New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia.
Pneumocystis carinii has been recognized as a human pathogen for nearly 50 years. We present a case of P carinii infection that typifies clinical presentation in the era of the acquired immunodeficiency syndrome epidemic. The high incidence of P carinii pneumonia in persons infected with human immunodeficiency virus (HIV) has served to focus laboratory and clinical research efforts on better understanding the biology of the organism and on improving diagnosis, treatment, and prevention of this disease. Although inability to culture P carinii has hampered research efforts, molecular and immunologic approaches have led to the recognition that the organism represents a family of fungi with a very restricted host range and have allowed characterization of clinically relevant antigens and enzymes. Molecular epidemiologic studies have identified more than 50 strains of human-derived P carinii and have suggested that recently acquired infection, as opposed to reactivation of latent infection, may account for many cases of clinical disease. Diagnosis has been improved by the development of organism-specific monoclonal antibodies and, more recently, by polymerase chain reaction using multicopy gene targets, together with induced sputum or oral wash samples. Chemotherapeutic prophylaxis is very effective in preventing P carinii pneumonia; the combination of trimethoprim-sulfamethoxazole remains the first-line agent for both therapy and prophylaxis. Prophylaxis needs to be administered only during periods of high risk; in HIV-infected patients responding to effective antiretroviral therapies, prophylaxis no longer needs to be lifelong. Molecular studies have identified mutations in the target of sulfa drugs that appear to represent emerging resistance in P carinii. Resistance to atovaquone, a second-line agent, may also be developing.
Kovacs
J A
JA
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bldg 10, Room 7D43, MSC1662, Bethesda, MD 20892-1662, USA. jkovacs@nih.gov
Gill
V J
VJ
Meshnick
S
S
Masur
H
H
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000635:transmission; D000465:Algorithms; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053626:Atovaquone; D004094:Dihydropteroate Synthase / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000150:complications / Q000175:diagnosis; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use; D010419:Pentamidine / Q000627:therapeutic use; D011010:Pneumocystis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000635:transmission; D013449:Sulfonamides / Q000494:pharmacology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology / Q000627:therapeutic use
D000890:Anti-Infective Agents; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D009285:Naphthoquinones; D013449:Sulfonamides; C077556:GPA protein, Pneumocystis carinii sp.; D010419:Pentamidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D004094:Dihydropteroate Synthase; D053626:Atovaquone