PCP and Steroids

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Motivation: For prevention of PCP in patients taking steroids, I have heard a variety of rumors on the needs of Pneumocystis pneumonia prophylaxis.  After what dose of steroid and what duration do patients need prophylaxis?  Some doctors prescribe Bactrim for more than 20 mg of prednisone use for more than a month to some GI doctors who do not prescribe prophylaxis even on higher doses of prednisone.  Recently, our medicine team wondered where the data came from.  One of the major studies addressing this question came from Mayo Clinic in 1996.

Paper: Yale, S.H. and Limper, A.H. "Pneumocystis carinii Pneumonia in Patients Without Acquired Immunodeficiency Syndrome: Associated Illnesses and Prior Corticosteroid Therapy." Mayo Clinical Proc.(1996) 71: 5-13.

Methods: Between 1985-1991, data on patients presenting to Mayo Clinic with Pneumocystis pneumonia but without HIV were retrospectively analyzed.  PCP was proven by bronchoalveolar lavage, lung biopsy, or autopsy.  Patients were excluded from analyses if clinical syndrome was suggestive of AIDS.

Results:
Cohort: Between 1985-1991, there were 116 patients with PCP pneumonia without AIDS.  These patients commonly had associated conditions of hematologic malignancy (30.2%), organ transplantation (25%), inflammatory diseases (22.4%), solid tumors (12.9%), and other diseases.

Steroid Use: Of the 116 patients, 105 (90.5%) had used steroid therapy within one month of diagnosis of PCP.  98 (84.5%) were using steroids at time of diagnosis.  Prednisone use dose and duration are depicted as below:

• Median dose: 30 mg of prednisone (25th percentile was 16 mg meaning 25% were using less than 16 mg)
• Median duration: 12 weeks (25th percentile was at 8 weeks)

Concurrent Infections: In 57.8% of patients, additional infectious agents were detected.  No significant differences in incidence of concurrent infections were noted among different underlying illnesses (such as malignancy vs inflammatory diseases).  The most common concurrent infection was CML (35.3%) followed by Candida infection (18.1%).

Outcome: Overall, in-hospital mortality was 34%.  Respiratory failure occurred in 43% of patients and was associated with 66% mortality.  Of note, PCP infection was associated with a 100% mortality in patients with solid malignancies.  Finally, survival to discharge from hospital was linked to lower dose of corticosteroid at the time of diagnosis.
Discussion: Overall, this paper provides a rough guide to the dose of steroid (median 30 mg) and duration (median 12 weeks) associated with PCP.  However, I think that this paper also shows that there is no absolute threshold effect beyond which the risk clearly skyrockets.  The 25th and 75th percentiles were very  wide.  Another interesting and cautionary outcome is that in the immunosuppressed, there is often co-infection of multiple pathogens, and the process of diagnosis should not stop after detecting PCP.  Also, 11 patients got PCP without using steroids.  PCP should remain on the differential for any immunosuppressed individual.
This paper also has some significant limitations.  First, patients who were selected in this analyses had received at least BAL or lung biopsy.  Currently, many patients are diagnosed by stains of sputum and may be less sick than those getting BAL.  Also, the paper does not address properly the more interesting question of what is a safe dose of prednisone to use without prophylaxis.  Perhaps if the authors picked a population with medium to low dose prednisone use, then a "safe" dose could be described.