Aerosol pentamidine for secondary prophylaxis of AIDS-related Pneumocystis carinii pneumonia. A randomized, placebo-controlled study

OBJECTIVE: To assess the safety and efficacy of aerosol pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). PARTICIPANTS: Patients recovering from a first confirmed episode of AIDS-related P. carinii pneumonia who had no evidence of either another active AIDS-defining opportunistic infection or another pulmonary abnormality were considered eligible for the study but were included only if they had received no immunomodulators or antiretroviral agents other than zidovudine within 30 days of entry. One hundred sixty-two patients were randomized and started on the study drug. INTERVENTION: Patients were randomly assigned to receive aerosol pentamidine, 60 mg per dose, or placebo, delivered using a hand-held, patient-triggered, ultrasonic nebulizer. The induction phase of treatment consisted of 5 doses over 14 days, followed by a maintenance phase beginning on day 21 and consisting of one dose every 2 weeks. RESULTS: Thirty-two cases of P. carinii pneumonia were diagnosed before the termination of the trial; 27 cases occurred among 78 patients receiving placebo and 5 occurred among 84 patients receiving aerosol pentamidine. Estimates of the cumulative relapse rate of P. carinii pneumonia by 24 weeks were 50% and 9% for the placebo and pentamidine groups, respectively (P less than 0.001). Adverse reactions attributed to the study drug occurred in 15 of 78 patients receiving placebo and in 28 of 84 patients receiving pentamidine (P = 0.04). These were all mild or moderate in severity and did not preclude continued administration of the study drug. CONCLUSION: Intermittent therapy with aerosol pentamidine is highly effective and well tolerated as secondary prophylaxis for AIDS-related P. carinii pneumonia.     

A meta-analysis of salvage therapy for Pneumocystis carinii pneumonia.

OBJECTIVE: To determine the relative efficacies of alternative antipneumocystis agents in human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia unresponsive to primary drug treatment with a combination product of trimethoprim and sulfamethoxazole or parenteral pentamidine. METHODS: Meta-analysis of 27 published clinical drug trials, case series, and case reports involving P carinii pneumonia. Data extracted included underlying disease, primary antipneumocystis treatment, days of failed primary treatment, salvage regimen, use of systemic corticosteroids and antiretroviral drugs, and clinical outcome. RESULTS: In 497 patients with microbiologically confirmed P carinii pneumonia (456 with HIV or acquired immunodeficiency syndrome), initial antipneumocystis treatment failed and they therefore required alternative drug therapy. Failed regimens included trimethoprim-sulfamethoxazole (160 patients), intravenous pentamidine (63 patients), trimethoprim-sulfamethoxazole and/or pentamidine (258 patients), aerosolized pentamidine (6 patients), atovaquone (3 patients), dapsone (3 patients), a combination product of trimethoprim and dapsone (2 patients), and trimethoprim-sulfamethoxazole followed by a combination of clindamycin and primaquine phosphate (2 patients). Efficacies of salvage regimens were as follows: clindamycin-primaquine (42 to 44 [88%-92%] of 48 patients; P<10(-8)), atovaquone (4 [80%] of 5), eflornithine hydrochloride (40 [57%] of 70; P<.01), trimethoprim-sulfamethoxazole (27 [53%] of 51; P<.08), pentamidine (64 [39%] of 164), and trimetrexate (47 [30%] of 159). CONCLUSION: The combination of clindamycin plus primaquine appears to be the most effective alternative treatment for patients with P carinii pneumonia who are unresponsive to conventional antipneumocystis agents.     

Pneumothorax in AIDS

OBJECTIVE: To determine risk factors for the development of pneumothorax in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective cohort study. SETTING: Tertiary care center. PATIENTS: Of 1030 patients with AIDS who were followed at Memorial Sloan-Kettering Cancer Center between 1 January 1980 and 30 September 1989, 20 (2%) developed pneumothorax that was unrelated to trauma or a pulmonary procedure. RESULTS: Of 20 patients with AIDS who presented with pneumothorax, 19 had compelling evidence of concurrent Pneumocystis carinii pneumonia. Using bivariate analysis, patients receiving aerosol pentamidine prophylaxis (relative risk, 17.6) and those with a history of P. carinii pneumonia (relative risk, 14.5) were more likely to develop pneumothorax. By Mantel-Haenszel stratified analysis, aerosol pentamidine use was a statistically significant risk factor independent of a history of P. carinii pneumonia. The pneumothorax-related mortality rate was 10% and there was considerable morbidity. CONCLUSIONS: Patients with AIDS at the highest risk for developing pneumothorax are those with a history of P. carinii pneumonia who are receiving aerosol pentamidine prophylaxis but who nevertheless develop P. carinii pneumonia. The benefits of aerosol pentamidine prophylaxis in these patients far outweigh this risk. Pneumocystis carinii pneumonia should be considered as the most likely diagnosis in any patient with AIDS who develops a pneumothorax.     

Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS. A randomized trial

OBJECTIVE: 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). DESIGN: Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS: 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. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.     

Effect of aerosolized pentamidine prophylaxis on the diagnosis of Pneumocystis carinii pneumonia by induced sputum examination in patients infected with the human immunodeficiency virus

This study assessed the effect of aerosolized pentamidine prophylaxis on the clinical presentation and diagnostic sensitivity of induced sputum examination for Pneumocystis carinii pneumonia. Between January 1, 1988 and October 27, 1990, 348 induced sputum examinations were performed as the initial diagnostic procedure for P. carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). Medical records were reviewed for all induced sputum examinations, and the study group consisted of patients who either had not received prophylactic therapy (n = 193) or had received aerosolized pentamidine prophylaxis (n = 126). A total of 29 induced sputum examinations in patients receiving either other prophylactic regimens or ongoing therapy for previously documented P. carinii pneumonia were excluded from the study group. A total of 72 consecutive episodes of P. carinii pneumonia were subsequently documented by induced sputum examination (n = 54), bronchoalveolar lavage (n = 16), thoracocentesis (n = 1), or autopsy (n = 1). A total of 44 episodes occurred in patients who had not received antipneumocystis prophylaxis, and 28 episodes occurred in patients who had received aerosolized pentamidine. Of patients capable of producing a sputum specimen for analysis, induced sputum examination had a significantly lower diagnostic yield of 64.3% in patients who had received aerosolized pentamidine prophylaxis compared with 92.3% in patients who did not receive prophylaxis (p less than 0.02, Fisher's exact test). When the data were analyzed on an intention to treat basis, although there was a trend suggesting a lower overall yield in the aerosolized pentamidine patients, the difference was not statistically significant (64.3 versus 81.8%, p = 0.17, Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of the effectiveness of three regimens in the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.

BACKGROUND--Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and the leading cause of death in patients with the acquired immunodeficiency syndrome. The prevention of the occurrence and recurrence of PCP is a cornerstone in the treatment of patients infected with the human immunodeficiency virus. There are few studies comparing PCP prophylactic regimens. METHODS--The efficacy of three regimens for prophylaxis against PCP was assessed in a retrospective chart review of 211 human immunodeficiency virus-infected patients at risk for the disease. Over the course of the 2-year study period, 133 patients were prescribed trimethoprim-sulfamethoxazole (one double-strength tablet twice a day, thrice weekly) for a mean of 7.4 months (range, 1 to 25 months). Seventy-seven patients received dapsone (50 mg daily) for a mean of 5.7 months (range, 1 to 23 months), and 125 patients received aerosolized pentamidine (300 mg via nebulizer once monthly) for a mean of 9.3 months (range, 1 to 21 months). The majority of patients (62%) received primary prophylaxis; 38% had one or more previous episodes of PCP; and 73% were receiving concomitant antiretroviral therapy. RESULTS--Pneumocystis carinii pneumonia did not develop in any patient receiving trimethoprim-sulfamethoxazole in 981 patient-months. Five patients receiving dapsone for 437 patient-months and 17 patients receiving aerosolized pentamidine for 1166 patient-months developed PCP. Fifty-six percent of the trimethoprim-sulfamethoxazole group and 55% of the dapsone group changed drug due to adverse reactions, while only 2% in the aerosolized pentamidine group required drug change. CONCLUSION--Despite its adverse reaction profile, trimethoprim-sulfamethoxazole is the most effective agent to prevent the occurrence and recurrence of PCP.     

Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases

Pentamidine isethionate, discovered to have antiprotozoal activity in 1938, has recently been approved in the United States for the treatment of Pneumocystis carinii pneumonia. Despite frequent adverse reactions, which are at times life-threatening, pentamidine remains an important alternative to trimethoprim-sulfamethoxazole for the treatment of P. carinii pneumonia in patients with a history of allergy to sulfonamides or who have severe reactions or a lack of response to treatment with trimethoprim-sulfamethoxazole. Although not approved for other indications, pentamidine has been shown to be effective when used prophylactically against Trypanosoma brucei gambiense, the cause of West African sleeping sickness, as well as for treatment of the early hemolymphatic stage of that disease, and for treatment of some forms of leishmaniasis.     

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.     

Deposition of aerosolized pentamidine and failure of pneumocystis prophylaxis.

OBJECTIVE: To determine if outcome of Pneumocystis carinii prophylaxis is related to total lung dose of aerosolized pentamidine. SETTING: AIDS treatment centers at a VA and University Hospital. PATIENTS: Fifty-eight HIV-infected patients receiving P carinii prophylaxis with aerosolized pentamidine using a nebulizer (CIS-US AeroTech II) were followed up over a 90-week period. Treatment consisted of 60 to 90 mg every two weeks. MEASUREMENTS: In all patients, deposition of pentamidine aerosol was measured using a radioaerosol filter technique. Factors thought to be important in deposition, nebulizer output and breathing pattern were also measured. Six months later, repeated deposition studies were performed in 20 patients. Pentamidine dose to the lung was related to occurrence of P carinii pneumonia and correlated with nebulizer function and breathing parameters. Outcome was assessed in terms of pentamidine deposition and patient characteristics, including demographic, immunologic, physiologic, and medical variables. RESULTS: Ten patients (17.2 percent) had development of P carinii pneumonia. However, pentamidine deposited in the failures (8.18 +/- 4.74 mg) was no different than deposition in protected patients (6.39 +/- 3.07 mg, p = NS). Most of the variability in deposition was accounted for by variability in nebulizer output (r = 0.919, p less than 0.001). Deposition did not significantly correlate with any of the measured breathing parameters. Serial deposition measurements were not significantly different by paired analysis. The incidence of P carinii pneumonia did not correlate with any measured patient characteristic. CONCLUSIONS: Failure of aerosolized pentamidine prophylaxis is not related to total lung dose of pentamidine. Other factors such as inadequate microscopic deposition between alveoli, pentamidine clearance, or drug resistance may be important. In HIV-infected patients, interpatient variability in aerosol deposition can be reduced by reducing variability in nebulizer output rather than control of breathing pattern.     

Aerosolized pentamidine as second line therapy in patients with AIDS and Pneumocystis carinii pneumonia

The use of aerosolized pentamidine was investigated in ten patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) who had previous or concurrent severe adverse reactions or contraindications to trimethoprim-sulfamethoxazole or parenteral pentamidine. A dose of 600 mg pentamidine in 6 ml sterile water, aerosolized in a small-particle producing jet nebulizer was administered for 25 minutes once daily for an average of 10.5 days to these ten patients. All patients improved their arterial O2 saturation and showed clinical and roentgenographic improvement within six to 21 days of aerosol pentamidine therapy. No adverse systemic reactions occurred. The results of this small open trial indicate that aerosolized pentamidine is effective and can be given safely to AIDS patients with PCP who have had adverse reactions to trimethoprim-sulfamethoxazole or parenteral pentamidine.     

Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia

STUDY OBJECTIVE: To determine the effect of previous aerosolized pentamidine therapy on diagnosis and presentation of Pneumocystis carinii pneumonia. DESIGN: A retrospective study. SETTING: A tertiary care hospital. PATIENTS: Fifty-two consecutive patients with P. carinii pneumonia and underlying infection with the human immunodeficiency virus (HIV) who had bronchoscopy. Twenty-one patients who were on aerosolized pentamidine therapy served as the study group. Thirty-one patients who had not received the drug served as the control group. MEASUREMENTS AND MAIN RESULTS: The yield of bronchoalveolar lavage for P. carinii pneumonia was 62% for the study group and 100% for the control group (P less than 0.05). This lower yield was significant for the subset of patients having their first episode of P. carinii pneumonia. The yield of transbronchial biopsy was similar for both groups of patients (81% compared with 84%). The yield of bronchoscopy was not influenced by use of zidovudine. Review of lavage specimen slides suggested that there may be fewer organisms present in patients receiving aerosolized pentamidine. An atypical roentgenographic presentation of upper lobe predominant infiltrates was seen in 38% of the study patients and 7% of the control patients. In addition, pneumothoraces and cystic changes were also frequently seen in the study patients. Gallium scans, when done, were also atypical in the study group. Markers of the severity of disease, however, were similar in both groups. CONCLUSION: The yield of bronchoalveolar lavage for P. carinii pneumonia in HIV-infected patients is lower in patients receiving aerosolized pentamidine. Unusual roentgenographic presentations and atypical gallium scans are also found in this setting.     

Extrapulmonary pneumocystosis: clinical features in human immunodeficiency virus infection

Pneumocystis carinii infection is reported with increasing frequency as a cause of disease outside of the respiratory tract in patients with human immunodeficiency virus (HIV) infection. Extrapulmonary pneumocystosis is not limited to patients in any discrete risk group for HIV infection. Patients with HIV infection who develop extrapulmonary pneumocystosis frequently do not have concurrent P. carinii pneumonia. Signs and symptoms of extrapulmonary pneumocystosis are nonspecific but when present are frequently referable to the tissues or organs involved. Extrapulmonary pneumocystosis can be diagnosed by examination of tissue biopsies from affected sites using standard histologic techniques. Therapy with antimicrobial agents used to treat P. carinii pneumonia has been effective in some patients. An association between use of aerosolized pentamidine for prevention of P. carinii pneumonia and development of extrapulmonary pneumocystosis has been suggested but remains unconfirmed. Other factors such as the use of zidovudine and duration of immunodeficiency may also be important to the pathogenesis of extrapulmonary pneumocystosis. Further studies are needed to better identify risk factors that may predispose patients to the development of extrapulmonary pneumocystosis.     

Effect of aerosolized pentamidine prophylaxis on the clinical severity and diagnosis of Pneumocystis carinii pneumonia.

To determine if the use of aerosolized pentamidine prophylaxis decreases the clinical severity or the sensitivity of diagnostic tests for Pneumocystis carinii pneumonia (PCP), we conducted a retrospective matched cohort comparison study of patients admitted to San Francisco General Hospital with PCP from August 1, 1989, to June 30, 1990. Patients who had received pentamidine prophylaxis during at least the 2 months prior to the diagnosis of PCP were matched with patients who had not received the drug. Matching was based on the number of prior episodes of PCP, sex, age, and risk factors for human immunodeficiency virus infection. As markers of clinical severity, we chose alveolar-arterial oxygen difference, serum lactate dehydrogenase levels, outpatient versus inpatient treatment, length of hospitalization, length of intravenous anti-pneumocystis treatment, development of respiratory failure, in-hospital mortality, and chest radiographic appearance. Although, of the 27 matched pairs identified, significantly fewer of the pentamidine cohort were treated as inpatients, and significantly more of this cohort had upper lobe dominant disease on chest radiograph, we found no other significant differences between markers of clinical severity for the two cohorts. In addition, we found no significant differences in the rate of sputum or bronchoalveolar lavage positivity for P. carinii between the two cohorts. We conclude that, although hospitalization is less common in patients with a history of prophylactic pentamidine use, aerosolized pentamidine prophylaxis does not decrease the clinical severity or the sensitivities of sputum induction or bronchoalveolar lavage as diagnostic tests for PCP.     

Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective randomized trial

Forty patients with the acquired immunodeficiency syndrome (AIDS) and their first episodes of Pneumocystis carinii pneumonia were assigned at random to receive either trimethoprim-sulfamethoxazole or pentamidine isethionate. The two groups did not differ significantly in the severity of pulmonary or systemic processes at enrollment. Five patients treated initially with trimethoprim-sulfamethoxazole and one patient treated initially with pentamidine died during the 21-day treatment period (p = 0.09, Fisher's exact test). No significant differences were seen between groups in rates of improvement, pulmonary function tests, or 67Ga uptake by the lungs in the survivors at completion of therapy. Adverse reactions necessitated changing from the initial drug in 10 patients in the trimethoprim-sulfamethoxazole group and 11 in the pentamidine group. Minor reactions occurred in all patients. In patients with AIDS, trimethoprim-sulfamethoxazole and pentamidine do not have statistically significant differences in efficacy or frequency of adverse reactions.     

Prophylaxis of Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus type 1

Immunosuppression due to human immunodeficiency virus type 1 (HIV) infection has led to a marked increase in Pneumocystis carinii pneumonia (PCP). Prophylaxis against PCP is standard practice in pediatric cancer patients but is associated with unique problems in HIV-infected patients, including the need for lifelong therapy, adverse reactions, and drug interactions. HIV-infected patients at highest risk for PCP are those with a prior episode of PCP and/or a CD4 lymphocyte count of less than 200 cells/microL. A combination of trimethoprim and sulfamethoxazole is effective prophylactically, although a significant rate of adverse reactions makes long-term prophylaxis difficult. Other oral medications such as dapsone and a combination of pyrimethamine and sulfadoxine are promising but not yet adequately tested. Inhalation of aerosolized pentamidine is an effective and safe means of prophylaxis if the proper dose and nebulizer are used. The only common adverse effects with the latter are airway irritation manifested by cough or wheezing. Zidovudine appears to have a synergistic benefit in further reducing the attack rate of PCP when used with aerosolized pentamidine.     

Atypical presentations of Pneumocystis carinii pneumonia in patients receiving inhaled pentamidine prophylaxis

Inhaled pentamidine is used commonly to prevent Pneumocystis carinii pneumonia (PCP) in patients with advanced human immunodeficiency virus infection. Case reports indicate that PCP can recur in patients who receive inhaled pentamidine and that clinical features may be atypical. To determine the magnitude of this problem, we reviewed retrospectively the medical records of patients with proven PCP during a 30-month period at two hospitals. Four (31 percent) of 13 patients with previous PCP who received inhaled pentamidine prophylaxis had recurrent P carinii infection, including one patient with widely metastatic extrapulmonary disease. Chest roentgenographic findings included cavities, pneumothoraces, bilateral and upper lobe interstitial infiltrates, and pleural effusion. False-negative bronchoalveolar lavage and induced sputum examinations were frequent. We conclude that recurrent PCP in patients maintained on a regimen of inhaled pentamidine prophylaxis occurs frequently, causes chest roentgenographic abnormalities other than interstitial infiltrates, and may be difficult to diagnose. Clinicians who choose to use this effective and convenient mode of prophylaxis should be aware of the problems attendant to its use.     

Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia. A pilot study

Study Objective: To evaluate inhaled or reduced-dose intravenous pentamidine for the treatment of patients with mild Pneumocystis carinii pneumonia. Design: Open, nonrandomized pilot study; measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. Patients: Of 22 men with mild P. carinii pneumonia (PO2 greater than or equal to 55 mm Hg), 15 (9 in the inhaled group and 6 in the intravenous group) received treatment for their first episode and 7 for a repeat episode. Interventions: Pentamidine isethionate, 4 mg/kg body weight by inhalation, or 3 mg/kg intravenously, was given once daily, as long as clinically indicated. Measurements and Main Results: Of the 13 patients in the inhaled group, 9 has a satisfactory response; and of the 10 in the reduced-dose intravenous group, 9 had a satisfactory response. Major adverse reactions occurred in two patients in each group. Three patients in the inhaled group appeared to have had early relapses. Bronchoalveolar lavage fluid concentrations of pentamidine ranged between 16.8 +/- 7.3 ng/mL and 149.7 +/- 38.2 ng/mL in the inhaled group and 3.4 +/- 0.2 ng/mL and 10.9 ng/mL in the intravenous group. Conclusions: Inhaled or reduced-dose intravenous pentamidine may be an effective and less toxic therapy for mild P. carinii pneumonia. These regimens are not recommended for general use until larger controlled trials are conducted.     

Extrapulmonary Pneumocystis carinii infections in the acquired immunodeficiency syndrome

Pneumocystis carinii is a frequent cause of interstitial pneumonitis in patients with cell-mediated immunodeficiencies. Extrapulmonary P carinii infection is a rare manifestation of disease caused by this organism. Nevertheless, reports of extrapulmonary P carinii infection are increasing in the setting of the acquired immunodeficiency syndrome (AIDS). We report two cases of extrapulmonary P carinii infection in patients with AIDS and review the literature on this subject. We identified 37 such cases: in 19 cases, P carinii pneumonia was present concurrently; in 18 cases, involvement was exclusively extrapulmonary. A minority of patients were receiving aerosolized pentamidine isethionate therapy. Most patients had a history of P carinii pneumonia, and other AIDS-related illnesses, such as cytomegalovirus infection, mycobacterial disease, candidiasis, Kaposi's sarcoma, and cryptococcosis were common. Concurrent cytomegalovirus infection indicated a poor prognosis, while otic pneumocytosis was associated with a favorable outcome. Pathologic evidence suggested that extrapulmonary pneumocystosis occurred by hematogenous and lymphatic dissemination from the lungs in most cases. In other cases, extrapulmonary pneumocystosis appeared to be due either to reactivation of latent infection in extrapulmonary sites or to primary infection of these sites. Further studies are needed to determine the true frequency of extrapulmonary involvement in P carinii infections and to define risk factors for acquisition of extrapulmonary pneumocytosis.     

Pneumocystis carinii isolated from lung lavage fluid in an infant with cystic fibrosis

Pneumocystis carinii (P. carinii) cysts were identified in bronchoalveolar lavage fluid from a 15-week-old child newly diagnosed with cystic fibrosis who presented with bronchitis, pneumonia, and weight loss. The child was not infected with human immunodeficiency virus (HIV), and there was no evidence of impaired immunity or exposure to individuals with known or suspected P. carinii disease. Culture of the lavage fluid also revealed pathogens typical of lung disease associated with cystic fibrosis. It is suspected that the presence of P. carinii in this patient represented a new acquisition, as has been described in immunocompetent infants and children. Whether P. carinii infection complicated cystic fibrosis-associated lung disease in this patient is unknown.     

Spontaneous pneumothorax in patients with acquired immunodeficiency syndrome treated with prophylactic aerosolized pentamidine

Spontaneous pneumothorax is a known complication of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. To evaluate the possible pathogenesis and natural history of pneumothorax in patients receiving aerosolized pentamidine prophylaxis, we retrospectively reviewed 327 outpatients positive for human immunodeficiency virus receiving aerosolized pentamidine. There were 12 spontaneous pneumothoraces in this group of patients. Seventy-five percent of patients with pneumothorax had roentgenographic evidence of fibrocystic lung parenchyma and clinical evidence of active Pneumocystis pneumonia. The majority (83%) required chest tube evacuation. There was a 50% mortality rate associated with this complication. These findings suggest that spontaneous pneumothorax in patients treated with aerosolized pentamidine most commonly represents a prophylaxis failure associated with a high mortality rate.