Pneumocystis jiroveci pneumonia in adult patients with AIDS: treatment strategies and emerging challenges to antimicrobial therapy.
Pneumocystis jiroveci (P. carinii) is an opportunistic pathogen that has gained particular prominence since the onset of the AIDS epidemic. Among several important advances in diagnosis and management, appropriately targeting chemoprophylaxis to HIV-infected patients at high clinical risk for P. jiroveci pneumonia and the introduction of effective combination anti-retroviral therapy (including highly active antiretroviral therapy [HAART]) have contributed to the reduced incidence of P. jiroveci pneumonia. Despite the success of these clinical interventions, P. jiroveci pneumonia remains the most common opportunistic pneumonia and the most common life-threatening infectious complication in HIV-infected patients. Trimethoprim/sulfamethoxazole (cotrimoxazole) remains the first-line agent for effective therapy and chemoprophylaxis, and corticosteroids represent an important adjunctive agent in the treatment of moderate-to-severe P. jiroveci pneumonia. However, problems of chemoprophylaxis and treatment failures, high rates of adverse drug reactions and drug intolerance to first-line antimicrobials, high rates of relapse or recurrence with second-line agents, and newer concerns about the development of P. jiroveci drug resistance represent formidable challenges to the management and treatment of AIDS-related P. jiroveci pneumonia. With the expanding global problem of HIV infection, the intolerance or unavailability of HAART to many individuals and limited access to healthcare for HIV-infected patients, P. jiroveci pneumonia will remain a major worldwide problem in the HIV-infected population. New drugs under development as anti-Pneumocystis agents such as echinocandins and pneumocandins, which inhibit beta-glucan synthesis, or sordarins, which inhibit fungal protein synthesis, show promise as effective agents. Continued basic research into the biology and genetics of P. jiroveci and host defense response to P. jiroveci will allow the development of newer antimicrobials and immunomodulatory therapeutic agents to more effectively treat life-threatening pneumonia caused by this organism.
Patel
Naimish
N
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, 330 Brookline Avenue, Boston, MA 02115, USA.
Koziel
Henry
H
D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D006801:Humans; D045363:Pneumocystis carinii; D011020:Pneumonia, Pneumocystis / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology
D000305:Adrenal Cortex Hormones; D000890:Anti-Infective Agents