Inclusion Criteria

Concurrent Medication:

Allowed:

• physiologic replacement doses of steroids.
• Pneumocystis carinii pneumonia (PCP) in patient who is HIV positive by ELISA, HIV culture, or p24 antigenemia, or is a member of a risk group for HIV infection.
• Failed at least 4 but not > 14 full days' therapy with either sulfamethoxazole/trimethoprim (SMX/TMP) or parenteral pentamidine. Patients must have received therapy with only one of the two conventional agents prior to enrollment.
• Patients in whom an unequivocal diagnosis of this episode of PCP has been or can be established by morphologic confirmation of three or more typical Pneumocystis carinii organisms in sputum, bronchoalveolar lavage fluid, or lung tissue obtained by transbronchial or open lung biopsy within 15 days prior to study entry.
• Patients in whom no significant improvement in arterial-alveolar oxygen pressure (defined as a decrease of at least 15mm Hg) is observed in the 24 hours prior to entry.
• Patient is willing to have maximal medical support, including pressors, invasive monitoring, and/or mechanical ventilation, during at least the first 7 days of protocol therapy if such support is necessary. Continuation of maximal medical support beyond 7 days is at discretion of investigator and patient.
• Patients with history of hypersensitivity less severe than type I may be enrolled if, in opinion of investigator, these adverse effects do not prohibit rechallenge with the drug.

Prior Medication:

Required:

• At least 4 full days but no greater than 14 full days of parenteral and/or oral therapy with sulfamethoxazole/trimethoprim (SMX/TMP) or pentamidine.

Allowed:

• Zidovudine (AZT).

Exclusion Criteria

Co-existing Condition:

Excluded:

• Patients with history of type I hypersensitivity (urticaria, angioedema, anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to trimetrexate, sulfamethoxazole/trimethoprim, or pentamidine.
• Presence of any process that, in the opinion of investigator, would be adversely and seriously affected by steroid therapy.
• Failure to meet inclusion criteria.

Concurrent Medication:

Excluded:

• Zidovudine (AZT).
• Myelosuppressive agents.
• Nephrotoxic agents.
• AZT may be resumed at completion of study.

Excluded:

• Patients with history of type I hypersensitivity (urticaria, angioedema, anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to trimetrexate, sulfamethoxazole/trimethoprim, or pentamidine.
• Presence of any process that, in the opinion of investigator, would be adversely and seriously affected by steroid therapy.
• Failure to meet inclusion criteria.

Prior Medication:

Excluded within 4 days of study entry:

• Any other investigational agent.
• Excluded within 14 days of study entry:
• Steroids (other than physiologic replacement doses).