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* 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
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Abstract |
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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.
Key Words: AIDS • Pneumocystis carinii pneumonia • pregnancy • sulfamethoxazole-trimethoprim
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Introduction |
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TOPAbstractIntroductionCase ReportsResultsDiscussionReferences |
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Case Reports |
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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.
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Results |
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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).
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Discussion |
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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.
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Footnotes |
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Received for publication July 11, 2000. Accepted for publication February 6, 2001.
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This article has been cited by other articles:
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  J. McIntyre Mothers infected with HIV: Reducing maternal death and disability during pregnancy Br. Med. Bull., December 1, 2003; 67(1): 127 - 135. [Abstract] [Full Text] [PDF]
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