Robert T. Adamson

Levofloxacin-Associated Achilles Tendon Rupture

OBJECTIVE: To describe a case of levofloxacin-induced partial Achilles tendon rupture; this occurred in the presence of known risk factors and acute renal failure. CASE SUMMARY: A 79-year-old white man received levofloxacin for presumed pneumonia, developed acute renal failure in the setting of dehydration, and began having ankle pain on the 12th day of admission. Levofloxacin was discontinued, and magnetic resonance imaging revealed a 6-cm partial tear and degenerative changes. DISCUSSION: The Naranjo probability scale indicates a possible association between levofloxacin and tendon rupture because the event occurred in the setting of known risk factors such as steroid use, renal failure, older age, and male gender. CONCLUSIONS: Levofloxacin, like other fluoroquinolones, may cause Achilles tendon rupture, and this may be particularly likely with known risk factors.

Sex and ethnicity may chiefly influence the interaction of fluconazole with calcineurin inhibitors.

Background. Calcineurin inhibitors (CNI) and azole antifungal agents have been reported to interact in a disparate manner. The azole dose and route and the level of involvement of the liver and intestines have been implicated, although data are limited. A significant interaction may result in CNI toxicity, and withdrawal of the azole may result in subtherapeutic CNI concentrations. Fluconazole, available in both intravenous and oral formulations, is commonly used in transplant recipients and is ideal for determining the presence of a disparate effect on CNI concentrations. We retrospectively investigated the interaction of CNIs with fluconazole, evaluating CNI blood troughs corrected for daily CNI dose, the factors influencing the interaction, and the effect on clinical outcomes in renal and simultaneous pancreas kidney transplant recipients. Methods. Twenty-eight patients received a CNI and fluconazole during the calendar year 1999, but only 19 patients had documented CNI blood troughs and outpatient follow-up. There were 25 episodes of use in the 19 included patients. CNI blood troughs were evaluated for changes induced by fluconazole, given by both routes, and clinical outcomes were tracked. Results. Data demonstrated both intravenous and oral fluconazole alter CNI blood concentrations. Two metabolic patterns were observed, and we termed these convergent and divergent. Divergent metabolizers did not have significant interaction (n=5), and convergent metabolizers did have a significant interaction (n=15). One patient had a divergent episode after a previous convergent episode. The main contributors to the lack of interaction appeared to be female sex and African American ethnicity. Additionally, tacrolimus levels were significantly more affected than cyclosporine, during and after fluconazole administration. No patient experienced nephrotoxicity or cellular rejection related to antifungal therapy. Conclusions. Oral and intravenous fluconazole appear to increase oral CNI trough concentrations to a similar extent even after adjusting for daily calcineurin dose. These interactions appear to be chiefly influenced by sex and ethnicity. Further prospective study is necessary to clarify this issue.

Accountable care organizations: impact on pharmacy.

The Patient Protection and Affordable Care Act (PPACA) has considerably transformed the approaches being used to deliver health care in the United States. It was enacted to expand health insurance access, improve funding for health professions education, and reform patient care delivery. The traditional fee-for-service payment system has been criticized for overspending and providing substandard quality of care. The Accountable Care Organization (ACO) was developed as a payment reform mechanism to slow rising health care costs and improve quality. Under this concept, networks of clinicians and hospitals share responsibility for a population of patients and are held accountable for the financial and clinical outcomes. Due to high rates of medication misuse, nonadherence to therapeutic medication regimens, and preventable adverse drug events, pharmacists are in an ideal position to manage drug therapy and reduce health care expenditures; as such, they may be valuable assets to the ACO team. This article discusses the role of the pharmacist in the era of ACOs specifically and health care reform globally. It outlines pharmacy-related quality of care measures, medication therapy management (MTM) programs (which may provide the foundation for pharmacist involvement in ACOs), and pharmacist functions in patient-centered medical homes (through which ACO services may be organized). The article concludes with a description of successful ACO models that have incorporated pharmacists into their programs.

Prescribing patterns and outcomes of enoxaparin for anticoagulation of atrial fibrillation

Study Objective. To determine prescribing patterns and clinical outcomes of enoxaparin for anticoagulation of atrial fibrillation.

Clinical response at Day 3 of therapy and economic outcomes in hospitalized patients with acute bacterial skin and skin structure infection (ABSSSI)

Abstract Objective: The FDA recently issued guidance for the types of infections that should be included in trials to support an indication for antibacterial treatment. The latest FDA guidance recommends assessing response to drug therapy at 48 to 72 hours as the primary endpoint in clinical trials. This study evaluated clinical and economic outcomes among acute bacterial skin and skin structure infections (ABSSSI) patients hospitalized at a 3000-bed healthcare system in New Jersey. Research design and methods: In this retrospective cohort analysis, adult ABSSSI patients hospitalized between July 2010 and December 2011 were stratified based on infection type: cellulitis/erysipelas and major cutaneous abscess, wound infection, and all ABSSSI. Initial antibiotic therapy was assessed by individual agent, regimen, and MRSA coverage. Day 3 response to initial antibiotic therapy was evaluated based on temperature and lesion cessation outcomes; clinical response rates were assessed by initial therapy and pathogen for each cohort. The impact of response on length of stay (LOS), cost of care, and antibiotic treatment duration were also evaluated. Results: Commonly used antibiotics included vancomycin, cefazolin, piperacillin–tazobactam, and ampicillin–sulbactam; over 40% of patients received empiric therapy with activity against MRSA. Clinical non-response to initial antimicrobial therapy at Day 3 was 39.9%, 30.3%, and 60.7%, for all ABSSSI, cellulitis/abscess, and wound infection patients, respectively. The cost of care among non-responders was over 1.5 times that of responders (p < 0.0001). Non-response to initial therapy was associated with a 3.7 day increase in duration of antibiotic treatment (p < 0.0001). Conclusions: Results of this study demonstrate that a significant percentage of ABSSSI patients, particularly those with wound infection, were not achieving clinical response at Day 3 of therapy. Failure to respond to drug therapy is associated with substantial increases in LOS, antibiotic treatment duration, and cost of care. Limitations: This had the inherent limitations associated with a retrospective chart review; because data was initially collected for clinical rather than research purposes, certain information may have been absent, incomplete, or missed by data abstractors.

Use of Filgrastim among Febrile Inpatients who Received Outpatient Filgrastim or Pegfilgrastim

Purpose To characterize the inpatient use of filgrastim in cancer patients hospitalized for management of post-chemotherapy fever after receiving either outpatient filgrastim or pegfilgrastim. Method Retrospective review of chart records in a single-center, tertiary-care, teaching hospital and outpatient oncology center of cancer patients hospitalized for fever after outpatient chemotherapy and proactive administration of filgrastim or pegfilgrastim. Patients with the following tumor types were included: breast cancer, cervical cancer, colon cancer, Hodgkin disease, intermediate- or high-grade non-Hodgkin lymphoma, small cell or non-small cell lung cancer, and ovarian cancer. Result Billing data identified 1,438 outpatient chemotherapy patients treated with filgrastim or pegfilgrastim; 261 (18.2%) of whom were hospitalized for fever. All patients in the filgrastim groups, and 78% of those in the pegfilgrastim group, were given inpatient filgrastim. Duration of filgrastim administration in the inpatient setting was significantly shorter (P < 0.001) for the pegfilgrastim group. Conclusions Filgrastim was frequently administered to cancer patients hospitalized for fever, even after outpatient pegfilgrastim was administered as an adjunct to chemotherapy. Patients treated with once-per-cycle pegfilgrastim in an outpatient setting do not require filgrastim if they are hospitalized for fever before neutrophil recovery. Thus, hospitals could realize immediate cost savings by not treating those patients with filgrastim. This study illustrates the need to develop operational procedures in institutions to rapidly identify prior outpatient pegfilgrastim administration as a patient is admitted for post-chemotherapy fever.

Cost and Quality Implications of Opioid-Based Postsurgical Pain Control in Total Abdominal Hysterectomy: A Study of Cost Outliers and Opioid-Related Adverse Events

Objective A retrospective medical record review, case-control study of patients undergoing total abdominal hysterectomy was conducted to determine the relationship between opioid burden, related adverse drug effects (ADEs), and extended length of stay (LOS) and acute care costs cause(s) of LOS outliers. Methods Ninety-seven case patients with extended LOS (≥ 5 days) met the study eligibility criteria and were matched with case controls (patients with a LOS <5 days). The medical records of cases and controls were reviewed to collect information describing pre-established data points: opioid doses and opioid-related ADEs. Difference between cases and controls were compared using McNemars test for matched pairs, paired t test, and signed rank test. Results Comparisons of opioid-related ADEs revealed the following statistically significant differences compared with controls: respiratory ADEs (eg, hypoxia) in 12% of cases versus 1% of controls (P < .01) and gastrointestinal ADEs (eg, nausea/vomiting) in 44% of cases versus 19% of controls (P < .01). Cases received higher doses during the 72 hours following postanesthesia care unit (PACU) discharge (P = .04). By hospital discharge, cases had received 2.5 times the total opioid dose of controls and, on average, remained hospitalized 132 hours (5.5 days) longer than controls. Approximately 33% of LOS difference between cases and controls occurred prior to operating room admission, whereas approximately 66% occurred between PACU admission and hospital discharge. Conclusions Case patients with unusually long length of hospital stay (LOS outliers) received higher opioid doses and experienced more opioid-related ADEs than controls. These factors appear to contribute to outlier status but cannot completely explain all LOS outliers.

Integrated Care of Anemia in Chronic Kidney Disease Patients: Concepts in Intravenous Iron Management: Part One

Chronic kidney disease (CKD) has become a worldwide public health issue with increasing prevalence in the United States. As kidney function declines, anemia or other complications may arise, and hemodialysis (HD) or kidney transplantation may be needed. Early intervention and treatment of CKD complications will improve clinical outcomes and may delay or prevent disease sequelae. Primary or adjuvant iron replacement in CKD patients with anemia is recommended. The National Kidney Foundation guidelines state that patients receiving erythropoiesis-stimulating agent (ESA) therapy and HD will require intravenous (IV) iron for optimal iron stores and ESA efficacy. This article, the first of a two-part series, details the optimization of IV iron therapy in CKD patients, clinical trial evaluation of IV versus oral iron in the non–HD-dependent CKD patient, and a comparison of the four available IV iron agents. The percent changes in ESA utilization in conjunction with iron therapy and the associated cost savings are also addressed. The second article in this series goes on to describe elements of the medication use process for care of CKD patients with anemia.