In 2005, pneumonia, along with influenza, was the eighth leading cause of death in the United States, the sixth leading cause of death in individuals over the age of 65 years, and the leading cause of death among infectious diseases. In cancer patients, the lung is a common site of infection, and pneumonia is the leading overall infectious cause of death.

The typical pneumonia history and presentation of cough with or without sputum production, fever, dyspnea, and chest pain or examination finding of abnormal focal chest signs may or may not be present in a cancer patient who is immunocompromised. A profoundly neutropenic patient with a pulmonary infection may have minimal or no signs, symptoms, or physical findings of pneumonia or pulmonary infiltrates on chest radiographs.

Pneumonia is categorized according to four types .

In the MD Anderson EC, 88 % of patients diagnosed with pneumonia have HCAP, whereas only 12 % have CAP. Recent chemotherapy, radiation therapy, or any other cancer therapy is considered a risk factor for HCAP. In comparison with patients with CAP, 82 % of whom receive treatment as outpatients, 89 % of patients who present with pneumonia are hospitalized.

The spectrum of pulmonary infections in the cancer population depends on the underlying immunologic deficit or deficits. Staphylococcus aureus and S. pneumoniae are the most common Gram-positive organisms. In neutropenic patients, as neutropenia persists, infection with resistant Gram-negative bacteria (e.g., Acinetobacter, Enterobacter, and Pseudomonas species; Stenotrophomonas maltophilia) and fungi (e.g., Aspergillus, Zygomyces, and Fusarium species) can occur, especially in those with hematologic malignancies (Rolston 2001). Other organisms isolated from cancer patients’ respiratory specimens include mycobacteria (mostly nontuberculous); Legionella, Candida, and Nocardia species; P. jirovecii; cytomegalovirus; and community respiratory viruses.

Many patients with HCAP, HAP, or VAP and some with CAP are at increased risk for colonization of and infection with MDR pathogens. Risk factors for MDR pathogen infection include exposure to antimicrobial therapy 90 days before pneumonia diagnosis, current hospitalization of 5 days or more, high frequency of antibiotic resistance (in the hospital or community), all risk factors for HCAP, and immunosuppressive disease and/or its therapy. The clinical and microbiologic features of HCAP are more similar to those of HAP and VAP than to those of CAP. In an epidemiologic retrospective cohort study, Kollef et al. (2005) analyzed 4543 patients with culture-positive pneumonia who were admitted to 59 U.S. hospitals. The distribution of pathogens varied according to the 4 types of pneumonia. Nevertheless, S. aureus (including methicillin-sensitive and -resistant strains) was the dominant pathogen. The incidence rate of methicillin-resistant S. aureus (MRSA) infection was markedly higher in patients with HCAP than in those with the other 3 types of pneumonia. Also, the proportions of patients with HCAP and VAP having Pseudomonas species infections (25 % and 21 %, respectively) were higher than that of patients with CAP (17 %). However, the S. pneumoniae infection prevalence rate was higher in patients with CAP than in those with the other 3 types of pneumonia. Although most pulmonary infections in cancer patients are caused by a single pathogen, a significant proportion can have polymicrobial infections.

Fever is defined as a single oral temperature of at least 38.3 °C (101 °F) or a temperature of at least 38 °C (100.4 °F) that persists for 1 h or longer. Neutropenia is defined as an absolute neutrophil count (ANC) of less than 500 cells/mm³ or an ANC of less than 1000 cells/mm³ that is projected to decrease to less than 500 cells/mm³. Profound neutropenia is defined as an ANC of no more than 100 cells/mm³.

In patients with neutropenic fever, knowledge of epidemiologic shifts, local microbiology , and resistance patterns is imperative to initiate effective prophylactic, empiric, and specific treatment. Bacterial infections are most common during the early phase of neutropenic fever, and Gram-positive bacteria have predominated in most cancer centers. The most common Gram-positive bacteria are viridans streptococci and Staphylococcus, Enterococcus, Corynebacterium, and Bacillus species. The most common Gram-negative bacteria are Escherichia coli, P. aeruginosa, Klebsiella and Proteus species, and S. maltophilia. Patients with prolonged, severe neutropenia and/or those who have been exposed to multiple broad-spectrum antibiotics are susceptible to fungal infections. The most common fungal organisms in neutropenic febrile patients are Candida species, Trichosporon beigelii, and Aspergillus, Zygomycetes, and Fusarium species (Rolston 2004).

The risk of complications of infection must be assessed upon initial evaluation of a patient with fever. Decisions such as site of treatment (inpatient versus outpatient), type of antibiotics, and duration of treatment will depend on classification of a patient as being at high or low risk. In general, high-risk patients are those with anticipated prolonged (more than 7 days), profound neutropenia and/or significant medical conditions.

At the MD Anderson EC, patients with hematologic malignancies, who undergo hematopoietic stem cell transplantation, or with comorbidities such as hypotension, organ dysfunction, bleeding, and altered mental status who present with neutropenic fever are considered to be at high risk. The high-risk population must be given aggressive treatment and admitted to the hospital.

The Multinational Association of Supportive Care in Cancer developed a scoring system (Table 9.1) to identify febrile neutropenic cancer patients at low risk for a serious medical complication (e.g., hypotension; respiratory, cardiac, or renal failure; disseminated intravascular coagulopathy; severe bleeding). In a prospective observational study, De Souza et al. (2008) found that the Multinational Association of Supportive Care in Cancer risk index score has a sensitivity of 88 %, specificity of 85 %, and positive predictive value of 90.6 %. This scoring system is simple and easy to apply and may be useful in the emergency setting.

A very important point to emphasize is that the inflammatory response to an infectious process is significantly altered in a patient with neutropenia, and the patient may not have symptoms or signs of infection or inflammation. A thorough history and complete physical examination are important, including examination of the mucous membranes, skin, catheters, and drains for sources of infection. If the patient has perianal symptoms, the perianal region is examined visually. Digital rectal examination is contraindicated.

Work-up consists of the following:

Low-risk patients with febrile neutropenia may be candidates for outpatient treatment. The following are the criteria for a patient to be considered for outpatient treatment at our institution: