68 Pulmonary Infections in the Immunocompromised Patient
Improvements in solid-organ and hematopoietic stem cell transplantation (SOT and HSCT) techniques, expanded use of chemotherapeutic treatments and glucocorticoids, and the appearance of new immunomodulatory therapies contribute to the increasing numbers of immunocompromised patients.1 Recognizing and managing pulmonary complications, particularly infections that result from immunosuppression, are challenging tasks for clinicians. Despite the introduction of potent broad-spectrum antimicrobial agents, complex supportive care modalities, and the use of preventive measures, pulmonary infections continue to be the most frequent complications in these patients and have a high associated mortality, especially when intubation and mechanical ventilation are required.2 In a prospective study of 200 immunocompromised patients with lung infiltrates, infectious agents were isolated from more than three-fourths of patients.3 Early diagnosis and intervention are essential to improving outcomes.
Evaluating the Net State of Immunosuppression
Proper assessment of factors involving the patient’s net state of immunosuppression is of paramount importance (Table 68-1). Most important among them are the specific type of underlying immune deficiency, the immunosuppressive therapy received, and the epidemiologic exposures the patient has encountered in both the community and hospital. A timetable with intervals during which each type of infection and noninfectious pulmonary complication tend to be most prevalent have also been adapted for SOT and HSCT patients (Table 68-2). Knowledge of these time-related complications, as well as the individual characteristics of each patient, will help guide diagnostic tests and allow implementation of appropriate empirical therapy.
TABLE 68-1 Variables to Be Considered in Evaluating the Net State of Immunosuppression
TABLE 68-2 Timetable of the Most Likely Pulmonary Complications in Immunocompromised Transplant Patients
| First 30 Days After Transplant |
| 2 to 6 Months After Transplant |
| More Than 6 Months After Transplant |
Etiology of Pneumonia in Intensive Care Patients
Bacterial Infections
Bacteria are the most frequent cause of pulmonary infections in immunocompromised patients. Jain et al., in a study evaluating 104 intensive care unit (ICU) patients with lung infiltrates, found that 49% of episodes were bacterial infections.4 The specific bacterial etiology of pulmonary infections in immunocompromised patients differs in frequency depending on underlying immune defects. Encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae are particularly common in patients with immunoglobulin defects, such as those suffering from multiple myeloma or in patients with chronic lymphocytic leukemia. Infections caused by penicillin-resistant S. pneumoniae are on the rise,5 and prophylactic use of antibiotics against gram-negative bacteria in patients with neutropenia has favored the emergence of Staphylococcus aureus infections (including methicillin-resistant [MRSA]) and multi-resistant gram-negative bacilli (Pseudomonas aeruginosa, Acinetobacter spp., and Stenotrophomonas maltophilia.)6 Epidemiologic studies have shown that Legionella pneumonia is more prevalent in the ICU host, particularly in renal transplant recipients and patients with lymphoma. It is important to consider that 15% to 30% of cases of bacterial pneumonia are mixed bacterial/opportunistic infections,1 a finding of particular therapeutic importance in patients who do not respond to what was initially considered to be appropriate specific antibiotic treatment.
Fungal Infections
Aspergillus spp. are some of the most common microorganisms causing pneumonia in the ICU patient. Since neutrophils are the key cells in defense against Aspergillus, neutropenic patients, particularly HSCT recipients, are at special risk for this infection. Among recipients of solid-organ transplants, the incidence of invasive pulmonary aspergillosis (IPA) is highest after lung transplantation. A steady increase in documented cases of IPA after organ transplantation has been reported.7 It is estimated that aspergillosis is found in 30% of patients with protracted severe neutropenia.8
Although mortality associated with IPA in IC patients has historically been as high as 80%, during the past 2 decades, the outcome of this infection seems to be changing. Early detection of infection using antigen-specific diagnostic techniques based on serum detection of either galactomannan or beta-D-glucan, two constituents of fungal cell walls, may improve diagnosis, particularly in patients with leukemia and HSCT recipients. Recent reports suggest that detection of galactomannan in bronchoalveolar lavage fluid might be more sensitive than detection in serum.9 Diagnosis of invasive fungal diseases with the use of polymerase chain reaction (PCR) assay, although promising, is currently investigational.10 Implementation of thoracic computed tomography (CT) scan in patients at high risk for invasive pulmonary aspergillosis may improve outcome.11 Prompt institution of azoles appears to have resulted in improved survival.12
Candida species colonize the respiratory tract and are often recovered from pulmonary specimens in ICU patients, but are only considered truly pathogenic if fungemia occurs or lung tissue invasion can be demonstrated. With expanded use of new antifungal therapies, an increased incidence of infections due to Candida krusei and Candida glabrata has been reported. Other fungi that can infect immunocompromised patients as a result of environmental exposures (e.g., Penicillium purpurogenum,13 Scedosporium prolificans14) can cause lethal infections.
A marked decrease in the incidence of Pneumocystis jiroveci pneumonia has been found recently, primarily owing to use of specific prophylaxis in patients at risk and the use of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients. In a recent report, P. jiroveci infection was documented in 2.5% of patients undergoing allogeneic HSCT. The majority of cases occurred late in the course following HSCT (median 14.5 months)15 and with a CD4+ count less than 200 cells/mm3.
Mycobacterium Infections
There has been a marked decrease in pulmonary tuberculosis in HIV-infected patients with the introduction of HAART.16 However, remarkable geographic differences in the incidence of pulmonary tuberculosis in such patients have been reported.17 A high level of suspicion is necessary to diagnose pulmonary tuberculosis in ICU patients; tuberculosis should be particularly considered in patients with T-cell defects (see Table 68-1
