Spencer E. Harpe

Medication risk factors associated with healthcare-associated Clostridium difficile infection: a multilevel model case–control study among 64 US academic medical centres

OBJECTIVES The main objective of this study was to determine patient- and hospital-level medication risk factors associated with Clostridium difficile infection (CDI) occurrence among patients clustered within hospitals using a multilevel model. METHODS Patients with healthcare-associated (HA)-CDI were identified from among 64 academic medical centres in 2009. A frequency match was conducted; for each case, up to two controls were selected, matched on similar pre-infection length of stay and clinical service line. Patient- and hospital-level medication use, including antibacterial and gastric acid-suppressant agents, was assessed using a two-level logistic regression model. RESULTS A total of 5967 CDI cases and 8167 controls were included in the analysis. The odds of acquiring HA-CDI increased with the following medications [OR (95% CI)]: anti-methicillin-resistant Staphylococcus aureus agents [1.38 (1.22-1.56)]; third- or fourth-generation cephalosporins [1.75 (1.62-1.89)]; carbapenems [1.60 (1.44-1.79)]; β-lactam/β-lactamase inhibitor combinations [1.49 (1.36-1.64)]; vancomycin [1.73 (1.57-1.89)]; and proton pump inhibitors [1.43 (1.30-1.57)]. The odds of acquiring HA-CDI decreased with the following medications: clindamycin [0.74 (0.63-0.87)]; and macrolides [0.88 (0.77-0.99)]. Controlling for patient-level covariates, no hospital-level medication covariates that we analysed had statistically significant effects on HA-CDI. The odds of acquiring HA-CDI increased with the hospital proportion of patients aged ≥ 65 years [1.01 (1.00-1.02)]. CONCLUSIONS We found several medications that were associated with the risk of patients developing HA-CDI, including β-lactam/β-lactamase inhibitor combinations, third- or fourth-generation cephalosporins, carbapenems, vancomycin, proton pump inhibitors and anti-methicillin-resistant S. aureus agents. There were no medication effects significant at the hospital level.

Economic impact of Clostridium difficile infection in a multihospital cohort of academic health centers.

Study Objective. To assess the economic impact of Clostridium difficile infection (CDI) in a large multihospital cohort.

Trends in Aminoglycoside Use and Gentamicin-Resistant Gram-Negative Clinical Isolates in US Academic Medical Centers: Implications for Antimicrobial Stewardship

OBJECTIVE To measure trends in aminoglycoside antibiotic use and gentamicin-resistant clinical isolates across a network of hospitals and compare network-level relationships with those of individual hospitals. DESIGN Longitudinal observational investigation. SETTING US academic medical centers. PARTICIPANTS Adult inpatients. METHODS Adult aminoglycoside use was measured from 2002 or 2003 through 2009 in 29 hospitals. Hospital-wide antibiograms assessed gentamicin resistance by proportions and incidence rates for Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Mixed-effects analysis of variance was used to assess the significance of changes in aminoglycoside use and changes in resistance rates and proportions. Generalized estimating equations were used to assess the relationship between aminoglycoside use and resistance. RESULTS Mean aminoglycoside use declined by 41%, reflecting reduced gentamicin (P < .0001) and tobramycin (P < .005) use; amikacin use did not change. The rate and proportion of gentamicin-resistant P. aeruginosa decreased by 48% (P < .0001) and 31% (P < .0001), respectively. The rate and proportion of gentamicin-resistant E. coli increased by 166% and 124%, respectively (P < .0001), and they were related to increasing quinolone resistance in E. coli. Resistance among K. pneumoniae and A. baumannii did not change. Relationships between aminoglycoside use and resistance at the network level were highly variable at the individual hospital level. CONCLUSIONS Mean aminoglycoside use declined in this network of US hospitals and was associated with significant and opposite changes in rates of resistance for some organisms and no change for others. At the individual hospital level, antibiograms appear to be an unreliable reflection of antibiotic use, at least for aminoglycosides.

SGLT2 Inhibitors: A Systematic Review of Diabetic Ketoacidosis and Related Risk Factors in the Primary Literature

Currently only minimal information is available regarding risk factors for the development of sodium glucose cotransporter‐2 inhibitor (SGLT2i)‐related diabetic ketoacidosis (DKA). We aim to identify individual patient characteristics associated with cases of SGLT2i‐related DKA to better describe potential risk factors.

Risk of Fracture and the Concomitant Use of Bisphosphonates With Osteoporosis-Inducing Medications

Objective: To review the literature on the concomitant use of bisphosphonates and medications that can influence bone metabolism and potentially attenuate bisphosphonate antifracture efficacy. Data Sources: MEDLINE and CINAHL were searched for articles published in English through December 2014 using the following terms: bisphosphonates, bone density conservation agents, acid-suppressive therapy, levothyroxine, thiazolidinediones (TZDs), selective serotonin reuptake inhibitors (SSRIs), bone fractures. Study Selection and Data Extraction: Studies were included if they reported results of concomitant use of any listed medications with bisphosphonates and risk of fractures and focused on women. Articles that focused generally on the use of one of the listed medications and fractures without explicitly examining the potential antifracture efficacy or attenuation of bisphosphonates were excluded. Data Synthesis: A total of 6 relevant studies were identified. Four epidemiological studies reported a statistically significant dose-dependent increase in the risk of fractures when bisphosphonates and acid-suppressive drugs were used together. One post hoc analysis of clinical trial data suggested no attenuation of the antifracture effects of bisphosphonates when used concomitantly with acid-suppressive therapy. One study involving bisphosphonates and SSRIs noted a statistically significant association between fracture risk and SSRI use. No study examining TZDs or levothyroxine with bisphosphonates was identified. Conclusions: Existing research suggests potential attenuation of bisphosphonate antifracture efficacy among patients taking acid-suppressive medications. Based on their pharmacological actions, TZDs, SSRIs, and levothyroxine have similar implications. The paucity of evidence in the literature associating the attenuation of bisphosphonate antifracture efficacy when combined with other medications suggests that further investigation is needed.

Increase in Use of Vancomycin for Clostridium difficile Infection in US Hospitals

Clostridium difficile infection (CDI) is a potentially serious disease for which the epidemiology has recently changed, because of an emerging drug-resistant strain of the pathogen. Metronidazole and oral vancomycin are the primary treatment agents.2 Metronidazole has been historically favored as the first-line agent, partly to reduce the selection pressure for vancomycin-resistant enterococci (VRE), although metronidazole can also select for VRE. Vancomycin was traditionally reserved for metronidazole treatment failure or life-threatening disease. In a study conducted before emergence of the epidemic strain, vancomycin was reported to be superior for the initial treatment of severe CDI and for treatment of CDI that does not respond to metronidazole. Expert opinion calling for the use of vancomycin as first-line therapy, especially for severe CDI emergence of the epidemic strain, and reports of decreased metronidazole efficacy may have impacted CDI treatment practices. The purpose of this study was to characterize trends in CDI treatment in US hospitals.

An Epidemiological Study of Anemia and Renal Dysfunction in Patients Admitted to ICUs across the United States

The aims of this study were to determine the associations between anemia of critical illness, erythropoietin stimulating agents (ESA), packed red blood cell transfusions and varying degrees of renal dysfunction with mortality, and ICU- and hospital length of stay (LOS). This was a cross-sectional retrospective study of 5,314 ICU patients from USA hospitals. Hospital, patient demographics, and clinical characteristics were collected. Predictors of mortality and hospital and ICU LOS were evaluated using multivariate logistic regression models. The mean ICU admission hemoglobin in this study was 9.4 g/dL. The prevalence of ESA use was 13% and was associated with declining renal function; 26% of the ICU patients in this study received transfusion. ESA utilization was associated with 28% longer hospital LOS (P < 0.001). ICU LOS was increased by up to 18% in patients with eGFR rates of <30 and 30–59 mL/min/1.73 m2, respectively (P < 0.05) but not in those receiving dialysis. Mortality was significantly associated with renal dysfunction and dialysis with odds ratios of 1.94, 2.66 and 1.40 for the dialysis, and eGFR rates of <30 and 30–59 and mL/min/1.73 m2, respectively (P < 0.05). These data provide a snapshot of anemia treatment practices and outcomes in USA ICU patients with varying degrees of renal dysfunction.

The Impact of Integrated Case Management on Health Services Use and Spending Among Nonelderly Adult Medicaid Enrollees.

Background:Medicaid plans, whose patients often have complex medical, social, and behavioral needs, seek tools to effectively manage enrollees and improve access to quality care while containing costs. Objectives:The aim of this study is to examine the effects of an integrated case management (ICM) program operated by a Medicaid managed care plan on health service use and spending for nonelderly, nonpregnant adults. Research Design:We estimate the relationship between intensity of ICM program involvement and changes in utilization and spending for patients who participated in ICM. We examine whether effects differ between high-risk and lower-risk individuals and between the early and late stages of the program, given that the latter relied on more targeted and patient-centered approaches. Specifically, we estimate linear regressions modeling changes in utilization and spending outcomes as a function of number of program contacts, conditional on number of days over which contacts occurred, as well as individual-level covariates and case manager fixed effects. Results:In the late ICM program period, we observe significant decreases in outpatient utilization associated with program involvement intensity among high-risk ICM participants. We also observe decreases in spending associated with program involvement intensity among the lower-risk group in the late period, although there is no significant impact on spending among high-risk enrollees. Conclusions:ICM can be a successful strategy for impacting health services use and spending. Our findings suggest that careful program targeting, well-structured client engagement, and direct one-on-one contact are vitally important for achieving program objectives.

An Active-Learning Laboratory on Immunizations

Objective. To implement and evaluate an active-learning laboratory activity to teach pharmacy students about influenza, pneumococcal, and shingles vaccines. Design. The laboratory session was divided into 6 immunization stations: 3 stations on influenza including a pediatrics station, and 1 station each for pneumococcal, shingles, and anaphylaxis. Assessment. Although 118 of 123 (95.9%) students had completed an immunization training certificate prior to attending the laboratory, the average score on a pre-assessment to measure immunization knowledge and confidence was 56%. The post-assessment score was 87.4%. Students’ confidence improved by 18.7% to 51.2% in each of the 5 areas assessed. Most respondents rated the activity overall as good or excellent on a post-activity evaluation. Conclusion. An active-learning approach to teaching immunizations allowed students to gain knowledge in simulated real-world experiences and reinforced key concepts on influenza, pneumococcal, and shingles vaccines.

Utilization Patterns of IV Iron and Erythropoiesis Stimulating Agents in Anemic Chronic Kidney Disease Patients: A Multihospital Study

Intravenous (IV) iron and Erythropoiesis Stimulating Agents (ESAs) are recommended for anemia management in chronic kidney disease (CKD). This retrospective cohort study analyzed utilization patterns of IV iron and ESA in patients over 18 years of age admitted to University Health System Hospitals with a primary or secondary diagnosis of CKD between January 1, 2006 to December 31, 2008. A clustered binomial logistic regression using the GEE methodology was used to identify predictors of IV iron utilization. Only 8% (n = 6678) of CKD patients on ESA therapy received IV iron supplementation in university hospitals. Those receiving iron used significantly less amounts of ESAs. Patient demographics (age, race, primary payer), patient clinical conditions (admission status, severity of illness, dialysis status), and physician specialty were identified as predictors of IV iron use in CKD patients. Use of IV iron with ESAs was low despite recommendations from consensus guidelines. The low treatment rate of IV iron represents a gap in treatment practices and signals an opportunity for healthcare improvement in CKD anemic patients.