Monday, October 24, 2011

Bactrim prophylaxis with high-dose steroid use?

This is a question we face quite often in the Nephrology clinic when we are commencing patients on high dose steroids for glomerular and other systemic inflammatory diseases.

I came across a couple of interesting retrospective studies while trying to find some evidence to help guide the decision-making process.

The first study analyzed 116 cases of pneumocystis pneumonia in non-HIV infected patients. The major common exposure was steroid treatment in the month preceding presentation (90.5% of patients) – the median dose was equivalent to 30mg prednisone for a median of 12 weeks before presentation.

The second reported risk factors in 41 cases in a French centre. Mortality was 29%; 85% had received steroids at a median daily steroid dose equivalent to 15mg prednisone. Only 17% had received prophylaxis.

The third used a matched case-control type analysis in patients with SLE – they reported 15 cases of pneumocystis infection; risk factors for infection compared to 60 matched controls included higher disease activity, renal involvement and higher mean cumulative steroid dose (49 vs 20mg/day; p<0.01).

Finally a Cochrane review of RCTs of prophylaxis against PCP (versus none/placebo/non-PCP agents) suggested that prophylaxis was warranted when the risk of PCP infection is higher than 3.5% for adults – the authors suggested this included the following groups – “recipients of solid organ or allogeneic bone allografts for the first 6 months after transplant and, for the latter, throughout the period of immunosuppression, as well as in patients with acute lymphoblastic leukemia and Wegener granulomatosis”

There are a number of factors to be considered when trying to answer this difficult scenario – the dose of steroids used, the duration of treatment, use of other immunosuppressive drugs (i.e. the net state of immunosuppression), medical co-morbid conditions and infection history.
Many experts suggest prophylaxis for patients with rheumatological diseases requiring treatment with ≥20mg prednisone for greater than one month when used in combination with another immunosuppressive drug. Overall the pros and cons of PCP prophylaxis must ultimately be judged on a case-by-case basis.


Tom Oates said...

Hi Finnian
Great post. I suppose I would have a few questions:

What was the mix of diagnoses in the first two studies?
Were all cases diagnosed by BAL?
And whilst steroid exposure is clearly important were there many patients who had received steroids only?

Lovely topic - it's one I've always thought about


Finnian Mc Causland said...

In the first study all diagnoses were made from sputum, BAL (around 90%), biopsy or autopsy material. 35 had haematological malignancies, 29 organ transplants, 26 inflammatory disease, 15 solid tumours, 11 others. They didn't report additional immunosuppressive agents, though presumably there many.
I only had the abstract for the second study.

Tom Oates said...

I know that the plural of anecdote is not data; but I have seen more PCP in malignancy and the vasculitides than in organ transplantation. I suppose that may just reflect more widespread use of prophylaxis in transplantation though.