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TMP-SMX has established efficacy for reducing the incidence of bacterial infections and toxoplasmosis. This drug is active against Nocardia, Legionella, most Salmonella, most methicillin-sensitive S. aureus, community-acquired MRSA (USA 300 strains), many gramnegative bacilli, most H. influenzae, and about 70% of S. pneumoniae. No other PCP prophylaxis regimen has this spectrum of activity.
ADVERSE REACTIONS: Adverse reactions sufficiently severe to require discontinuation of the drug are noted in 25% to 50% with TMP-SMX, 25 to 40% with dapsone, and 2 to 4% with aerosolized pentamidine (NEJM 1995:332:693). Patients who have a non-life-threatening reaction to TMP-SMX should continue this drug if it can be tolerated. Those who have had such a reaction in the past could be rechalleng-ed, possibly using desensitization (see pg ____). Gradual initiation of TMPSMX prophylaxis reduces the rate of rash and/or fever by about 50% (JAIDS 2000;24:337). This suggests that most reactions are not allergic or IgE mediated. Pyrimethamine/sulfadonine (Fansidar) is affective, but rarely used due to the risk of severe hypersensitivity reactions.
DISCONTINUATION OF PRIMARY OR SECONDARY PROPHYLAXIS: CD4 count > 200 cells/mm3 x 3 mo. An exception is patients who develop PCP with a CD4 >200/mm3; continuation of PCP prophylaxis for life "is probably prudent" (2008 NIH/CDC/IDSA Guidelines for Prevention and Treatment of Opportunistic Infections in Adults and Adolescents http://AIDS info.nih.gov ). A meta-analysis of 14 controlled trials involving discontinuation of PCP prophylaxis (Clin Infect Dis 2001;33: 1901) found no difference in risk for PCP between those who continued prophylaxis and those who discontinued with a CD4 count >200 cells/mm3. The rates were 19.1 vs 18.2 PCP episodes per 1000 patientyears for primary prophylaxis and 43.5 vs 41.9 PCP cases per 1000 patient-years for secondary prophylaxis. The rate of adverse reactions was 34.5 vs 8.6 cases per 1000 patient-years favoring discontinuation. For secondary prophylaxis, a review of 96 cases followed an average of 42 months showed no risk of PCP (AIDS 2004;18:2047). A more recent review with follow-up averaging 40 months in 78 patients showed no cases of PCP (AIDS 2004;18:2047).
RESTARTING PRIMARY PROPHYLAXIS: CD4 count decreases to <200 cells/ mm3
SECONDARY PROPYLAXIS:Indications, regimens, stopping rules and restarting rules are the same as for primary prophylaxis.
TRANSMISSION RISK:Some authorities recommend avoidance of “high -intensity exposure", meaning that a patient with PCP should not be placed in a room with a vulnerable patient (NEJM 2000;342:1416; Am J Respir Crit Care Med 2000;162:167; Emerg Infect Dis
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