associated with implementing this pathway among patients with MSSA-BSI. Definitive treatment with cefazolin increased over the study period from 17.3% to 69.8% post-implementation. Clinical failure (5.8% vs. 2.3%; P = 0.62) and in-hospital mortality (3.8% vs. 0%; P = 0.50) were rare pre- and post-implementation. Median hospital length of stay among survivors was similar between pre- and post-implementation periods (P = 0.31). Duration of bacteraemia [median (IQR) 3 (2-4) days vs. 2 (2-3) days; P = 0.002] and rates of re-infection after culture clearance (9.6% vs. 0%; P = 0.06) were reduced post-implementation. Frequency of source control (P = 0.71) and time to source control (P = 0.52) were similar between study periods. Significant increases in ID consultations (33.3% [3/9] vs. 73.3% [22/30]; P = 0.047) and median (IQR) 24-h daily doses [2 (1-3) g vs. 6 (3-6) g; P < 0.01] were seen for patients treated with cefazolin post-implementation. ASPs may find implementation of a similar pathway to be an effective means of improving the care of patients infected with MSSA.

Days of Therapy and Antimicrobial Days: Similarities and Differences Between Consumption Metrics

Benchmarks for antimicrobial consumption measured in antimicrobial days are beginning to emerge. The relationship between the traditional measure of days of therapy and antimicrobial days is unclear. We observed a high intermethod correlation (R2=0.99): antimicrobial days were 1.9-fold lower than days of therapy across agents. Individual institutions should correlate these measures. Infect Control Hosp Epidemiol 2016;37:971-973.

Factors contributing to vancomycin-resistant Enterococcus spp. horizontal transmission events: exploration of the role of antibacterial consumption

BACKGROUND The relationship between antibiotic consumption and resistance is relatively well defined at the population/ecologic level. Increases in antimicrobial consumption correlate with increased antibiotic resistance for clinical and surveillance isolates. However, the impact of antimicrobial consumption on nosocomial transmission of resistant bacteria is less well defined. This study explores the association between antimicrobial consumption, hand hygiene, and horizontal resistant organism transmission. METHODS A retrospective cohort pilot study was conducted. Vancomycin-resistant Enterococcus spp. (VRE) horizontal transmission events during a 2-year period were identified. VRE transmission events were defined as isolation of genetically similar VRE strain-types (determined using pulsed field gel electrophoresis) from patients who were temporally and geographically co-localized within our hospital. The Centers for Disease Control and Prevention Antimicrobial Use and Resistance Module was utilized to collect antibacterial consumption data of commonly utilized agents. Hand hygiene was quantified using floor-by-floor peer audit data. Regression techniques were employed to assess population-level relationships between study variables and transmission events. RESULTS One hundred nineteen transmission events were identified. Hand hygiene estimates were homogeneous and did not correlate with VRE transmission rates. Stepwise-multivariate linear regression revealed that aztreonam consumption was associated with a lower rate of transmissions in the medical intensive care unit (P=0.031), and carbapenem consumption was associated with a higher rate of VRE transmission events on one of two oncology floors (P=0.033). DISCUSSION/CONCLUSION Consumption of aztreonam and carbapenems was associated with VRE horizontal transmission rates. Further studies are necessary to identify other associations and elucidate the full clinical significance of this finding.

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.

Correlation between hospital-level antibiotic consumption and incident health care facility-onset Clostridium difficile infection

Background: The purpose of this single‐center, ecologic study is to characterize the relationship between facility‐wide (FacWide) antibiotic consumption and incident health care facility‐onset Clostridium difficile infection (HO‐CDI). Methods: FacWide antibiotic consumption and incident HO‐CDI were tallied on a monthly basis and standardized, from January 2013 through April 2015. Spearman rank‐order correlation coefficients were calculated using matched‐months analysis and a 1‐month delay. Regression analyses were performed, with P < .05 considered statistically significant. Results: FacWide analysis identified a matched‐months correlation between ceftriaxone and HO‐CDI (&rgr; = 0.44, P = .018). A unit of stem cell transplant recipients did not have significant correlation between carbapenems and HO‐CDI in matched months (&rgr; = 0.37, P = .098), but a significant correlation was observed when a 1‐month lag was applied (&rgr; = 0.54, P = .014). Discussion: Three statistically significant lag associations were observed between FacWide/unit‐level antibiotic consumption and HO‐CDI, and 1 statistically significant nonlagged association was observed FacWide. Antibiotic consumption may convey extended ward‐level risk for incident CDI. Conclusions: Consumption of antibiotic agents may have immediate and prolonged influence on incident CDI. Additional studies are needed to investigate the immediate and delayed associations between antibiotic consumption and C difficile colonization, infection, and transmission at the hospital level.

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.

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.