Kayla R. Stover

A Review of Antibiotic Use in Pregnancy

During pregnancy, untreated sexually transmitted or urinary tract infections are associated with significant morbidity, including low birth weight, preterm birth, and spontaneous abortion. Approximately one in four women will be prescribed an antibiotic during pregnancy, accounting for nearly 80% of prescription medications in pregnant women. Antibiotic exposures during pregnancy have been associated with both short‐term (e.g., congenital abnormalities) and long‐term effects (e.g., changes in gut microbiome, asthma, atopic dermatitis) in the newborn. However, it is estimated that only 10% of medications have sufficient data related to safe and effective use in pregnancy. Antibiotics such as beta‐lactams, vancomycin, nitrofurantoin, metronidazole, clindamycin, and fosfomycin are generally considered safe and effective in pregnancy. Fluoroquinolones and tetracyclines are generally avoided in pregnancy. Physiologic changes in pregnancy lead to an increase in glomerular filtration rate, increase in total body volume, and enhanced cardiac output. These changes may lead to pharmacokinetic alterations in antibiotics that require dose adjustment or careful monitoring and assessment.

Cardiac toxicity of some echinocandin antifungals

Background: Unexplained cardiovascular decompensation has been observed during central venous administration of some echinocandins. Objective: The purpose of this study was to assess cardiac toxicity associated with the echinocandins. Methods: Isolated rat hearts (Langendorff model) were perfused with anidulafungin (ANID), caspofungin (CASP), or micafungin (MICA) at exposures of 1, 4, and 10 times therapeutic concentrations. Changes in left ventricular contractility with experimental exposure were compared to control, and histologic and transmission electron microscopy (TEM) examinations of tissue were performed. Results: Mean concentrations of ANID (10 – 80 µg/ml) and CASP (6 – 48 µg/ml) were associated with significant decreases in contractility (-77.1 ± 9.4% and -40.6 ± 15.6%, respectively; p < 0.05). MICA was associated with an increase in contractility (13.6 ± 2.8%, p = NS). On TEM, samples exposed to ANID and CASP had enlarged mitochondria and disintegrating myofibrils. Samples exposed to MICA showed some enlarged mitochondria. Conclusion: Mean concentrations of ANID and CASP were associated with statistically significant decreases in left ventricular contractility at concentrations that may be achievable in humans after peripheral administration, while MICA caused no change. TEM studies suggest this may be a result of mitochondrial damage. Caution may be warranted with central administration of these agents to patients with preexisting cardiac dysfunction.

Therapeutic options for vancomycin-resistant enterococcal bacteremia

Enterococcal infections are relatively common among hospitalized patients, likely because these organisms are commensals of human gastrointestinal and genitourinary tracts. With widespread usage of glycopeptides in both humans and livestock, vancomycin-resistant enterococci (VRE) quickly emerged. Bloodstream infections caused by these isolates are of significant concern with limited bactericidal options for treatment. Presently, daptomycin and linezolid serve as the mainstays of therapy, although resistance to both agents has been documented. Newer antimicrobials, specifically lipoglycopeptides and oxazolidinones, have been developed with in vitro activity against these organisms. However, no clinical data are available with their usage for VRE infections, let alone those in the bloodstream. This review focuses on the epidemiology, current and potential future therapeutic options for the treatment of VRE bacteremia.

Cardiac toxicity of the echinocandins: chance or cause and effect association?

Fungal infections pose a constant risk to critically ill and immunosuppressed patients. The echinocandin antifungals give practitioners an arsenal of agents with apparently lower toxicity relative to older agents. The objective of this commentary is to review the cardiac toxicity of the echinocandin antifungals in the light of recent evidence and published case reports.

A Fatal Case of Kaposi Sarcoma Due to Immune Reconstitution Inflammatory Syndrome

The prevalence of AIDS-related Kaposi sarcoma (KS) has markedly declined in the era of highly active antiretroviral therapy (HAART) although it remains one of the most common AIDS-defining malignancies. Although immune reconstitution inflammatory syndrome (IRIS)-related KS (IRIS-KS) represents only a fraction of the IRIS cases, it can be a life-threatening situation. This report describes a fatal case of IRIS-KS. A 32-year-old man with HIV/AIDS was initiated on HAART and experienced rapid immunological and virological response to therapy. He subsequently experienced progressively severe dyspnea and papulonodular skin lesions and was admitted to the hospital with hypoxic respiratory failure. Bronchoscopy revealed numerous friable endobronchial lesions. Histopathology of a skin lesion was consistent with KS. The relatively rapid progression of disease in the setting of improvement in immune function after initiating HAART suggested IRIS-KS. This report reviews previously published cases of IRIS-KS and describes risk factors, immunopathogenesis and treatment options.

Epidemiology and Management of Antiretroviral-Associated Cardiovascular Disease

Risk and manifestations of cardiovascular disease (CVD) in patients infected with human immunodeficiency virus (HIV) will continue to evolve as improved treatments and life expectancy of these patients increases. Although initiation of antiretroviral (ARV) therapy has been shown to reduce this risk, some ARV medications may induce metabolic abnormalities, further compounding the risk of CVD. In this patient population, both pharmacologic and nonpharmacologic strategies should be employed to treat and reduce further risk of CVD. This review summarizes epidemiology data of the risk factors and development of CVD in HIV and provides recommendations to manage CVD in HIV-infected patients.

Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C

Hepatitis C virus (HCV) is estimated to affect up to 150 million people worldwide. Despite worldwide prevalence, treatment modalities prior to 2011 remained suboptimal, with low virologic response rates and intolerable side effect profiles. Fortunately, the landscape of treatment for chronic hepatitis C has rapidly evolved since the introduction of HCV NS3/4 protease inhibitors in 2011. Elbasvir, a NS5A inhibitor, combined with grazoprevir, a NS3/4A protease inhibitor, is the latest FDA-approved therapy for patients with genotype 1 or 4 chronic hepatitis C, with or without compensated cirrhosis. This review will focus on the current literature and clinical evidence supporting elbasvir/grazoprevir as first-line therapy in patients with genotypes 1 and 4 chronic hepatitis C.

Physical Assessment Experience in a Problem-Based Learning Course

Objective. To evaluate the impact of a physical-assessment learning experience implemented in the problem-based learning (PBL) format of the third year of a doctor of pharmacy (PharmD) program. Design. Students enrolled in a PBL course completed survey instruments to measure knowledge and confidence before and after participating in the learning experience. A simulation stethoscope was used to teach students abnormal pulmonary and cardiovascular sounds in 1-hour sessions for each of 12 PBL groups. Assessment. The 92 students enrolled in the PBL course completed pre- and post-experience survey instruments. Students’ scores on knowledge questions increased significantly (p < 0.0001) from 40.4% ± 11.4% at baseline to 62.5% ± 13.7% and 63.1 ± 11.6%, respectively, on the 2 sets of post-experience questions. Students scored a median of 3 or 4 on a 5-point Likert scale after a learning experience on questions measuring confidence. Conclusion. Use of a simulation stethoscope in a physical-assessment learning experience increased pharmacy students’ knowledge in performing pulmonary and cardiovascular assessment techniques.

Cardiac response to centrally administered echinocandin antifungals.

The purpose of this study was to determine the effect of the echinocandin antifungals on the cardiac system, including cardiac output, blood pressure and heart rate, when administered in an in‐vivo model.

Antifungal-Associated Drug-Induced Cardiac Disease

The etiology of cardiomyopathies are classified into 4 main groupings (dilated, hypertrophic, restrictive, and idiopathic) and can be mechanistically caused by myocarditis, conduction abnormalities, focal direct injury, or nutritional deficiency. Based on our review of this topic, evidence suggests that echinocandin-related cardiac dysfunction is a mitochondrial drug-induced disease caused by focal direct myocyte injury. With caspofungin or anidulafungin administration into the heart via central line, exposure is likely extreme enough to induce the acute toxicity. Chronic or low-dose exposure may lead to hypertrophic cardiomyopathy; however, only acute exposures have been explored to date.