Atovaquone Compared with Dapsone for the Prevention of<i>Pneumocystis carinii</i>Pneumonia in Patients with HIV Infection Who Cannot Tolerate Trimethoprim, Sulfonamides, or Both

El‐Sadr, Wafaa; Murphy, Robert L.; Yurik, Teresa Mc Cabe; Luskin-Hawk, Roberta; Cheung, Tony; Balfour, Henry H.; Eng, Robert H. K.; Hooton, Thomas M.; Kerkering, Thomas M.; Schütz, Malte; Horst, Charles D. Van Der; Hafner, Richard

doi:10.1056/nejm199812243392604

Cited by 161 publications

(89 citation statements)

References 18 publications

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“…As demonstrated in HIV-infected patients (Martin et al, 1993;Warnock and Rimland, 1996;El-Sadr et al, 1998), alternative prophylactic agents may be used, but are associated with higher rates of failure. Dapsone prophylaxis (50 mg three times per week) in allogeneic transplant recipients has a significantly higher incidence of failure when compared to TMP -SMX (Souza et al, 1999).…”

Section: Alternative Agentsmentioning

confidence: 99%

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital

et al. 2005

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Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (X25 mg prednisolone or X4 mg dexamethasone daily) for X4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, Po0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis.

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Section: Alternative Agentsmentioning

confidence: 99%

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital

et al. 2005

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“…9,10 The alternatives include aerosolized pentamidine, dapsone with or without pyrimethamine, and atovaquone. 11, 12 The use of highly active antiretroviral therapy has changed the course of HIV infection, resulting in a striking reduction in morbidity and mortality. 13,14 The The New Eng land Jour nal of Medicine persistent suppression of HIV replication leads to a sustained increase in CD4 cells, even in patients with severe immunosuppression.…”

Section: Resultsmentioning

confidence: 99%

A Randomized Trial of the Discontinuation of Primary and Secondary Prophylaxis againstPneumocystis cariniiPneumonia after Highly Active Antiretroviral Therapy in Patients with HIV Infection

Quirós

Miró

Peña³

et al. 2001

N Engl J Med

181

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“…2,6 Atovaquone was generally well tolerated in patients intolerant to TMP/ SMX in that only 11% of patients were discontinued from the study. The potential benefit of TMP/SMX therapy against other pathogens will not be observed except for possible activity against toxoplasmosis.…”

Section: Discussionmentioning

confidence: 99%

“…Discontinuation of TMP/SMX therapy in up to 30% to 40% of cases had led to consideration of alternative drugs. 2,3 Atovaquone was previously shown to be effective for PCP prophylaxis at a dose of 1,500 mg once daily, [4][5][6] with a trend for lower efficacy at a dose of 750 mg once daily. 5 Reduced efficacy may have been related to poor tablet absorption.…”

mentioning

confidence: 99%

Pneumocystis carinii pneumonia prophylaxis with atovaquone in trimethoprim-sulfamethoxazole–intolerant orthotopic liver transplant patients: A preliminary study

Meyers

Borrego

Papanicolaou

2001

Liver Transplantation

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Pneumocystis carinii pneumonia (PCP) is an opportunistic infection associated with increased morbidity and mortality in solid-organ and bone-marrow transplant recipients. Side effects of trimethoprim-sulfamethoxazole (TMP/SMX) are frequent; therefore, we performed a preliminary study using atovaquone suspension, 750 mg once daily, for 1 year for the prevention of PCP in liver transplant recipients intolerant to TMP/SMX therapy. Twenty-eight patients were treated, and data were analyzed for efficacy and toxicity. Adverse events occurred in 14 subjects, mainly related to the gastrointestinal tract. P neumocystis carinii pneumonia (PCP) is an opportunistic infection associated with increased morbidity and mortality in solid-organ and bone-marrow transplant recipients. Before instituting PCP prophylaxis, the incidence in this population was reported to be up to 10%. 1 Trimethoprim-sulfamethoxazole (TMP/SMX) is almost 100% effective in preventing PCP in immunosuppressed patients, but its use is limited by the high incidence of adverse reactions (in up to 50% of patients), in particular, bone-marrow suppression and skin manifestations, both major concerns in transplant patients. Discontinuation of TMP/SMX therapy in up to 30% to 40% of cases had led to consideration of alternative drugs. 2,3 Atovaquone was previously shown to be effective for PCP prophylaxis at a dose of 1,500 mg once daily, 4-6 with a trend for lower efficacy at a dose of 750 mg once daily. 5 Reduced efficacy may have been related to poor tablet absorption. The new suspension formulation used in this study produced greater serum levels and efficacy. All these studies were performed in patients with HIV rather than in solid-organ transplant recipients, with presumably greater T 4 cell counts, and bone marrow transplant recipients. Our study, the first efficacy study in transplant patients, was designed to test the effectiveness of PCP prevention and monitor adverse effects of atovaquone at a dose of 750 mg/d of suspension formulation in this population that was intolerant to TMP/SMX. MethodsThis is a prospective study in which we enrolled 28 patients with solid-organ transplants (liver) who had been started on the standard PCP prophylaxis with TMP/SMX (80/400 mg/d), but because of drug-related side effects, the drug was withdrawn. Institutional review board approval was obtained. Intolerance to TMP/SMX included rash in 9 of 28 patients (32%); 1 patient each with Stephens-Johnson syndrome and angioedema; bone-marrow suppression in 14 of 28 patients (50%); diarrhea in 1 of 28 patients (3.5%); and elevated creatinine levels in 1 of 28 patients (3.5%; Table 1).Patients were treated with atovaquone suspension, 750 mg once daily or 250 mg three times daily, for 1 year. Patients who were pregnant, unable to ingest oral medication, or had diarrhea (Ͼ3 loose bowel movements a day for Ͼ4 days) were excluded. All patients were followed up prospectively. The total length of follow-up was 37 months. Adverse effects were observed at each patient's clinical follow-u...

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Atovaquone Compared with Dapsone for the Prevention ofPneumocystis cariniiPneumonia in Patients with HIV Infection Who Cannot Tolerate Trimethoprim, Sulfonamides, or Both

Cited by 161 publications

References 18 publications

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital

A Randomized Trial of the Discontinuation of Primary and Secondary Prophylaxis againstPneumocystis cariniiPneumonia after Highly Active Antiretroviral Therapy in Patients with HIV Infection

Pneumocystis carinii pneumonia prophylaxis with atovaquone in trimethoprim-sulfamethoxazole–intolerant orthotopic liver transplant patients: A preliminary study

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