Pneumocystis carinii, with AIDS

Para MF, Finkelstein D, Becker S, Dohn M, Walawander A, Black JR. Reduced toxicity with gradual initiation of trimethoprim-sulfamethoxazole as primary prophylaxis for Pneumocystis carinii pneumonia AIDS Clinical Trials Group 268. J Acquir Immune Defic Syndr 2000 24(4) 337 3. 

AIDS (acquired immunodeficiency syndrome) is the final stage of disease caused by infection with HIV. In this stage, the vims infection has severely affected the immune system, causing a depletion of CD4+ T-helper cells. AIDS is characterized by the manifestation of typical diseases caused by opportunistic infections (Pneumocystis carinii pneumonia, CMV retinitis, candidiasis of the esophagus, cerebral toxoplasmosis), neurological manifestations, cachexia, or certain tumors (Kaposi sarcoma of the skin, B-cell lymphoma). 

Primaquine is also gametocytocidal and a single dose of 30-45 mg has been suggested to prevent transmission of falciparum malaria particularly in areas where there is a potential for reintroduction of malaria. Primaquine is also used in the treatment of Pneumocystis carinii pneumonia in AIDS patients in combinations with clindamycin [3]. 

The most common opportunistic diseases and their frequencies found before death in patients with AIDS between 1990 and 1994 were Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex, and cytomegalovirus disease. 

It was found that the HIV envelope glycoprotein in vitro increases the production of NO by human monocyte-derived macrophages [114]. NO production is increased in patients who have AIDS [115], and the increased concentrations of nitrite in AIDS patients with opportunistic infections is caused by T gondii, Pneumocystis carinii, Mycobacterium tuberculosis, and Mycobacterium avium, whereas nitrite concentrations are normal in symptom-free patients. It was also confirmed that there was increased production of NO in the sera of children with HIV-1 infection, and of circulating cytokines, such as interleukin lp, tumor necrosis factor a, and interferon y. It is postulated that rises in the concentrations of these cytokines may represent a substantial stimulation of NO production [116]. In contrast, it has been shown that there was no altered endogenous nitrate formation in eight patients with AIDS, most of whom had opportunistic infections [117]. It has also been noted that there were high... 

Alternative, also stereoselective, routes to allenic steroids take advantage of cationic cyclization reactions [108] or [2,3]-sigmatropic rearrangements [109]. For example, the allenic Michael acceptor 112 was prepared with 57% chemical yield by reaction of mestranol (111) with diethyl chlorophosphite and was found to inhibit the sterol biosynthesis of the pathogen responsible for Pneumocystis carinii pneumonia (PCP), the most abundant AIDS-related disease (Scheme 18.36) [110]. 

As an alternative therapy with concurrent leucovorin administration (leucovorin protection) for the treatment of moderate to severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS), who are intolerant of or refractory to TMP-SMZ therapy, or for whom TMP-SMZ is contraindicated. 

Dapsone, combined with other antUeprosy agents like rifampin and clofazimine, is used in the treatment of both multibacillary and paucibacillary M. leprae infections. Dapsone is also used in the treatment and prevention of Pneumocystis carinii pneumonia in AIDS patients who are allergic to or intolerant of trimethoprim-sulfamethoxazole. 

Pentamidine is active against Pneumocystis carinii, trypanosomes, and leishmaniasis unresponsive to pentavalent antimonials. It is an alternative agent for the treatment of P. carinii pneumonia. Although it is more toxic than trimethoprim-sulfamethoxazole, it has been widely used in patients with acquired immunodeficiency syndrome (AIDS), in whom P. carinii infection is common. 

It is used in the treatment of severe anaerobic infections caused by bacteroides and other anaerobes. It is also used in combination with aminoglycoside in the treatment of abdomen and GIT wounds, infections of female genital tract, pelvic abscesses, aspiration pneumonia and septic abortion. It is also used for prophylaxis of endocarditis. It is also used along with primaquine in Pneumocystis carinii pneumonia in AIDS patients and with pyrimethamine for toxoplasmosis. 

Hughes WT, LaFon SW, Scott JD, Masur H. Adverse events associated with trimethoprim-sulfamethoxazole and atovaquone during the treatment of AIDS-related Pneumocystis carinii pneumonia. J Infect Dis 1995 171(5) 1295-301. 

Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community Program for Clinical Research on AIDS and the AIDS Clinical Trials Group. N Engl J Med... 

Dohn MN, Weinberg WG, Torres RA, Follansbee SE, Caldwell PT, Scott JD, Gathe JC Jr, Haghighat DP, Sampson JH, Spotkov J, Deresinski SC, Meyer RD, Lancaster DJ. Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Atovaquone Study Group. Ann Intern Med 1994 121(3) 174-80. 

McIntosh K, Cooper E, Xu J, Mirochnick M, Lindsey J, Jacobus D, Mofenson L, Yogev R, Spector SA, Sullivan JL, Sacks H, Kovacs A, Nachman S, Sleasman J, Bonagura V, McNamara J. Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus. ACTG 179 Study Team. AIDS Clinical Trials Group. Pediatr Infect Dis J 1999 18(5) 432-9. 

Toma E, Thorne A, Singer J, Raboud J, Lemieux C, Trottier S, Bergeron MG, Tsoukas C, Falutz J, Lalonde R, Gaudreau C, Therrien R. Clindamycin with primaquine vs. trimethoprim-sulfamethoxazole therapy for mild and moderately severe Pneumocystis carinii pneumonia in patients with AIDS a multicenter, double-blind, randomized trial (CTN 004). CTN-PCP Study Group. Clin Infect Dis 1998 27(3) 524-30. 

Schurmann D, Bergmann F, Albrecht H, Padberg J, Grunewald T, Behnsch M, Grobusch M, Vallee M, Wunsche T, Ruf B, Suttorp N. Twice-weekly pyrimeth-amine-sulfadoxine effectively prevents Pneumocystis carinii pneumonia relapse and toxoplasmic encephalitis in patients with AIDS. J Infect 2001 42(1) 8-15. 

Safrin S, Lee BL, Sande MA. Adjunctive fohnic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. I Infect Dis 1994 170(4) 912-17. 

HPI CJ is a 32-year-old man with acquired immunodeficiency syndrcMne (AIDS) (CD4+ cell count 160 cells/mm viral load 35,000 copies/mL) who presents to the clinic with altered taste sensation and difficulty swallowing. G is noted to have white plaques on the tongue and upper oral pharynx that are easily scraped off with a tongue depressor. PMH is significant for renal insufficiency secondary to his HIV. His antiretroviral regimen includes stavudine, lamivudine, and lopinavir/ritonavir and he is receiving TMP-SMX for Pneumocystis carinii pneumonia (PCP) prophylaxis. He has NKDA. 

Zidovudine i.s recommended for the management of adult patients with symptomatic HIV infection (AIDS or ARC) who have a history of confirmed Pneumocystis carinii pneumonia or an absolute CD4 (T4 or Th cell) lymphocyte count below 2(X)/mm before therapy. The hematological toxicity of the drug precludes its use in asymptomatic patients. Anemia and granulocytopenia are the most common toxic effects associated with AZT. 

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