188 Brief Reports cm 1996; 22 (January)

literature, peak serum concentrations of 9-18 J.Lg/rnL and trough

levels of <2 J.Lg/mL are efficacious and below apparent neurotoxic
concentrations of acyclovir [3]. In several of the previously re-
ported cases of acyclovir neurotoxicity, peak concentrations of
> 18 J.Lg/mL were described [3].
In summary, we have described a patient with neurotoxicity
associated with high serum concentrations of acyclovir. Since se-
rum levels of acyclovir are not usually available on a timely basis,
their utility is limited in the immediate management of a patient
with suspected drug toxicity. It is imperative that patients with
diminished renal function be dosed according to the recommended
guidelines for acyclovir.
Adriane Collins, Dina Krieff, Candace Smith,
and Carol Singer
Division of Infectious Diseases, Department ofMedicine, and
Department ofPharmacy Services, Long Island Jewish Medical Center,
The Long Island Campus for Albert Einstein College of Medicine, New
Hyde Park; and College ofPharmacy and Allied Health Professions, St.
Johns University, Jamaica, New York
Septic Shock Due to Disseminated Tuberculosis
Tuberculosis is not the usual disease that comes to mind when
a patient presents with hemodynamic parameters suggestive of
septic shock. However, with the increased incidence of HIV dis-
ease, tuberculosis needs to be considered in the differential diagno-
sis for patients with sepsis syndrome.
A 32-year-old female with a history of iv drug abuse and prosti-
tution was admitted to the hospital with lower abdominal pain,
diarrhea, and vomiting of 1 week's duration and fever of 3 days'
duration. She had recently received therapy with amoxicillin/ cla-
vulanate for bronchitis. She had a history of discoid lupus erythe-
matosus and endocarditis. The patient reported that a test for HIV
antibodies that was performed 3 months before admission was
negative, but she was unreliable in terms ofrecounting her medical
history.
On physical examination the patient was hypotensive and had
an initial blood pressure of 88/58 mm Hg. Her temperature was
39.8C. Cardiovascular examination revealed a short ejection sys-
tolic murmur at the left sternal border. Findings of a respiratory
examination and a chest roentgenogram were normal. An area of
cellulitis was present on the left forearm; this area had localized
fluctuation that was presumed to be due to iv drug abuse. She
also had lower quadrant abdominal tenderness and cervical motion
tenderness on pelvic examination.
Reprints or correspondence: Dr. Richard Magnussen, Department of Medi-
cine, St. Mary's Hospital, 89 Genesee Street, Rochester, New York 14611.
Clinical Infectious Diseases 1996;22:188-9
1996 by The University of Chicago. All rights reserved.
1058--4838/96/2201-0047$02.00
References
1. Bataille P, Devos P, Noel JL, Dautrevaux C, Lokiec F. Psychiatric side
effects with acyclovir [letter]. Lancet 1985;2:724.
2. Becker BN, Fall P, Hall C, et a1. Rapidly progressive acute renal failure
due to acyclovir: case report and review of the literature. AmJ Kidney
Dis 1993;22:611-5.
3. Feldman S, Rodman J, Gregory B. Excessive serum concentrations of
acyclovir and neurotoxicity. J Infect Dis 1988; 157:385-8.
4. Rubin R. Overdose with acyclovir in a CAPD patient. Peritoneal Dialysis
Bulletin 1987;7:42-3.
5. Swan SK, Bennett WM. Oral acyclovir and neurotoxicity. Ann Intern Med
1989; 111:188.
6. Eck P, Silver SM, Clark EC. Acute renal failure and coma after a high
dose of oral acyclovir. N Engl J Med 1991; 325: 1178.
7. Blum MR, Liao SH, DeMiranda P. Overview ofacyclovir pharmacokinetic
disposition in adults and children. Am J Med 1982;73:186-92.
8. Laskin OL, Longstreth JA, Whelton A, et a1. Effect of renal failure on the
pharmacokinetics of acyclovir. AmJ Med 1982; 73: 197- 201.
9. Tomson CR, Goodship TH, Rodger RS. Psychiatric side-effects of
acyclovir in patients with chronic renal failure [letter]. Lancet
1985;2:385-6.
10. Rashiq S, Briewa L, Mooney M, Giancarlo T, Khatib R, Wilson FM.
Distinguishing acyclovir neurotoxicity from encephalomyelitis. J Intern
Med 1993;234:507-11.
Her WBC count was 3,400/mm
3,
her hemoglobin level was 7.9
g/ dL, and her hematocrit was 22.3%. The patient's platelet count
was 201,OOO/mm
3.
Three sets of blood cultures were sterile. Inci-
sion and drainage ofthe forearm fluctuance revealed a small quan-
tity of purulent material, and culture ofthis material yielded Staph-
ylococcus aureus. Culture of stool specimens did not yield any
enteric pathogens, and culture of cervical specimens yielded nor-
mal flora. Serological tests revealed hepatitis C and hepatitis B
core antibodies.
The admission diagnosis was pelvic inflammatory disease, and
the patient was treated with iv fluids and antibiotics. Intravenous
nafcillin was administered to treat the staphylococcal infection,
and cefoxitin was used to treat the presumed pelvic inflammatory
disease. Over the next 2 days some of her symptoms decreased,
but she continued to have diarrhea and fever. Tests of stool speci-
mens were negative for Clostridium difficile toxin. An analysis of
arterial blood gases performed while the patient was breathing
room air showed compensated metabolic acidosis with a pH of
7.36, a Pcoz of 22 mm Hg, a Paz of 99 mm Hg, an HC03 of 13
mEq/L, and an oxygen saturation of 96%.
On day 4 of hospitalization the patient remained febrile and
developed hypotension in spite of receiving iv fluids; she was then
transferred to the intensive care unit. Ultrasonographic examina-
tion showed enlarged kidneys measuring 15 em in the long axis.
Some free fluid was present in the pelvis, and scant fluid was seen
around the kidneys. An abdominal CT scan confirmed the same
findings, and no localized collections were seen. Skin tests with
purified protein derivative revealed that the patient was anergic
(control tests were performed).
The patient then developed acute oliguric renal failure. A pulmo-
nary artery catheter was placed, and the following parameters were
consistently recorded: central venous pressure, 12 mm Hg; cardiac

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em1996;22 (January) Brief Reports 189
Figure 1. Ziehl-Neelsen stain of a lymph node section from a patient with
septic shock due to disseminated tuberculosis shows numerous acid-fast bacilli
(arrows) (original magnification, X400).
output, 12.5 L/min; cardiac index, 7.21; mean arterial pressure,
80 mm Hg; pulmonary capillary wedge pressure, 11 mm Hg; and
systemic vascular resistance, 435 dynes/t sec- em"). These find-
ings were consistent with the sepsis syndrome. The patient's hy-
poxia worsened, and bilateral infiltrates were noted on a chest
roentgenogram, prompting intubation and mechanical ventilation.
She underwent hemodialysis once but declined further dialysis.
The patient's hypotension persisted in spite of iv dopamine ther-
apy, and she also had a seizure. She developed anasarca, uremia,
and progressive hypoxia and died 10 days after admission. Subse-
quently, blood tests performed on admission revealed that she had
antibodies to HIV and a CD4 lymphocyte count of 31/mrrr' .
At autopsy, necrotizing lymphadenitis involving the peripan-
creatic and paraesophageal lymph nodes was seen. The lymph
nodes and spleen had an abscess-like pattern with only rare epithe-
lioid cells and giant cells. Numerous acid-fast bacilli were seen in
sections of lymph node (figure 1), and stains were negative for
fungi. Typical granulomas with multinucleated giant cells were
seen in the lungs, bone marrow, and liver. The kidneys showed
focal segmental sclerosing glomerulopathy of the collapsing type
with marked tubular atrophy and dilatation consistent with HIV
nephropathy. There was also evidence of hepatic cirrhosis and
mild chronic salpingitis. Multiple small subarachnoid hemorrhages
were noted.
Our patient had an acute fulminant illness that lead to multiorgan
failure and death in 10 days. She had multiple risk factors but
denied being infected with HIV; the results of tests for HIV anti-
bodies were not available until the postmortem period. Tuberculo-
sis is not the usual diagnosis that comes to mind when a patient
has fever, diarrhea, and hemodynamic parameters suggestive of
septic shock, especially if the chest roentgenogram is normal on
presentation. The patient's rapid downhill course was suggestive
of gram-negative septicemia, toxic shock syndrome, or a systemic
inflammatory response syndrome due to an unidentified pathogen.
The autopsy provided conclusive evidence for widespread Myco-
bacterium tuberculosis infection, but there was no evidence of any
other fatal condition.
Gachot and colleagues reported the cases of four patients who
developed septic shock due to disseminated tuberculosis. With use
of the Isolator (DuPont, Wilmington, DE) centrifugation method,
culture of blood yielded M. tuberculosis [1]. Ahuja and colleagues
also reported the cases of two patients with risk factors for HIV
disease and tuberculosis who had hemodynamic parameters sug-
gestive of septic shock, with a high cardiac output and low systemic
vascular resistance. Both patients died within 2 weeks, and the
diagnosis of tuberculosis was made at autopsy [2]. In addition,
Vadillo et al. reported the case of a similar patient whose illness
was diagnosed as tuberculosis on day 2 of hospitalization on the
basis of the results of bronchial and bone marrow biopsies; this
patient started treatment immediately but died on day 3 [3]. The
term sepsis tuberculosis gravissima has been used to describe such
cases [2].
In summary, disseminated tuberculosis that is predominantly
extrapulmonary can present as an acute fulminant illness inpatients
who are infected with HIV. Hemodynamic parameters consistent
with septic shock can be recorded with a pulmonary artery catheter.
The diagnosis of disseminated tuberculosis should especially be
considered for patients with such parameters if initial cultures of
specimens of pyogenic material are negative. Tuberculin skin test-
ing may not be helpful for patients with advanced HIV disease
because of anergy. It remains to be seen if antituberculous treat-
ment will be effective for such immunocompromised hosts. How-
ever, measures to protect health care providers can be instituted
if the diagnosis of tuberculosis is suspected.
Sushil George, Louis Papa, Lucy Sheils, and
C. Richard Magnussen
Departments of Medicine and Pathology, St. Mary's Hospital,
Rochester .. and University of Rochester School of Medicine and
Dentistry, Rochester, New York
References
I. Gachot B, Wolff M, Clair B, Regnier B. Severe tuberculosis in patients
with human immunodeficiency virus infection. Intensive Care Medicine
1990; 16:487-8.
2. Ahuja SS, Ahuja SK, Phelps KR, Thelmo W, Hill AR. Hemodynamic
confirmation of septic shock in disseminated tuberculosis. Crit Care Med
1992; 20:901- 3.
3. Vadillo M, Corbella X, Carratala 1. AIDS presenting as septic shock caused
by Mycobacterium tuberculosis. Scand J Infect Dis 1994;26:105-6.

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