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Infections in cancer patients. By Alfred Elias Namour ; M.D. NCI, Cairo University. Objectives. To know the risk factors that predispose cancer patients to infection. To highlight different preventive measures that could be used in cancer patients.
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Infections in cancer patients By Alfred Elias Namour; M.D. NCI, Cairo University
Objectives To know the risk factors that predispose cancer patients to infection. To highlight different preventive measures that could be used in cancer patients. To discuss management of febrile neutropenic cancer patients. To highlight the possibility of outpatient management of low risk neutropenic patients.
Risk Factor for Infection Factors that predispose to infectious diseases include those related to the underlying malignancy and treatment-related immunosuppression. • A. Hematologic Malignancies: Lymphoid malignancies are associated with impaired lymphocyte function, predisposing to intracellular (T-cell malignancies) or bacterial (B-cell malignancies) infections.
B. Solid Tumors : Head and neck tumors may erode into the mouth and through fascial planes of the neck, predisposing to serious infections by oral flora. They also increase the risk of aspiration pneumonia. Endobronchial tumors may cause recurrent postobstructive pneumonias. Abdominal tumors may obstruct the genitourinary or hepatobiliary tracts, predisposing to pyelonephritis and cholangitis, respectively. Direct invasion through the colonic mucosa is associated with local abscess formation and sepsis by enteric flora.
C.Asplenia: The spleen is important for antigen presentation, production of antibodies by B cells, and removal of bacteria. Besides splenectomy, functional asplenia is present after splenic irradiation and also with chronic graft-versus-host disease (GVHD). The most common pathogen is Streptococcus pneumoniae, but other pathogens include Hemophilusinfluenzae and Neisseriameningitidis.
D. Treatment-Related Factors: 1. Mucositis: Besides the physical barrier, mucosal epithelial cells secrete a variety of antimicrobial peptides. Chemo- and radiation therapy impair mucosal immunity. 2. Chemotherapy-Induced Neutropenia:The lack of granulocytes facilitates bacterial and fungal infections and blunts the inflammatory response.
3. Immunomodulatory Agents: CorticosteroidsPatients treated with corticosteroids have impaired phagocytic function and cell-mediated immunity. Fludarabine is lymphotoxic, primarily affecting CD4+ lymphocytes. Interleukin-2 Patients have an increased risk of bacterial infections, mainly S. aureus and coagulase-negative staphylococci. Monoclonal Antibodies e.g. Rituximab. cyclosporine A and tacrolimusImmunosuppressive Agents to Prevent and Treat Graft Versus Host Disease
General measures Appropriate hand hygiene is the single most important mean. Skin care. Fresh flowers should not be present in the rooms. High-efficiency particulate air filters & laminar airflow rooms are expensive & of questionable benefit.
Prevention of Bacterial Infections • Prophylaxis with levofloxacin may be beneficial and cost-effective in high-risk patients with prolonged neutropenia (stem cell transplant and induction of remission of acute myelogenous leukemia), but not so much in low-risk patients (solid tumors with short neutropenia). • Oral levofloxacin 500 mg, starting at the beginning of neutropenia, for some patients expected to have absolute neutrophil counts less than 1,000 mcL for more than 7 days.
Prevention of Fungal Infections The term invasive fungal infection encompasses two main processes namely candidiasis and mold infections (aspergillosis). • Most patients with cancer do not require antifungal prophylaxis. High-risk patients include those receiving treatment for acute leukemia & hematopoietic stem cell transplant (HSCT) recipients. • Candidiasis during prolonged neutropenia is prevented by the use of fluconazole 400 mg/d. When the risk of aspergillosis is significant, the preferred drug is posaconazolewhich showed improved survival compared with fluconazole.
Prophylaxis of Viral Infections Herpes simplex virus (HSV) predominantly affects patients during profound neutropenia. Antiviral prophylaxis (acyclovir, valacyclovir, or famciclovir) against HSV is advised in patients receiving chemotherapy for acute leukemia, in all HSV seropositive HSCT recipients.
Carriers of hepatitis B virus may develop severe hepatitis flare when they receive cytotoxic chemotherapy. Lamivudine100 mg daily started 7 days before chemotherapy and continued for 8 weeks after completion of chemotherapy is safe and effective to prevent hepatitis B flares in this setting. Significant acute hepatic dysfunction related to HCV reactivation is uncommon in nontransplant HCV-positive patients receiving chemotherapy for hematologic malignancies.
Fever and Neutropenia • Fever: A single oral temperature of greater than 38.3°C or 38.0°C or greater for over 1 hour. • Neutropenia: absolute neutrophil count less than 500 mcL or less than 1,000 mcL with predicted rapid decline. Infection is documented only in a minority of febrile neutropenic patients. In approximately 50% no infection is found, in 30% an infection is microbiologically documented (most commonly, bacteremia), and in 20% an infection is clinically documented.
Initial Evaluation • complete history • meticulous physical examination with special attention to the mouth, skin, catheter exit site, and perianal region. • The oral cavity may show mucositis. • A detailed inspection of the skin, including the nails, may disclose a lesion suggestive of a possible portal of entry or of systemic infection. • Catheter sites and sites of prior skin penetration (such as surgical wounds and biopsy sites) should be palpated.
Laboratory studies: • complete and differential blood count. • serum chemistry including liver function tests, at least two sets of blood cultures, and a urine culture. • a chest radiograph as part of the initial evaluation in patients requiring hospitalization and in patients at higher risk for infections. • Cutaneous lesions or sputum, should be sampled prior to instituting antibiotics. • However, fever in neutropenic patients is a medical emergency, and prompt initiation of empirical antibiotics should not be delayed if cultures cannot be readily obtained .
Antibiotic Regimens • Monotherapy with a β-lactam with activity against pseudomonas aeruginosais the cornerstone of the management of fever in neutropenic patients. • The agents recommended are ceftazidime, cefepime, imipenem, and meropenem. • Piperacillin/tazobactam (4.5 g every 6 hours) is an acceptable alternative except where the frequency of P. aeruginosa or extended spectrum β-lactamase-producing Gram-negative bacilli is high.
Adding a Second Agent with Activity against Gram-Negative Bacilli: an aminoglycoside, which used to be standard of care, should be limited to patients with hemodynamic instability and when there is a high suspicion for antibiotic-resistant Gram-negative bacterial infections based on local susceptibility patterns. Ciprofloxacin is an acceptable alternative to an aminoglycoside as part of a combination regimen.
Initial empirical addition of vancomycin has not been associated with improved outcome and it results in increased toxicity and cost. • Vancomycin is added in specific settings during neutropenia, which include (1) clinically apparent, catheter-related infection (2) blood culture positive for a Gram-positive bacterium (3) colonization with methicillin-resistant S. aureus (MRSA) (4) hypotension or septic shock without an identified pathogen.
Modification of the Antibiotic Regimen • The initial antibiotic regimen needs to be modified depending on clinical evolution and/or microbiological results. • Daily evaluation of the patient is essential to search for new findings (tachypnea, tachycardia, hypotension, new skin lesions, pain or tenderness) that may suggest persistent or breakthrough infection.
Duration of Treatment • If fever resolves following initiation of empirical therapy, one should assume that an infection existed that has responded to antibiotics. • The standard recommendation is to continue antibiotics until resolution of neutropenia. If the neutropenia persists, classic studies showed that 2 weeks may be adequate.
Persistent Fever in the Neutropenic Patient • The longer the fever persists without new findings, the higher the risk of fungal infection. The majority of persistently febrile neutropenic patients do not harbor an identifiable fungal infection • Delay in initiating antifungal therapy was clearly associated with treatment failure and death.
Amphotericin B was associated with a trend toward fewer invasive fungal infections in antibiotic-treated neutropenic patients with persistent fever. • liposomal amphotericin B, itraconazole, voriconazole, and caspofungin are acceptable alternatives as empirical antifungal therapy to be added on day 5 of persistent neutropenic fever.
Serial serum galactomannan and chest computed tomography (CT) scanning can detect early aspergillosis . • CT scan, galactomannan, and bronchoalveolarlavage results were used to guide modification of the antifungal regimen.
Viral infections • Varicella-Zoster virus(VZV) Shingles is characterized by the development of vesicles in clusters on erythematous bases along one to three dermatomes. Disseminated & ophthalmic infections are treated by IV acyclovir 10mg/kg every 8 hours for 7 days while localized disease can be treated by initial IV then oral acyclovir 800mg PO five times daily. . • Herpes simplex virus can be treated safely by acyclovir at a dose of 200mg PO five times daily for 7 to 10 days.
Colony-Stimulating Factors In neutropenic patients with life-threatening infections, survival is strongly influenced by the rapidity of neutrophil recovery. Thus CSFs could potentially be used in these settings to augment the number of circulating neutrophils.
Although the benefit of any CSF for established infections is unproven, it may be considered in selected cases of profound neutropenia (absolute neutrophil count less than 100 mcL), uncontrolled primary disease, and in serious infections, such as pneumonia, hypotension, and invasive fungal infection. • ASCO recommendations for CSF use: https://pilotguidelines.atlassian.net/wiki/display/WBCGF
Lower-risk Patients with Fever and Neutropenia • Independent factors that predicted a low risk of complicationsare: (1) burden of illness characterized by low or moderate symptoms (2) absence of hypotension (3) absence of chronic obstructive pulmonary disease (4) presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (5) absence of dehydration
Outpatient Management of Febrile Neutropenic Patients • Outpatient oral antibiotic therapy can be used in carefully selected lower-risk patients with neutropenic fever. Ciprofloxacin plus amoxicillin/clavulanate is recommended. In patients allergic to penicillin, Guidelines recommend substituting amoxicillin/clavulanate with clindamycin. • Patients must live in close proximity to a facility that can provide emergency care.
