PNEUMONIA
IN THE COMPROMISED HOST
When patients with specific immune impairments related to an underlying primary illness (often malignancy or HIV infection) or arising as a consequence of medical therapy (e.g., chemotherapy-or transplant-related immunosuppression) develop respiratory infections, they are referred to as immunocompromised hosts (ICHs). In recent years, HIV infection has led to a large and important population of ICH patients who may develop pneumonia. In any ICH, a new lung infiltrate may be infectious or noninfectious in origin (e.g., adverse drug reaction, pulmonary hemorrhage, acute lung injury). Because of the broad spectrum of potential pathogens and the seriousness of pneumonia in the ICH, empiric therapy is often supplemented by vigorous efforts at making a specific etiologic diagnosis.
The cause of infection in an ICH is generally dictated by the type of immune impairment (see Plate 4-82). Thus, patients who have had a splenectomy (including those with sickle cell anemia and autosplenectomy) are usually infected by encapsulated bacteria such as pneumococcus, staphylococci, Haemophilus influenzae, and Neisseria meningitides. Patients with chemotherapy-induced neutropenia may be infected with Pseudomonas aeruginosa, other gram-negative bacteria, and Aspergillus spp. Patients with abnormal T-lymphocyte function, such as those with certain lymphomas or HIV infection, may be infected by bacteria such as Listeria monocytogenes, Salmonella spp., Legionella spp., Mycobacterium avium, or Mycobacterium tuberculosis; fungi such as Cryptococcus neoformans, Histoplasma capsulatum, or Coccidioides immitis; viruses such as cytomegalovirus (CMV) and herpes simplex; or parasites such as Pneumocystis jiroveci, Toxoplasma gondii, or Cryptosporidium spp. In HIV- infected patients, the type of infection that develops is directly related to the patient’s CD4 lymphocyte count. Those with little immune dysfunction and a CD4 count above 500 per mm3 usually do not develop opportunistic infection, and their predominant pneumonia is bacterial, especially pneumococcal. Those with counts between 200 and 500 per mm3 are prone to infection with bacteria and M. tuberculosis. As the CD4 count decreases further, the risk of opportunistic infection increases, and patients with a count below 200 per mm3 are at particular risk for such infections as P. jiroveci. With a count below 100 per mm3, toxoplasmosis is a concern, and below 50 per mm3, CMV, M. avium, and Cryptococcus spp. are more likely.
Immunocompromised patients should have a careful clinical examination with attention to the skin, gastrointestinal tract, central nervous system, optic fundi, liver, and lungs. Cough and dyspnea may be present, but respiratory symptoms may be minimal, with fever as the only finding. An etiologic agent can be suggested by certain extrapulmonary findings in conjunction with a specific immune defect. Skin lesions can occur with infection caused by P. aeruginosa, Aspergillus spp., M. tuberculosis, Nocardia spp., varicella zoster, herpes simplex, Cryptococcus spp., and Blastomyces spp. The central nervous system may be affected by Nocardia spp., pneumococcus, H. influenzae, P. aeruginosa, M. tuberculosis, Legionella spp., Aspergillus spp., Cryptococcus spp., Toxoplasma spp., varicella zoster, and CMV. Liver function abnormalities can be seen with CMV, Legionella spp., and Nocardia spp. infection; tuberculosis; histoplasmosis; toxoplasmosis; and Staphylococcus aureus and Pseudomonas aeruginosa infection. Diarrhea may occur with Legionella spp., Cryptosporidium spp., CMV, or herpes simplex.
After organ
transplant, patients can acquire infection that is related to hospitalization,
the presence of serious illness, or transplant immunosuppression. Within the
first month of transplant, patients’ infections are with nosocomial bacterial
and Candida spp. In the period from 1 to 6 months after transplant,
infection is related to immunosuppression and can be with CMV, P. jiroveci,
fungal agents (molds such as Aspergillus spp. and the zygomycoses, and
yeasts such as Histoplasmosis spp. and Coccidioidomycosis
spp.),
L.
monocytogenes, and Legionella spp. After 6 months, these
same pathogens may cause infection in patients who are heavily
immunosuppressed, although chronic viral infection (e.g., CMV) may develop in
those less heavily immunosuppressed.
Chest
radiography may show specific patterns with certain pathogens. Focal lung
lesions may be seen with bacterial, fungal, and mycobacterial illness. Diffuse
infiltrates are seen with P. jiroveci, CMV, Legionella infection,
miliary tuberculosis, viral pneumonia, and infection with Aspergillus spp.
and Candida spp. Management usually involves empiric therapy based
on risk factors for specific pathogens supplemented by diagnostic procedures
(often bronchoscopy or open lung biopsy), especially in nonresponding patients.
PNEUMONIA WITH
HIV INFECTION
Patients with
HIV infection have impairment of T-cell function but also have humoral immune
dysfunction and can be infected with bacteria, fungi, viruses, or parasites.
The most common pneumonias in immuno-suppressed patients with HIV infection are
caused by P. jiroveci (see Plate
4-83) and pneumococcus. In early HIV infection with profound immune
suppression, P. jiroveci is common, but after therapy with
antiretroviral agents, bacterial pathogens are more common causes of
respiratory infection. P. jiroveci can be recognized by methenamine
silver stain or by Giemsa stain, usually of lung tissue or bronchoalveolar
lavage (BAL) fluid. Most patients probably acquired P. jiroveci from
environmental sources before the onset of HIV infection, and pneumonia often
represents reactivation, but new primary infection and reinfection are also
possible. Most patients present with a subacute course of fever, cough,
dyspnea, and weight loss. Chest pain, malaise, fatigue, and night sweats may
also occur, and some patients are even asymptomatic. Chest radiograph usually
shows bilateral diffuse interstitial or alveolar infiltrates. Asymmetric or
focal infiltrates may occasionally be seen, as can pre-dominantly upper lobe
disease and solitary pulmonary nodules. Less common findings include
pneumothorax and pleural effusion. Upper lobe disease and pneumothorax were
reported in the past, especially when patients were receiving aerosolized
pentamidine for prophylaxis of P. jiroveci infection.
The diagnosis
of P. jiroveci infection is usually made bronchoscopically by BAL or transbronchial biopsy. In
addition to a compatible radiograph, other clinical features include leucopenia
and lymphopenia, elevated serum lactate dehydrogenase, oral candidiasis, and a
widened alveolar-arterial oxygen tension gradient. P. jiroveci may
coexist with other opportunistic infections such as CMV, toxoplasmosis, or
mycobacterial illness. With therapy, improvement is slower in the AIDS patient
than in other ICHs with P. jiroveci infection. Fever may persist for 7
to 10 days, and overall survival from the infection is as high as 90%. Therapy is begun
with intravenous trimethoprim/sulfamethoxazole (15- 20 mg/kg/d of trimethoprim
and 75-100 mg/kg/d of sulfamethoxazole), but if the patient cannot tolerate
this therapy or does not respond, then treatment with alternative agents such
as pentamidine (4 mg/kg/d) or atovaquone (750 mg orally three times daily)
should be started. Trimetrexate and aerosolized pentamidine have been tried but
are generally less effective than standard therapy. Therapy with most regimens is continued for
21 days, and if the illness leads to hypoxemia, with a room-air arterial PO2 below
70 mm Hg, then corticosteroids should be added to ameliorate the host inflammatory
response to the killing of organisms that accompanies therapy. After recovery
from pneumonia, patients should receive chemoprophylaxis against recurrent
infection, which can be done with oral trimethoprim/sulfamethoxazole or
alternative agents.
