1. 
   

   What is the approach to an immunocompromised patient with suspected infection?

   
   
2. 
   

   What are common infectious complications in patients receiving chronic corticosteroids, or recently treated with tumor necrosis factor inhibitors or rituximab?

   
   
3. 
   

   Should preventative measures be taken to prevent infectious complications in patients taking these medications?

   
   
4. 
   

   What infectious complications are common among patients who have undergone splenectomy?

   
   
5. 
   

   How should a transplant patient presenting with possible infection be evaluated?

With the advent of newer immunosuppressive medications and the rise in organ transplantation internationally, the numbers of immunocompromised patients are rising. The diagnosis and management of infection in this growing population is challenging. In immunocompromised patients, the usual signs and symptoms of infection may be obscured, and they often have a higher burden of pathogens and disseminated infection, leading to worse outcomes. These patients are also prone to infection with a broad array of less familiar pathogens, including opportunists such as Listeria monocytogenes and Pneumocystis jiroveci, and latent pathogens such as cytomegalovirus (CMV), toxoplasma, and Mycobacterium tuberculosis, as well as typical community-acquired and nosocomial microbes.

Two pieces of information are essential to the care of the patient with impaired immunity: the patient’s epidemiologic exposures and overall severity of immunosuppression.

The net state of immunosuppression is determined by the type, intensity, and duration of immunosuppression (including the dose and number of immunosuppressive agents or the presence of innate immunodeficiencies); anatomic factors causing a mechanical breakdown in the host defenses, such as abnormal lymphatic drainage at the site of previous surgery or radiation; and the presence or absence of immunosuppressive infections such as HIV or CMV.

Patients should be questioned about epidemiology that places them at risk for specific pathogens. These include recent events (sick contacts, animal exposure, travel, consumption of undercooked meat or unpasteurized dairy products), as well as remote residence in countries where tuberculosis is endemic, or regions of the United States where histoplasmosis, blastomycosis, or coccidioidomycosis are endemic.

Dozens of medications, used in a wide variety of medical conditions, may impair immunologic function; an abbreviated list is shown in Table 198-1. Some agents, such as corticosteroids and alemtuzumab, undermine several layers of host defenses. Others have a more targeted effect, such as tacrolimus and cyclosporine, which prevent normal T lymphocyte responses to immunologic stimuli. Understanding the impact of medications on immunity helps to predict which infections the host may develop.

Corticosteroids

Corticosteroids are prescribed for rheumatologic conditions, inflammatory bowel disease, allergic disease, asthma, among others. The immediate impact of corticosteroids on host defenses includes depletion of circulating lymphocytes (particularly T lymphocytes) and monocytes, and suppression of phagocyte migration and function. Long-term effects that increase infection risk include impaired skin and soft tissue healing.

Corticosteroid use increases susceptibility to common bacterial infections (Table 198-2). Reactivation of latent tuberculosis is also increased among previously exposed patients started on corticosteroid therapy. Patients should be screened for latent tuberculosis before starting corticosteroid therapy. Chronic corticosteroid use also increases susceptibility to opportunistic infections. Infrequently, infection with invasive fungi such as Aspergillus and Fusarium occurs with chronic glucocorticoid use.

Two infection syndromes associated with corticosteroid use deserve special mention: Pneumocystis jiroveci pneumonia (PCP) and Strongyloides hyperinfection syndrome.

PCP is associated with prolonged corticosteroid use; the risk for PCP rises with increasing steroid dose and duration. Clinically, PCP causes fever, dyspnea, and dry cough. It is characterized radiographically by diffuse bilateral pulmonary infiltrates (Figure 198-1). Patients with PCP may be profoundly hypoxic, particularly with ambulation. The mortality associated with PCP infection in non HIV-infected patients is high—up to 50% in some case series. Therefore, suspected PCP should be treated empirically while the diagnostic work-up is ongoing.

There are several methods of diagnosing PCP (Table 198-3). The gold standard is lung biopsy, with demonstration of characteristic cysts. More often, patients undergo bronchoscopy with bronchoalveolar lavage (BAL) or sputum induction, with testing of BAL fluid or sputum with direct fluorescent antigen or silver stain. A useful non-invasive test is the serum fungal marker beta-D-glucan, which may be very elevated in PCP, sometimes above the upper limit of the assay. (For the treatment of PCP in the non–HIV-infected population, see Practice Point.)