Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + INTRODUCTION Download Section PDF Listen +++ ++ Pneumocystis, an opportunistic fungal pulmonary pathogen, is an important cause of pneumonia in immunocompromised hosts. + MICROBIOLOGY Download Section PDF Listen +++ ++ P. jirovecii infects humans, whereas P. carinii—the original species described—infects rodents. Developmental stages include the small trophic form, the cyst, and the intermediate precyst stage. + EPIDEMIOLOGY Download Section PDF Listen +++ ++ Pneumocystis is found worldwide, and most people are exposed to the organism early in life. Infections resulting from environmental sources and person-to-person transmission have been demonstrated; the role of airborne transmission is unclear. Defects in cellular and humoral immunity (e.g., due to HIV infection, malignancy, transplantation, immunosuppressive medications) predispose to Pneumocystis pneumonia (PCP). The incidence among HIV-infected pts is inversely related to the CD4+ T-cell count: ≥80% of cases occur at counts <200 cells/μL, and most cases develop at counts <100/μL. + PATHOGENESIS Download Section PDF Listen +++ ++ The organisms are inhaled into the alveolar space, where they proliferate, provoking a mononuclear cell response. Alveoli become filled with and are damaged by proteinaceous material, with consequently increased alveolar–capillary injury and surfactant abnormalities. On histology, alveoli are seen to be filled with foamy, vacuolated exudates. + CLINICAL MANIFESTATIONS Download Section PDF Listen +++ ++ Pts develop dyspnea, fever, and nonproductive cough. – HIV-infected pts often have an indolent course that presents as mild exercise intolerance or chest tightness without fever or cough. Over days to months, these pts develop the more typical symptoms of PCP. – Some pts with HIV infection and most pts with other types of immunosuppression have more acute disease that progresses over a few days to respiratory failure. Physical examination findings are nonspecific and invariably include hypoxemia. Pts may initially have a normal chest examination but later, without treatment, develop diffuse rales and signs of consolidation. Serum levels of LDH may be elevated because of pulmonary damage, but this finding is neither sensitive nor specific. CXR classically reveals bilateral diffuse interstitial infiltrates that are perihilar and symmetrical, although this finding is not specific for PCP. Cysts and pneumothoraces are common CXR findings. Chest CT shows diffuse ground-glass opacities in virtually all pts with PCP, and a normal chest CT essentially rules out the diagnosis. Rare cases of disseminated infection have been described, generally involving lymph nodes, spleen, and liver. + DIAGNOSIS Download Section PDF Listen +++ ++ Histopathologic staining makes the definitive diagnosis. – Cell-wall stains (e.g., methenamine silver) are used for Pneumocystis cysts and Wright-Giemsa stains for the nuclei of all developmental stages. – Immunofluorescence with monoclonal antibodies increases diagnostic sensitivity. The demonstration of organisms in bronchoalveolar lavage fluid is almost 100% sensitive and specific for PCP in immunocompromised pts. While detection of organisms in expectorated sputum or throat swabs has very low sensitivity, detection in an induced sputum sample can be—depending on the experience of the center conducting the test—highly sensitive (up to 90%) and specific. DNA amplification by PCR is most sensitive but may not distinguish colonization from infection. ++ TREATMENT: PNEUMOCYSTIS INFECTIONS Trimethoprim-sulfamethoxazole (TMP-SMX) for 14–21 days is the regimen of choice for all pts. For doses and adverse effects of TMP-SMX and alternative regimens, see Table 107-1. For HIV-infected (and likely all) pts with moderate to severe cases (a room air Pao2 ≤70 mmHg or a Pao2 – Pao2 gradient ≥35 mmHg), adjunctive glucocorticoids improve the survival rate. For pts with HIV infection who present with PCP before the initiation of antiretroviral therapy (ART), ART should usually be started within the first 2 weeks of therapy for PCP. Pts typically do not respond to therapy for 4–8 days. Pts whose condition continues to deteriorate after 3–4 days or has not improved after 7–10 days should be reevaluated for other infectious processes and for noninfectious processes (e.g., CHF, pulmonary emboli) that may be causing pulmonary dysfunction. ++Table Graphic Jump LocationTABLE 107-1TREATMENT OF PNEUMOCYSTOSIS (14–21 DAYS)View Table||Download (.pdf) TABLE 107-1TREATMENT OF PNEUMOCYSTOSIS (14–21 DAYS) Drug(s) Dose, Route Adverse Effects First-Choice Agent TMP-SMX TMP (5 mg/kg) plus SMX (25 mg/kg) q6–8h PO or IV (two double-strength tablets tid or qid) Fever, rash, cytopenias, hepatitis, hyperkalemia Alternative Agents TMP plus Dapsone 5 mg/kg q6–8h PO 100 mg qd PO Hemolysis (G6PD deficiency), methemoglobinemia, rash, fever, gastrointestinal disturbances Atovaquone 750 mg bid PO Rash, fever, hepatitis Clindamycin plus Primaquine 300–450 mg q6h PO or 600 mg q6–8h IV 15–30 mg qd PO Hemolysis (G6PD deficiency), methemoglobinemia, neutropenia, rash Pentamidine 3–4 mg/kg qd IV Hypotension, azotemia, cardiac arrhythmias (torsades des pointes), pancreatitis, dysglycemias, hypocalcemia, neutropenia, hepatitis Adjunctive Agent Prednisone or methylprednisolone 40 mg bid × 5 d, 40 mg qd × 5 d, 20 mg qd × 11 d; PO or IV Peptic ulcer disease, hyperglycemia, mood alteration, hypertension Abbreviations: TMP-SMX, trimethoprim-sulfamethoxazole. + PROGNOSIS Download Section PDF Listen +++ ++ Factors that influence mortality risk include advanced age, high degree of immunosuppression, preexisting lung disease, low serum albumin level, need for mechanical ventilation, and development of a pneumothorax. + PREVENTION Download Section PDF Listen +++ ++ The most effective method for preventing PCP is to eliminate the cause of immunosuppression (e.g., withdraw immunosuppressive therapy, treat HIV infection). Prophylaxis is indicated for HIV-infected pts with CD4+ T-cell counts <200/μL or a history of oropharyngeal candidiasis and for any pt with a history of PCP. Guidelines for other compromised hosts are less clear, but prophylaxis should be considered for pts receiving >20 mg of prednisone daily (or its equivalent) for ≥30 days. For prophylactic regimens, see Table 107-2. TMP-SMX is the drug of choice. ++Table Graphic Jump LocationTABLE 107-2PROPHYLAXIS OF PNEUMOCYSTOSISView Table||Download (.pdf) TABLE 107-2PROPHYLAXIS OF PNEUMOCYSTOSIS Drug(s) Dose, Route Comments First-Choice Agent TMP-SMX One tablet (double- or single-strength) qd PO Incidence of hypersensitivity is high. Rechallenge for non-life-threatening hypersensitivity; consider dose-escalation protocol. Alternative Agents Dapsone 50 mg bid or 100 mg qd PO Hemolysis is associated with G6PD deficiency. Dapsone plus Pyrimethamine plus Leucovorin 50 mg qd PO 50 mg weekly PO 25 mg weekly PO Leucovorin ameliorates cytopenias due to pyrimethamine. Dapsone plus Pyrimethamine plus Leucovorin 200 mg weekly PO 75 mg weekly PO 25 mg weekly PO Leucovorin ameliorates cytopenias due to pyrimethamine. Pentamidine 300 mg monthly via Respirgard II nebulizer Aerosol may cause bronchospasm. Pentamidine is probably less effective than TMP-SMX or dapsone regimens. Atovaquone 1500 mg qd PO Requires fatty meal for optimal absorption. Abbreviations: TMP-SMX, trimethoprim-sulfamethoxazole. ++ For a more detailed discussion, see Masur H, Morris A: Pneumocystis Infections, Chap. 244, p. 1358, in HPIM-19.