Update on the diagnosis and treatment ofPneumocystispneumonia

Abstract

Pneumocystis is an opportunistic fungal pathogen that causes an often-lethal pneumonia in immunocompromised hosts. Although the organism was discovered in the early 1900s, the first cases of Pneumocystis pneumonia in humans were initially recognized in Central Europe after the Second World War in premature and malnourished infants. This unusual lung infection was known as plasma cellular interstitial pneumonitis of the newborn, and was characterized by severe respiratory distress and cyanosis with little or no fever and no pathognomic physical signs. At that time, only anecdotal cases were reported in adults and usually these patients had a baseline malignancy that led to a malnourished state. In the 1960-1970s additional cases were described in adults and children with hematological malignancies, but Pneumocystis pneumonia was still considered a rare disease. However, in the 1980s, with the onset of the HIV epidemic, Pneumocystis prevalence increased dramatically and became widely recognized as an opportunistic infection that caused potentially life-treating pneumonia in patients with impaired immunity. During this time period, prophylaxis against this organism was more generally instituted in high-risk patients. In the 1990s, with widespread use of prophylaxis and the initiation of highly active antiretroviral therapy (HAART) in the treatment of HIV-infected patients, the number of cases in this specific population decreased. However, Pneumocystis pneumonia still remains an important cause of severe pneumonia in patients with HIV infection and is still considered a principal AIDS-defining illness. Despite the decreased number of cases among HIV-infected patients over the past decade, Pneumocystis pneumonia continues to be a serious problem in immunodeficient patients with other immunosuppressive conditions. This is mostly due to increased use of immunosuppressive medications to treat patients with autoimmune diseases, following bone marrow and solid organ transplantation, and in patients with hematological and solid malignancies. Patients with hematologic disorders and solid organ and hematopoietic stem cell transplantation are currently the most vulnerable groups at risk for developing this infection. However, any patient with an impaired immunity, such as those receiving moderate doses of oral steroids for greater than 4 weeks or those receiving other immunosuppressive medications are at also at significant risk.

Glycosphingolipids Mediate Pneumocystis Cell Wall β-Glucan Activation of the IL-23/IL-17 Axis in Human Dendritic Cells

“…More recently, CD4-independent mechanisms were also demonstrated to be important in clearing this infection (12). This is also supported by the fact that patients receiving B cell-suppressive therapy, and animal models of B-cell deficiency, also reveal a higher risk for developing PcP (13,14). Thus, inadequate immune response across multiple components of host defense can render an individual susceptible to this infection.…”

AIDS and Opportunistic Infections

“…The IV formulation of pentamidine has better coverage and greater efficacy than the aerosolized route. However, it is at times poorly tolerated due to side effects that include hypotension, hypoglycemia and pancreatitis (Carmona & Limper, 2011). Another important aspect of Pneumocystis treatment is the use of corticosteroids.…”

“…Less-common features can include reticular, granular, and cystic lesions. Since Pneumocystis cannot be cultured, the gold standard for diagnosis is microscopic visualization of the organism of the characteristics cysts or trophic forms on stained respiratory specimens including expectorated or induced sputum, pulmonary secretions obtained by nasotracheal suction, percutaneous aspiration of the lung parenchyma; via flexible bronchoscopy including BAL, washing, brushing and transbronchial biopsy; or via thoracoscopic or open-lung biopsy (Carmona & Limper, 2011). Induced sputum can be the first diagnostic procedure.…”

Serum (1->3)-Β-D-Glucan Assay for Diagnosis of Pneumocystis Pneumonia in Immunocompromised Patients

“…The area under the HSROC curve was 0.965 (0.945-0.978) [9]. The pooled specificity was moderate for PCP because the BG assay could be positive for various fungal infections and the presence of factors such as use of intravenous amoxicillin-clavulanic acid, treatment of patients with immunological preparations (albumins or globulins), use of cellulose membranes and filters made from cellulose in hemodialysis, and use of cotton gauze swabs/packs/pads and sponges during surgery [10]. If the aim is to increase the specificity of the test, slightly higher cut-off level than the one used in invasive fungal infections may potentially provide higher specificity, without unacceptable loss in sensitivity [4].…”