Infection in the Patient with Cancer
Summary of Key Points
• Risk assessment is an important tool for evaluation and treatment in patients with cancer who have fever and neutropenia. Patients who are expected to have neutropenia lasting more than 7 days, including those undergoing allogeneic stem cell transplantation or therapy for acute leukemia, are considered to be at high risk for infectious complications. Most patients with solid tumors will have neutropenia lasting fewer than 7 days and are considered to be at low risk.
• Other risk factors for infection in patients with cancer, beside chemotherapy- and disease-related neutropenia, are the presence of indwelling catheters, comorbid medical conditions such as diabetes or chronic obstructive pulmonary disease, recent surgery, malnutrition, and cellular and humoral immune defects from an underlying tumor and its treatment.
• Fever during neutropenia necessitates immediate evaluation, assessment of risk as high or low, appropriate cultures, and prompt institution of empirical broad-spectrum antibacterial therapy with a defined regimen that covers Pseudomonas aeruginosa and enteric gram-negative organisms, as well as common institutional pathogens. Gram-positive active agents are not a standard component of the empirical treatment regimen for fever and neutropenia.
• Antibiotic prophylaxis with levofloxacin has been shown to decrease fever and infection in high-risk patients with acute leukemia or those undergoing stem cell transplantation, with neutropenia (<1000 neutrophils/mm3) lasting more than 7 days, although no morality benefit has been consistently shown.
• Posaconazole prophylaxis reduces the incidence of invasive fungal infections and mortality in patients undergoing induction for acute leukemia and reduces fungal infections in patients treated for higher grade graft-versus-host disease. Voriconazole has been shown to be equivalent to fluconazole for prevention of fungal infections in allogeneic stem cell transplant recipients.
• Newer agents used to treat a variety of lymphoproliferative disorders (e.g., alemtuzumab and purine analogs) result in prolonged suppression of cellular immunity and predispose persons to certain infections; patients receiving these agents may benefit from prophylaxis against opportunistic infections.
• An epidemic strain of Clostridium difficile has emerged as a major cause of morbidity and mortality in many centers, and fluoroquinolone use is a risk factor. Metronidazole is recommended for mild disease, but oral vancomycin should be given for more severe symptoms of C. difficile infection.
• Numerous antifungal agents may be used for empirical antifungal therapy after 4 to 7 days of broad-spectrum antibiotic use in patients who are still febrile; however, some debate continues regarding whether all patients definitely require empirical antifungal therapy. A high-resolution computed tomography scan of the chest and serial galactomannan assay results may identify possible mold infections and guide antifungal management.
• Patients scheduled for allogeneic hematopoietic stem cell transplantation should be screened for evidence of latent herpesvirus and hepatitis virus infections, and prophylaxis should be instituted accordingly.
1. A 57-year-old woman with metastatic colon cancer is admitted with fever and is treated with vancomycin and cefepime. She is not currently neutropenic; blood cultures grow methicillin-resistant Staphylococcus aureus (MRSA). Her central venous catheter is removed, but blood cultures obtained 4 days after admission remain positive. Her fever resolves, and blood cultures obtained 5 days after admission are negative. Which of the following is the best treatment course?
A Replace the catheter and treat with intravenous vancomycin for 2 weeks
C Replace the catheter and treat with intravenous vancomycin for 4 to 6 weeks
D Perform a transesophageal echocardiogram, and if negative, treat for 2 weeks with oral linezolid
2. A 49-year-old man had an allogeneic stem cell transplant for acute myelogenous leukemia (AML) 3 weeks ago. Acute mental status changes develop, and a magnetic resonance imaging scan demonstrates edema with some hemorrhage in the medial temporal lobe. Prophylactic antimicrobial agents include acyclovir, fluconazole, and penicillin. Which virus would be most likely to cause his symptoms?
3. A 62-year-old woman is about to receive chemotherapy for breast cancer. With her last cycle, she experienced 4 days of neutropenia and had a fever for 48 hours that resolved with 7 days of treatment with amoxicillin/clavulanic acid and levofloxacin. She has no history of HSV reactivation. Appropriate antimicrobial prophylaxis would include:
4. Which of the following statements are true regarding the antifungal drug posaconazole? (Select all that apply):
A It provides superior activity against Candida albicans compared with fluconazole.
B It has a mortality benefit in patients with AML who are undergoing induction chemotherapy compared with fluconazole or itraconazole.
C It provides reduced invasive mold infections in patients with graft-versus-host disease (GVHD) compared with fluconazole.
5. Patients with multiple myeloma who are treated with bortezomib require prophylaxis to prevent reactivation of what organism?
1. Answer: C. Patients with complicated MRSA bloodstream infections (e.g., bacteremia >48 hours, deep-seated focus of infection) typically require at least 4 weeks of intravenous antibiotics.
2. Answer: A. HHV-6 has a tropism for the hippocampus (medial temporal lobe), and reactivation after stem cell transplantation (usually in the first 30 days) may result in encephalitis. Acyclovir would likely prevent reactivation of HSV (which may also cause temporal lobe bleeding) and VZV, but it does not have activity against HHV-6. CMV would be a very rare cause of encephalitis early after stem cell transplantation, and temporal lobe hemorrhage would be unusual.
3. Answer: D. For low-risk patients with solid tumors, antimicrobial prophylaxis is generally not indicated. Although levofloxacin may reduce her risk of fever, administration will make empiric oral treatment of fever during neutropenia more difficult, and most experts do not recommend it in this situation. Antifungal prophylaxis is not recommended for brief duration of neutropenia, and antiviral prophylaxis would only be needed if the patient had a history of HSV reactivation.
4. Answer: B and C. Posaconazole has been demonstrated to be effective in preventing mold infections in patients with hematologic malignancies requiring treatments that result in prolonged neutropenia and in patients with GVHD. Unlike fluconazole, posaconazole is active against molds such as Aspergillus spp., but activity against Candida albicans is similar to fluconazole. Posaconazole is currently available only as a liquid formulation that is best absorbed with a fatty meal, and achieving adequate levels can be challenging. Fluconazole, in contrast, has excellent bioavailability.
5. Answer: B. Studies have demonstrated an increased risk for varicella-zoster virus reactivation, and thus patients with multiple myeloma who are treated with bortezomib should receive prophylaxis with acyclovir, valacyclovir, or famciclovir.
