Anabolic steroids increase blood levels and effects of cyclosporine by decreasing the breakdown of Cyclosporine. They also reduce the breakdown of Warfarin (Coumadin), increasing blood levels of Warfarin and the risk of bleeding from warfarin.
High-dose steroid therapy has been proven effective in AIDS-related Pneumocystis pneumonia (PCP) but not in non-AIDS-related cases. We evaluated the effects on survival of steroids in HIV-negative patients with PCP. Retrospective study patients admitted to the ICU with hypoxemic PCP.
HDS were associated with increased mortality in HIV-negative patients with PCP via a mechanism independent from an increased risk of infection. Pneumocystis jiroveci pneumonia (PCP) is a major cause of acute respiratory failure in immunocompromised patients. Malignant disease, steroid treatment, and transplantation of solid organs or bone marrow are the leading causes of T-cell suppression, which is associated with a high risk of opportunistic infections, including PCP. The number of patients with T-cell suppression has risen in recent years, resulting in an increased incidence of PCP. In recent studies, more than 8% of patients with hematological malignancies admitted to the ICU for acute respiratory failure had PCP. Mortality rates of up to 30% have been reported in cancer patients with PCP.
Studies done in the 1990s showed that adjunctive treatment with high-dose steroids (HDS) was associated with a dramatic decrease in mortality during PCP episodes in HIV-positive patients. Corresponding proof of efficacy is not available for HIV-negative patients with PCP, and findings from the three available studies, all retrospective, are conflicting. In a 1998 study in 30 patients, the 16 patients given adjunctive HDS had no difference in mortality but spent less time on mechanical ventilation compared to the 14 patients managed without steroids. The second study, reported in 1999, compared 15 patients with HDS and 8 without HDS and found no significant differences in mortality or ICU stay length. The most recent study was published in 2011 and found no significant difference in mortality between the 59 patients given HDS and the 29 other patients. More over two retrospective studies from our group could not conclude of outcome improvement with adjunctive steroid in that setting. The small sample sizes may have jeopardized the ability of these studies to detect significant differences between patients given HDS and other patients.
The pathophysiology of PCP may differ between patients with and without HIV infection. Studies have shown that HIV-negative patients with PCP were older and had a larger number of co-morbidities, longer symptom duration at diagnosis and higher neutrophil counts in bronchoalveolar lavage fluid, compared to HIV-positive patients. Conceivably, these differences between the two populations might affect the ability of steroid therapy to provide therapeutic benefits.
Here, our objective was to determine whether HDS produced therapeutic benefits in HIV-negative patients with severe PCP requiring admission to the intensive care unit (ICU). To increase the sample size for our investigation, we included patients from four different sources, namely, three previously published studies and a teaching-hospital ICU database. We analyzed data from three retrospective studies of HIV-negative patients with Pneumocystis jiroveci pneumonia. The first study included HIV-negative patients admitted to two ICUs between 1988 and 1996 for PCP and compared patients who did (n=23) and did not (n=8) receive HDS in addition to standard treatment. The second study described HIV-negative patients with PCP managed in the ICU between 1989 and 1990 and looked for predictors of mortality, 33 of the 39 patients received HDS. Finally, the third study compared 56 cancer patients with PCP to 56 cancer patients with bacterial pneumonia admitted to the ICU between 2001 and 2006 of the patients with PCP, 21 received HDS. Only patients from theses studies who were admitted in ICU were included in the present study. In addition to the data from these three studies, we included data from patients admitted for PCP to the ICU of the Saint Louis Teaching Hospital, Paris, France, between 2006 and 2011. The IRB from Clermont Ferrand approved data collection for the addition of patients from St Louis hospital in this non international study. Medical chart were reviewed by the investigators (VL or AD) for all included patients . For all four sources of patients, inclusion criteria were age over 18 years, ICU admission, and PCP. Only definite case of PCP were considered (positive IF for pneumocystis or MGG coloration in BAL). Exclusion criteria were patients with HIV infection and patients who were not admitted to the ICU. Moreover, colonized patients defined with positive P. jiroveci PCR only, without any pulmonary symptom or treatment of P. jiroveci were not included.