Efficacy and Toxicity of Two Doses of Trimethoprim-Sulfamethoxazole as Primary Prophylaxis against Pneumocystis carinii Pneumonia in Patients with Human Immunodeficiency Virus

Schneider, Margriet M E; Nielsen, T. L.; Nelsing, Suzanne; Hoepelman, Andy I. M.; Schattenkerk, J. K. M. E.; Graaf, Y. van der; Kolsters, Afp; Borleffs, Jan C. C.

doi:10.1093/infdis/171.6.1632

Cited by 71 publications

(29 citation statements)

References 8 publications

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“…Prophylaxis with trimethoprim-sulfamethoxazole also appears to protect against toxoplasmic encephalitis, but the optimal dose is unknown and the assessments of efficacy have been based only on a retrospective analysis [24], observational data [34,35], or results of controlled trials that did not primarily target prophylaxis for toxoplasmic encephalitis and therefore yielded small numbers of events [5,6,31,[36][37][38]. While none of these trials revealed a significant protective effect on an intent-to-treat basis, toxoplasmic encephalitis in fact rarely occurred during treatment with trimethoprim-sulfamethoxazole.…”

Section: Discussionmentioning

confidence: 99%

Once-Weekly Administration of Dapsone/Pyrimethamine vs. Aerosolized Pentamidine as Combined Prophylaxis for Pneumocystis carinii Pneumonia and Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients

Opravil

Hirschel

Lazzarin

et al. 1995

Clinical Infectious Diseases

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To evaluate combined prophylaxis for Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis, 533 patients with symptomatic human immunodeficiency virus infection and/ or CD4 lymphocyte counts of <200/AL were randomized to receive dapsone/pyrimethamine (200/75 mg once weekly) or aerosolized pentamidine (300 mg every 4 weeks). The median CD4 lymphocyte count was 110/AL; 47.5% were seropositive for toxoplasma antibodies. The median duration of follow-up was 483 days. In the intent-to-treat analysis, 12 cases of PCP and 14 of toxoplasmic encephalitis occurred in the dapsone/pyrimethamine group and 13 and 20 cases, respectively, in the aerosolized pentamidine group (adjusted relative risk for toxoplasmosis, 0.56; P = .10). However, only two of the 14 cases of toxoplasmic encephalitis in the dapsone/ pyrimethamine group developed during actual treatment. The mortality among the two groups was similar. Dapsone/pyrimethamine was not tolerated by 30% of participants. A subanalysis of 240 matched, tolerant patients yielded a relative risk for toxoplasmosis of 0.21 (P = .014), a result favoring the use of dapsone/pyrimethamine. Dapsone/pyrimethamine was as effective as aerosolized pentamidine as prophylaxis for PCP and significantly reduced the incidence of toxoplasmic encephalitis among those participants who tolerated it.Prophylaxis for opportunistic infections has had a strong impact on the management of immunosuppressed human immunodeficiency virus (HIV)-infected patients in recent years, and epidemiological data indicate that Pneumocystis carinii pneumonia (PCP) has become less frequent as a consequence of prevention [1]. Aerosolized pentamidine became available in Switzerland in 1987 and was subsequently proven effective for both primary and secondary prophylaxis for PCP in controlled trials [2,3]. Among systemic prophylactic agents, trimethoprim-sulfamethoxazole became widely used [4] and was later shown to be more effective but also more toxic than aerosolized pentamidine [5,6] nations, such as dapsone and trimethoprim [7] or pyrimethamine and sulfadiazine [8], have been used for treatment of PCP before, but sparse data exist concerning their prophylactic efficacy [9]. Only recently, the prophylactic efficacy of the combination of dapsone and pyrimethamine against PCP and toxoplasmosis was demonstrated [ 10].Since in >95% of all AIDS patients with toxoplasmic encephalitis there is serological evidence of previous infection with Toxoplasma gondii [10][11][12][13], reactivation of a latent infection is the principal pathogenetic step in the development of toxoplasmic encephalitis during immunodeficiency. Considering the increasing frequency of toxoplasmic encephalitis among AIDS-defining opportunistic infections [ 1] and the 50% seroprevalence of toxoplasma antibodies in Switzerland [14], primary prophylaxis for toxoplasmic encephalitis seems desirable and clinically important, at least for seropositive patients.The sequential inhibition of dihydrofolate reductase by pyrimethamine and of dihydropteroate sy...

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Section: Discussionmentioning

confidence: 99%

Once-Weekly Administration of Dapsone/Pyrimethamine vs. Aerosolized Pentamidine as Combined Prophylaxis for Pneumocystis carinii Pneumonia and Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients

Opravil

Hirschel

Lazzarin

et al. 1995

Clinical Infectious Diseases

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“…Studies of low-and high-dose regimens (single-or doublestrength TMP-SMZ tablets) for prophylaxis in patients with AIDS suggest no mortality advantage with the higher dose (12% incidence vs. 15% in the lower-dose group) and earlier occurrence of toxicity in the high-dose group [74,81]. Although no Pneumocystis infection was observed in compliant individuals in either group at 1 year of treatment, 63 of 156 patients dropped out because of toxicity.…”

Section: Specific Agentsmentioning

confidence: 99%

Prevention of Infection Caused byPneumocystis cariniiin Transplant Recipients

2001

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Pneumocystis carinii remains an important pathogen in patients who undergo solid-organ and hematopoietic transplantation. Infection results from reactivation of latent infection and via de novo acquisition of infection from environmental sources. The risk of infection depends on the intensity and duration of immunosuppression and underlying immune deficits. The risk is greatest after lung transplants, in individuals with invasive cytomegalovirus disease, during intensive immunosuppression for allograft rejection, and during periods of neutropenia. Prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) prevents many opportunistic infections, including infection with P. carinii, Toxoplasma gondii, and community-acquired respiratory, gastrointestinal, and urinary tract pathogens. Intolerance of TMP-SMZ is common; desensitization is useful less often in transplant patients than in patients with AIDS. Alternative agents provide a narrower spectrum of protection than does TMP-SMZ and less adequate protection against Pneumocystis species. Clinically, the diagnosis of breakthrough Pneumocystis pneumonia often requires invasive procedures. Strategies for the prevention of Pneumocystis infection must be individualized on the basis of a stratification of risk for each patient.

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“…About one-quarter of HIV-infected patients experience adverse reactions to cotrimoxazole (especially cutaneous intolerance), often leading to withdrawal of treatment (11). The mechanisms underlying these adverse reactions are unclear [toxic (12)(13)(14) and:or immunologic (15)].…”

Section: Introductionmentioning

confidence: 99%

Adverse Reactions to Cotrimoxazole in HIV-infected Patients: Predictive Factors and Subsequent HIV Disease Progression

Charreau

Izard

Raffi³

et al. 2001

Scandinavian Journal of Infectious Diseases

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The relationship between the onset of adverse events to cotrimoxazole in HIV-infected patients and the subsequent development of toxoplasmosis, other AIDS-defining events and survival was studied in 592 French patients who first received cotrimoxazole during the Delta trial. Low CD4+ cell count at cotrimoxazole introduction was the only factor associated with the onset of adverse reactions. The occurrence of toxoplasmosis and first AIDS-defining events were significantly and independently linked to a low CD4+ cell count at cotrimoxazole introduction (p < 0.0001) and to previous cotrimoxazole withdrawal for adverse events (p = 0.004 and p < 0.0001, respectively), but not to previous cotrimoxazole withdrawal for reasons other than adverse events, as compared to patients who did not discontinue taking cotrimoxazole during this survey. The survival rate was significantly shorter among both patients who stopped taking cotrimoxazole for adverse events and for other reasons (p = 0.03 and p = 0.0001, respectively), as compared to patients who continued to take cotrimoxazole.

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Efficacy and Toxicity of Two Doses of Trimethoprim-Sulfamethoxazole as Primary Prophylaxis against Pneumocystis carinii Pneumonia in Patients with Human Immunodeficiency Virus

Cited by 71 publications

References 8 publications

Once-Weekly Administration of Dapsone/Pyrimethamine vs. Aerosolized Pentamidine as Combined Prophylaxis for Pneumocystis carinii Pneumonia and Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients

Once-Weekly Administration of Dapsone/Pyrimethamine vs. Aerosolized Pentamidine as Combined Prophylaxis for Pneumocystis carinii Pneumonia and Toxoplasmic Encephalitis in Human Immunodeficiency Virus-Infected Patients

Prevention of Infection Caused byPneumocystis cariniiin Transplant Recipients

Adverse Reactions to Cotrimoxazole in HIV-infected Patients: Predictive Factors and Subsequent HIV Disease Progression

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