Case Studies December 2018
KG is a 55-year-old man presenting to the outpatient heart failure (HF) clinic for his scheduled 6-month follow-up appointment. He notes feeling short of breath when walking up 1 flight of stairs and has had difficulty dressing himself on occasion. KG also complains of some dyspnea on exertion and has had a persistent, nonproductive cough. He says that these symptoms have worsened over the past 2 weeks, though he denies any chest pain or neurological deficit. KG has a medical history of HF with reduced ejection fraction (HFrEF), classified as New York Heart Association class III, with an ejection fraction of 30%, hyperlipidemia, and hypertension. Today his physical exam indicates a blood pressure of 130/85 mm Hg and bilateral 2+ pitting edema in his legs, and previsit laboratory testing shows a B-type natriuretic peptide level of 255 pg/dL (normal = <120). KG’s home medications include atorvastatin 40 mg once daily, carvedilol 12.5 mg twice daily, enalapril 10 mg twice daily, and furosemide 20 mg once daily.
What changes to his medications might you suggest to decrease morbidity and mortality associated with HFrEF?
LH is a 78-year-old woman presenting to the emergency department complaining of a fever, a productive cough, and shortness of breath. She was recently hospitalized for flulike symptoms and was discharged 4 days ago. LH has a blood pressure of 122/80 mm Hg, a heart rate of 70 beats per minute, a respiratory rate of 22 breaths per minute, and a temperature of 102°F. A chest x-ray is ordered and shows “patchy opacities in the lower portion of both lungs.” LH does not have a history of recent antibiotic use. Her glomerular filtration rate is >60 mL per minute, or 1.73 m2, and her white blood cell (WBC) count is elevated, at 13,000 cells per cm3. Blood cultures and sputum are pending. LH’s physician makes a preliminary diagnosis of hospital-acquired pneumo- nia (HAP) and asks you as a pharmacist for antibiotic recommendations.
What treatment options should you recommend for empiric therapy of HAP for her?
Current guidelines suggest that changing KG’s enalapril therapy to sacubitril/valsartan (Entresto) can further decrease morbidity and mortality in patients with class III HFrEF like him who have previously tolerated angiotensin- converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Sacubitril/valsartan is a neprilysin inhibitor/ARB combination drug that lowers mortality risk more than enalapril alone. Neprilysin is an enzyme that breaks down natriuretic peptides, resulting in a decrease in sodium and water reten- tion, systemic vascular resistance, and ventricular hypertrophy.
Initiation of sacubitril/valsartan 49 mg/51 mg twice daily would be reason- able after enalapril is discontinued for 36 hours. The purpose of delaying the initiation of sacubitril/valsartan when switching from an ACEI is to lower the risk of developing angioedema. An eventual target dose of 97/103 mg twice daily should be recommended.
The Infectious Diseases Society of America treatment guidelines for HAP suggest broad-spectrum antibiotic coverage for empiric therapy. Important pathogens to cover in HAP include gram-negative Pseudomonas aeruginosa and gram-positive methicillin-resistant Staphylococcus aureus (MRSA). For MRSA coverage, standard treatment is vancomycin 15 mg/kg every 8 to 12 hours, though hospitals often have established protocols for initiating therapy, based on body weight and renal function. For pseudomonal coverage, local resistance patterns should be consulted when determining the optimal empiric treatment option. Agents with antipseudomonal coverage include cefepime, ceftazidime, levofloxacin, and piperacillin-tazobactam (Zosyn).
As a pharmacist, you might recommend empiric therapy with vancomycin 1 g every 12 hours and piperacillin-tazobactam 4.5 g every 6 hours for at least 7 days or until clinical resolution (absence of elevated WBC counts or fever) is achieved.