Prevention Of Pneumocystis Carinii Pneumonia Research Articles

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

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.)

Comparing treatment strategies using a synthesized clinical trial: an analysis of late versus early use of trimethoprim-sulfamethoxazole for AIDS patients

Abstract This paper applies methodology of Finkelstein and Schoenfeld [Stat. Med. 13 (1994) 1747.] to consider new treatment strategies in a synthetic clinical trial. The methodology is an approach for estimating survival functions as a composite of subdistributions defined by an auxiliary event which is intermediate to the failure. The subdistributions are usually calculated utilizing all subjects in a study, by taking into account the path determined by each individual's auxiliary event. However, the method can be used to get a composite estimate of failure from different subpopulations of patients. We utilize this application of the methodology to test a new treatment strategy, that changes therapy at later stages of disease, by combining subdistributions from different treatment arms of a clinical trial that was conducted to test therapies for prevention of pneumocystis carinii pneumonia.

PCP Prophylaxis Failure: Is It in the Genotypes?

Primary or secondary prophylaxis with sulfa drugs or other agents, such as pentamidine or atovaquone, is standard care for prevention of Pneumocystis carinii pneumonia (PCP) in AIDS patients. Nevertheless, prophylaxis fails in some patients; the reason remains unclear. A recently developed molecular typing system that can be used on bronchoalveolar lavage …

Twice-weekly Pyrimethamine–sulfadoxine Effectively Prevents Pneumocystis carinii Pneumonia Relapse and Toxoplasmic Encephalitis in Patients with AIDS

Objective: To evaluate the safety and efficacy of a fixed 25mg pyrimethamine–500mg sulfadoxine combination plus 15mg folinic acid given twice weekly for the prevention of relapses of Pneumocystis carinii pneumonia (PCP) andprimary episodes of toxoplasmic encephalitis.Methods: Ninety-five HIV-infected patients with successfully treated PCP and without history of toxoplasmic encephalitis were enrolled between January 1990 and October 1995 in a single-arm open-label prospective study. No patient was receiving highly active antiretroviral treatment, including protease inhibitors or non-nucleoside reverse transcriptase inhibitors, while on study medication. Efficacy was analysed on an “as-treated” basis.Results: Five patients (5.3%) suffered a PCP relapse while on study medication, three of whom had been non-compliant. No relapse occurred in the first year. Probabilities of freedom from relapse were 0.96 after 24 months and 0.90 after 36 months. Of 69 patients positive for anti-toxoplasma IgG antibodies, one (1.5%) developed cerebral lesions compatible with toxoplasmic encephalitis after 50 months. Cutaneous allergic reactions were observed in 16 patients (16.8%) resulting in permanent discontinuation in six patients (6.3%). Two patients (2.1%) developed serious adverse reactions (Stevens–Johnson syndrome), both of whom had continued prophylaxis despite progressive hypersensitivity reactions.Conclusions: The prophylactic regimen used is effective in preventing PCP relapses and toxoplasmic encephalitis. The regimen appears to be safe. Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted. Rechallenge frequently results in tolerance of the regimen. Efficacy and safety compare favourably with previously studied regimens. This simple prophylactic regimen may provide a convenient alternative for patients unable to tolerate approved regimens.

Factors impacting on drug choices. Issues for developing countries.

In considering factors that impact on drug choices for children in developing countries, it is important to learn from the advances in antiretroviral therapy that have been made in the United States and other developed countries. Abundant clinical data indicate that monotherapy with antiretroviral agents, no matter how potent, is inadequate and the children should be treated with three or more drugs. When treatment regimens are changed, at least two new drugs should be started simultaneouly to avoid the rapid development of resistance. Understanding the impact of host and viral genotypes may provide information as to how best to treat the individual child. However, at present, I believe that with limited resources, the best use of antiretrovirals for children is in disease prevention. Thus, antiretrovirals to prevent mother-to-infant transmission should be given the highest priority. Second, children in the first year of life are at highest risk of progression and should be treated with trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, and targeted for receiving antiretrovirals. Moreover, treating children without an overall plan is unacceptable. Treatment with drugs because they are available will have little impact on the quality of life or disease progression unless they are used in combination. There should be no reason for children, no matter where they might live, to receive suboptimal antiretroviral therapy. For this reason, I call upon industrialized countries and the World Bank to help provide resources for the care and treatment of HIV-infected children. Additionally, I would propose that pharmaceutical companies provide support for the care and treatment of HIV-infected children. The drugs and financial support provided by pharmaceutical companies should go to a central foundation or group that will optimize the use of these resources for children in developing countries. I would also propose that in the United States, Europe, and other industrialized countries the patents on antiretroviral drugs be extended according to a formula based on the donation of a pharmaceutical company. It is only through a unified effort that we will be able to adequately treat all children infected with HIV regardless of where they might live.

Trimethoprim-sulfamethoxazole–graded challenge in HIV-infected patients: Long-term follow-up regarding efficacy and safety

Trimethoprim-sulfamethoxazole–graded challenge in HIV-infected patients: Long-term follow-up regarding efficacy and safety

Discontinuing Medications Used To Prevent Pneumocystis carinii Pneumonia in Patients with HIV Infection

Discontinuing Medications Used To Prevent Pneumocystis carinii Pneumonia in Patients with HIV Infection

Efficacy of azithromycin in prevention of Pneumocystis carinii pneumonia: a randomised trial

Azithromycin in combination with sulphonamides is active against Pneumocystis carinii pneumonia (PCP) in animals. We assessed the clinical efficacy of azithromycin for PCP prophylaxis in human beings. We identified HIV-1-infected patients with PCP during a prospective randomised trial comparing azithromycin, rifabutin, and the two drugs in combination for prevention of disseminated Mycobacterim avium infection. Patients had CD4-cell counts less than 100/microL at entry and received PCP prophylaxis according to the standard practice of their clinician. Analysis was by intention to treat. Patients receiving azithromycin, either alone (n=233) or in combination with rifabutin (n=224), had a 45% lower risk of developing PCP than those receiving rifabutin alone (n=236; p=0.008). Compared with rifabutin alone, hazard ratio for azithromycin was 0.54 (95% CI 0.32-0.94), for azithromycin plus rifabutin was 0.55 (0.32-0.94), and for regimens containing azithromycin was 0.55 (0.35-0.86). The most common side-effects involved the gastrointestinal tract with dose-limiting toxicities, and were mainly seen in patients receiving combination therapy. Azithromycin as prophylaxis for M. avium complex disease provides additional protection against P. carinii over and above that of standard PCP prophylaxis. Use of azithromycin is beneficial only as primary prophylaxis.

Discontinuation of prophylaxis for Pneumocystis carinii pneumonia in HIV-1-infected patients treated with highly active antiretroviral therapy

Prophylactic drugs for Pneumocystis carinii pneumonia (PCP) are strongly recommended for HIV-1-infected patients with CD4 cell counts of less than 200 cells/microL. Because of the highly active antiretroviral therapy (HAART) currently available, we speculated that prophylaxis can be discontinued in patients with CD4 cell counts of more than 200 cells/microL. In this prospective observational study, PCP prophylaxis (primary or secondary) was discontinued in HIV-1-infected patients whose CD4 cell count had increased above 200 cells/microL (documented twice with an interval of at least 1 month) as a result of HAART. Patients and their CD4 cell counts were monitored every 3 months. The primary endpoint of the study was the occurrence or reoccurrence of PCP. 78 patients were enrolled: 62 patients were receiving prophylaxis for primary prevention of PCP and 16 patients for secondary prevention of PCP. At the time of discontinuation of prophylaxis, the mean CD4 cell count was 347 cells/microL, and HIV-1-RNA was not detectable in 61 patients. The lowest mean CD4 cell count during prophylaxis was 79 cells/microL. Patients stopped prophylaxis 9.8 (SD 6.4) months after they started HAART. The mean follow-up after discontinuation of prophylaxis was 12.7 (SD 7.6) months, and none of the patients developed PCP (97.5% one-sided CI 0-4.4%). The preliminary results of this study indicate that PCP prophylaxis can be stopped safely in HIV-1-infected patients whose CD4 cell counts have increased above 200 cells/microL after treatment with HAART.

Analysis of life-long strategies to prevent Pneumocystis carinii pneumonia in patients with variable HIV progression rates.

To compare strategies for life-long prophylaxis of Pneumocystis carinii pneumonia (PCP) in a group of AIDS patients with a wide range of disease progression rates. Markov decision models. Prophylaxis strategies using high and low doses of trimethoprim-sulfamethoxazole (TS), dapsone, and/or aerosolized pentamidine in sequence, were compared. Efficacy and toxicity rates for prophylaxis regimens were taken from a meta-analysis of pertinent randomized controlled trials. Outcomes measured included lifetime episodes of PCP and drug toxicity per 100 patients treated, average life expectancy, and cost. For patients with an expected survival of 3 years after commencement of prophylaxis, the use of standard or low dose TS as the first choice agent was comparable, and both were superior to the other strategies for preventing PCP (between nine and 26 fewer episodes of PCP per 100 patients treated) though they were more toxic (11-44 more episodes of toxicity per 100 patients treated). Life expectancy was similar for all of the treatment strategies. With slower rates of disease progression (expected survival > 3.8 years), as seen with current antiretroviral regimens, the use of low dose TS as the first choice agent dominated the use of standard dose TS; when the expected survival time was 7 years, initial use of low dose TS led to 2.8 fewer episodes of PCP per 100 patients treated, 32 fewer episodes of toxicity per 100 patients treated, and US$1381 per patient lower cost, compared with prophylaxis with standard dose TS. For patients with AIDS and expected survival > 3.8 years, low dose TS is better than standard dose TS as the first choice agent for preventing PCP. As patients with AIDS live longer, the routine use of low dose TS will be more than adequate for patients at risk for PCP.

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

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

A controlled trial of dapsone versus pyrimethamine-sulfadoxine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with AIDS

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic human immunodeficiency virus (HIV)-related infection, occurring in 85% of HIV infected patients without prophylaxis. Preventive treatment is required when CD4 cell count falls below 200 cells per cubic millimeter. Cotrimoxazole has been shown to be highly effective but alternative drug regimens are often necessary because of the frequent drug hypersensitivity exhibited by HIV infected patients. The aim of this prospective, open, randomized, one-site study, involving HIV-infected patients with a CD4 cell count below 200/mm3, or a percentage under 20%, randomly assigned to receive either dapsone 50 mg daily or Fansidar one tablet weekly, was to compare the efficacy and safety of these drugs in the primary prophylaxis of PCP. Both dapsone and Fansidar appear to be safe and effective alternative agents for the prevention of PCP. Their role in Toxoplasma gondii prophylaxis requires further evaluation.

Meta-Analysis of Prophylactic Treatments Against Pneumocystis carinii Pneumonia and Toxoplasma Encephalitis in HIV-Infected Patients

In a meta-analysis, we examined the efficacy of aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone or dapsone/pyrimethamine for the prevention of Pneumocystis carinii pneumonia and toxoplasma encephalitis in patients with HIV infection. Of 22 trials, 13 compared trimethoprim-sulfamethoxazole with aerosolized pentamidine, nine compared dapsone alone or in combination with pyrimethamine with aerosolized pentamidine, and eight compared trimethoprim-sulfamethoxazole with dapsone/pyrimethamine. In total, 1484 patients were treated with trimethoprim-sulfamethoxazole, 1548 patients with dapsone/pyrimethamine or dapsone, and 1800 patients with aerosolized pentamidine. For dapsone/pyrimethamine versus aerosolized pentamidine, the risk ratio for P. carinii pneumonia was 0.90 (95% confidence interval [CI], 0.71-1.15), and for toxoplasma encephalitis it was 0.72 (95% CI, 0.54-0.97). For trimethoprim-sulfamethoxazole versus aerosolized pentamidine, the risk ratio of P. carinii pneumonia was 0.59 (95% CI, 0.45-0.76), and for toxoplasma encephalitis it was 0.78 (95% CI, 0.55-1.11). For trimethoprim-sulfamethoxazole versus dapsone/pyrimethamine, the risk ratio of P. carinii pneumonia was 0.49 (95% CI, 0.26-0.92), and for toxoplasma encephalitis it was 1.17 (95% CI, 0.68-2.04). Although current evidence does not allow a definitive recommendation, administration of trimethoprim-sulfamethoxazole for prophylaxis of P. carinii pneumonia and toxoplasmosis in patients with HIV infection is consistent with the available data.

The safety of pyrimethamine and sulfadoxine for the prevention of Pneumocystis carinii pneumonia.

The medical records of 157 patients taking pyrimethamine-sulfadoxine for Pneumocystis carinii pneumonia prophylaxis were reviewed for assessment of safety and tolerance. 11 patients had experienced side effects, 7 (1 each: neutropenia, Stevens-Johnson, hepatic abnormalities; 2 each: subjective and hypersensitivity reactions) leading to a discontinuation of the drugs.

Preventing Opportunistic Infections in Human Immunodeficiency Virus-Infected Persons: Implications for the Developing World

More than 18 million persons in the world are estimated to have been infected with human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). As immunodeficiency progresses, these persons become susceptible to a wide variety of opportunistic infections (OIs) The spectrum of OIs varies among regions of the world. Tuberculosis is the most common serious OI in sub-Saharan Africa and is also more common in Latin America and in Asia than in the United States. Bacterial and parasitic infections are prevalent in Africa; protozoal infections such as toxoplasmosis, cryptosporidiosis, and isosporiasis are also common in Latin America. Fungal infections, including cryptococcosis and Penicillium marneffei infection, appear to be prevalent in Southeast Asia. Despite limited health resources in these regions, some measures that are recommended to prevent OIs in the United States may be useful for prolonging and improving the quality of life of HIV-infected persons. These include trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, toxoplasmosis, and bacterial infections; isoniazid to prevent tuberculosis; and 23-valent pneumococcal vaccine to prevent disease due to Streptococcus pneumoniae. Research is needed to determine the spectrum of OIs and the efficacy of various prevention measures in resource-poor nations, and health officials need to determine a minimum standard of care for HIV-infected persons. An increasing problem in the developing world, HIV/AIDS should receive attention comparable to other tropical diseases.

Off-label drug use in human immunodeficiency virus disease.

We wished to determine the extent to which drugs used to treat HIV disease and its clinical manifestations are prescribed for conditions other than those listed on the U.S. Food and Drug Administration's approved drug label, how such "off-label" use varies by patient characteristics and type of HIV-related medical condition, and the extent to which physicians alter the way they treat HIV-related conditions because of reimbursement problems associated with off-label drug use. We surveyed 1,530 primary care providers for people with HIV disease between February and May 1993. A three-part survey instrument was used to obtain data on the drugs prescribed for the last three patients with HIV disease treated by the provider, the preferred choice of therapy for 32 specific HIV-related conditions, and the extent to which providers faced reimbursement problems regarding the use of drugs for off-label indications. Three drug compendia were used as cited sources of off-label drug uses. In all, 387 (32%) evaluable surveys were returned, yielding data on 1,148 patients. The majority (81%) of patients received at least one drug off-label, and almost half (40%) of all reported drug therapy was off-label. Most off-label drug use was for treatment and prevention of HIV-related opportunistic infections, which frequently represented the community standard of practice (e.g., trimethoprim/sulfamethoxazole for prevention of Pneumocystis carinii pneumonia), or the de facto standard of practice when no licensed therapies were available (e.g., drugs for treatment of Mycobacterium avium complex, MAC). More than 75% of off-label usage was cited in at least one of the three authoritative medical compendia. The use of drugs for off-label indications in HIV care is common and frequently represents community standards of care. Reliance on drug compendia for support of off-label drug use accounts for the majority of such uses, although many legitimate off-label uses may not be included because of compendia publication lag. The prevalence of off-label drug use in routine clinical practice and the development of newer and more costly drugs for treatment of HIV and its medical complications argues for the articulation of an explicit national reimbursement policy for off-label uses of prescription drugs so that medically appropriate therapies will be available to those with insurance in a rational, consistent way.

Preventing Pneumocystis carinii pneumonia in persons infected with human immunodeficiency virus.

Although the incidence of Pneumocystis carinii pneumonia (PCP) among adults infected with human immunodeficiency virus (HIV) has declined, no decline in PCP incidence has been observed among HIV-infected children, and PCP remains the most common serious opportunistic infection among both adults and children in the United States. Some evidence of airborne transmission of P. carinii exists, and some clusters of cases of PCP have been reported; however, data are insufficient to recommend that persons with PCP be separated from immunosuppressed persons as a standard practice. The incidence of PCP can be reduced substantially if persons at risk for PCP are identified and receive adequate chemoprophylaxis. Several drugs and drug combinations are highly effective in preventing PCP. For both adults and children, oral trimethoprim-sulfamethoxazole (TMP-SMZ) is the preferred form of prophylaxis. Adverse effects are commonly associated with the use of TMP-SMZ and in some cases may necessitate withdrawal of the drug until the effects resolve. However, reintroduction at the same dose or at a lower and gradually increasing dose will often permit the continued use of TMP-SMZ. For persons intolerant of TMP-SMZ, dapsone alone and dapsone plus pyrimethamine are effective alternatives. A third alternative is aerosolized pentamidine. Additional drugs of unproven efficacy but of potential use in exceptional cases are available.

THE BEST DOSE OF TMP-SMX TO PREVENT PCP.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for preventing Pneumocystis carinii pneumonia (PCP) in HIV-infected patients, but toxicity is a problem. This open, randomized European study compared regular-strength TMP-SMX (80 mg TMP and 400 mg …

Management of Adverse Reactions to Trimethoprim-Sulfamethoxazole in Human Immunodeficiency Virus—Infected Patients

Trimethoprim-sulfamethoxazole is an important medication for the treatment and prevention of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Use of this medication has been limited by the high frequency of adverse reactions that occur in patients with human immunodeficiency virus disease. This article reviews the incidence and spectrum of adverse reactions and options for continuing therapy with trimethoprim-sulfamethoxazole in human immunodeficiency virus-infected patients who have adverse reactions.

Efficacy of primary chemoprophylaxis against Pneumocystis carinii pneumonia during the first year of life in infants infected with human immunodeficiency virus type 1

To evaluate the efficacy of primary chemoprophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in infants with perinatal human immunodeficiency virus-1 infection during the first year of life, we conducted a retrospective chart review of infants with human immunodeficiency virus-1 infection born at New York University Medical Center-Bellevue Hospital Center, in New York. Between March 1989 and March 1993, 24 infants received primary chemoprophylaxis with trimethoprim-sulfamethoxazole in the first year of life and 24 infants did not receive primary prophylaxis. The CD4+ T-lymphocyte counts in the two groups did not differ during the first year of life. The median age at the time of initiation of prophylaxis was 3 months, and the average duration of prophylaxis was 5.5 months. Among the infants who had not received prophylaxis, five cases of PCP were diagnosed at a median age of 5 months; in contrast, no cases of PCP were observed in the infants receiving prophylaxis (log-rank test, p = 0.017). The probability of surviving after 1 year of age was 92% for the children who received prophylaxis and 74% for those who did not (log-rank test, p = 0.035). These data indicate that chemoprophylaxis is highly effective in preventing primary PCP and improving survival time in infants with human immunodeficiency virus-1 infection.