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Pneumocystis carinii Pneumonia in Pregnancy* FREE TO VIEW

Hussain Ahmad, MD; Nirav J. Mehta, MD; Vivek M. Manikal, MD; Teresita J. Lamoste, MD; Edward K. Chapnick, MD; Larry I. Lutwick, MD; Douglas V. Sepkowitz, MD
Author and Funding Information

*From the Division of Infectious Diseases (Drs. Ahmad, Manikal, Lamoste, Chapnick, and Lutwick), Department of Medicine, Maimonides Medical Center, Brooklyn, NY; and the Division of Infectious Diseases (Drs. Mehta and Sepkowitz), Department of Medicine, Long Island College Hospital, Brooklyn, NY.

Correspondence to: Douglas Sepkowitz, MD, Division of Infectious Diseases, Long Island College Hospital, 339 Hicks St, Brooklyn, NY 11201



Chest. 2001;120(2):666-671. doi:10.1378/chest.120.2.666
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Published online

Objective: To report five new cases of Pneumocystis carinii pneumonia (PCP) and to review and analyze the existing reports on the subject.

Method: Five new cases of PCP during pregnancy are described. The cases, case series, and related articles on the subject in the English language were identified through a comprehensive MEDLINE search and reviewed.

Results: More than 80% of women with AIDS are of reproductive age, and PCP is the most common cause of AIDS-related death in pregnant women in the United States. Among 22 reviewed cases, the mortality rate was 50% (11 of 22 patients), which is higher than that usually reported for HIV-infected individuals with PCP. Respiratory failure developed in 13 patients (59%), and mechanical ventilation was therefore required, and the survival rate in patients requiring mechanical ventilation was 31%. Maternal and fetal outcomes were better in cases of PCP during the third trimester of the pregnancy. A variety of treatment regimens were used, including sulfamethoxazole-trimethoprim (SXT) alone or in combination with pentamidine, steroids, and eflornithine. The survival rate in patients treated with SXT alone was 71% (5 of 7 patients) and for those treated with SXT and steroids was 60% (3 of 5 patients), with an overall survival rate in both groups of 66.6% (8 of 12 patients).

Conclusion: PCP has a more aggressive course during pregnancy, with increased morbidity and mortality. Maternal and fetal outcomes remain dismal. Treatment with SXT, compared to other therapies, may result in an improved outcome. Withholding appropriate PCP prophylaxis may adversely affect maternal and fetal outcomes.

The number of women with HIV disease in the United States has been steadily increasing during the past decade. The greatest increase in AIDS incidence was observed in heterosexually infected women born between 1970 and 1974.1 As of 1995, > 80% of women with AIDS were of reproductive age1; among pregnant women, Pneumocystis carinii pneumonia (PCP) was the most common cause of AIDS-related death in the United States.2 Although there have been sporadic reports of PCP in pregnancy, there has been no comprehensive review in order to provide guidelines regarding its management in pregnancy. This article presents five cases of PCP in pregnant women as well as a review of the literature.

Case 1

A pregnant 34-year-old African-American woman presented at 27 weeks of gestation with a 3-week history of shortness of breath, fever, and cough. On admission to the hospital, she had a temperature of 37.2°C, a respiratory rate of 30 breaths/min, and oral thrush. CBC count showed no leukocytosis and a predominance of polymorphonuclear cells. The lactate dehydrogenase (LDH) level was 284 IU/L, and the CD4 count was 27 cells/μL. An arterial blood gas analysis done with the patient breathing room air revealed a Pao2 of 60 mm Hg with an alveolar-arterial gradient of 53. The chest radiograph showed bilateral interstitial infiltrates, and an abdominal sonogram showed a gravid uterus at 24 weeks and a viable fetus. She was empirically treated with sulfamethoxazole-trimethoprim (SXT), erythromycin, and oral prednisone. PCP was diagnosed using BAL. SXT was continued with a tapering dose of oral prednisone for 21 days. She was discharged and was readmitted to the hospital at 33 weeks of gestation with labor pains of a few hours in duration. She had noticed no fetal movements over the previous 2 weeks, and an abdominal sonogram confirmed fetal death. She vaginally delivered a macerated fetus (male, weighing 605 g), complicated by retained placenta and endometritis, but she recovered and was discharged home.

Case 2

A 31-year-old white woman was admitted to the hospital with respiratory distress at 29 weeks of gestation with a 10-day history of a minimally productive cough and shortness of breath. Laboratory studies revealed LDH level of 1,294 IU/L and a CD4 count of 24 cells/μL. The chest radiograph showed diffuse bilateral interstitial infiltrates. She was presumptively treated for PCP with IV SXT and methylprednisone. Respiratory failure developed, and the patient required mechanical ventilation. The diagnosis was confirmed using open-lung biopsy on the fifth hospital day. Five days later, the treatment was changed to IV pentamidine due to lack of adequate response. On day 22, she delivered a live fetus vaginally. Both mother and neonate died 3 days later.

Case 3

A 31-year-old African-American woman was admitted to the hospital at 26 weeks of gestation with cough, severe shortness of breath, fever, and a 20-lb weight loss. A chest radiograph revealed diffuse bilateral infiltrates. The Pao2 was 48 mm Hg on a nonrebreathing mask. She was placed on mechanical ventilation and empirically treated with cefuroxime and erythromycin. An abdominal sonogram showed a gravid uterus at 25 weeks of gestation, and fetal heart sounds were detected. Further investi-gation revealed a CD4 count of 33 cells/μL, and the therapy was changed to SXT and oral prednisone. The HIV-antibody test result was positive, and PCP was confirmed using BAL. On day 10, because of poor response to SXT, the therapy was again changed to IV pentamidine. She responded well and was successfully extubated on day 17. Her hospital course was complicated by Escherichia coli sepsis, but she recovered and was discharged home. She was readmitted to the hospital at 37 weeks with sonographic findings of oligohydramnios. She had a normal vaginal delivery of a live female infant.

Case 4

A 30-year-old white woman at 17 weeks of gestation was admitted to the hospital with dry cough, progressive shortness of breath, and occasional fever with night sweats of a 2-week duration. The chest radiograph revealed bilateral interstitial infiltrates, and Pao2 was 56 mm Hg on room air with an alveolar-arterial gradient of 45. She was treated with erythromycin, SXT, and oral prednisone. The CD4 count was 33 cells/μL. On day 3, she was prophylactically intubated for bronchoscopy but she desaturated after intubation, became hypotensive, and the chest radiograph findings worsened. Bronchoscopy was deferred. On day 4, she had a cardiac arrest and died. A limited autopsy was done that confirmed the diagnosis of PCP in the mother; the fetus was not examined.

Case 5

A 23-year-old Hispanic woman at 20 weeks of gestation was admitted to the hospital with a 2-month history of progressive dyspnea, nonproductive cough, fever, and weight loss. She had a temperature of 38.9°C, a respiratory rate of 40 breaths/min, oral thrush, and scattered rhonchi in both lung fields. The LDH level was 562 IU/L, and Pao2 was 92 mm Hg on room air. The chest radiograph revealed bilateral diffuse infiltrates. She was treated with erythromycin but subsequently deteriorated. On day 6 of her hospitalization, a fiberoptic bronchoscopy was performed and her therapy was changed to SXT. The diagnosis of PCP was confirmed using BAL, and she completed a 21-day course of IV SXT with clearing of her chest radiograph. The patient was discharged home, but she was lost to follow-up.

Data Collection and Analysis

The MEDLINE (National Library of Medicine, Bethseda, MD) search of the literature was performed using the following key words: “human immunodeficiency virus,” “HIV,” “acquired immunodeficiency virus,” “AIDS,” “Pneumocystis carinii pneumonia,” and “PCP,” which were cross-referenced with the word“ pregnancy.” All English-language articles were reviewed. Data were manually extracted from all cases, case series, and studies, and emphasis was placed on to arrange and formulate all information and observations reported so far into a format that provides a brief but comprehensive overview of the subject. Seventeen cases of PCP during pregnancy reported previously were identified. All 22 cases (including the 5 cases presented in this article) were analyzed for clinical characteristics, maternal and fetal outcomes, and management.

All cases of PCP during pregnancy in HIV-infected patients are summarized in Tables 1 and 1A , and 2 . In this series of 22 pregnant women with PCP, 11 patients (50%) died of pneumonia. The incidence of respiratory failure among pregnant women with PCP is also quite high. Thirteen of 22 patients (59%) required mechanical ventilation, 4 of 22 patients (18%) did not require mechanical ventilation, and in five case reports (22%) the issue was not addressed. Of those requiring mechanical ventilation, the survival rate was 31%.

The duration of respiratory symptoms ranged from 5 days to 8 weeks. The average gestational age was 25 weeks, with range of 6 weeks to 1 week postpartum. In the 15 cases where the chest radiograph was mentioned, all had diffuse bilateral infiltrates. Fifteen of the 22 patients had CD4 counts performed, and the mean was 93 cells/μL. P carinii was diagnosed using BAL in 12 of 22 patients (54%), by transbronchial biopsy in 4 of 22 patients, by open-lung biopsy in 2 of 22 patients, and at autopsy in 1 patient. In one patient, PCP was a presumptive diagnosis.

The patients in this series were treated with a variety of regimens (Table 2.) Six patients were treated with SXT alone, and six were treated with SXT and steroids; four patients (66%) survived in each group. Four patients were treated with SXT and then switched to pentamidine; three of these women died, but three of four of the babies survived this regimen. One patient was initially treated with pentamidine and subsequently treated with SXT; the mother died and the child survived. Another mother and child died when the antibiotic regimen included the subsequent use of SXT, then pentamidine, and then eflornithine and steroids. In two cases, the antibiotic regimen was not described.

The outcome of the pregnancies was nearly as dismal as the maternal survival rate. Twelve babies survived. There were five stillbirths, and four babies died shortly after birth. In two cases, the outcome of the pregnancy was not noted. The average weight of the surviving babies was 2.01 kg. Ten of the women had vaginal deliveries, 5 women underwent cesarean sections, and 1 woman had her pregnancy terminated. In three cases, the outcome of the pregnancy was not noted.

Although the numbers are small, when analyzed for each trimester, the cases of PCP in the third trimester had better maternal and fetal outcomes. In the first trimester, the maternal mortality rate was 50% (one of two patients); the mother who survived delivered a live full-term infant. In the second trimester, of six pregnant women with HIV-related PCP, only two patients survived (33%). Fetal survival was 40% (2 of 5 fetuses), while one woman had termination of pregnancy at 18 weeks. In the third trimester, the maternal survival was 57% (8 of 14 patients) and the fetal survival was 60% (9 of 15 fetuses).

Despite the success of PCP prophylaxis resulting in a declining incidence of PCP, PCP was the most common opportunistic infection for persons with HIV infection in 1997. It also occurs during the course of AIDS for 53% of persons who die with AIDS.15PCP is also the most common cause of respiratory failure and ICU admissions.16 In this review of pregnant women with HIV-related PCP, the mortality rate (50%) is much higher than that usually seen in HIV-infected individuals with PCP; different series have reported mortality rates ranging from 1 to 16%.17,18 There is a suggestion from the data presented here that PCP in the first and second trimesters confers a worse maternal and fetal prognosis. The clinical presentation was not altered by pregnancy and was similar to other reports of HIV-infected persons with PCP.19

There were several different treatment regimens used in this series, and although the numbers are small, there is a suggestion that SXT treatment with or without steroids was associated with an increased survival rate. Since the babies were followed up for only a short period of time, the long-term effects of treatment on fetal development cannot be assessed. SXT remains the treatment of choice for PCP, despite the fact that it readily crosses the placenta. Experience with its use in human pregnancy has been limited because of the theoretical concern of unconjugated bilirubinemia and kernicterus in the newborn.20 Pentamidine treatment has been shown to inhibit protein and nucleic acid synthesis in vitro and, thus, is a potential teratogen.21 Because dapsone significantly affects the glucose-6-phosphate dehydrogenase system, its use in pregnancy is of concern. Thus far, there is no reported clinical experience with its use in HIV-infected pregnant women.22 There is no information regarding the use of atovaquone in pregnancy. There have been no studies assessing the adjunctive use of corticosteroids in the treatment of pregnancy-associated PCP, but it is reasonable to consider it as an option in more severe cases.

There are several possible reasons for the poor survival rates reported in this review. It is known that cellular immunity wanes during pregnancy.23 Perhaps PCP, like listeriosis and some other infections, is more severe in pregnancy when compared to general population. The high mortality rate noted in this series may be skewed by the fact that this is a retrospective review, and severe cases are more apt to be reported than mild ones.

Additionally, all of the women in this series were unaware of their HIV infection until the diagnosis of PCP was made. Thus, none had received PCP prophylaxis, which is known to be very effective, with rates of prevention in the range of 90 to 95%.24 All of these cases of PCP predated the onset of protease inhibitor therapy, which has been shown to decrease the incidence of opportunistic infections.24 However, since all of these patients were unaware of their HIV status, the availability of such therapy would not have affected their clinical course. Wider application of early prenatal testing for HIV infection would allow for earlier use of antiretroviral therapy and PCP prophylaxis, and would significantly lessen the occurrence of PCP in pregnancy.

Abbreviations: LDH= lactate dehydrogenose; PCP = Pneumocystis carinii pneumonia; SXT = sulfamethoxazole-trimethoprim

Table Graphic Jump Location
Table 1. Disease Characteristics of the Reported Cases of PCP During Pregnancy*
Table Graphic Jump Location
Table 1A. Continued
* 

NI = not investigated; NA = not available.

Table Graphic Jump Location
Table 2. Outcomes of Treatment Strategies
Wortley, PM, Fleming, PL (1997) AIDS in women in the United States: recent trends.JAMA278,911-916. [PubMed] [CrossRef]
 
Koonin, LM, Ellerbrock, TV, Atrash, HK, et al Pregnancy-associated deaths due to AIDS in the United States.JAMA1989;261,1306-1309. [PubMed]
 
Rogers, MF, Ewing, EP, Jr, Warfield, D, et al Virologic studies of HTLV-III/LAV in pregnancy: case report of a woman with AIDS.Obstet Gynecol1986;68(3 Suppl),2S-6S
 
Kell, PD, Barton, SE, Smith, DE, et al A maternal death caused by AIDS: case report.Br J Obstet Gynecol1991;98,725-727
 
Johnstone, FD, Willox, L, Brettle, RP Survival time after AIDS in pregnancy.Br J Obstet Gynecol1992;99,633-636
 
Mortier, E, Pouchot, J, Bossi, P, et al V. Maternal-fetal transmission ofPneumocystis cariniiin human immunodeficiency virus infection [letter].N Engl J Med1995;332,825. [PubMed]
 
Jensen, LP, O’Sullivan, MJ, Gomez-del-Rio, M, et al Acquired immunodeficiency (AIDS) in pregnancy.Am J Obstet Gynecol1984;148,1145-1146. [PubMed]
 
Antoine, C, Morris, M, Douglas, G, et al Maternal and fetal mortality in acquired immunodeficiency syndrome.NY State J Med1986;86,443-445
 
Minkoff, HL, Willoughby, A, Mendez, H, et al Serious infections during pregnancy among women with advanced human immunodeficiency virus infection.Am J Obstet Gynecol1990;162,30-34. [PubMed]
 
Albino, JA, Shapiro, JM Respiratory failure in pregnancy due toPneumocystis carinii: report of a successful outcome.Obstet Gynecol1994;83,823-824. [PubMed]
 
Minkoff, H, deRegt, RH, Landesman, S, et al Pneumocystis cariniipneumonia associated with acquired immunodeficiency syndrome in pregnancy: a report of three maternal deaths.Obstet Gynecol1986;67,284-287. [PubMed]
 
Gates, HS, Barker, CD Pneumocystis cariniipneumonia in pregnancy: a case report.J Reprod Med1993;38,483-486. [PubMed]
 
Hicks, ML, Nolan, GH, Maxwell, SL, et al Acquired immunodeficiency syndrome andPneumocystis cariniiinfection in a pregnancy woman.Obstet Gynecol1990;76,480-481. [PubMed]
 
Schwebke, K, Balfour, HH, Jr, Olson, D, et al Congenital cytomegalovirus infection as a result of nonprimary cytomegalovirus disease in a mother with acquired immunodeficiency syndrome.J Pediatr1995;126,293-295. [PubMed]
 
Jones, JL, Hanson, DL, Dworkin, MS, et al Surveillance for AIDS-defining opportunistic infections, 1992–1997.MMWR Morb Mortal Wkly Rep1999;48(ss2),1-22
 
Curtis, JR, Yarnold, PR, Schwartz, DN, et al Improvements in outcomes of acute respiratory failure for patients with human immunodeficiency virus- relatedPneumocystis cariniipneumonia.Am J Respir Crit Care Med2000;162,393-398. [PubMed]
 
Bozzette, SA, Finkelstein, DM, Spector, SA, et al A randomized trial of three antipneumocystis agents in patients with advance human immunodeficiency virus infection.N Engl J Med1995;332,693-699. [PubMed]
 
Bozzette, SA, Sattler, FR, Chiu, J, et al A controlled trial of adjunctive treatment with corticosteroids forPneumocystis cariniipneumonia in the acquired immunodeficiency syndrome.N Engl J Med1990;323,1451-1457. [PubMed]
 
Kovacs, JA, Hiemenz, JW, Macher, AM, et al Pneumocystis cariniipneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies.Ann Intern Med1984;100,663-671. [PubMed]
 
Hardman, JG Limbird, LE eds.Goodman and Gilman’s pharmacologic basis of therapeutics 9th ed.1996,1046 McGraw-Hill. New York, NY:
 
MacCallum LR, Johnston FD, Brettle RP, et al. Population-based, controlled study of the effect of HIV infection on infectious complications during pregnancy [abstract]. Int Conf AIDS 1991; 7:355; abstract No. W.C. 3238.
 
Sperling, RS, Stratton, P Treatment options for human immunodeficiency virus-infected pregnant women: Obstetric-Gynecologic Working Group of the AIDS Clinical Trial Group of the National Institute of Allergy and Infectious Diseases.Obstet Gynecol1992;79,443-448. [PubMed]
 
Weinberg, ED Pregnancy-associated depression of cell-mediated immunity.Rev Infect Dis1984;6,814-831. [PubMed]
 
Palella, FJ, Jr, Delaney, KM, Moorman, AC, et al Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection.N Engl J Med1998;338,853-860. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Disease Characteristics of the Reported Cases of PCP During Pregnancy*
Table Graphic Jump Location
Table 1A. Continued
* 

NI = not investigated; NA = not available.

Table Graphic Jump Location
Table 2. Outcomes of Treatment Strategies

References

Wortley, PM, Fleming, PL (1997) AIDS in women in the United States: recent trends.JAMA278,911-916. [PubMed] [CrossRef]
 
Koonin, LM, Ellerbrock, TV, Atrash, HK, et al Pregnancy-associated deaths due to AIDS in the United States.JAMA1989;261,1306-1309. [PubMed]
 
Rogers, MF, Ewing, EP, Jr, Warfield, D, et al Virologic studies of HTLV-III/LAV in pregnancy: case report of a woman with AIDS.Obstet Gynecol1986;68(3 Suppl),2S-6S
 
Kell, PD, Barton, SE, Smith, DE, et al A maternal death caused by AIDS: case report.Br J Obstet Gynecol1991;98,725-727
 
Johnstone, FD, Willox, L, Brettle, RP Survival time after AIDS in pregnancy.Br J Obstet Gynecol1992;99,633-636
 
Mortier, E, Pouchot, J, Bossi, P, et al V. Maternal-fetal transmission ofPneumocystis cariniiin human immunodeficiency virus infection [letter].N Engl J Med1995;332,825. [PubMed]
 
Jensen, LP, O’Sullivan, MJ, Gomez-del-Rio, M, et al Acquired immunodeficiency (AIDS) in pregnancy.Am J Obstet Gynecol1984;148,1145-1146. [PubMed]
 
Antoine, C, Morris, M, Douglas, G, et al Maternal and fetal mortality in acquired immunodeficiency syndrome.NY State J Med1986;86,443-445
 
Minkoff, HL, Willoughby, A, Mendez, H, et al Serious infections during pregnancy among women with advanced human immunodeficiency virus infection.Am J Obstet Gynecol1990;162,30-34. [PubMed]
 
Albino, JA, Shapiro, JM Respiratory failure in pregnancy due toPneumocystis carinii: report of a successful outcome.Obstet Gynecol1994;83,823-824. [PubMed]
 
Minkoff, H, deRegt, RH, Landesman, S, et al Pneumocystis cariniipneumonia associated with acquired immunodeficiency syndrome in pregnancy: a report of three maternal deaths.Obstet Gynecol1986;67,284-287. [PubMed]
 
Gates, HS, Barker, CD Pneumocystis cariniipneumonia in pregnancy: a case report.J Reprod Med1993;38,483-486. [PubMed]
 
Hicks, ML, Nolan, GH, Maxwell, SL, et al Acquired immunodeficiency syndrome andPneumocystis cariniiinfection in a pregnancy woman.Obstet Gynecol1990;76,480-481. [PubMed]
 
Schwebke, K, Balfour, HH, Jr, Olson, D, et al Congenital cytomegalovirus infection as a result of nonprimary cytomegalovirus disease in a mother with acquired immunodeficiency syndrome.J Pediatr1995;126,293-295. [PubMed]
 
Jones, JL, Hanson, DL, Dworkin, MS, et al Surveillance for AIDS-defining opportunistic infections, 1992–1997.MMWR Morb Mortal Wkly Rep1999;48(ss2),1-22
 
Curtis, JR, Yarnold, PR, Schwartz, DN, et al Improvements in outcomes of acute respiratory failure for patients with human immunodeficiency virus- relatedPneumocystis cariniipneumonia.Am J Respir Crit Care Med2000;162,393-398. [PubMed]
 
Bozzette, SA, Finkelstein, DM, Spector, SA, et al A randomized trial of three antipneumocystis agents in patients with advance human immunodeficiency virus infection.N Engl J Med1995;332,693-699. [PubMed]
 
Bozzette, SA, Sattler, FR, Chiu, J, et al A controlled trial of adjunctive treatment with corticosteroids forPneumocystis cariniipneumonia in the acquired immunodeficiency syndrome.N Engl J Med1990;323,1451-1457. [PubMed]
 
Kovacs, JA, Hiemenz, JW, Macher, AM, et al Pneumocystis cariniipneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies.Ann Intern Med1984;100,663-671. [PubMed]
 
Hardman, JG Limbird, LE eds.Goodman and Gilman’s pharmacologic basis of therapeutics 9th ed.1996,1046 McGraw-Hill. New York, NY:
 
MacCallum LR, Johnston FD, Brettle RP, et al. Population-based, controlled study of the effect of HIV infection on infectious complications during pregnancy [abstract]. Int Conf AIDS 1991; 7:355; abstract No. W.C. 3238.
 
Sperling, RS, Stratton, P Treatment options for human immunodeficiency virus-infected pregnant women: Obstetric-Gynecologic Working Group of the AIDS Clinical Trial Group of the National Institute of Allergy and Infectious Diseases.Obstet Gynecol1992;79,443-448. [PubMed]
 
Weinberg, ED Pregnancy-associated depression of cell-mediated immunity.Rev Infect Dis1984;6,814-831. [PubMed]
 
Palella, FJ, Jr, Delaney, KM, Moorman, AC, et al Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection.N Engl J Med1998;338,853-860. [PubMed]
 
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