Pneumocystis Carinii Pneumonia In Patients Research Articles

Aerosolized Pentamidine for Prophylaxis againstPneumocystis cariniiPneumonia

Pneumocystis carinii pneumonia (PCP) is the most frequent life-threatening opportunistic infection associated with human immunodeficiency virus (HIV) infection. To assess the possible value of aerosolized-pentamidine prophylaxis in different doses, a controlled clinical trial was begun in 1987 with 408 subjects at 12 treatment centers. The participants were randomly assigned to receive 30 mg of pentamidine every two weeks, 150 mg every two weeks, or 300 mg every four weeks. Eighteen months after randomization, the subjects in the 300-mg arm had had 8 confirmed episodes of PCP while receiving treatment, as compared with 22 in the 30-mg arm (P = 0.0008). The 150-mg arm had intermediate results but ones not significantly different from those of the 300-mg arm. Participants with previous episodes of PCP and CD4-cell counts less than 200 per cubic millimeter were at the highest risk for PCP. Aerosolized pentamidine was effective for prophylaxis against PCP in patients infected with HIV, according to the dose and schedule of administration. It and zidovudine were well tolerated together and had independent prophylactic benefits.

Oral Therapy forPneumocystis cariniiPneumonia in the Acquired Immunodeficiency Syndrome

Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic. In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day). The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone. In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

Intravenous or Inhaled Pentamidine for TreatingPneumocystis cariniiPneumonia in AIDS

To evaluate the efficacy and toxicity of aerosolized pentamidine and of reduced-dose intravenous pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (Pao2 greater than or equal to 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine. Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks. The planned 60-patient study was stopped after 45 patients had been enrolled. The rates (aerosolized compared with intravenous pentamidine) of initial failure, early recrudescence of symptoms, and relapse were 12% and 19% (difference, 7%; 99% confidence interval [CI], - 23% to 37%; P = 0.67), 35% and 0% (difference, 35%; CI, 13% to 58%; P = 0.02), and 24% and 0% (difference, 24%; CI, 4% to 49%; P = 0.03). The rates (aerosolized compared with intravenous pentamidine) of major toxicity were 0% (0 of 17 patients) and 10% (2 of 21 patients) (difference 10%; CI, -1% to 29%; P = 0.24). The mean (+/- SD) pentamidine concentration in bronchoalveolar lavage fluid for patients receiving aerosolized pentamidine was 96.6 +/- 65.1 ng/mL compared with 14.4 +/- 17.7 ng/mL for patients receiving intravenous treatment. Trough concentrations of pentamidine in plasma increased from 0 to 25.4 +/- 16.4, 56.5 +/- 26.1, and 61.1 +/- 56.0 ng/mL at the end of weeks 1, 2, and 3 of intravenous therapy, respectively. The data suggest that reduced-dose intravenous pentamidine was more effective than aerosolized pentamidine for treating mild to moderate P. carinii pneumonia. Systemic absorption during aerosolized therapy was minimal; daily doses of intravenous pentamidine resulted in increased accumulation of pentamidine in plasma.

Scintigraphic Pattern of Pneumothorax Complicating Pneumocystis carinii Pneumonia in Patients with AIDS

Spontaneous pneumothorax is a serious though infrequently reported pulmonary complication of AIDS. An unsuspected lung collapse was discovered via gallium scintigraphy for the study of Pneumocystis carinii pneumonia. Neither the pneumonia nor the pneumothorax were apparent on the most recent chest roentgenogram. In evaluating gallium images during the work-up of AIDS patients with associated pulmonary pathology, the possible complication of lung collapse should be considered. If pneumothorax is suspected on gallium imaging, a chest roentgenogram in expiration must be obtained for prompt delineation of this serious, yet correctable, condition.

Aerosolised pentamidine for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome

The goal of this study was to evaluate inhaled pentamidine for the treatment of patients with mild and moderate Pneumocystis carinii pneumonitis. Eight adults with AIDS and pneumocystis pneumonia (4 with a first episode and 4 with a repeat pneumocystosis) received daily inhalations of aerosol pentamidine isethionate for 21 days. Six patients were treated with doses of 300 mg of pentamidine and the remaining 2 received 600 mg every day. In the 300 mg treatment group, 2 individuals showed discrete and transient neutropenia. However, both subjects that received 600 mg of aerosol pentamidine daily developed leukopenia. One of them had major toxicity (overall severe intolerance of 12.5%) that required drug discontinuation and did not allow any analysis of the treatment efficacy. Of the 7 evaluable patients, 6 (88%) completed the treatment successfully. One subject of the 300 mg regimen experienced an early recurrence. In conclusion, inhaled pentamidine is an effective treatment for mild and moderate cases of P. carinii pneumonia. It is less toxic than standard anti-pneumocystis therapy and is suitable for outpatient use.

Radiographic distribution of Pneumocystis carinii pneumonia in patients with AIDS treated with prophylactic inhaled pentamidine.

The radiographic distribution of Pneumocystis carinii pneumonia was studied in 64 consecutive patients with acquired immunodeficiency syndrome to determine the demographic and clinical factors that might be associated with predominance of the disease in the upper zones of the lungs. Twenty-three patients were receiving monthly prophylaxis with 300 mg of aerosolized pentamidine by means of inhalation; the other 41 were not receiving pentamidine and served as a control group. Parenchymal abnormalities were present in 63 of 64 patients. Pleural effusion and cystic lung lesions were uncommon and did not differ between the two groups. Patients receiving aerosolized pentamidine were more likely than control patients to have disease isolated or predominant in the upper lobes (odds ratio = 3.9, confidence interval = 1.1-14.1). After the possible effects of confounding variables were taken into account, prophylaxis remained a significant risk factor. Age and a previous history of P carinii pneumonia were not significant cofactors. The pattern of deposition or retention of the aerosolized pentamidine could be responsible for the finding of predominant P carinii pneumonia in the upper lobes of the lungs.

Pneumocystis carinii pneumonia in patients with AIDS in Central Africa

Over a period of 11 months, 37 patients infected with the Human Immunodeficiency Virus (HIV) presenting with symptoms of bronchopulmonary disease were investigated. Patients presented with cough, weight loss, fever and dyspnoea. Investigations included fibreoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. In eight patients (22%) Pneumocystis carinii was found. Pulmonary infiltrates were found on chest radiographs of six patients, while in the remaining two patients chest radiographs showed clear lung fields. P. carinii was found in two patients with pulmonary Kaposi's sarcoma. Infection with P. carinii often occurred with other pathogens: Streptococcus pneumoniae was found in four patients, Staphylococcus aureus in two and tuberculosis in two. P. carinii pneumonia does occur in patients with HIV infection in Africa and the diagnosis is relatively simple to make provided that transbronchial biopsy and bronchoalveolar lavage are carried out through a fibreoptic bronchoscope and specimens examined after appropriate staining. However, the prevalence of P. carinii in patients with HIV infection in Africa appears to be lower than that found in patients with HIV infection in Europe and North America.

Pulmonary cysts associated with Pneumocystis carinii pneumonia in patients with AIDS.

A diffuse, bilateral interstitial infiltrate is the most common radiographic finding in Pneumocystis carinii pneumonia (PCP) in patients with the acquired immunodeficiency syndrome (AIDS). However, atypical roentgenographic patterns also exist. Chest radiographs of 100 consecutive AIDS patients with PCP were retrospectively analyzed for the presence of pulmonary air-filled cysts, or pneumatoceles, which were identified in 10% of the cases. The pneumatoceles were typically thin-walled with no intracystic material and no predilection for a particular area of the lung. They appear to behave like pneumatoceles due to other infectious processes. They were present on the initial radiograph or developed during treatment of PCP. Analysis of available follow-up radiographs indicated resolution of the pulmonary cysts within 7 months in most cases. The cause of these cysts is unknown, but a "check-valve" obstruction or, perhaps less likely, parenchymal necrosis may be involved. Rupture of these pulmonary cysts may lead to spontaneous pneumothorax.

Survival following mechanical ventilation for pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome: a different perspective

Pulmonary infection is a frequent cause of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS), and Pneumocystis carinii pneumonia (PCP) is the predominant infection in these patients. In those patients who experience progression to respiratory failure from PCP, the reported mortality rate has been between 87% to 100%. This, in addition to the ultimately fatal outcome of patients with AIDS, has led many physicians to question the advisability of instituting mechanical support for respiratory failure in the setting of PCP. It had been our impression that the outcome of patients on our service was not as poor as was generally reported. We therefore undertook a retrospective analysis of our clinical experience. We reviewed the clinical course of patients admitted to our service between December 1984 and June 1988 who required intubation and mechanical ventilation for PCP or presumed PCP. Thirty-three cases were identified with 18 survivors (54.5%) and 15 non-survivors (45.5%). Twenty-five of the 33 patients were intubated for their first episode of PCP, with 16 survivors (64%), whereas the remaining eight patients were intubated for their second episode of PCP, with two survivors (25%). We were not able to identify any parameters that predicted survival, although the serum lactate dehydrogenase level was useful in following the response to treatment. It is our belief that there is a reasonable chance of survival for patients requiring mechanical ventilation for PCP. We question the wisdom of avoiding intubation and mechanical ventilation altogether in patients with PCP due to the presumption of fatality in this clinical situation.

Spectrum of pathologic manifestations of Pneumocystis carinii pneumonia in patients with neoplastic diseases.

Pneumocystis carinii is the most common protozoan organism causing infection in immunosuppressed patients. This study, based on a review of 32 lung biopsies and 13 autopsies of patients with neoplastic diseases who developed P carinii pneumonia, emphasizes the morphologic variation of this disease. Excluded from this study are those patients with PCP secondary to bone marrow transplantation and AIDS. P carinii pneumonia occurred predominately in patients with malignant lymphoreticular neoplasms, 73% of those in our series, and the remaining 27% had solid tumors. There were 27 males and 18 females and their ages ranged from 1 to 73 years, with a median age of 30 years. Microscopically, the diagnostic intraalveolar foamy exudate of P carinii pneumonia was present in only 58% of the cases. Furthermore, diffuse alveolar damage alone was present in 26% of cases. This change was especially prominent when the characteristic foamy material was scanty. Other tissue reactions to P carinii included the presence of giant cells, epithelioid granulomas, desquamative interstitial-like pneumonitis, and interstitial lymphoid infiltrate. Extrapulmonary dissemination was not observed in this patient population. The pathologist should be aware of the marked variations that occur in the morphologic appearance of PCP, and the diagnosis of Pneumocystis infection should not be discarded until a careful search for the organisms using silver stains is rendered negative.

Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: diagnosis using minilavage samples.

Over a 30-month period, we evaluated 74 patients with acquired immunodeficiency syndrome (AIDS) for suspected opportunistic pulmonary infection. All had abnormal findings on chest roentgenogram. Sixty patients (81%) were found to have Pneumocystis carinii pneumonia (PCP). We assessed the yield of various diagnostic methods, and found that bronchoalveolar lavage samples obtained by the instillation of 20 to 50 ml of normal saline (minilavage) contained detectable organisms in 51 of 53 patients (sensitivity of 96%) when the samples were embedded in plastic, cut in thick sections (1 micron), stained with toluidine blue O, and evaluated by light microscopy. In comparison, the diagnostic yield was 94% for lung biopsy, 85% for touch preparation of lung tissue, 32% for bronchial washing, and 14% for brush biopsy. It is significant that minilavage samples embedded in plastic were positive in all seven patients who did not have transbronchial lung biopsy because they were at high risk for complications. We conclude that the process of embedding minilavage samples in plastic and evaluating thick sections stained with toluidine blue O is a sensitive method of diagnosing PCP in patients with AIDS.

The Use of a Simple Exercise Test for the Diagnosis ofPneumocystis cariniiPneumonia in Patients with AIDS

Because Pneumocystis carinii pneumonia (PCP) is so common among patients infected with the human immunodeficiency virus-1 (HIV-1), a quick, simple test to evaluate for its presence or absence would be helpful. We report our results on the role of an exercise blood gas test as a useful procedure for the detection of Pneumocystis pneumonia in patients with respiratory symptoms who have or who are at risk for developing the acquired immunodeficiency syndrome (AIDS). Results show that a normal exercise test, as defined in the study and in our patient population, eliminated PCP from the differential diagnosis. An abnormal test was most useful in separating out a group of patients who urgently needed a diagnosis because PCP was a likely possibility. There were no significant complications associated with this test.

Dapsone, Trimethoprim, and Sulfamethoxazole Plasma Levels during Treatment of Pneumocystis Pneumonia in Patients with the Acquired Immunodeficiency Syndrome (AIDS)

To examine the interaction between dapsone and trimethoprim in patients with the acquired immunodeficiency syndrome (AIDS). Measurement of drug levels as part of an open study of dapsone alone and randomized, double-blind comparison of trimethoprim-dapsone with trimethoprim-sulfamethoxazole in treating Pneumocystis carinii pneumonia in patients with AIDS. County hospital and AIDS clinic. Eighteen patients treated with dapsone alone, 30 with trimethoprim-dapsone, and 30 with trimethoprim-sulfamethoxazole. Dapsone, 100 mg/d; trimethoprim, 20 mg/kg body weight per day, and sulfamethoxazole, 100 mg/kg.d; administered for 21 days. Concentrations of dapsone were 40% higher in patients treated with trimethoprim-dapsone than in those treated with dapsone alone (2.1 compared with 1.5 micrograms/mL; P less than 0.05). Trimethoprimdapsone-treated patients had fewer treatment failures but more side effects and treatment terminations due to toxicity than those treated with dapsone alone. The concentration of trimethoprim was 48.4% higher in patients treated with trimethoprim-dapsone than in those treated with trimethoprim-sulfamethoxazole, (18.4 compared with 12.4 micrograms/mL; P less than 0.05). Discontinuation of therapy due to toxicity was commoner in the trimethoprim-sulfamethoxazole group (57% compared with 30%). A bidirectional drug interaction exists between dapsone and trimethoprim, resulting in higher concentrations of each in the presence of the other.

Elevated Levels of Angiotensin-converting Enzyme in Pneumocystis carinii Pneumonia

Serum angiotensin-converting enzyme (ACE) levels are elevated in sarcoidosis and have been used both to diagnose and to assess response to treatment of this disease. We report significantly (p less than .0005) elevated ACE levels in patients with Pneumocystis carinii pneumonia (PCP) (49 +/- 14 U/L) compared with normal control subjects (32 +/- 11 U/L) tested within 48 hours of hospital admission. Serum ACE levels in smoking control subjects (33 +/- 11 U/L) were not significantly (alpha = .05) different from nonsmoking control subjects (32 +/- 11 U/L), but the levels in PCP patients who smoked (55 +/- 15 U/L) were significantly (p less than .025) higher than in those who did not smoke (42 +/- 10 U/L). In addition to suggesting a possible clinical use for measuring ACE levels in suspected or confirmed PCP, we speculate that elevations in serum ACE levels may reflect macrophage dysfunction in patients with PCP.

Prognostic Indicators in the Initial Presentation of Pneumocystis carinii Pneumonia

We prospectively evaluated 150 consecutive patients with Pneumocystis carinii pneumonia (PCP) as their sole initial manifestation of AIDS (group 1). Admission laboratory and radiographic criteria were analyzed for diagnostic and prognostic indicators and compared with those of patients presenting with non-PCP pulmonary manifestations of AIDS (group 2). Mean admission serum LDH level was 465 +/- 67 IU/L in PCP patients (group 1) and 211 +/- 28 IU/L in group 2 (p less than 0.01). Seventy-eight percent of PCP patients (117 of 150) survived. Comparing survivors with nonsurvivors, the mean admission LDH level was 394 +/- 45 vs 717 +/- 51 IU/L (p less than 0.01), and the mean P(A-a)O2 gradient was 42 +/- 6 vs 55 +/- 6 mm Hg (p less than 0.05). Serum LDH levels and P(A-a)O2 gradients have diagnostic and prognostic implications in patients with AIDS-related PCP.

Survival following mechanical ventilation for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome: A different perspective

Survival following mechanical ventilation for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome: A different perspective

Fatal Toxic Epidermal Necrolysis During Prophylaxis With Pyrimethamine and Sulfadoxine in a Human Immunodeficiency Virus—Infected Person

The combination of pyrimethamine and sulfadoxine (Fansidar) has been reported to cause severe skin reactions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Recently, this drug combination has been used for prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. After two months of weekly prophylaxis with pyrimethamine and sulfadoxine, a 48-year-old homosexual man who was antibody positive for human immunodeficiency virus developed severe widespread erythema, blisters, and loss of skin in sheets, and subsequently died. To our knowledge, this is the first reported case of fatal toxic epidermal necrolysis occurring in a patient with acquired immunodeficiency syndrome-related complex. The lack of absolute safety of prophylaxis with pyrimethamine and sulfadoxine is emphasized in our case, and mandates cautious use and the consideration of less toxic prophylactic measures such as therapy with the recently introduced aerosolized pentamidine.

Chemoprophylaxis for Pneumocystis Carinii Pneumonia in AIDS

To the Editor.— The article by Fischl et al 1 presents impressive results for the use of sulfamethoxazole and trimethoprim for the prophylaxis of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome (AIDS). In this randomized, controlled trial, the authors do show a high degree of correlation between treatment and the prevention of P carinii pneumonia, as well as increasing survival. The study is consistent both with previous studies that show effective prophylaxis for P carinii pneumonia in immunodeficient patients and with known information on AIDS and P carinii pneumonia. Measurement bias was reduced by providing a methodology for diagnosing Pneumocystis that reduced interobserver error, false-positive error, and false-negative error. However, use of a blinded study would have increased the reliability of the diagnosis of Pneumocystis by reducing intraobserver error and interobserver bias as well as placebo effect. Since the study was not blinded, it is possible that a

Management of Pneumocystis carinii pneumonia in patients with AIDS and other conditions: experience in a Philadelphia University Teaching Hospital.

We reviewed the records of 49 patients who had 55 episodes of Pneumocystis carinii pneumonia (PCP) from January 1984 to January 1987. Thirty-three patients had acquired immunodeficiency syndrome (AIDS), with the risk groups being homosexual/bisexual practices (26), hemophilia (6), and blood transfusion (1). Fourteen patients had a history of malignancy or chemotherapy and two underwent organ transplantation. Overall response to therapy of PCP was 75% (77% of patients with AIDS, 68% of those with other conditions). All six relapses occurred in patients with AIDS. Both trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine were associated with a higher rate of toxicity in those patients than in patients with other conditions. A 30% rate of failure due to side effects occurred when TMP-SMX was used as initial therapy, but the combination is considered effective and should be given an adequate therapeutic trial. Pentamidine was an effective alternative for patients who failed with TMP-SMX and for those who failed therapy due to side effects, but was associated with serious toxicities. Our experience was similar in some respects to previous published results from New York and California.

Elevated Lactate Dehydrogenase Values in Patients with Pneumocystis carinii Pneumonia

We investigated the source of elevated serum lactate dehydrogenase (LDH) levels in seven patients with Pneumocystis carinii pneumonia (PCP) by analyzing blood and bronchoalveolar lavage (BAL) albumin (ALB) and LDH, with isoenzyme fractionation. Four patients with non-PCP lung disease served as control subjects. In PCP patients, BAL LDH was sixfold higher, and BAL ALB, fourfold higher than in the non-PCP patients. The increased LDH/ALB in BAL as compared to serum, in addition to a BAL isoenzyme pattern characteristic of lung, suggest that BAL LDH arises from a pulmonary source. We postulate that the high correlation observed between BAL and serum LDH (r = 0.93, p less than 0.001) reflects backflow of pulmonary-derived LDH into the blood through an alveolocapillary membrane (ACM) compromised by PCP. Furthermore, a comparison of BAL LDH/ALB for each isoenzyme with the same serum ratio showed less backflow for the cationic isoenzymes. The ACM appears to sieve proteins on an electrical basis which may account for the LDH isomorphic pattern observed in the serum of PCP patients.