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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