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.