Brief Scientific Reports
Bacterial Infections in the Acquired Immune
Deficiency Syndrome
Clinicopathologic Correlations in a Series of Autopsy Cases
LARRY NICHOLS, M.D., KAROLY BALOGH, M.D., AND MARK SILVERMAN, M.D.
In a group of 46 adult patients with acquired immunodeficiency
Departments of Pathology, New England Deaconess
Hospital, Lahey Clinic, and Harvard Medical School,
syndrome (AIDS) who came to autopsy in 1983-1987, the auBoston, Massachusetts
thors found that 38 (83%) had bacterial (nonmycobacterial) infections some time during the course of their illness, compared
with 34 (74%) who had parasitic infections, 31 (67%) who had
viral infections, 28 (61%) who had fungal infections, and 12 (26%)
who had mycobacterial infections. Twenty-five of these patients
reports of findings at autopsy in patients with
(54%) had Staphylococcus aureus infections, compared with 7 AIDS.3'4-6-7-"-13
(15%) who had Pseudomonas aeruginosa infections and 6 (13%)
Throughout the first five years of our AIDS autopsy
who had enterococcal infections. Overall, undiagnosed infections
series in the Boston area, in contrast to the results in earlier
or malignancies were found in 48%, 22 of the 46 autopsies, inAIDS autopsy reports, we have frequently identified baccluding 12 cases of undiagnosed bacterial infections, 8 of these
due to S. aureus. These results suggest that bacterial infections
terial (nonmycobacterial) infections postmortem and
in general, and S. aureus infections in particular, are important
found them to be major factors contributing to the pacauses of morbidity and mortality in patients with AIDS. (Key
tients' deaths. Autopsies of patients with AIDS are inveswords: Acquired immunodeficiency syndrome; Staphylococcus
tigations uniquely capable of determining the full and final
aureus; Autopsy; Opportunistic infections) Am J Clin Pathol
extent of opportunistic infections, neoplasms, and other
1989;92:787-790
conditions. 13 Hence, we are reporting the following analysis of our AIDS autopsy cases for the evidence it provides
UNTIL THE RECENT ADDITION of recurrent Salof the importance of bacterial infections in AIDS.
monella septicemia to the list of indicator diseases for the
diagnosis of the acquired immunodeficiency syndrome
(AIDS) in adults, bacterial (nonmycobacterial) infections
Methods
were not counted as opportunistic infections indicative
The clinical charts, autopsy reports, and histologic secof immunodeficiency secondary to infection with the hutions of all cases from the New England Deaconess Hosman immunodeficiency virus (HIV) in adults.2 As a result,
pital and the Lahey Clinic that fulfilled CDC criteria for
the incidence of bacterial infections at presentation with
AIDS2 were reviewed. Complete autopsies with extensive
AIDS has been underrepresented in reports to health auhistologic sampling and postmortem cultures (including
thorities such as the United States Centers for Disease
fungal, mycobacterial, and viral cultures in many cases)
Control (CDC).9 Bacterial infections have also been unwere performed in all except five cases. These five autopderrepresented in what could potentially be much more
sies were limited by exclusion of the brain; in one of these
definitive studies of the complications of AIDS, namely,
five cases, the lower abdominal organs were also excluded.
To secure tissue for viral cultures and immunoperoxidase
Received February 8, 1989; received revised manuscript and accepted
studies, efforts were made to perform these autopsies soon
for publication April 4, 1989.
Presented in part at the Ninth International Congress of Infectious
after death; 32 of the 46 autopsies were performed within
and Parasitic Diseases, Munich, West Germany, July 1986.
nine hours after the patients' deaths and 18 were perAddress reprint requests to Dr. Nichols: Department of Pathology,
formed
within three hours. Infection at the time of death
Room 2520, General Hospital, LAC/USC Medical Center, 1200 North
State Street, Los Angeles, CA 90033.
was diagnosed by postmortem culture results supported
787
788
NICHOLS, BALOGH, AND SILVERMAN
by histologic evidence of infection or by histologic results
supported by clinical evidence (e.g., Pneumocystis carinii
pneumonia). Gomori's methenamine silver (GMS), cresyl
echt violet, Brown and Brenn (modified Gram's stain),
periodic acid-Schiff (PAS), and acid-fast stains were used
routinely to identify infecting organisms in histologic sections. Postmortem cultures yielding bacteria were not
counted as infections without corresponding histologic
findings of infection, including infiltration by polymorphonuclear leukocytes, fibrinopurulent exudation, and
tissue destruction, particularly abscess formation. In addition, postmortem cultures yielding bacteria were not
counted as infections without the identification of corresponding gram-positive or gram-negative organisms in
the Brown and Brenn-stained sections.
Forty-six cases with postmortem examinations performed between January 1983 and January 1988 form
the basis of this study. The patients included 43 men and
3 women, ranging from 20 to 62 years of age. The patients'
risk factors for the development of AIDS included homosexuality or bisexuality in 41 cases, red blood cell
transfusions in 2 cases, and clotting Factor VIII therapy
for hemophilia in 2 cases. Two patients had intravenous
drug abuse as well as homosexuality as risk factors for
AIDS. One patient denied all risk factors for AIDS.
Results
Nonmycobacterial bacterial infections, diagnosed antemortem or postmortem, occurred during the course of
AIDS in 38 (83%) of the 46 cases in our autopsy series.
The full assessment of all the infectious complications of
AIDS provided by the analysis of our autopsy cases shows
such infections to have been more common than parasitic,
viral, fungal, or mycobacterial infections (Table 1). The
assessment of the cause of death provided by the autopsies
in particular shows bacterial infections to have been a
sole or contributing cause of death only slightly less often
than parasitic or viral infections (Table 2). Bacterial infections were the sole cause of death in four cases (9%)
and were one of two immediate causes of death in seven
additional cases (15%). Overall, bacterial infections played
a significant role in the death of 17 of our 46 autopsied
patients who had AIDS (37%).
Bacterial (nonmycobacterial) infections were more
likely than other types of infection to be diagnosed for
Table 1. Types of Infection in 46 AIDS Cases
(diagnosed antemortem or postmortem)
1.
2.
3.
4.
5.
Bacterial infections
Parasitic infections
Viral infections
Fungal infections
Mycobacterial infections
38/46 (83%)
34/46 (74%)
31/46(67%)
28/46(61%)
12/46(26%)
A.J.C.P. • January 1990
Table 2. Sole or Contributing Cause of Death
1.
2.
3.
4.
5.
Parasitic infections
Viral infections
Bacterial infections
Fungal infections
Mycobacterial infections
22/46 (48%)
18/46(39%)
17/46(37%)
7/46(15%)
3/46 (7%)
the first time at autopsy (Table 3). Approximately onefourth of our autopsies of patients with AIDS (12 of 46)
uncovered clinically undiagnosed bacterial infections. Six
additional autopsies uncovered other types of infections
that were diagnosed for the first time at autopsy, for a
total of 18 patients (39%) with clinically undiagnosed opportunistic infections at the time of death. Seven autopsies
(15%) revealed clinically undiagnosed malignant tumors
(Kaposi's sarcoma or lymphoma). Overall, 22 (48%) of
our 46 autopsies of patients with AIDS from 1983-1987
disclosed undiagnosed opportunistic infections, malignancies, or both. To put this incidence of undiagnosed
conditions in proper perspective, however, it should be
noted that two of these patients with undiagnosed conditions died within 24 hours of hospital admission, five
of them had a "do not resuscitate" status focused on comfort measures for 1-8 weeks antemortem, and three of
these patients died at home.
Among the 38 patients (83%) who had bacterial (nonmycobacterial) infections diagnosed antemortem or postmortem, 14 (30%) had two or more bacterial infections.
Twelve patients (26%) had bacteremic infections, including four Staphylococcus aureus bacteremias, three Escherichia coli infections, two catheter-related coagulasenegative staphylococcal infections, and one bacteremic
infection each with P. aeruginosa, Yersinia pseudotuberculosis, and Capnocytophaga. Twenty-four of the patients
(52%) had one or more lower respiratory tract infections,
including 21 due to S. aureus, three due to Streptococcus
pneumoniae, three due to Hemophilus influenzae, and
one each involving various gram-negative bacilli. Seven
patients (15%) had urinary tract infections, including three
due to enterococcus and two due to P. aeruginosa. Thus,
as shown in Table 4, S. aureus was by far the most common bacterial pathogen causing infection among patients
in our AIDS autopsy series.
Staphylococcus aureus infections were diagnosed postmortem in 11 (24%) of our autopsies of patients with
AIDS, and bacterial infections due to other species were
Table 3. Infections First Diagnosed at Autopsy
1.
2.
3.
4.
5.
Bacterial infections
Parasitic infections
Fungal infections
Viral infections
Mycobacterial infections
12/46 (26%)
6/46(13%)
4/46 (9%)
2/46 (4%)
1/46 (2%)
BRIEF SCIENTIFIC REPORTS
Vol. 92 • No. 6
Table 4. Bacterial Pathogens Causing Infection
Diagnosed Antemortem or Postmortem
1.
2.
3.
4.
5.
6.
Staphylococcus aureus
Pseudomonas aeruginosa
Enterococcus
Streptococcus pneumoniae
Hemophilus influenzae
Escherichia coli
25/46(54%)
7/46(15%)
6/46(13%)
3/46 (6%)
3/46 (6%)
3/46 (6%)
identified in only six additional cases (13%), for a total of
17 cases (37%) with bacterial infections at the time of
death. P. aeruginosa was responsible for two of the other
bacterial infections diagnosed postmortem, and no other
species was involved in more than one case. As shown in
Table 5, S. aureus infection was the fourth most common
specific infection identified at autopsy among our patients
with AIDS, behind cytomegalovirus infection, Pneumocystis carinii pneumonia (PCP), and invasive candidiasis.
Bacterial infection at the time of death was diagnosed
on the basis of a pure culture in 10 of the 17 cases with
bacterial infections diagnosed postmortem, including 7
of the 11 cases of S. aureus infection diagnosed postmortem. A mixed bacterial infection was diagnosed postmortem in 4 of the 17 cases, including 2 of the S. aureus
cases. Additional bacterial isolates without corresponding
gram-positive or gram-negative organisms in the Brown
and Brenn-stained tissue sections were categorized as
contaminants in three cases. Abscess formation was evident in five cases, including three of the cases of S. aureus
infection.
All 11 of the S. aureus infections diagnosed postmortem
involved the lungs and, in one case, there were also hematogenous abscesses in the kidneys, liver, spleen, heart,
and brain. In 9 of the 11 cases of staphylococcal pneumonia at autopsy, there was simultaneous PCP, cytomegalovirus pneumonia, pulmonary Kaposi's sarcoma,
or Candida albicans pneumonia. In one of the two remaining cases, the staphylococcal pneumonia was superimposed on lung injury from previous PCP and, in the
other case, it immediately followed a pneumococcal
pneumonia.
Eight of the 11 staphylococcal infections diagnosed
postmortem were diagnosed for the first time at autopsy.
In five of these eight cases, however, diagnostic and therapeutic efforts were eschewed in favor of comfort measures
in the weeks just before the patients' deaths. Another of
these patients died only 24 hours after hospital admission,
and one of them died at home.
Discussion
The rate of finding clinically undiagnosed opportunistic
infections or malignant tumors in our AIDS autopsy series
is similar to the rates reported in previous AIDS autopsy
789
series. A small series of 12 autopsies performed on patients
with AIDS between January 1982 and April 1983 at the
Los Angeles County-University of Southern California
Medical Center found previously undiagnosed opportunistic infections or malignancies in ten cases (83%).4 In
36 autopsies of patients with AIDS from San Francisco,
22 (61%) disclosed clinically undiagnosed opportunistic
infection or tumor.'' Half of the opportunistic infections
experienced by the first 12 patients with AIDS for whom
postmortem examinations were performed at the Lenox
Hill Hospital in New York City were diagnosed for the
first time at autopsy.6 In the New York Hospital-Cornell
Medical Center series, 75 of the 101 autopsies (74%) uncovered clinically undiagnosed opportunistic infections
or tumors. 13 The rate of undiagnosed opportunistic conditions in our AIDS autopsy series was lower, at 48%,
perhaps partly because of our not having cases from 1981
or 1982, the earliest years of the AIDS epidemic. In many
of the AIDS autopsy series that are reported without stating the rate of new diagnoses at autopsy, it is likely to be
much closer to our 48% rate than the higher rates previously reported because such lower rates add little interest
and punishability to an AIDS autopsy report. In any case,
even at 48%, the rate of finding clinically undiagnosed
opportunistic conditions at autopsy is sufficient to warrant
performing postmortem examinations in AIDS cases.
Only a few AIDS autopsy reports provide data on bacterial infections. Thirty of the autopsies on patients with
AIDS in the New York Hospital-Cornell Medical Center
series (30%) uncovered bacterial pneumonias, which had
contributed significantly to the patients' deaths, and these
were clinically undiagnosed in 22 of the 30 cases.13 Bacterial infections are a frequent and recognized complication of intravenous drug abuse, but only 16% of the
patients in that autopsy series had been intravenous drug
abusers. In a series of 50 autopsies on patients with AIDS
from Frankfurt, West Germany, 21 (42%) showed terminal bacterial pneumonia and 5 (10%) showed pyelonephritis.3 Neither of these two reports identified the bacterial species causing the infections seen at autopsy.
Twenty-nine of the 56 patients with AIDS in an autopsy
series from Bellevue-New York University Medical Center (52%) had bacterial infections, which involved the
lungs in nearly all cases and contributed to death in 25
of the 29 patients.7 Only six (11%) of the patients in that
study had been intravenous drug abusers, so such activity
Table 5. Most Common Infections Diagnosed at Autopsy
1.
2.
3.
4.
5.
Cytomegalovirus infection
Pneumocystis carinii pneumonia
Invasive candidiasis
Staphylococcus aureus infection
Mycobacterium avium-intracellulare infection
23/46 (50%)
21/46(46%)
12/46(26%)
11/46(24%)
10/46 (22%)
790
NICHOLS, BALOGH, AND SILVERMAN
cannot be the reason for most of those bacterial infections.
The most common bacterial pathogen in that study,
causing pulmonary infection contributing to death in
seven cases, was S. aureus.7
Staphylococcus aureus is also becoming recognized as
a cause of bacteremia in patients with AIDS. One study
found S. aureus to be second only to Mycobacterium avium-intracellulare as a cause of bacteremia among patients
with AIDS.12 Another study reported 22 cases of S. aureus
bacteremia among 14 patients with AIDS and 4 with
AIDS-related complex, none of whom had neutropenia,
a recent history of intravenous drug abuse, or lymphedema
secondary to Kaposi's sarcoma, suggesting the importance
of S. aureus as a pathogen in this patient population even
without these factors predisposing to staphylococcal infection.5 A study from the era before AIDS found S. aureus
to be the most common pathogen (tied with Pseudomonas) causing concurrent systemic infection among all
the patients with PCP in the United States from 1967 to
1970.10 S. aureus was overwhelmingly the most common
bacterial pathogen among our patients with AIDS who
came to autopsy, causing infection in 54% of them, including 24% with pulmonary or disseminated infection
that contributed significantly to their deaths.
S. aureus already has a reputation for causing pneumonia in patients with lung tumors,12 and it is acquiring
a reputation for causing pneumonia in patients with
AIDS.' In patients with AIDS, S. aureus pneumonia frequently follows or is superimposed on PCP or cytomegalovirus pneumonia. This probably reflects the particular
propensity of S. aureus to superinfect lungs injured by
other infections, especially viral pneumonia. This propensity was recognized in the wave of S. aureus pneumonias after the 1918 influenza epidemic and has been
evident in multiple similar secondary epidemics of 5. aureus pneumonia after subsequent influenza outbreaks.8
Thus, one might expect S. aureus to emerge as a secondary
opportunist in the lungs of patients with AIDS with opportunistic infections or other lung-injuring conditions.
The results ofour study suggest that >S. aureus pneumonia
should be given a place in the differential diagnosis of
pulmonary conditions in patients with AIDS. Perhaps the
most important context for considering the possibility of
A.J.C.P. • January 1990
a superimposed 5". aureus pneumonia is in a patient with
PCP who appears to be having a relapse or failing standard
therapy. Overall, the results ofour study and others suggest
that bacterial infections in general, and S. aureus infections in particular, are important causes of morbidity and
mortality in patients with AIDS.
Acknowledgments. The authors thank Dr. J. Davis Allan of the New
England Deaconess Hospital Department of Medicine for his thoughtful
review and critique ofthe first draft manuscript and Dr. Edward C. KJatt
ofthe Los Angeles County-University of Southern California Department
of Pathology for his insightful review of a later draft.
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