Pneumocystis jiroveci Pneumonia

Since the first identification of cases in 1981, Pneumocystis infection has been the most common respiratory complication in untreated patients with AIDS, frequently representing the initial opportunistic infection that establishes the diagnosis of AIDS in the absence of other known causes of immunosuppression. The risk of developing this opportunistic infection is highly dependent on the patient’s peripheral blood CD4⁺ count, with a level less than 200 cells/mm³ the cutoff below which patients are at high risk for infection. Fortunately the availability of increasingly effective antiretroviral agents and more frequent use of prophylaxis against Pneumocystis have significantly decreased the likelihood of infection and death resulting from this opportunistic infection.

A general discussion of Pneumocystis as a respiratory pathogen was given in Chapter 25. In patients with AIDS, onset of the disease is often more indolent than in immunosuppressed patients without AIDS. Fever, cough, and dyspnea are the usual symptoms bringing the patient to medical attention. The typical chest radiograph shows diffuse interstitial or alveolar infiltrates. Often the lung fields look hazy, a pattern that may be difficult to characterize specifically as either interstitial or alveolar and commonly described as looking like “ground glass” (see Fig. 25-3). However, atypical radiographic presentations are clearly recognized with documented Pneumocystis pneumonia, including even the finding of a normal chest radiograph. High-resolution computed tomographic (CT) scanning is particularly sensitive for demonstrating subtle changes associated with Pneumocystis pneumonia and generally shows abnormal results even in patients with a normal chest radiograph.

Diagnosis is generally based on finding the organism in respiratory secretions by any number of techniques, especially immunofluorescent staining with a monoclonal antibody. Patients with AIDS often have a surprisingly large burden of organisms, making the organisms easier to obtain than from patients without AIDS. Inducing sputum by having the patient inhale a solution of hypertonic saline is frequently effective and now often used as the initial diagnostic method when Pneumocystis is suspected. Flexible bronchoscopy with bronchoalveolar lavage (BAL) is another means for recovering the organism, with a positive yield of greater than 85% in patients eventually proven to have Pneumocystis pneumonia. Transbronchial biopsy provides a small incremental increase in sensitivity over BAL alone.

Treatment of severe pneumonia caused by Pneumocystis organisms usually involves one of four regimens: the combination antimicrobial trimethoprim-sulfamethoxazole, the combination of clindamycin and primaquine, or trimetrexate or pentamidine as single agents given intravenously. These four regimens appear to be equally effective; each is successful in about 80% of cases. In patients without AIDS treated for Pneumocystis pneumonia, the combination trimethoprim-sulfamethoxazole is generally preferred because of fewer side effects. However, patients with AIDS have a peculiar predisposition to allergic reactions to sulfonamides, making the frequency of adverse side effects equivalent to that seen with pentamidine and making necessary a switch to therapy with other drugs in a relatively high proportion of patients. Other agents such as atovaquone or the combination of trimethoprim and dapsone have been used, especially in patients who do not respond to or cannot tolerate one of the more standard agents or have less severe disease.

In patients with moderate to severe disease caused by Pneumocystis pneumonia, adjunctive therapy with corticosteroids is often helpful in averting significant respiratory failure. Although corticosteroid therapy might be expected to cause more immunosuppression and make the infection worse, this has not been the case, and the presumed benefit of reducing the inflammatory response in the lung to lysing organisms outweighs any negative effects of the corticosteroids.

In patients with AIDS, oral administration of trimethoprim-sulfamethoxazole (in low doses) or dapsone (either alone or with pyrimethamine) can be used with reasonable effectiveness to prevent Pneumocystis pneumonia. Alternatively, patients can receive aerosolized or intravenous pentamidine once a month or daily oral atovaquone. Such prophylactic therapy is routinely recommended in HIV-infected patients who have a CD4⁺ count less than 200 cells/mm³ and in selected other circumstances. Unfortunately, the propensity for development of allergic reactions to trimethoprim-sulfamethoxazole frequently makes this regimen difficult to use in patients with AIDS, so many patients are maintained on one of the other forms of prophylaxis. When Pneumocystis pneumonia develops despite use of aerosolized pentamidine prophylaxis, the clinical presentation may be atypical. Unusual radiographic patterns are often seen, especially pulmonary infiltrates limited to the upper lung zones rather than the more typical pattern of diffuse pulmonary infiltrates.

Mycobacterial Infection

Mycobacterium tuberculosis has emerged as an important respiratory pathogen in patients with AIDS, not only because it is common but also because it is potentially treatable. Clinical disease may result from primary infection, reactivation of previous infection, or exogenous reinfection. Rather than occurring in all categories of AIDS patients, disease due to M. tuberculosis is a particular problem in those groups of individuals with a high background prevalence of tuberculosis—for example, intravenous drug users and indigent and immigrant populations.

Because M. tuberculosis is a relatively virulent organism that does not require the same degree of immunosuppression to produce disease as do many of the other opportunistic infections, it is often seen early in the course of the disease in patients with AIDS. In this setting, its clinical presentation is similar to that seen in the typical patient with tuberculosis who does not have AIDS. However, it also may occur in AIDS patients who are in a late stage of their disease with more severe immunosuppression, in which case the clinical manifestations are often atypical. In this latter circumstance, upper lobe cavitary disease is less frequent, and disseminated disease is more frequent than is usually seen in patients without AIDS. Interestingly, for patients with AIDS and tuberculosis (or for that matter, with other opportunistic infections), improvement in the patient’s overall immune status, particularly as a result of antiretroviral therapy, can be associated with a paradoxical clinical worsening of the opportunistic infection. In these cases, “reconstitution” of the immune system results in an augmented inflammatory reaction to the opportunistic infection, leading to the apparent clinical worsening.

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