naphthoquinones and Pneumonia--Pneumocystis

Topics: Atovaquone; Clindamycin; Corticosterone; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii is an opportunistic eukaryotic pathogen most common causing pneumonia in immunocompromised host. DNA P. carinii f. sp. hominis has been frequently detected in air samples collected from environments of P. carinii pneumonia (PCP) patients and nasal swabs samples from contact health care workers and family. Epidemiological studies suggested not-only the possibility of person-to-person infection transmission. First hypothesis of reactivation latent infection of the causing the new episode of PCP based on serological studies. Recently findings based molecular studies has suggested new acquired infection may to be cause of many cases of PCP. Early diagnosis, therapy and effective prophylaxis of PCP is a very important strategy to reduce morbidity and mortality among infected patients. The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is effective for prophylaxis and treatment P. carinii pneumonia. Empiric therapy in immunocompromised host also including AIDS patients with anti-Pneumocystis prophylaxis is also not recommended. Both dapsone and sulfamethoxazole act inhibiting the folate biosynthetic enzyme DHPS. Mutations identified in P. carinii in gene coding this enzyme are associated with resistance to sulfonamide. P. carinii may also developing resistance to atovaquone, second-line therapeutic and prophylactic agent.

Topics: Anti-Infective Agents; Antifungal Agents; Atovaquone; Drug Resistance, Multiple, Fungal; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: Animals; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Babesia; Humans; Naphthoquinones; Plasmodium; Pneumocystis; Pneumonia, Pneumocystis; Protozoan Infections; Randomized Controlled Trials as Topic; Toxoplasma

Pneumocystis carinii pneumonitis (PCP) is one of the most important opportunistic infections in children and adolescents with cancer. Its high frequency and a considerable mortality have led to primary chemoprophylaxis in patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. Although less well characterized, patients with autologous stem cell transplantation and patients with dose-intensive chemotherapy for pediatric solid tumors may have a similarly high risk for PCP based on their profound T-cell depletion. For more than two decades, effective chemoprophylaxis for PCP has been available. Trimethoprim and sulfamethoxazole (TMP/SMX) is the prophylactic modality of first choice. The combination has been shown to be almost 100 % efficacious in pediatric cancer patients at highest risk, and it is usually well tolerated in this setting. Secondary alternatives to TMP/SMX include oral dapsone, oral atovaquone, and aerosolized pentamidine-isethionate. These modalities are less effective than TMP/SMX, and have been evaluated predominantly in HIV-infected patients. This article reviews epidemiology and current approaches to chemoprophylaxis for PCP in children and adolescents with cancer and/or hematopoietic stem cell transplantation, and provides evidence-based guidelines for indications and modalities of PCP prophylaxis in this population.

Topics: Adolescent; Age Factors; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Atovaquone; Child; Child, Preschool; Dapsone; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Naphthoquinones; Neoplasms; Odds Ratio; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Animals; Antibiotic Prophylaxis; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Fungal Vaccines; Humans; Microbial Sensitivity Tests; Naphthoquinones; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Atovaquone; Clindamycin; Dapsone; Eflornithine; Humans; Macrolides; Naphthoquinones; Pentamidine; Pneumocystis; Pneumocystis Infections; Pneumonia, Pneumocystis; Pyrimidines; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Early effective management of Pneumocystis carinii pneumonia improves outcome in patients with this disorder. Trimethoprim-sulfamethoxazole remains the agent of choice for treatment of severe P. carinii pneumonia. Pentamidine, trimethoprim-dapsone, atovaquone, and other regimens are useful in selected clinical situations. Adjunctive corticosteroids are indicated in patients with acquired immune deficiency syndrome and P. carinii pneumonia who have moderate to severe P. carinii pneumonia defined as a room air arterial PaO2 less than 70 mm Hg or an alveolar-arterial oxygen gradient of greater than 35 mm Hg. The use of trimethoprim-sulfamethoxazole, dapsone, and aerosolized pentamidine in immunocompromised patients without AIDS is also reviewed.

Topics: Adrenal Cortex Hormones; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clinical Trials as Topic; Dapsone; Female; Humans; Male; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Prognosis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole remains the treatment of choice in patients with Pneumocystis carinii pneumonia (PCP) requiring intravenous therapy. Those patients who require intravenous therapy who cannot tolerate or who fall therapy with trimethoprim-sulfamethoxazole may be treated with either pentamidine or trimetrexate (plus folinic acid), with or without orally administered dapsone. The toxicity of the former drug makes trimetrexate-based therapy the preferred second choice for parenteral use. Treatment with trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine is approximately of equivalent efficacy, but variable toxicity, in patients with mild to moderate PCP for whom an oral route of administration is appropriate. Atovaquone, formulated as an oral suspension, is also effective, but, in the absence of additional data, must be considered as second line therapy. Adjunctive corticosteroid therapy is indicated for patients with [PAO2-PaO2] more than 30 mm Hg or PaO2 less than 70 mm Hg [corrected] while breathing ambient air in the absence of contraindications. Recognition of the apparent fungal nature of P carinii as well as improved understanding of the pathophysiology of PCP will lead to further improvements in antipneumocystis therapy.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Humans; Infusions, Intravenous; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

The increased resistance, intolerance, or allergy to trimethoprim/sulfamethoxazole (TMP/SMX) has brought much attention to alternative treatment of pneumonia caused by Pneumocystis carinii (PCP). Pentamidine is considered when there is documented allergy or intolerance to TMP/SMX. Similarly, either dapsone/trimethoprim or clindamycin/primaquine is effective in the treatment of mild to moderate PCP, but both regimens are contraindicated in glucose 6-phosphate dehydrogenase (G6PD) deficiency. For this purpose, atovaquone should be used in patients who are deficient in G6PD or who are unable to be on TMP/SMX or pentamidine. On the other hand, in severe disease, adjunctive corticosteroids can enhance the efficacy of either TMP/SMX or pentamidine. If these therapies yield no response, trimetrexate with leucovorin has been approved as initial and salvage therapy in severe PCP. We review alternative treatment to TMP/SMX and propose ideal and practical therapeutic and prophylactic guidelines in the treatment and prevention of PCP.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Combinations; Drug Hypersensitivity; Drug Resistance, Microbial; Humans; Leucovorin; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Atovaquone has been investigated as an alternative agent for oral use in the treatment of both mild to moderate Pneumocystis carinii pneumonia (PCP) and toxoplasmosis, opportunistic infections commonly experienced by patients with AIDS. In patients with mild to moderate PCP, a dosage of 750mg 3 times daily (administered in tablet form) has similar overall therapeutic efficacy (defined as clinical response without a treatment-limiting adverse event) to the conventional therapies oral cotrimoxazole (trimethoprim-sulfamethoxazole) and intravenous pentamidine, respectively. Response rates to atovaquone are lower than those achieved with cotrimoxazole, but atovaquone has superior tolerability. Atovaquone recipients experienced significantly fewer treatment-limiting adverse effects than patients treated with cotrimoxazole (7 vs 20%) or pentamidine (4 vs 36%). Mortality rates were higher among atovaquone-treated patients than in cotrimoxazole recipients (7 vs 0.6%) 4 weeks after completion of therapy in a large comparative trial, although most deaths were caused by bacterial infections. However, a similar rate of mortality was reported for atovaquone- and pentamidine-treated patients (16 vs 17% 8 weeks after discontinuation of therapy) in another study. In predominantly small numbers of patients with toxoplasmosis, of whom most were unresponsive to conventional agents, atovaquone 750mg 4 times daily (administered as tablets) produced a complete or partial radiological response rate of 37 to 87.5% 52% of patients achieved a complete or partial clinical response after 6 weeks of treatment in the largest trial (n = 87), although the incidence of toxoplasmosis-related death was 24% 18 weeks after therapy was initiated. Thus, atovaquone will be a useful option for the treatment of patients with mild to moderate PCP who are intolerant or unresponsive to cotrimoxazole, especially if the increased plasma drug concentrations observed with the suspension further improve response rates. Atovaquone should also be considered a promising agent for the treatment of toxoplasmosis.

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Clinical Trials as Topic; Drug Evaluation; Drug Interactions; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis

At the start of the AIDS epidemic, the only agents licensed for treatment of Pneumocystis carinii pneumonia (PCP) were trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine. Both are effective against PCP, but their use has been compromised by adverse reactions that necessitate discontinuing therapy in < or = 54% of patients. As a result of the limitations in the use of these therapies, research efforts have been directed toward the development of effective agents with an improved safety profile. Of these agents, one of the best studied is atovaquone, a hydroxynaphthoquinone that has been licensed by the U.S. Food and Drug Administration for use in the treatment of mild to moderate PCP in patients intolerant to TMP-SMX. Clinical studies have shown that atovaquone is associated with overall therapeutic success rates equivalent to those of intravenous pentamidine and TMP-SMX, although its therapeutic efficacy rates are somewhat lower. However, atovaquone is associated with fewer treatment-limiting side effects than the other drugs. The literature concerning the efficacy and safety of atovaquone for the treatment of PCP will be reviewed.

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Cohort Studies; Humans; Male; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Rats; Tablets; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Atovaquone; Clindamycin; Clinical Trials as Topic; Dapsone; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Eflornithine; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Primaquine; Trimethoprim; Trimetrexate

The mechanism of action, pharmacokinetics and pharmacodynamics, clinical efficacy, adverse effects, and dosage of atovaquone in the management of mild to moderate Pneumocystis carinii pneumonia (PCP) are reviewed. Atovaquone has a novel mechanism of action that has been hypothesized to result in microbicidal rather than microbistatic activity against Pneumocystis carinii. Absorption of the drug is significantly enhanced by the presence of food, particularly food with a high fat content. In comparative trials, atovaquone was slightly less effective than trimethoprim-sulfamethoxazole and as effective as pentamidine isethionate in treating mild to moderate PCP. Atovaquone is associated with a lower incidence of treatment-limiting adverse reactions than are trimethoprim-sulfamethoxazole and pentamidine isethionate. The most commonly occurring adverse effect in patients receiving atovaquone is rash, and the drug does not appear to cause bone marrow suppression. The FDA-approved dosage regimen for atovaquone in treating mild to moderate PCP is 750 mg (three 250-mg tablets) administered orally three times daily with food for 21 days. Atovaquone may be considered a first-line treatment for patients with the acquired immunodeficiency syndrome who have mild to moderate PCP and have demonstrated an intolerance to trimethoprim-sulfamethoxazole.

Topics: Antifungal Agents; Atovaquone; Drug Costs; Drug Interactions; Food; Humans; Intestinal Absorption; Naphthoquinones; Pneumonia, Pneumocystis

To review the chemistry, pharmacology, pharmacokinetics, clinical efficacy, and safety of atovaquone.. An English-language literature search using MEDLINE (1984-1993), programs and abstracts of the 30th, 31st, and 32nd Interscience Conferences on Antimicrobial Agents and Chemotherapy, program and abstracts of the VIII International Conference on AIDS, and unpublished information from Burroughs Wellcome, the manufacturer of atovaquone.. All available pharmacokinetic and clinical trials were reviewed.. Study quality was assessed by a critical appraisal of study design and methods. Pharmacokinetic studies were evaluated for sampling, methods used to determine pharmacokinetic properties, and the presence of concentration-response and concentration-toxicity relationships. Clinical trials were assessed primarily for comparative efficacy and toxicity.. Atovaquone is a novel hydroxynaphthoquinone with potent activity against Pneumocystis carinii and Toxoplasma gondii. Its pharmacokinetic properties are characterized by relatively poor bioavailability, excretion almost exclusively through the feces, lack of hepatic metabolism and urinary excretion, low steady-state plasma concentrations, high protein binding, and a long elimination half-life (50-70 h). Results from comparative clinical trials in AIDS patients with mild-to-moderate P. carinii pneumonia (PCP) reveal similar overall treatment success rates for atovaquone, trimethoprim/sulfamethoxazole (TMP/SMX), and pentamidine. Treatment failure because of lack of therapeutic response was significantly greater in patients who received atovaquone compared with those treated with TMP/SMX (p = 0.002). More atovaquone-patients experienced treatment failure compared with their pentamidine-treated counterparts, although statistical significance was not achieved. Treatment failure secondary to drug toxicity was significantly higher in the TMP/SMX- and pentamidine-treated patients (p < or = 0.01). Atovaquone has not been studied for PCP prophylaxis. Limited data exist on the use of atovaquone for toxoplasmic encephalitis (TE); however, results from an open trial reveal that the drug may be useful in treating this disorder. To date, atovaquone has been well tolerated by most patients administered the drug. The most common adverse effects include maculopapular rash, gastrointestinal disturbances, and fever. Atovaquone is considerably more costly than other oral agents used to treat PCP.. Atovaquone appears to be better tolerated but less effective than TMP/SMX and pentamidine in the treatment of mild-to-moderate PCP. There is not enough information available on the use of atovaquone for PCP prophylaxis or the treatment of TE to definitively describe its efficacy. Comparative clinical trials are needed to assess its role in this clinical setting.

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Clinical Trials as Topic; Humans; Male; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral

The armamentarium of drugs to treat and to prevent Pneumocystis pneumonia has expanded substantially over the past decade. In all patient populations trimethoprim-sulfamethoxazole is the preferred regimen for both acute treatment and prophylaxis. Clindamycin-primaquine and atovaquone are both effective agents for acute therapy but there are no data yet suggesting that they are preferable to trimethoprim-sulfamethoxazole. Corticosteroid therapy is now standard for severe AIDS-associated Pneumocystis pneumonia, and should probably be used in other patient populations with severe pneumocystis pneumonia as well.

Topics: Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Clindamycin; Clinical Trials as Topic; Drug Tolerance; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children. Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin.. A randomized, double-blind, placebo-controlled trial was designed to determine whether atovaquone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV-infected children aged 3 months to 19 years. Children qualified for PCP prophylaxis (on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone-azithromycin or TMP-SMZ daily for >or=2 years.. Data from 366 of the 369 eligible patients (median duration of follow-up, 3 years) showed that the estimated rates of serious bacterial infection-related events were lower among atovaquone-azithromycin recipients than among TMP-SMZ recipients (17.3 vs. 24.2 events per 100 patient-years; difference, 6.9 events per 100 patient-years; 95% confidence interval [CI], -0.22 to 14.12). Rates for all end points (serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection-related deaths) were 19.7 and 27.7 events per 100 patient-years, respectively (difference, 7.9 events per 100 patient-years; 95% CI, -0.28 to 15.54 events per 100 patient-years). The results marginally favored atovaquone-azithromycin therapy statistically. Atovaquone-azithromycin and TMP-SMZ therapies had similar adverse event profiles.. We conclude that, in HIV-infected children, atovaquone-azithromycin is as effective as TMP-SMZ for the prevention of serious bacterial infections and is similarly tolerated.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Atovaquone; Azithromycin; Bacterial Infections; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Infant; Infant, Newborn; Male; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Atovaquone suspensions (750 mg and 1500 mg once a day) were compared with aerosolized pentamidine (300 mg once a month) for the prevention of Pneumocystis carinii pneumonia (PCP) in subjects with human immunodeficiency virus (HIV) infection who were intolerant to trimethoprim or sulfonamides (or both). Median time using the assigned therapy was 6.6 months, and the median follow-up was 11.3 months. Intent-to-treat analyses (n=549) showed no statistically significant differences among subjects with regard to the incidence of PCP (26%, 22%, and 17%, respectively) or mortality (20%, 13%, and 18%, respectively). The incidence of treatment-limiting adverse events with atovaquone was significantly higher (P<.01). There was, however, no significant difference in the time using therapy. Incidences of PCP and death were higher in subjects receiving 750 mg of atovaquone than in subjects receiving 1500 mg. Atovaquone suspension at 1500 mg once a day has an efficacy similar to that of aerosolized pentamidine for prevention of PCP in HIV-infected subjects and is a safe, effective alternative in those who are intolerant to trimethoprim or sulfonamides.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Sulfonamides; Trimethoprim

Pneumonia due to Pneumocystis carinii is an infrequent complication following autologous stem cell transplantation (ASCT) which is associated with a high mortality. Although administration of trimethoprim/sulfa- methoxazole (TMP/SMX) is an effective prophylactic strategy for Pneumocystis carinii pneumonia (PCP), treatment-associated toxicity frequently results in discontinuation of therapy. We have conducted a prospective randomized trial comparing atovaquone, a new anti-Pneumocystis agent, with TMP/SMX for PCP prophylaxis following autologous peripheral blood stem cell (PBSC) transplantation. Thirty-nine patients were studied. Twenty patients received atovaquone suspension and 19 patients received TMP/SMX. The median ages were 44 (range 20-68) and 47 (range 32-63) years, respectively. A similar number of patients with solid tumors (14 vs 15) and hematologic malignancies (five vs five) were treated in each group. Either TMP/SMX (160/800 mg) or atovaquone (1500 mg) was administered daily from transplant day -5 until day -1, discontinued from day 0 to engraftment, then resumed 3 days per week until day +100 post-transplant. The median time to engraftment (ANC >0.5 x 109/l) was similar in both groups. Eighty percent of the patients randomized to atovaquone prophylaxis completed the study. Four atovaquone-treated patients were removed from study; two patients (10%) did not receive a transplant and two patients (10%) were removed due to a protocol violation. None of the 16 patients treated with atovaquone experienced treatment-associated adverse effects. Of the 19 patients randomized to receive TMP/SMX, 55% completed the study. Nine TMP/SMX-treated patients were removed from the study; one patient (5%) did not receive a transplant and eight patients (40%) were removed due to drug intolerance (P < 0.003). The rate of intolerance to TMP/SMX led to the early discontinuation of this randomized trial. Intolerance of TMP/SMX included elevated transaminase levels (n = 1), nausea or vomiting (n = 3), thrombocytopenia (n = 2) and neutropenia (n = 2). All episodes of TMP/SMP intolerance occurred following transplantation after a median duration of 17.5 (range 2-48) days and a median of 7 (range 1-20) doses. Resolution of adverse side-effects occurred in all eight patients within a median of 7 (range 2-20) days following discontinuation of therapy. Neither PCP nor bacterial infections were identified in any of the patients treated. This prospective randomized study demon

Topics: Adult; Aged; Antifungal Agents; Atovaquone; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Male; Middle Aged; Naphthoquinones; Neoplasms; Pneumocystis; Pneumonia, Pneumocystis; Prospective Studies; Transplantation, Autologous; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the pharmacokinetics and safety of atovaquone suspension in volunteers infected with the human immunodeficiency virus ((HIV).. Open-label, nonrandomized study.. Two clinical research centers.. Twenty-two HIV-infected volunteers with a median CD4 cell count of 37 cells/mm3.. Patients received atovaquone suspension fasting or fed for 2-week periods with crossover at dosages of 500 mg/day, and randomization to fasting or fed at dosages of 750 and 1000 mg/day. A subset of patients also received 750 mg twice/day with food, and a subset of those who received 1000 mg/day fasting also received 1000 mg with food. During a long-term dosing phase, a subset of subjects were evaluated for an interaction between atovaquone and trimethoprim-sulfamethoxazole (TMP-SMX).. Average steady-state atovaquone concentrations at 500 mg were 6.7 +/- 3.2 microg/ml fasted and 11.3 +/- 5.0 microg/ml with food; at 750 mg, 9.9 +/- 7.1 microg/ml fasted and 12.5 +/- 5.9 microg/ml with food; at 1000 mg, 9.7 +/- 4.3 microg/ml fasted and 13.6 +/- 5.0 microg/ml with food; and at 1500 mg, 21.1 +/- 5.0 microg/ml with food. Thus, plasma concentrations were not proportional to dose. Concomitant food ingestion resulted in a 1.3- to 1.7-fold increase in values. Average steady-state concentrations were less than 10 microg/ml in 21% and more than 15 microg/ml in 36% of patients at 1000 mg/day with food; at 750 mg twice/day, all five patients had levels above 15 microg/ml. Atovaquone suspension was well tolerated; diarrhea, nausea, fatigue, and rash were the most common adverse events. Concomitant administration of TMP-SMX did not change atovaquone concentrations and resulted in small decreases in concentrations of TMP (16%) and SMX (10%).. Plasma concentrations are significantly higher when atovaquone suspension is administered with food compared with fasting. Total doses of 1500 mg/day are likely to achieve concentrations effective for prophylaxis of Pneumocystis carinii pneumonia.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Fasting; Female; Food-Drug Interactions; Humans; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A phase I dose-escalating safety and pharmacokinetic study evaluated an oral suspension of micronized atovaquone (m-atovaquone) in infants and children stratified into age groups from 1 month to 12 years of age. Dosages of 10, 30, and 45 mg/kg of body weight/day were evaluated as single daily doses over a period of 12 days. Steady-state concentrations in plasma were determined on day 12, and single postdose concentrations were measured on days 1, 3, 5, 7, 9, 13, 15, 18, 21, and 24. Prior studies with adults suggest that the average plasma atovaquone concentration of 15 micrograms/ml is associated with therapeutic success in more than 95% of patients with Pneumocystis carinii pneumonitis. The results showed m-atovaquone to be safe and well tolerated. Dosages of 30 mg/kg/day were adequate to achieve an average steady-state concentration of greater than 15 micrograms/ml in children ages 1 to 3 months and 2 to 12 years, but a dosage of 45 mg/kg/day was needed to reach this concentration in infants 3 to 24 months of age. The oral suspension of atovaquone is safe and well tolerated in children. A single daily dose of 30 mg/kg provides bioavailability considered adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months of age may require a dosage of 45 mg/kg/day.

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Child; Child, Preschool; Humans; Infant; Naphthoquinones; Pneumonia, Pneumocystis

In 1995 and 1997, the United States Public Health Service (USPHS) and the Infectious Disease Society of America (IDSA) published recommendations for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), and toxoplasmosis in HIV-infected adults. We evaluated their implementation at four hospital-based HIV clinics in New York City in patients who initially met the CD4+ criterion for prophylaxis between January, 1995 and April, 1997. Medical records were reviewed at 6-month intervals to determine drugs prescribed. We identified 149 patients for the PCP sample, 130 for MAC, and 138 for toxoplasmosis. In the three samples, 91% were black and Hispanic, 75% to 81% were male, and 43% to 47% had a history of injection drug use (IDU); median age was between 39 and 40 years. PCP prophylaxis was prescribed during 93% of intervals and did not vary significantly by clinic or patient characteristics. Over the study period, MAC prophylaxis increased from 22% to 62%, and prescriptions for macrolides increased from 38% to 87% of all prescriptions. In the logistic regression analysis, prescription for MAC prophylaxis at any time during the study period was less likely in blacks compared with whites (odds ratio [OR] = .08; 95% confidence interval [CI] = .01, .52) and patients attending the clinic with the lowest rate of MAC prophylaxis (clinic D) compared with the clinic with the highest rate (clinic B; OR = .04; 95% CI = .01, .26). Toxoplasmosis prophylaxis was prescribed in 73% of intervals and did not differ significantly by antibody status (p = .42). Prescribing patterns were uniform across gender, HIV risk behavior, and age for PCP and MAC prophylaxis but differed by clinic and race for MAC prophylaxis. Trends in prophylaxis for opportunistic illnesses must continue to be monitored in light of the success of antiretroviral therapy in reducing the morbidity and mortality associated with HIV/AIDS.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Atovaquone; Azithromycin; Clarithromycin; Dapsone; Ethnicity; Female; HIV Infections; Humans; Longitudinal Studies; Male; Medical Records; Mycobacterium avium-intracellulare Infection; Naphthoquinones; New York City; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Regression Analysis; Rifabutin; Risk-Taking; Time Factors; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Public Health Service

Although trimethoprim-sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent.. We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months.. Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P<0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001).. Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Atovaquone; Dapsone; Female; Follow-Up Studies; HIV Infections; Humans; Male; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) is the most common severe opportunistic infection, and one of the most costly, among people with AIDS. Over 50% of patients experience toxic effects of the major anti-PCP medications- cotrimoxazole (trimethoprim-sulfamethoxazole) and pentamidine. Recently, the US Food and Drug Administration approved a new oral drug therapy, atovaquone, as an alternative to pentamidine for the treatment of people with mild-to-moderate PCP who are intolerant of cotrimoxazole. We developed a decision tree model to estimate the costs and cost effectiveness of atovaquone therapy compared with intravenous pentamidine therapy for cotrimoxazole-intolerant patients with mild-to-moderate PCP. Clinical outcomes were based on data from a phase III trial comparing the 2 medications. Our economic outcomes were based on treatment algorithms derived from discharge data, published reports and the clinical judgement of the co-authors. We estimate the total expected cost of treating a patient for an episode of PCP with atovaquone to be $US3990 compared with $US6545 for pentamidine under our baseline scenario (1995 dollars). Our decision model also provides insight into the large cost-savings benefits of treating mild-to-moderate PCP on an outpatient basis.

Topics: Antifungal Agents; Atovaquone; Costs and Cost Analysis; Decision Trees; Humans; Injections, Intravenous; Monte Carlo Method; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis

Atovaquone was compared to trimethoprim-sulfamethoxazole (TMP-SMZ) for the relationship of time receiving therapy, plasma drug concentrations, and incidence of adverse reactions in patients with AIDS-associated Pneumocystis carinii pneumonia. Treatment-limiting adverse events occurred in 9% of atovaquone-treated patients and 24% of TMP-SMZ-treated patients. Adverse events usually did not occur before day 7 for either treatment. Only the incidence of rash increased with increasing plasma concentrations of atovaquone. The incidence of anemia, neutropenia, and azotemia increased with increasing trimethoprim plasma concentration, while other adverse events (gastrointestinal disorders, rash, fever, and liver function abnormalities) were independent of plasma drug concentration.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Double-Blind Method; Female; Humans; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical experience of human immunodeficiency virus (HIV) + patients treated with oral atovaquone for acute Pneumocytstis carinii pneumonia (PCP) under a Treatment Investigational New Drug (IND) protocol (mild or moderate PCP) and an Open-Label Study protocol (severe PCP) was evaluated. A total of 940 patients intolerant of or unresponsive to trimethoprimsulfamethoxazole were enrolled from private practices, clinics, and institutional HIV treatment centers in the United States. Demographics data and the history and severity of PCP were collected at enrollment. The number of therapy days, adverse experiences, clinical response to therapy, and mortality were collected at day 21. Reporting of serious, unexpected adverse experiences attributable to therapy was required. Of the 760 (96%) patients with mild to moderate disease for whom follow-up observation was complete, 591 (78%) responded clinically to treatment, 177 patients (23%) discontinued treatment prematurely, and 50 patients (7%) died. Of the 140 patients (95%) with severe PCP with follow-up data, 79 (56%) responded to treatment, 45 (32%) discontinued treatment early, and 53 patients (38%) died. Adverse events that resulted in temporary or permanent discontinuation of therapy included diarrhea, vomiting, elevated liver enzyme levels, nausea, and fever. No serious unexpected adverse events attributable to the drug were reported. The treatment IND mechanism enabled a large number of patients with acute PCP to be treated with this experimental therapy while the drug was under regulatory view.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Child; Child, Preschool; Drugs, Investigational; Female; Follow-Up Studies; HIV Seropositivity; Humans; Infant; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis

At the start of the AIDS epidemic, the only agents licensed for treatment of Pneumocystis carinii pneumonia (PCP) were trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine. Both are effective against PCP, but their use has been compromised by adverse reactions that necessitate discontinuing therapy in < or = 54% of patients. As a result of the limitations in the use of these therapies, research efforts have been directed toward the development of effective agents with an improved safety profile. Of these agents, one of the best studied is atovaquone, a hydroxynaphthoquinone that has been licensed by the U.S. Food and Drug Administration for use in the treatment of mild to moderate PCP in patients intolerant to TMP-SMX. Clinical studies have shown that atovaquone is associated with overall therapeutic success rates equivalent to those of intravenous pentamidine and TMP-SMX, although its therapeutic efficacy rates are somewhat lower. However, atovaquone is associated with fewer treatment-limiting side effects than the other drugs. The literature concerning the efficacy and safety of atovaquone for the treatment of PCP will be reviewed.

Topics: AIDS-Related Opportunistic Infections; Animals; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Cohort Studies; Humans; Male; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Rats; Tablets; Trimethoprim, Sulfamethoxazole Drug Combination

To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments.. Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily.. Multicenter study including university and community treatment facilities.. Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized.. Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued.. As initial therapy for a histologically confirmed episode of P. carinii pneumonia, 56 patients received atovaquone and 53 received pentamidine. More patients were successfully treated with atovaquone (57%) than with pentamidine (40%), a difference of 17% (95% CI, -3% to 38%; P = 0.085), but more patients failed to respond to atovaquone (29%) than to pentamidine (17%), a difference of 12% (CI, -6% to 29%; P = 0.18). Discontinuation of original therapy because of treatment-limiting adverse events was more frequent in the pentamidine group (36%) than in the atovaquone group (4%) (difference, -32%; CI, -48% to -17%; P < 0.001). Nine patients in each treatment group died during the study.. Oral atovaquone and intravenous pentamidine have similar rates for successful treatment of mild and moderate P. carinii pneumonia, but atovaquone has significantly fewer treatment-limiting adverse events.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Female; Humans; Male; Middle Aged; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Survival Analysis; Treatment Outcome

Atovaquone is a new hydroxynapthoquinone antiprotozoal agent active against Pneumocystis carinii in vitro and in animal models. The authors report an experience using atovaquone to treat 25 patients with mild to moderate P. carinii pneumonia. Eligible patients were treated for 21 days with 750 mg of atovaquone orally three times daily. Prednisone was added when the P(A-a)O2 gradient was between 35-45 mm Hg. Patients were treated under three treatment protocols. Patients in Group 1 participated in one of two randomized comparative drug trials, designed for patients with and without sulfonamide intolerance. Six of seven patients successfully completed treatment, and one patient discontinued treatment because of an adverse reaction (> 5 times baseline increase in transaminase level). Patients in Group 2 were treated with atovaquone for mild to moderate P. carinii pneumonia under a treatment Investigational New Drug protocol because of prior sulfonamide reactions. Fifteen of these 18 patients successfully completed treatment; one died from other complications during treatment and two discontinued treatment for adverse reactions (> 5 times baseline increase in transaminase levels, and a diffuse rash). Serum transaminase levels returned to normal at the end of treatment in all patients with elevated levels. All patients demonstrated clinical resolution of their pneumonia and improvement of pretreatment hypoxemia (Group 1: pretreatment PaO2 = 82 +/- 14 mm Hg, posttreatment PaO2 = 92 +/- 9 mm Hg). Overall, 21 (84%) of 25 patients successfully finished therapy without significant adverse reactions. Atovaquone appears to be an effective and well-tolerated oral treatment for mild to moderate P. carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Female; Humans; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis; Treatment Outcome

Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii.. We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg).. Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group.. For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Confidence Intervals; Double-Blind Method; Female; Humans; Male; Middle Aged; Naphthoquinones; Odds Ratio; Pneumonia, Pneumocystis; Regression Analysis; Trimethoprim, Sulfamethoxazole Drug Combination

The drug 566C80 is an investigational hydroxynaphthoquinone that is active against Pneumocystis carinii in vitro and in animal models. Initial studies in humans indicate that 566C80 is safe and has adequate bioavailability after oral administration.. We conducted an open-label trial of 566C80 in 34 adults with the acquired immunodeficiency syndrome (AIDS) and untreated pneumocystis pneumonia. All the patients had a partial pressure of arterial oxygen of at least 60 mm Hg while breathing room air. They were enrolled sequentially in three cohorts taking 566C80 at different dosages, all administered orally: 750 mg three times daily for 5 days, then twice daily for 16 days; 750 mg three times daily for 21 days; and 750 mg four times daily for 21 days.. All 34 patients survived, and 27 (79 percent) were successfully treated with 566C80 alone. The mean partial pressure of oxygen in 33 patients was 78 mm Hg at entry and 93 mm Hg after the course of 566C80 (P less than 0.001). In five patients (15 percent) the drug was discontinued because of lack of response. In four patients (12 percent), the drug was discontinued because of toxicity (fever and rash in two patients each). In two of these, treatment was considered to have succeeded because 566C80 was not discontinued because of toxicity until after day 14. Five of the successfully treated patients had rashes that resolved despite continued therapy. In nine patients, serum alanine aminotransferase levels rose above 100 U per liter. During the first three months after the completion of therapy, pneumocystis pneumonia recurred in 4 of the 27 successfully treated patients, and another 3 patients had recurrences between month 3 and month 6 of follow-up. The mean (+/- SEM) steady-state plasma levels of 566C80 were similar in the three cohorts: 16.3 +/- 2.10, 20.4 +/- 2.48, and 18.9 +/- 3.08 micrograms per milliliter in the patients taking the drug twice daily, three times daily, and four times daily, respectively.. From these preliminary data, the investigational compound 566C80 appears to be a safe, effective, and well-tolerated therapy for P. carinii pneumonia of mild-to-moderate severity in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Atovaquone; Drug Administration Schedule; Drug Evaluation; Female; Follow-Up Studies; Humans; Male; Naphthoquinones; Partial Pressure; Pneumonia, Pneumocystis; Recurrence; Treatment Outcome

A hydroxynaphthoquinone compound (566C80) has been shown to be effective in the prevention and treatment of murine Pneumocystis carinii pneumonitis. In a phase I study, five cohorts of four human immunodeficiency virus-infected men received 100, 250, 750, 1500, and 3000 mg of the compound orally once daily for 12 days. A sixth cohort received 750 mg three times daily for 5 days, then twice daily for 16 days. Evaluation included clinical, hematologic, and biochemical studies and the pharmacokinetics of 566C80. The only drug-related adverse effect was a maculopapular rash in one patient that resolved without discontinuation of the drug. With the largest dosage tested (3000 mg) the following pharmacokinetic measures were achieved: maximum plasma concentration, 39 micrograms/ml; time to maximum plasma concentration, 8.0 h; area under plasma concentration-time curve at steady state, 1088 h.micrograms/ml; plasma half-life, 51 h; and total plasma clearance, 4.09 l/h. Compound 566C80 offers promise as a new drug class for P. carinii pneumonia.

Topics: Adult; Antifungal Agents; Atovaquone; Cohort Studies; Drug Evaluation; Drug Tolerance; Half-Life; HIV Infections; Homosexuality; Humans; Male; Naphthoquinones; Pneumonia, Pneumocystis

Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against Pneumocystis jiroveci pneumonia. Alternative agents are used in treating patients who do not tolerate this medication. We report 2 cases of prophylaxis failure in patients receiving low-dose atovaquone. We discuss the use of atovaquone as an alternative agent for prophylaxis in transplant recipients.

Topics: Aged; Antifungal Agents; Atovaquone; Chemoprevention; Humans; Liver Transplantation; Male; Middle Aged; Naphthoquinones; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Atovaquone; Clinical Protocols; Dapsone; Drug Therapy, Combination; HIV Infections; Hospital Administration; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Retreatment; Trimethoprim, Sulfamethoxazole Drug Combination

Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) have experienced a dramatic decrease in Pneumocystis carinii pneumonia (PCP), necessitating reassessment of clinical guidelines for prophylaxis.. A simulation model of HIV infection was used to estimate the lifetime costs and quality-adjusted life expectancy (QALE) for alternative CD4 cell count criteria for stopping primary PCP prophylaxis in patients with CD4 cell count increases receiving HAART and alternative agents for second-line PCP prophylaxis in those intolerant of trimethoprim-sulfamethoxazole (TMP/SMX). The target population was a cohort of HIV-infected patients in the United States with initial CD4 cell counts of 350/microL who began PCP prophylaxis after their first measured CD4 lymphocyte count less than 200/microL. Data were from randomized controlled trials and other published literature.. For patients with CD4 cell count increases during HAART, waiting to stop prophylaxis until the first observed CD4 cell count was greater than 300/microL prevented 9 additional cases per 1000 patients and cost $9400 per quality-adjusted life year (QALY) gained compared with stopping prophylaxis at 200/microL. For patients intolerant of TMP/SMX, using dapsone increased QALE by 2.7 months and cost $4500 per QALY compared with no prophylaxis. Using atovaquone rather than dapsone provided only 3 days of additional QALE and cost more than $1.5 million per QALY.. Delaying discontinuation of PCP prophylaxis until the first observed CD4 cell count greater than 300/microL is cost-effective and provides an explicit "PCP prophylaxis stopping criterion." In TMP/SMX-intolerant patients, dapsone is more cost-effective than atovaquone.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; Atovaquone; CD4 Lymphocyte Count; Cost-Benefit Analysis; Dapsone; Drug Costs; Humans; Life Expectancy; Models, Theoretical; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Quality-Adjusted Life Years

This retrospective cohort study was conducted to determine whether Pneumocystis carinii cytochrome b gene mutations in patients with AIDS and P. carinii pneumonia (PCP) are associated with atovaquone exposure. Portions of the P. carinii cytochrome b genes that were obtained from 60 patients with AIDS and PCP from 6 medical centers between 1995 and 1999 were amplified and sequenced by using polymerase chain reaction. Fifteen patients with previous atovaquone prophylaxis or treatment exposure were matched with 45 patients with no atovaquone exposure. Cytochrome b coenzyme Q binding site mutations were observed in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=.018). There was no difference in survival 1 month after treatment between patients with or without cytochrome b mutations (P=.14). Thus, cytochrome b mutations are significantly more common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of these mutations remains unknown.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antifungal Agents; Atovaquone; Case-Control Studies; Cohort Studies; Cytochrome b Group; Female; Gene Amplification; Humans; Male; Middle Aged; Molecular Sequence Data; Naphthoquinones; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Polymorphism, Genetic; Retrospective Studies; Survival; Treatment Outcome; Ubiquinone

To describe clinical experience with atovaquone suspension for the treatment of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients.. A retrospective chart review.. The medical records of 54 HIV-infected patients with PCP treated with atovaquone were examined. The outcomes of 34 patients treated with atovaquone suspension (750 mg twice a day) were compared with those of 20 patients treated with atovaquone tablets (750 mg three times a day).. The proportion of patients successfully treated was similar with the suspension (74%) and tablet (70%) formulations of atovaquone. The proportion of patients with an inadequate response to therapy was lower for patients treated with atovaquone suspension (15%) than tablets (30%). Both formulations were well tolerated.. Atovaquone suspension is effective and well tolerated for the treatment of PCP.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Female; Humans; Male; Naphthoquinones; Pharmaceutical Solutions; Pneumonia, Pneumocystis; Retrospective Studies; Tablets; Treatment Outcome

Collecting and documenting subjective prior beliefs from knowledgeable clinicians about the potential results of a clinical trial has many advantages. Two large trials of prophylactic treatments in an HIV-positive population are used as examples. The trials recruited patients of primary care physicians and compared treatments which were in use in clinical practice. Opinions about these trials were elicited from 58 practising HIV clinicians. It is shown how the documented opinions can be used to augment the monitoring process; the prior opinions are updated with interim data using approximate Bayesian methods to give posterior opinions incorporating interim results. These posterior opinions can be used by the monitoring board to anticipate the clinicians' reaction to the results. Eliciting prior beliefs is also ethically important for documenting the nature of the uncertainty or equipoise. Important information is provided for the informed consent process and Institutional Review Board (IRB).

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Attitude of Health Personnel; Bayes Theorem; Clinical Trials as Topic; Dapsone; Ethics, Medical; HIV Infections; Humans; Naphthoquinones; Physicians; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Sample Size; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

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. Side effects from TMP/SMX, i.e., rash, completely resolved and bone-marrow suppression improved in 62% of patients. No patients developed Pneumocystis carinii infection. Although a lower dose of atovaquone once daily may be effective in transplant recipients, further studies are necessary to confirm this preliminary observation. Liver Transpl 2001;7:750-751.)

Topics: Antifungal Agents; Atovaquone; Bone Marrow; Drug Eruptions; Humans; Liver Transplantation; Naphthoquinones; Pneumonia, Pneumocystis; Postoperative Care; Prospective Studies; Retreatment; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii has been recognized as a human pathogen for nearly 50 years. We present a case of P carinii infection that typifies clinical presentation in the era of the acquired immunodeficiency syndrome epidemic. The high incidence of P carinii pneumonia in persons infected with human immunodeficiency virus (HIV) has served to focus laboratory and clinical research efforts on better understanding the biology of the organism and on improving diagnosis, treatment, and prevention of this disease. Although inability to culture P carinii has hampered research efforts, molecular and immunologic approaches have led to the recognition that the organism represents a family of fungi with a very restricted host range and have allowed characterization of clinically relevant antigens and enzymes. Molecular epidemiologic studies have identified more than 50 strains of human-derived P carinii and have suggested that recently acquired infection, as opposed to reactivation of latent infection, may account for many cases of clinical disease. Diagnosis has been improved by the development of organism-specific monoclonal antibodies and, more recently, by polymerase chain reaction using multicopy gene targets, together with induced sputum or oral wash samples. Chemotherapeutic prophylaxis is very effective in preventing P carinii pneumonia; the combination of trimethoprim-sulfamethoxazole remains the first-line agent for both therapy and prophylaxis. Prophylaxis needs to be administered only during periods of high risk; in HIV-infected patients responding to effective antiretroviral therapies, prophylaxis no longer needs to be lifelong. Molecular studies have identified mutations in the target of sulfa drugs that appear to represent emerging resistance in P carinii. Resistance to atovaquone, a second-line agent, may also be developing.

Topics: AIDS-Related Opportunistic Infections; Algorithms; Anti-Infective Agents; Atovaquone; Dihydropteroate Synthase; Drug Resistance, Fungal; Fungal Proteins; Humans; Lymphoma, AIDS-Related; Male; Membrane Glycoproteins; Middle Aged; Mutation; Naphthoquinones; Pentamidine; Pneumocystis; Pneumonia, Pneumocystis; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Atovaquone; Dapsone; Drug Costs; HIV Infections; Humans; Naphthoquinones; Pneumonia, Pneumocystis

Topics: Animals; Carbamates; Cryptosporidiosis; Cryptosporidium parvum; Dexamethasone; Disease Models, Animal; Female; Ileum; Immunocompromised Host; Lung; Naphthoquinones; Pneumocystis; Pneumonia, Pneumocystis; Prodrugs; Rats; Rats, Sprague-Dawley

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Drug Overdose; Humans; Naphthoquinones; Pneumonia, Pneumocystis

Terbinafine is a synthetic antifungal agent which has recently been found to be highly effective against Pneumocystis carinii. This study evaluated the efficacy of terbinafine on rat P. carinii antigenic profile and the immune response by Western blot analysis, in comparison with atovaquone and co-trimoxazole in rats with pneumocystosis. Terbinafine was shown to target two specific major antigens, particularly those of 116 and 35-40 kDa. Antibodies reactive against these moieties were found in all rats treated with atovaquone and co-trimoxazole, but not in those treated with terbinafine. These surface antigen modifications could be related to disease severity and could provide additional information for monitoring the efficacy of this treatment.

Topics: Animals; Antifungal Agents; Antigens, Fungal; Atovaquone; Blood; Blotting, Western; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Electrophoresis; Immunosuppression Therapy; Male; Naphthalenes; Naphthoquinones; Pneumocystis; Pneumonia, Pneumocystis; Rats; Rats, Sprague-Dawley; Survival Rate; Terbinafine; Trimethoprim, Sulfamethoxazole Drug Combination

An immunosuppressed rat model was used to determine the pharmacokinetics of aerosolized atovaquone (administered with and without a synthetic surfactant) and to evaluate the efficacy of inhaled atovaquone in the prevention and treatment of Pneumocystis carinii pneumonia (PCP). After a single dose by aerosol, mean peak concentrations of atovaquone averaged 52 microg/mL in plasma and 31 microg/g in lungs of rats infected with P. carinii. When atovaquone was combined with surfactant, mean peak concentrations of 94 microg/mL in plasma and 51 microg/g in lung were achieved. Aerosolized synthetic surfactant alone significantly increased survival of rats with PCP and, when combined with atovaquone, increased plasma and lung concentrations of the drug and eradication of the organism.

Topics: Administration, Inhalation; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antifungal Agents; Atovaquone; Dexamethasone; Drug Therapy, Combination; Lung; Male; Naphthoquinones; Pneumonia, Pneumocystis; Pulmonary Surfactants; Rats; Rats, Sprague-Dawley; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis carinii pneumonia (PCP) remains the most frequently reported serious opportunistic infection in AIDS patients and the second highest cause of mortality among persons with AIDS in the United States, despite the availability of effective chemoprophylaxis.. To evaluate incidence of PCP and determinants of PCP chemoprophylaxis failure, we analyzed data from 2842 patients visits to infectious diseases physicians at 10 HIV clinics (eight private and two public) in eight U.S. cities from January 1992 through June 1996 as part of the HIV Outpatient Study (HOPS). We performed a time-dependent regression analysis to examine potential determinants of PCP chemoprophylaxis failure.. The incidence of chemoprophylaxis failure was 4.6 PCP cases/100 person-years on chemoprophylaxis; these cases represent 67% of all incident episodes of PCP. In a multivariate analysis, the only significant predictors of chemoprophylaxis failure were the use of agents other than trimethoprim-sulfamethoxazole (TMP-SMX), history of prior PCP, and a CD4+ T-lymphocyte cell count of <50 cells/microl. Dosing or frequency of TMP-SMX did not seem to influence risk of chemoprophylaxis failure.. Chemoprophylaxis failure, especially among those with the most advanced immunosuppression or history of prior PCP, was the most significant source of new PCP cases in the HOPS cohort and thus represents one of the largest contributors to morbidity and mortality in this cohort.

Topics: Adult; AIDS-Related Opportunistic Infections; Ambulatory Care; Anti-Infective Agents; Antifungal Agents; Atovaquone; Cohort Studies; Dapsone; Drug Therapy, Combination; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Morbidity; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Atovaquone (Mepron, 566c80) is an effective agent against Pneumocystis carinii, which probably acts by binding to cytochrome b and inhibiting electron transport. To assess the possibility that atovaquone resistance might be developing, the genes for the cytochrome b from P. carinii sp. f. carinii and P. carinii sp. f. hominis were partially sequenced. Eight of 10 patient isolates had cytochrome b genes with the same amino acid sequence. The P. carinii cytochrome b genes from 2 of 4 patients who had atovaquone prophylaxis failure contained mutations resulting in amino acid changes in one of the ubiquinone (coenzyme Q) binding sites (Qo). These mutations are homologous to mutations in other microorganisms that confer resistance to similar inhibitors. Variations in the sequence of the P. carinii cytochrome b gene suggest but do not prove the development of drug resistance.

Topics: Amino Acid Sequence; Animals; Antifungal Agents; Atovaquone; Cytochrome b Group; DNA Primers; Evolution, Molecular; Humans; Lung; Mice; Molecular Sequence Data; Naphthoquinones; Phylogeny; Pneumocystis; Pneumonia, Pneumocystis; Point Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Protein Binding; Rats; Saccharomyces cerevisiae; Sequence Alignment; Sequence Homology, Amino Acid; Treatment Failure

Research results to determine the best prophylactic regimen for Pneumocystis carinii pneumonia (PCP) are reported. Overall results from these studies indicate patients who are eligible for PCP prophylaxis should be advised to take double-strength trimethoprim/sulfamethoxazole (TMP/SMX) on a daily basis, a dosage found more effective than thrice-weekly. To handle problems with side effects, one study demonstrated the success of using a 6-day dose escalation method that allowed 80 percent of the participants to complete treatment for 6 months. Patients remaining intolerant to TMP/SMX have the options of using atovaquone (not yet FDA-approved for PCP prophylaxis) or aerosolized pentamidine (not approved for treatment of PCP), which have been shown to be safe and effective in PCP prophylaxis. Due to recent FDA reforms, the use of off-label drugs may increase, but patients and physicians are cautioned that problems with insurance reimbursement may develop.

Topics: Aerosols; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; CD4 Lymphocyte Count; Clinical Trials as Topic; Dapsone; Drug Administration Schedule; Encephalitis; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

A rapid high-performance liquid chromatography assay has been developed for the drug atovaquone, which is currently being used to treat Pneumocystis carinii pneumonia and Toxoplasma gondii encephalitis associated with the acquired immunodeficiency syndrome (AIDS). Protein is precipitated from plasma with acetonitrile-aqueous 1% acetic acid (85:15). The supernatant is assayed on a C6 column using methanol-10 mM triethylamine in aqueous 0.2% trifluoroacetic acid (76:24) with detection at 254 nm. The working assay range was 0.5 to 50 micrograms/ml. Recovery was 97% and the between-day coefficients of variation were 2.1% at 50 micrograms/ml and 10.3% at 1 microgram/ml. A number of drugs commonly used to treat AIDS and its complications did not interfere with the assay.

Topics: Acquired Immunodeficiency Syndrome; Antifungal Agents; Atovaquone; Chromatography, High Pressure Liquid; Naphthoquinones; Pneumonia, Pneumocystis; Reproducibility of Results; Spectrophotometry, Ultraviolet

The anti-Pneumocystis carinii response of terbinafine together with that of three other compounds, trimethoprim sulphamethoxazole (TMP-SMX), atovaquone (ATQ) and albendazole (ALB), has been investigated in immunosuppressed Sprague-Dawley rats with established pneumocystosis. Drugs were administered orally (terbinafine in dosages of 40 and 80 mg/kg per day, TMP 12.5 mg/kg per day plus SMX 62.5 mg/kg per day, ATQ 100 mg/kg per day and ALB 600 mg/kg per day) to six rat groups except one which served as a control. P. carinii pneumonia (PCP) was identified post-mortem in nine (90%) of the control rats which exhibited a marked P. carinii burden, and mean lung weights were higher with respect to the other treatment groups. During treatment, five rats in the control group died, whereas between 11 and 13 rats in all treatment groups survived. In the terbinafine groups (40 mg and 80 mg/kg per day), a mild P. carinii infection developed in three and two rats (27.2 and 18%), respectively, and almost the same infectivity score was obtained for those treated with 40 mg and 80 mg/kg per day. Histological changes in the lungs in animals receiving terbinafine treatment were minimal. Among the remaining compounds the rate of infection was seven (58.3%) for the ALB treatment group and five (45.4%) for the ATQ group (mean score 19.4 +/- 7.1 and 23 +/- 2.1, respectively). In the TMP-SMX treatment group, there were 13 surviving rats and P. carinii organisms were found in two (15.3%, mean infection score 8 +/- 1.1).

Topics: Administration, Oral; Albendazole; Animals; Antifungal Agents; Atovaquone; Drug Administration Schedule; Immunosuppression Therapy; Lung; Naphthalenes; Naphthoquinones; Pneumonia, Pneumocystis; Rats; Rats, Sprague-Dawley; Terbinafine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents, Urinary; Atovaquone; Biopsy; Diagnosis, Differential; Drug Therapy, Combination; Granuloma; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lung; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis; Pseudolymphoma

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; CD4 Lymphocyte Count; Female; Humans; Naphthoquinones; Pneumonia, Pneumocystis

We studied a case of vortex keratopathy that was associated with the use of atovaquone.. A patient with acquired immunodeficiency syndrome (AIDS) with pulmonary Pneumocystis carinii was treated with 750 mg of atovaquone three times a day.. Similar to previous findings of drug-induced vortex keratopathy, atovaquone vortex keratopathy is presumably caused by its lipophilic properties. This property is similar to that of other lipophilic agents such as amiodarone, chloroquine, chlorpromazine, quinacrine, and suramin.. Atovaquone should be added to the list of agents causing vortex keratopathy involving the corneal epithelium.

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Cornea; Corneal Diseases; Epithelium; Humans; Male; Middle Aged; Naphthoquinones; Pneumonia, Pneumocystis

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiprotozoal Agents; Antiviral Agents; Atovaquone; Candidiasis, Oral; Clindamycin; Clotrimazole; Cryptosporidiosis; Cytomegalovirus Infections; Dapsone; Didanosine; Drug Combinations; Drug Therapy, Combination; Fluconazole; Flucytosine; Folic Acid Antagonists; Foscarnet; Glucuronates; Herpes Simplex; Herpes Zoster; Humans; Isoniazid; Itraconazole; Ketoconazole; Lamivudine; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Nystatin; Pentamidine; Pneumocystis Infections; Pneumonia, Pneumocystis; Prednisone; Primaquine; Reverse Transcriptase Inhibitors; Stavudine; Syphilis; Toxoplasmosis; Trimetrexate; Tuberculosis; Zalcitabine; Zidovudine

The prophylactic efficacies of atovaquone (ATQ) alone and in combination with azithromycin, clarithromycin, rifabutin, proguanil, PS-15, trimethoprim, co-trimoxazole, or dapsone were investigated in a SCID mouse model of Pneumocystis carinii pneumonia (PCP). ATQ alone was shown to have a significant dose-related effect, and at 200 mg/kg of body weight per day administered orally, the efficacy of ATQ was comparable to that of Septrin (co-trimoxazole). Of the drugs investigated orally in combination with ATQ, only dapsone (25 mg/kg/day) and to a lesser extent PS-15 (5 mg/kg/day) had any noteworthy antipneumocystis activity (at the doses examined) when administered alone. ATQ drug combinations affected the prophylactic efficacy of a subcurative dosage of ATQ (50 mg/kg/day given orally) in the following ways: dapsone (25 mg/kg/day) or co-trimoxazole (25 mg of sulfamethoxazole plus 5 mg of trimethoprim per kg/day) had no significant effect on ATQ, azithromycin (200 mg/kg/day) or clarithromycin (200 mg/kg/day) had a slight additive effect with ATQ, trimethoprim (100 mg/kg/day) or PS-15 (5 mg/kg/day) had an additive effect with ATQ, and proguanil (25 mg/kg/day) or rifabutin (200 mg/kg/day) had a marked synergistic effect on ATQ. The last result was particularly noteworthy as neither proguanil nor rifabutin was effective against PCP when administered alone. None of the drugs examined antagonized the prophylactic activity of ATQ in experimental PCP in SCID mice. The results suggest that clinical trials of ATQ with synergistic drug combinations may now be justified, particularly if such drug combinations improve ATQ's efficacy and broaden its spectrum of activity.

Topics: Animals; Antifungal Agents; Atovaquone; Dapsone; Drug Therapy, Combination; Mice; Mice, SCID; Naphthoquinones; Pneumonia, Pneumocystis; Proguanil; Rifabutin; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Treatment Failure

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Treatment Failure

Topics: Administration, Oral; Adult; Antifungal Agents; Antiprotozoal Agents; Atovaquone; Clinical Protocols; Drug Monitoring; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Humans; Microbial Sensitivity Tests; Naphthalenes; Naphthoquinones; Pneumocystis; Pneumonia, Pneumocystis; Terbinafine; Trimethoprim, Sulfamethoxazole Drug Combination

The prophylactic efficacy of 17C91, a carbamate prodrug of atovaquone (ATQ), was investigated in a severe combined immunodeficient mouse model of Pneumocystis carinii pneumonia (PCP). At an oral dosage equivalent to 100 mg of ATQ per kg of body weight per day, 17C91 protected 9 of 10 mice from PCP and had a prophylactic efficacy comparable to that of co-trimoxazole (at 250 mg of sulfamethoxazole plus 50 mg of trimethoprim per kg per day orally). The intensity of P. carinii infection (infection score) of mice treated with 17C91 correlated with the concentration of ATQ in the plasma, with clearance of the infection associated with plasma ATQ levels of >35 micrograms/ml. 17C91 given orally provided enhanced levels of ATQ in the plasma compared with the conventional ATQ formulation. Additional studies reported in this paper demonstrate that the prophylactic activity of 17C91 against PCP in severe combined immunodeficient mice is comparable to that of a new oral microparticulate formulation of ATQ.

Topics: Animals; Antifungal Agents; Atovaquone; Carbamates; Female; Mice; Mice, SCID; Naphthoquinones; Pneumonia, Pneumocystis; Prodrugs

Studies being conducted on opportunistic infections among people with HIV are presented in list form. The list includes new studies, those still in development, and those slated to begin in 1995. Areas of interest include candidiasis, cryptosporidiosis/microsporidiosis, cytomegalovirus (CMV), Mycobacterium avium complex (MAC) infection, Pneumocystis carinii pneumonia (PCP), toxoplasmosis, and tuberculosis (TB). Enrollment information can be obtained by calling 1-(800)-TRIALS-A (TDD 1- 800-448-0440).

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antitubercular Agents; Atovaquone; Candidiasis; Clinical Trials as Topic; Cryptosporidiosis; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Immunotherapy; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Paromomycin; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis; Tuberculosis

The newly approved use of an Atovaquone (Mepron) suspension for treating mild to moderate Pneumocystis carinii (PCP) in patients unable to tolerate trimethoprim-sulfamethoxazole (TMP-SMX), has shown that it is twice as bioavailable compared with the previously licensed tablet formulation. However, Atovaquone use has produced more deaths than TMP-SMX, a problem that may in part be due to its lack of a broad antibacterial spectrum.

Topics: Antifungal Agents; Atovaquone; Biological Availability; Clinical Trials as Topic; Drug Approval; Humans; Naphthoquinones; Pneumonia, Pneumocystis; United States; United States Food and Drug Administration

Pneumocystis carinii pneumonia (PCP) is common in children and adults who are HIV-positive. More than half of the babies who have PCP never received preventive drugs. It is suggested that a greater number of HIV-exposed infants must be identified at an earlier stage, and preventive medication should be prescribed. It is further recommended that HIV testing and monitoring be made more available to infants at risk so that preventive PCP medication can be given at four to six weeks of age, regardless of the CD4 count and HIV test results. The first choice of treatment is Bactrim or Septra. More information can be obtained by calling the Network at (800) 734-7104.

Topics: Antifungal Agents; Atovaquone; Clinical Trials as Topic; Dapsone; HIV Infections; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; United States

The U.S. Food and Drug Administration (FDA) recently approved a suspension formulation of atovaquone (Mepron) for treating mild to moderate cases of pneumocystis carinii pneumonia (PCP) in patients intolerant of trimethoprim/sulfamethoxazole (TMP-SMX). The liquid form offers better bioavailability and convenient dosing. At least one study has shown that the drug is less toxic than intravenous pentamidine and may have possible action against microsporidiosis. The use of the suspension formulation for chronic preventive therapy against PCP also is being studied.

Topics: Antiviral Agents; Atovaquone; Chemistry, Pharmaceutical; Drug Approval; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Suspensions; Tablets; United States Food and Drug Administration

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Humans; Immunocompromised Host; Naphthoquinones; Pneumonia, Pneumocystis

Topics: Advertising; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Radiography; X-Ray Film

Topics: Antifungal Agents; Atovaquone; Biological Availability; Drug Costs; Humans; Naphthoquinones; Pneumonia, Pneumocystis

Topics: Antifungal Agents; Atovaquone; Clinical Trials as Topic; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Drug Approval; Humans; Naphthoquinones; Pneumonia, Pneumocystis; United States; United States Food and Drug Administration

Topics: Administration, Oral; Antifungal Agents; Atovaquone; Humans; Naphthoquinones; Pneumonia, Pneumocystis

Topics: AIDS-Related Opportunistic Infections; Atovaquone; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Administration, Oral; AIDS-Related Opportunistic Infections; Antiprotozoal Agents; Atovaquone; Humans; Naphthoquinones; Pneumonia, Pneumocystis

Topics: Acquired Immunodeficiency Syndrome; Antifungal Agents; Atovaquone; Humans; Naphthoquinones; Pneumonia, Pneumocystis

Topics: Acquired Immunodeficiency Syndrome; Antifungal Agents; Atovaquone; Clinical Protocols; Drugs, Investigational; Humans; Naphthoquinones; Pneumonia, Pneumocystis

Topics: Acquired Immunodeficiency Syndrome; Antifungal Agents; Atovaquone; Drugs, Investigational; Humans; Naphthoquinones; Pneumonia, Pneumocystis

Topics: Antifungal Agents; Atovaquone; HIV Infections; Humans; Naphthoquinones; Opportunistic Infections; Pneumonia, Pneumocystis

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Atovaquone; Drugs, Investigational; Humans; Naphthoquinones; Pneumonia, Pneumocystis

The efficacy of a new class of drugs for Pneumocystis carinii pneumonitis was demonstrated. 566C80, a hydroxynaphthoquinone, administered orally in a dose of greater than or equal to 100 mg/kg of body weight per day prophylactically prevented P. carinii pneumonitis in 90% or more of rats, while all untreated control animals developed pneumonitis. When 566C80 (100 mg/kg per day) was administered for 3 weeks after P. carinii pneumonitis was established, therapy was totally effective and all of the untreated controls had progressive P. carinii pneumonitis. A dose of 566C80 of between 25 and 50 mg/kg per day protected 50% of the rats from P. carinii pneumonitis, and a dose of between 50 and 100 mg/kg per day cured 50% of those treated for P. carinii pneumonitis. Both prophylaxis and treatment with 566C80 were at least as effective as with trimethoprim-sulfamethoxazole. Animals maintained on immunosuppression after completion of treatment remained free of P. carinii, suggesting a killing effect. Clearance of P. carinii was associated with levels of 60 micrograms or more of 566C80 per ml of plasma. This hydroxynaphthoquinone offers promise as an anti-P. carinii drug.

Topics: Animals; Anti-Infective Agents; Atovaquone; Dexamethasone; Lung; Male; Naphthoquinones; Pneumonia, Pneumocystis; Rats; Rats, Inbred Strains; Tetracyclines; Trimethoprim, Sulfamethoxazole Drug Combination