Lalitha Parameswaran and Monika K. Shah
Background: Identification of the High Risk Host
Pts undergoing CA tx are at ↑ risk for infxn due to disease itself or its therapies. NCCN divides pts into risk categories based on w/c tx & prophylactic strategies are advised (J Natl Compr Canc Netw 2012;10:1412).
Predisposing Diseases and Conditions
• Disease: Leukemias, MDS, or lymphoma: Leukopenia 2° to marrow dysfunction or leukemic infiltration; MM: Functional hypogammaglobulinemia- predisposes to infxn w/encapsulated organisms. CLL:Hypogammaglobulinemia; heavily pretreated w/lymphotoxic purine analogs such as Fludarabine or Pentostatin causes defects in cell-mediated immunity against pathogens like Listeria, Pneumocystis jiroveci, mycobacteria, opportunistic viral & bacterial pathogens (Cancer 2002;94:2033; Clin Exp Immunol 1992;89:374; Oncology (Huntingt) 2000;14:41). Refractory CA: ↑ risk due to marrow infiltration or poor marrow function due to previous toxic therapies.
• Chemotherapy: Monoclonal Ab: Anti CD52- Alemtuzumab causes sev. & prolonged T cell depletion; Anti CD20- rituximab & Ofatumumab cause reactivation of viral diseases such as Hepatitis B and PML (Ann Hematol2011;90:1219; Blood 2009;113:4834). Bortezomib, Temozolomide: Lymphocyte-depleting agents; can cause disseminated VZV, Pneumocystis jiroveci infxn. Corticosteroids: Dose & duration dependent- Pneumocystis jiroveci & Nocardiosis can occur.
• Tumor size: Bulky tumors overgrow their blood supply & necrose, serving as nidus for infxn. Anatomical disruption: Hepatobiliary, urinary or GI tract tumors cause stasis due to obstruction w/infxn; culprit organisms are usually commensal bacteria.
• Transplantation: Allogeneic transplant: ↑ predisposition for infxn compared to autologous. Splenic radiation; sev. GVHD: Functional asplenia- can cause overwhelming infxn w/ encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae, & Neisseria meningitidis(J Natl Compr Canc Netw 2012;10:1412).
Strategies for Antimicrobial Therapy
A. Therapeutic: Use of antimicrobials to treat an established infxn
B. Preemptive: Tx of a subgroup of pts who are predisposed to high rates of clinically relevant disease
C. Prophylactic: Administering antimicrobials to high risk population of pts in order to prevent infxn w/c have high morbidity or mortality (N Engl J Med 1998;338:1741).
Fever and Neutropenia
• Definitions: ANC < 500 cells/mm3 or if expected to ↓ in next 48 h; profound neutropenia: ANC < 100 cells/mm3; functional neutropenia: Counts are nl or ↑, but do not function appropriately
• Epidemiology: Occurs in 10–50% of pts w/ solid tumors & >80% of pts w/hematologic tumors (Clin Infect Dis 2004;39:32). Infxn occur in 20–30% of febrile episodes; common sites are intestinal tract, lung, & skin. Bacteremia occurs in 10–25% of all pts, particularly in profound & prolonged neutropenia (Ann Intern Med 1966;64:328; Blood 2006;107:4628; Clin Infect Dis 2004;39:25).
Antibiotic Therapy of Fever and Neutropenia
• First-line Rx: Should be w/antipseudomonal abx. Vancomycin & aztreonam can be used in case of allergy (hives/bronchospasm) to first-line abx.
• Adjunct abx: Should not be started first line, unless there are specific indications, like suspected catheter-related infxn, skin or soft tissue infxn, PNA, hemodynamic instability, or multidrug-resistant organisms (such as MRSA, resistant gram-negative organisms) (Clin Infect Dis 2011;52:56). Must use local antibiogram & institution-specific guidelines to make choices.
• Empiric fungal coverage: Choices are echinocandins, liposomal Amphotericin B, or Voriconazole