• Pneumocystis carinii is an organism of uncertain taxonomic position with ribosomal RNA sequences of fungi but DNA content, absent fungal protein elongation factor EF-3, and antimicrobial susceptibility characteristics all suggestive of protozoa. 
• Its life cycle resembles sporozoa (protozoa). Similar (?identical) organisms are found in lungs of lower animals. 
• It is a cause of serious pulmonary infections almost exclusively in immunocompromised humans.

2. How is Pneumocystis carinii acquired? Was this patient recently infected?

• Study of epidemics suggest that person to person spread by airborne droplets occurs.
•  Most cases in the US including those in AIDS patients are thought to represent reactivation of latent infection. 
• Nursery outbreaks in post-WWII Europe and more recently in Southeast Asia as well as reports of increased numbers of secondary cases on oncology wards in the US suggest person to person spread still occurs.

3. What is the mechanism by which Pneumocystis carinii causes pneumonia?

• Pneumonia occurs in persons with suppressed T lymphocyte function as might be seen with starvation, corticosteroid administration or in HIV infection when CD4 T-lymphocyte count has dropped below 200/mM3. 
• Virulence factors have not been identified.
•  Pneumonia is characterized by alveoli filled with desquamated alveolar cells, monocytes, organisms and fluid producing a distinctive foamy appearance.
• Type II pneumocytes are present. Round cells may be increased in the widened septa. 
• Healing is generally complete but some fibrosis and even residual thin-walled cavities may be left.

4. How is infection with Pneumocystis carinii diagnosed?

• Organisms can be identified morphologically in tissue biopsy or in pulmonary secretions.
• Induced sputum, bronchoalveolar lavage (obtained with bronchoscope) have reasonable yield. 
• Organisms can be stained with Geimsa (trophozoite) or Gomori methenamine silver (cyst). 
• A fluorescent tagged anti-pneumocystis monoclonal antibody direct fluorescence test is very useful.

The patient is started on intravenous trimethoprim/sulfamethoxazole (20 mg/kg/D trimethoprim: 100 mg/kg/D sulfamethoxazole) plus prednisone 40 mg twice daily. Two days later she is improved: respiratory rate is down to 18/min, O2 saturation is 98% with FiO2 of 21%. Trimethoprim sulfamethoxazole therapy is changed to oral. On day 5, she develops fever, a morbilliform rash and elevations of AST, ALT and alkaline phosphatase.

Rash, fever and hepatitis are characteristic of reaction to trimethoprim/sulfamethoxazole.

6. What alternative therapies are available? 

• Alternative treatments include pentamidine, trimetrexate, a dihydrofolate reductase inhibitor, atovaquone, a hydroxynapthoquinone, or the combination of primaquine and clindamycin can all be used. 
• Seriously ill patients as indicated by a large a-A gradient benefit from systemic corticosteroids. 
• In patients with moderate to severe pneumonia, pentamidine should probably be the first alternative.

7. What is the likelihood of an adverse reaction to trimethoprim sulfamethoxazole in a patient with AIDS?  

• Over 50%.

8. Can relapses of pneumonia due to Pneumocystis carinii be prevented? How?

• Yes, prophylactic low dose T/S or dapsone or aerosolized pentamidine will reduce the frequency or prevent recurrences.