- Email: [email protected]
Fatal, disseminated pneumocystosis in a patient with acquired immunodeficiency syndrome receiving prophylactic aerosolized pentamidine
Fatal, Disseminated Pneumocystosis in a Patient with Acquired Immunodeficiency Syndrome Receiving Prophylactic Aerosolized Pentamidine W. DAVID HARDY, M.D., DON W. NORTHFELT, M.D., THOMAS A. DRAKE, M.D. LosAnge/es, ca/ifornia
mg/day (200 mg five doses/day) for 16 months (for recurrent herpes proctitis), AL-721 (egg lecithin) 20 g/ day for eight months, and aerosolized pentamidine 150 mg every two weeks administered by baffled jet-type though effective therapy is available, PCP remains the nebulizer (Respigard II, Marquest Medical Products, most significant cause of morbidity and mortality in patients with AIDS. A number of strategies have been Englewood, Colorado) for 10 months. Compliance with aerosol pentamidine treatments had been exceldevised to provide prophylaxis of PCP, including both systemic and aerosolized antimicrobial agents. Prolent. phylaxis with aerosolized pentamidine limits distribuPhysical examination on admission revealed a thin tion of the drug to the lungs. Its negligible systemic man in moderate distress with oral temperature of absorption obviates the development of toxicities that 38.2”C, blood pressure of 110/70 mm Hg, pulse of 96/ sometimescomplicate systemically administered prominute and respiratory rate of 16 to 18/minute. Physiphylactic regimens. This lack of systemic distribution cal findings of note included scleral icterus, tender may, however, have significant drawbacks. We report hepatomegaly (liver edge palpable 4 cm below right a case of fatal, disseminated pneumocystosis in a pacostal margin), easily demonstrable ascites,and hematient with AIDS, without clinical evidence of pneumo- tochezia. Laboratory data included the following: henia, who had received long-term therapy with prophymoglobin, 8.8 g/dL; white blood cell count, 1,7OO/pL lactic aerosolized pentamidine. with 51% neutrophils, 24% band forms, 15% lymphocytes, 10% monocytes, and 0% eosinophils; platelet CASE REPORT count, 141,OOO/pL; fibrinogen, less than 60 mg/dL; A 37-year-old man with AIDS presented complainprothrombin time, 22.7 seconds (control: 11.4 secing of a one-month history of intermittent fevers, onds); partial thromboplastin time, 56.7 seconds(conchills, and night sweats. He also described a one-week trol: 30.6 seconds); total bilirubin, 3.3 mg/dL; alkaline history of abdominal distention, crampy abdominal phosphatase, 1,080 U/L; lactate dehydrogenase, 979 pain, and melena. He denied dyspnea at rest or with U/L; aspartate aminotransferase, 1,300 U/L; and alaexertion, cough, sputum production, or chest discom- nine aminotransferase, 309 U/L. Hepatitis B serolofort. gies revealed the following: hepatitis B surface antiHis past medical history was significant for recovery gen, negative; anti-hepatitis B surface antibody from two previous episodes of histologically proven positive; and anti-hepatitis B core antibody (IgM) PCP diagnosed 24 and 18 months, respectively, prior negative. The chest radiograph demonstrated clear to admission. The initial episode of PCP was success- lung fields and a normal cardiac silhouette. fully treated with a 21-day course of sequential intraDiagnostic paracentesis revealed transudative, venous then oral trimethoprim-sulfamethoxazole grossly hemorrhagic fluid with hematocrit of 10%. All (2O:lOOmg/kg/day). For his recurrent episodeof PCP, smearsand cultures of blood, urine, stool, and peritohe received eight days of intravenous pentamidine (4 neal fluid for bacteria, acid-fast organisms, fungi, and mg/kg/day) followed by four days of oral therapy with cytomegalovirus failed to demonstrate pathogens on combined trimethoprim (20 mg/kg/day) and dapsone immediate review or after appropriate incubation pe(100 mg/day). The development of significant azote- riods. Computerized tomography of the abdomen remia (serum creatinine 3.5 mg/dL) and subsequently vealed multiple, hypodense lesions in the liver and neutropenia (absolute neutrophil count less than spleen (Figure 1). Despite daily administration of vil,OOO/mL) abbreviated this course of therapy. Since tamin K, infusion of 16 units of cryoprecipitate, and 60 his pneumonia had clinically resolved, no further therunits of fresh-frozen plasma, the severe coagulopathy apy was given. persisted, preventing invasive procedures including At the time of admission, he had been receiving liver biopsy. Hepatic encephalopathy ultimately entherapy with zidovudine 1,200 mglday (200 mg every sued and the patient died on the seventh hospital day. four hours) for 16 months, intermittent acyclovir 1,000 At autopsy, limited to the abdominal contents, 5.5 liters of hemorrhagic, ascitic fluid and a pelvic hematoma were present. The liver was grossly enlarged From the Departments of Medicine and Pathology, School of Medicine, University of California at Los Angeles, Los Angeles, California. Requests for (2,400 g) and diffusely studded with pinpoint, firm, reprints should be addressed to W. David Hardy, M.D.. UCLA AIDS Clinical gritty, yellow lesions. The biliary system was patent Research Center, 60-042 CHS. 10833 Le Conte Avenue, Los Angeles, California 90024. Manuscript submitted February 3. 1989, and accepted in throughout. The spleen was enlarged (600 g) and conrevised form May 18, 1989. tained multiple, round, red-white lesions, 1 to 3 cm in Current addresses: Dr. Northfelt: 611. Cancer Research Institute. UC San Francisco Medical Center, Moffitt 1282. San Francisco, California 94143. diameter, with umbilicated, necrotic centers. Similar Dr. Drake: Department of Pathology, lP-166 CHS. 10833 Le Conte Avenue, lesionswere alsofound in both kidneys. On microscopLos Angeles, California 90024. ic examination, all lesions were similar, consisting of pneumonia (PCP) is the P most common presenting manifestation of the acquired immunodeficiency syndrome (AIDS). Alneumocystosis
carinii
September 1989 The American Journal of Medicine
Volume 87
329
DISSEMINATED
PNEUMOCYSTOSIS
WITH AEROSOLIZED
PENTAMIDINE
/ HARDY ET AL
without human immunodeficiency syndrome (HIV) infection, in patients with AIDS, and in at least one patient with no known immunodeficiency. In patients without AIDS, reported sites of extrapulmonary involvement have included lymph nodes, spleen, bone marrow, thymus, liver, heart, pericardium, gastrointestinal tract, pancreas, homograft kidney, hard palate, and adrenal and thyroid glands. Clinically evident lung diseasewasnoted in all but one of these cases,and antemortem diagnosis was made in only three [l]. To date, 13 casesof extrapulmonary and/or disseminated pneumocystosis in patients with previously diagnosedAIDS or HIV infection have been reported. In four of these reports, extrapulmonary pneumocystosis wasdiagnosedconcomitantly with PCP. Retinal infection was documented by electron microscopy in a patient who died of associated pneumonia [2]. Widely disseminated infection involving the lungs, lymph Figure 1. Radiographic section from computerized tomogram of abnodes, heart, liver, spleen, pancreas, kidneys, adrenal domen demonstrating multiple, hypodense lesions in left and right glands, gastrointestinal organs, thyroid, or retina was lobes of liver and spleen. noted at autopsy in two patients [3,4]. Isolated antemortem bone marrow infection was noted in one pamasses of acellular, foamy material with focal calcifitient [5]. cation and hemorrhage (Figure 2A). Typical P. carinii Extrapulmonary pneumocystosis has been reported cysts were demonstrable within these lesions by Go- in three AIDS patients without previous or concurrent mori methenamine-silver stain (Figure 2B). Tissue PCP. P. carinii organismshave been found in bilateral Gram and acid-fast stains were negative. Microscopic polyps of the external auditory canals [6], spleen [7], involvement of a para-aortic lymph node was also ob- and thyroid [8]. Extrapulmonary pneumocystosis has served, whereas no evidence of P. carinii cysts was been reported as the initial manifestation of AIDS in found in sections of stomach, adrenal, prostate, pan- four patients, three of whom were previously asympcreas, or aorta. No other inflammatory, infectious, or tomatic and one with AIDS-related complex (ARC). neoplastic processeswere present in these or other Presentations have included temporal bone-based organs (Figure 2). polyps of the external auditory canal [9] in two patients, otitis media with associated mastoiditis in one COMMENTS patient [lo], and an obstructing small intestinal mass Extrapulmonary pneumocystosis has been de- presenting asan acute abdomen in one patient [l]. One scribed in a number of immunodeficient patients patient who recovered from two previous episodesof
Figure 2. A, histologic section of liver at the margin of a typical lesion, showing a mass of foamy exudate adjacent to intact hepatocytes (hematoxylin and eosin stain; original magnification X 346, reduced by 10%). B, four darkly stained cysts typical of P. cariniiin foamy exudate of liver lesion (Gomori methenamine-silver stain; original magnification x 865, reduced by 10%). 330
September
1989
The American
Journal
of Medicine
Volume
87
PCP presented with profound weakness and pancytopenia and was found to have bone marrow invasion by P. carinii, Another patient with a previous history of PCP presented with pulmonary infiltrates, pneumothorax, and hepatitis and was found to have P. carinii cysts on liver biopsy. Concurrent PCP was not definitively diagnosed in either patient, although both had significant pulmonary abnormalities [11,12]. Twelve of these I3 patients were reported to have received treatment for their pneumocystosis with trimethoprim-sulfamethoxazole, parenteral pentamidine, or combined dapsone and trimethoprim. The four patients with PCP died during or soon after the cessation of therapy [2-51. The seven patients without PCP responded to treatment with notable clinical improvement of their involved tissue or organ [1,610,121. Only one of these patients was reported as having received previous aerosol prophylaxis of PCP
would, however, be expected to have little, if any, effect on P. carinii organisms outside the lungs. Thus, the advantage of targeting delivery of pentamidine to the lungs may also carry with it the significant disadvantage of not providing systemic prophylaxis of pneumocystosis. The growing number of case reports describing extrapulmonary pneumocystosis have taught us that infection with this organism is not limited solely to the lung but can occur in any tissue or organ throughout the body, especially in immunocompromised hosts. This is the second reported case of extrapulmonary pneumocystosis occurring in a patient receiving prophylactic aerosolized pentamidine. As this means of PCP prophylaxis becomes more widely utilized and heightened awareness of extrapulmonary pneumocystosis grows, an increasing number of similar cases may be seen.
WI*
Secondary prophylaxis of PCP has become widely utilized in patients with AIDS due to the well-documented high recurrence rate of this pneumonia in the absence of prophylactic measures. Several systemically administered agents including daily trimethoprimsulfamethoxazole, weekly pyrimethamine-sulfadoxine, twice or four times daily dapsone, and biweekly or monthly parenteral and aerosolized pentamidine have all been shown to be effective in decreasing the incidence of recurrent PCP. Although systemic prophylactic agents are generally well-tolerated, adverse reactions to these agents have included mild to severe cutaneous eruptions (including Stevens-Johnson syndrome), nausea, cytopenias, increased hepatic transaminase levels, azotemia, and phlebitis. Persistent cough, reversible bronchospasm, and dysgeusia have been associated with aerosol administration of pentamidine [13]. Prophylactic aerosolized pentamidine is becoming increasingly utilized because of reports of its efficacy in preventing PCP and its minimal systemic toxicity. Measurements of the concentration of pentamidine in broncho-alveolar lavage fluid following aerosol versus intravenous administration have revealed 10 to 75 times greater drug levels after aerosol delivery compared with intravenous infusion. Concomitant plasma concentrations of pentamidine after aerosol delivery have been negligible [Id]. The selective pulmonary distribution and minimal systemic absorption of aerosolized pentamidine have been exploited as a novel means of PCP prophylaxis. Aerosolized pentamidine
REFERENCES 1. Carter TR. Cooper PH, Petri WA. Kim CK. Walzer PD. Guerrant RL: fneumocp tosis carinii infection of the small intestine in a patient with acquired immune deficiency syndrome. Am J Clin Pathol 1988; 89: 679-683. 2. Kwok S, O’Donnell JJ. Wood IS: Retinal cotton-wool spots in a patient with Pneumocystosis carinii infection, N Engl J Med 1982; 307: 184-185. 3. Grimes MM, LaPook JD, Bar MH. Wasserman HS. Dwork A: Disseminated Pneumocystosis wriflii infection in a patient with acquired immunodeficiency syndrome. Hum Pathol 1987; 18: 307-308. 4. Macher AM. Bardenstein OS. Zimmerman LE. et at Pneumocystosis wrinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinii infection (letter). N Engi J Med 1987; 316: 1092. 5. Heyman MR. Rasmussen P: Pneumocystosis carinii involvement of the bone marrow in acquired immunodeficiency syndrome. Am J Clin Pathol 1987; 87: 780783. 6. Coulman CU. Greene I, Archibald RWR: Cutaneous pneumocystosis. Ann Intern Med 1987; 106: 396-398. 7. Pilon VA, Echols RM. Celo JS. Elmendort SL: Disseminated Pneumocystosis carinii infection in AIDS. N Engl J Med 1987: 316: 141D-1411. 8. Gallant JE, Enriquez RE. Cohen KL. Hammers LW: Pneumocystosis wriniithyroiditis. Am J Med 1988; 84: 303-306. 9. Breda SD. Hammerschlag PE. Gigliotti F, Schinella R: Pneumocystosis wriniiin the temporal bone as a primary manifestation of the acquired immunodeficiency syndrome. Ann Otol Rhino1 Laryngol 1988: 97: 427-431. 10. Gherman CR, Ward RR. Bassis ML: Pneumocvstosis wrinii otitis media and mastoiditis as the initial manifestation of the acquired immunodeficrency syndrome. Am J Med 1988; 85: 25G-252. 11. Raviglione MC. Garner GR. Mullen MP: Pneumocystosis cariniiin bone marrow (letter). Ann Intern Med 1988: 109: 253, 12. Poblete RB. Rodriquez K. Foust RT. et al: Pneumocystis carinii hepatitis in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1989; 110: 737738. 13. Hardy WD: Prophylaxis of AIDS-related opportunistic infections. In: Volberding PA, Jacobson MA, eds. 1989 AIDS clinical review. New York: Marcel Dekker. 1989; 125-150. 14. Montgomery AB. Debs RJ, Lute JM. etalrselective delivery of pentamidine to the lung by aerosol. Am Rev Respir Dis 1988; 137: 477-478.
September
1989
The American
Journal
of Medicine
Volume
87
331
mg/day (200 mg five doses/day) for 16 months (for recurrent herpes proctitis), AL-721 (egg lecithin) 20 g/ day for eight months, and aerosolized pentamidine 150 mg every two weeks administered by baffled jet-type though effective therapy is available, PCP remains the nebulizer (Respigard II, Marquest Medical Products, most significant cause of morbidity and mortality in patients with AIDS. A number of strategies have been Englewood, Colorado) for 10 months. Compliance with aerosol pentamidine treatments had been exceldevised to provide prophylaxis of PCP, including both systemic and aerosolized antimicrobial agents. Prolent. phylaxis with aerosolized pentamidine limits distribuPhysical examination on admission revealed a thin tion of the drug to the lungs. Its negligible systemic man in moderate distress with oral temperature of absorption obviates the development of toxicities that 38.2”C, blood pressure of 110/70 mm Hg, pulse of 96/ sometimescomplicate systemically administered prominute and respiratory rate of 16 to 18/minute. Physiphylactic regimens. This lack of systemic distribution cal findings of note included scleral icterus, tender may, however, have significant drawbacks. We report hepatomegaly (liver edge palpable 4 cm below right a case of fatal, disseminated pneumocystosis in a pacostal margin), easily demonstrable ascites,and hematient with AIDS, without clinical evidence of pneumo- tochezia. Laboratory data included the following: henia, who had received long-term therapy with prophymoglobin, 8.8 g/dL; white blood cell count, 1,7OO/pL lactic aerosolized pentamidine. with 51% neutrophils, 24% band forms, 15% lymphocytes, 10% monocytes, and 0% eosinophils; platelet CASE REPORT count, 141,OOO/pL; fibrinogen, less than 60 mg/dL; A 37-year-old man with AIDS presented complainprothrombin time, 22.7 seconds (control: 11.4 secing of a one-month history of intermittent fevers, onds); partial thromboplastin time, 56.7 seconds(conchills, and night sweats. He also described a one-week trol: 30.6 seconds); total bilirubin, 3.3 mg/dL; alkaline history of abdominal distention, crampy abdominal phosphatase, 1,080 U/L; lactate dehydrogenase, 979 pain, and melena. He denied dyspnea at rest or with U/L; aspartate aminotransferase, 1,300 U/L; and alaexertion, cough, sputum production, or chest discom- nine aminotransferase, 309 U/L. Hepatitis B serolofort. gies revealed the following: hepatitis B surface antiHis past medical history was significant for recovery gen, negative; anti-hepatitis B surface antibody from two previous episodes of histologically proven positive; and anti-hepatitis B core antibody (IgM) PCP diagnosed 24 and 18 months, respectively, prior negative. The chest radiograph demonstrated clear to admission. The initial episode of PCP was success- lung fields and a normal cardiac silhouette. fully treated with a 21-day course of sequential intraDiagnostic paracentesis revealed transudative, venous then oral trimethoprim-sulfamethoxazole grossly hemorrhagic fluid with hematocrit of 10%. All (2O:lOOmg/kg/day). For his recurrent episodeof PCP, smearsand cultures of blood, urine, stool, and peritohe received eight days of intravenous pentamidine (4 neal fluid for bacteria, acid-fast organisms, fungi, and mg/kg/day) followed by four days of oral therapy with cytomegalovirus failed to demonstrate pathogens on combined trimethoprim (20 mg/kg/day) and dapsone immediate review or after appropriate incubation pe(100 mg/day). The development of significant azote- riods. Computerized tomography of the abdomen remia (serum creatinine 3.5 mg/dL) and subsequently vealed multiple, hypodense lesions in the liver and neutropenia (absolute neutrophil count less than spleen (Figure 1). Despite daily administration of vil,OOO/mL) abbreviated this course of therapy. Since tamin K, infusion of 16 units of cryoprecipitate, and 60 his pneumonia had clinically resolved, no further therunits of fresh-frozen plasma, the severe coagulopathy apy was given. persisted, preventing invasive procedures including At the time of admission, he had been receiving liver biopsy. Hepatic encephalopathy ultimately entherapy with zidovudine 1,200 mglday (200 mg every sued and the patient died on the seventh hospital day. four hours) for 16 months, intermittent acyclovir 1,000 At autopsy, limited to the abdominal contents, 5.5 liters of hemorrhagic, ascitic fluid and a pelvic hematoma were present. The liver was grossly enlarged From the Departments of Medicine and Pathology, School of Medicine, University of California at Los Angeles, Los Angeles, California. Requests for (2,400 g) and diffusely studded with pinpoint, firm, reprints should be addressed to W. David Hardy, M.D.. UCLA AIDS Clinical gritty, yellow lesions. The biliary system was patent Research Center, 60-042 CHS. 10833 Le Conte Avenue, Los Angeles, California 90024. Manuscript submitted February 3. 1989, and accepted in throughout. The spleen was enlarged (600 g) and conrevised form May 18, 1989. tained multiple, round, red-white lesions, 1 to 3 cm in Current addresses: Dr. Northfelt: 611. Cancer Research Institute. UC San Francisco Medical Center, Moffitt 1282. San Francisco, California 94143. diameter, with umbilicated, necrotic centers. Similar Dr. Drake: Department of Pathology, lP-166 CHS. 10833 Le Conte Avenue, lesionswere alsofound in both kidneys. On microscopLos Angeles, California 90024. ic examination, all lesions were similar, consisting of pneumonia (PCP) is the P most common presenting manifestation of the acquired immunodeficiency syndrome (AIDS). Alneumocystosis
carinii
September 1989 The American Journal of Medicine
Volume 87
329
DISSEMINATED
PNEUMOCYSTOSIS
WITH AEROSOLIZED
PENTAMIDINE
/ HARDY ET AL
without human immunodeficiency syndrome (HIV) infection, in patients with AIDS, and in at least one patient with no known immunodeficiency. In patients without AIDS, reported sites of extrapulmonary involvement have included lymph nodes, spleen, bone marrow, thymus, liver, heart, pericardium, gastrointestinal tract, pancreas, homograft kidney, hard palate, and adrenal and thyroid glands. Clinically evident lung diseasewasnoted in all but one of these cases,and antemortem diagnosis was made in only three [l]. To date, 13 casesof extrapulmonary and/or disseminated pneumocystosis in patients with previously diagnosedAIDS or HIV infection have been reported. In four of these reports, extrapulmonary pneumocystosis wasdiagnosedconcomitantly with PCP. Retinal infection was documented by electron microscopy in a patient who died of associated pneumonia [2]. Widely disseminated infection involving the lungs, lymph Figure 1. Radiographic section from computerized tomogram of abnodes, heart, liver, spleen, pancreas, kidneys, adrenal domen demonstrating multiple, hypodense lesions in left and right glands, gastrointestinal organs, thyroid, or retina was lobes of liver and spleen. noted at autopsy in two patients [3,4]. Isolated antemortem bone marrow infection was noted in one pamasses of acellular, foamy material with focal calcifitient [5]. cation and hemorrhage (Figure 2A). Typical P. carinii Extrapulmonary pneumocystosis has been reported cysts were demonstrable within these lesions by Go- in three AIDS patients without previous or concurrent mori methenamine-silver stain (Figure 2B). Tissue PCP. P. carinii organismshave been found in bilateral Gram and acid-fast stains were negative. Microscopic polyps of the external auditory canals [6], spleen [7], involvement of a para-aortic lymph node was also ob- and thyroid [8]. Extrapulmonary pneumocystosis has served, whereas no evidence of P. carinii cysts was been reported as the initial manifestation of AIDS in found in sections of stomach, adrenal, prostate, pan- four patients, three of whom were previously asympcreas, or aorta. No other inflammatory, infectious, or tomatic and one with AIDS-related complex (ARC). neoplastic processeswere present in these or other Presentations have included temporal bone-based organs (Figure 2). polyps of the external auditory canal [9] in two patients, otitis media with associated mastoiditis in one COMMENTS patient [lo], and an obstructing small intestinal mass Extrapulmonary pneumocystosis has been de- presenting asan acute abdomen in one patient [l]. One scribed in a number of immunodeficient patients patient who recovered from two previous episodesof
Figure 2. A, histologic section of liver at the margin of a typical lesion, showing a mass of foamy exudate adjacent to intact hepatocytes (hematoxylin and eosin stain; original magnification X 346, reduced by 10%). B, four darkly stained cysts typical of P. cariniiin foamy exudate of liver lesion (Gomori methenamine-silver stain; original magnification x 865, reduced by 10%). 330
September
1989
The American
Journal
of Medicine
Volume
87
PCP presented with profound weakness and pancytopenia and was found to have bone marrow invasion by P. carinii, Another patient with a previous history of PCP presented with pulmonary infiltrates, pneumothorax, and hepatitis and was found to have P. carinii cysts on liver biopsy. Concurrent PCP was not definitively diagnosed in either patient, although both had significant pulmonary abnormalities [11,12]. Twelve of these I3 patients were reported to have received treatment for their pneumocystosis with trimethoprim-sulfamethoxazole, parenteral pentamidine, or combined dapsone and trimethoprim. The four patients with PCP died during or soon after the cessation of therapy [2-51. The seven patients without PCP responded to treatment with notable clinical improvement of their involved tissue or organ [1,610,121. Only one of these patients was reported as having received previous aerosol prophylaxis of PCP
would, however, be expected to have little, if any, effect on P. carinii organisms outside the lungs. Thus, the advantage of targeting delivery of pentamidine to the lungs may also carry with it the significant disadvantage of not providing systemic prophylaxis of pneumocystosis. The growing number of case reports describing extrapulmonary pneumocystosis have taught us that infection with this organism is not limited solely to the lung but can occur in any tissue or organ throughout the body, especially in immunocompromised hosts. This is the second reported case of extrapulmonary pneumocystosis occurring in a patient receiving prophylactic aerosolized pentamidine. As this means of PCP prophylaxis becomes more widely utilized and heightened awareness of extrapulmonary pneumocystosis grows, an increasing number of similar cases may be seen.
WI*
Secondary prophylaxis of PCP has become widely utilized in patients with AIDS due to the well-documented high recurrence rate of this pneumonia in the absence of prophylactic measures. Several systemically administered agents including daily trimethoprimsulfamethoxazole, weekly pyrimethamine-sulfadoxine, twice or four times daily dapsone, and biweekly or monthly parenteral and aerosolized pentamidine have all been shown to be effective in decreasing the incidence of recurrent PCP. Although systemic prophylactic agents are generally well-tolerated, adverse reactions to these agents have included mild to severe cutaneous eruptions (including Stevens-Johnson syndrome), nausea, cytopenias, increased hepatic transaminase levels, azotemia, and phlebitis. Persistent cough, reversible bronchospasm, and dysgeusia have been associated with aerosol administration of pentamidine [13]. Prophylactic aerosolized pentamidine is becoming increasingly utilized because of reports of its efficacy in preventing PCP and its minimal systemic toxicity. Measurements of the concentration of pentamidine in broncho-alveolar lavage fluid following aerosol versus intravenous administration have revealed 10 to 75 times greater drug levels after aerosol delivery compared with intravenous infusion. Concomitant plasma concentrations of pentamidine after aerosol delivery have been negligible [Id]. The selective pulmonary distribution and minimal systemic absorption of aerosolized pentamidine have been exploited as a novel means of PCP prophylaxis. Aerosolized pentamidine
REFERENCES 1. Carter TR. Cooper PH, Petri WA. Kim CK. Walzer PD. Guerrant RL: fneumocp tosis carinii infection of the small intestine in a patient with acquired immune deficiency syndrome. Am J Clin Pathol 1988; 89: 679-683. 2. Kwok S, O’Donnell JJ. Wood IS: Retinal cotton-wool spots in a patient with Pneumocystosis carinii infection, N Engl J Med 1982; 307: 184-185. 3. Grimes MM, LaPook JD, Bar MH. Wasserman HS. Dwork A: Disseminated Pneumocystosis wriflii infection in a patient with acquired immunodeficiency syndrome. Hum Pathol 1987; 18: 307-308. 4. Macher AM. Bardenstein OS. Zimmerman LE. et at Pneumocystosis wrinii choroiditis in a male homosexual with AIDS and disseminated pulmonary and extrapulmonary P. carinii infection (letter). N Engi J Med 1987; 316: 1092. 5. Heyman MR. Rasmussen P: Pneumocystosis carinii involvement of the bone marrow in acquired immunodeficiency syndrome. Am J Clin Pathol 1987; 87: 780783. 6. Coulman CU. Greene I, Archibald RWR: Cutaneous pneumocystosis. Ann Intern Med 1987; 106: 396-398. 7. Pilon VA, Echols RM. Celo JS. Elmendort SL: Disseminated Pneumocystosis carinii infection in AIDS. N Engl J Med 1987: 316: 141D-1411. 8. Gallant JE, Enriquez RE. Cohen KL. Hammers LW: Pneumocystosis wriniithyroiditis. Am J Med 1988; 84: 303-306. 9. Breda SD. Hammerschlag PE. Gigliotti F, Schinella R: Pneumocystosis wriniiin the temporal bone as a primary manifestation of the acquired immunodeficiency syndrome. Ann Otol Rhino1 Laryngol 1988: 97: 427-431. 10. Gherman CR, Ward RR. Bassis ML: Pneumocvstosis wrinii otitis media and mastoiditis as the initial manifestation of the acquired immunodeficrency syndrome. Am J Med 1988; 85: 25G-252. 11. Raviglione MC. Garner GR. Mullen MP: Pneumocystosis cariniiin bone marrow (letter). Ann Intern Med 1988: 109: 253, 12. Poblete RB. Rodriquez K. Foust RT. et al: Pneumocystis carinii hepatitis in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1989; 110: 737738. 13. Hardy WD: Prophylaxis of AIDS-related opportunistic infections. In: Volberding PA, Jacobson MA, eds. 1989 AIDS clinical review. New York: Marcel Dekker. 1989; 125-150. 14. Montgomery AB. Debs RJ, Lute JM. etalrselective delivery of pentamidine to the lung by aerosol. Am Rev Respir Dis 1988; 137: 477-478.
September
1989
The American
Journal
of Medicine
Volume
87
331