gas gangrene in an immunocompromised girl due to a clostridium ramosum infection

910

BRIEF REPORTS

Patient A is a 36-year-old man who presented 60 days after anPrimary Lamivudine Resistance in Acute/Early Humanacute retroviral syndrome that began 2 weeks after receptive analImmunodeficiency Virus Infectionintercourse with an unknown male partner. At the time of initialevaluation, the patient was well. Physical examination was entirelyPrimary resistance of HIV to zidovudine was first described inunremarkable. A test for HIV antibodies was positive. His baseline1992 [1] and has since been identified in up to 10% of antiretrovi-plasma virus load was 136,000 copies/mL of plasma, and his CD4ral-naive patients in some centers [2]. Primary resistance to nevira-cell count was 190/mL (figure 1A). Therapy was initiated withpine [3] has also been reported, but the prevalence of primaryzidovudine (500 mg/day) and lamivudine (300 mg/day). At weekresistance to other agents in widespread use in clinical practice in8, the plasma virus load was 4,800 copies/mL. Saquinavir (en-unknown. We now report two cases of primary lamivudine resis-hanced oral formulation, 3,600 mg/day) was added at week 10.tance in two antiretroviral-naive patients who presented with acuteWith this regimen, maximal virologic suppression was achievedHIV infection.(õ400 copies/mL) and has been maintained to week 86, the mostPatients with acute/early HIV infection (documented acquisitionrecent CD4 cell count being 1,020/mL.of infection in the previous 6 months) were recruited as part of

Patient B is a 20-year-old man who presented 35 days after anan ongoing pilot study, initiated in March 1995. Patients haveacute illness that followed sexual contact with a female partner.been recruited from community physicians, street clinics, sexuallyPhysical examination revealed oral candidiasis. He received localtransmitted disease clinics, cohort studies of gay or bisexual mentherapy with nystatin (to which the candidiasis responded), and anand intravenous drug users, and high-risk persons admitted to hos-HIV antibody test was ordered, which was positive. Prior testingpital. At the time of the initial evaluation, a blood sample wasearlier in the year had yielded negative results. His baseline plasmaobtained for measurement of the CD4 cell count and the plasmavirus load was 3,600 copies/mL, and his CD4 cell count wasvirus load (Amplicor HIV Monitor kit; Roche Diagnostics, Missis-380/mL (figure 1B). Therapy was initiated 5 weeks later withsauga, Canada).zidovudine (500 mg/day) and lamivudine (300 mg/day). By weekFor resistance testing, HIV RNA was isolated from the base-3, the virus load had fallen to unquantifiable levels but then in-line plasma sample and then reverse-transcribed and amplifiedcreased to 970 copies/mL, and his treatment regimen was changedby use of primer NE1 (5*-CCCACTAACTTCTGTATGTCA-to stavudine (80 mg/day), didanosine (400 mg/day), and indinavirTTGACAGTCCAGCT-3*) and primer A (5*-TTGGTTGCA-(2,400 mg/day) and then changed again to stavudine and lamivud-CTTTAAATTTTCCCATTAGTCCTATT-3*), respectively, un-ine at week 18 because of intolerance. His plasma virus load wasder standardized conditions. Dilutions of this first PCR productõ400 copies/mL until week 36 and was then found to be 670were used as templates for specific PCR-based detection of thecopies/mL after a recurrence of genital herpes. Four months later,M184V mutation characteristic of resistance to lamivudine. Thiswhile the patient is receiving the same therapy, his plasma viruswas done with primer 184 (5*-GTAATCCCCACCTCA-load is 53,000 copies/mL.ACAGA-3*) and either primer 184M (5*-CAGACATAGTTA-

It is not surprising that the first cases of transmission of resistantTCTATCAATACG-3*) or 184W (5*-CAGACATAGTTATCT-virus strains involved isolates with decreased susceptibility to zido-ATCAATACA-3*), designed to selectively amplify viruses withvudine [1]. Additional cases of primary drug resistance have beenthe appropriate mutation at codon 184 (184M) or wild-typeslow to be identified but are now being described. The transmissionHIV (184W). Experimental controls (provided by J. Mellors)of nevirapine-resistant HIV likely relates to the ease with whichconsisted of clinical plasma samples known to contain wild-high-grade phenotypic resistance may develop in vivo [4]. A paral-type or mutant virus strains. Selective PCR findings were con-lel can be drawn with lamivudine [5]. This study should not befirmed by formal sequencing of DNA obtained from the initialtaken as a measure of the prevalence of primary lamivudine resis-reverse transcription–PCR reaction.tance in British Columbia, as our study population was largelyThe M184V mutation was identified at baseline in isolates takenunselected. It is of interest that none of 17 injection drug usersfrom 2 of 35 patient samples. These consisted of 1 of 12 homosex-evaluated had primary drug resistance, and this should be moni-ual men (patient A), 0 of 17 injection drug users, and 1 of 6tored on an ongoing basis.heterosexual subjects (patient B).

The prospective mapping of spread of primary drug resistance(to lamivudine and any other agents) may allow us to followthe spread of HIV infection in specific groups or communities.

Presented in part: 6th Annual Canadian Conference on HIV/AIDS Research, Comprehensive sampling of sentinel populations is beingOttawa, May 1997 (abstract 345). planned at a national level in Canada to begin to address these

The opinions and assertions contained herein are the private views of theissues.authors and are not to be construed as official or as reflecting the views of the

Departments of the U.S. Army, U.S. Navy, or U.S. Department of Defense.Financial support: U.S. Army Medical Research and Materiel Command.Reprints or correspondence: Dr. Brian Conway, 1134 Burrard Street, Van- Brian Conway, Valentina Montessori, Danielle Rouleau,

couver, BC, Canada V6Z 1Y8 ([email protected]).Julio S. G. Montaner, Michael V. O’Shaughnessy,

Clinical Infectious Diseases 1999;28:910–1 Signe Fransen, Andrew Shillington, Owen Weislow,q 1999 by the Infectious Diseases Society of America. All rights reserved.

and Douglas L. Mayers1058–4838/99/2804–0039$03.00

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911CID 1999;28 (April) Brief Reports

Figure 1. Serial plasma virus load measurements (copies/mL, j), CD4 cell counts (cells/mL, s), and antiretroviral therapy administered topatients A and B, HIV-infected patients with virus isolates with primary resistance to lamivudine (ddI Å didanosine; D4T Å stavudine; IDVÅ indinavir; SQV Å saquinavir; 3TC Å lamivudine; ZDV Å zidovudine).

University of British Columbia, Vancouver, Canada; HIV Clinical 3. Imrie A, Beveridge A, Genn W, Vizzard J, Cooper DA. TransmissionResearch Unit, SRA Technologies, Inc., and the Naval Medical Research of human immunodeficiency virus type 1 resistant to nevirapine and

Institute, Bethesda, Maryland zidovudine. J Infect Dis 1997;175:1502–6.4. de Jong MD, Vella S, Carr A, et al. High-dose nevirapine in previously

References untreated human immunodeficiency virus type 1–infected persons doesnot result in sustained suppression of viral replication. J Infect Dis 1997;1. Erice A, Mayers DL, Strike DG, et al. Brief report: primary infection with175:966–70.zidovudine-resistant human immunodeficiency virus type 1. N Engl J

5. Schuurman R, Nijhuis M, van Leeuwen R, et al. Rapid changes in humanMed 1993;328:1163–65.immunodeficiency virus type 1 RNA load and appearance of drug-resis-2. Yerly S, Rakik A, Kinloch-de-Loes S, et al. Prevalence of transmission oftant virus populations in persons treated with lamivudine (3TC). J Infectzidovudine-resistant viruses in Switzerland. l’Etude suisse de cohorte

VIH. Schweiz Med Wochenschr 1996;126:1845–8. Dis 1995;171:1411–9.

history of intravenous drug use until a few months before admission.Massive Hemoperitoneum: A New Manifestation ofA diagnosis of HIV infection had been made 8 years earlier, but theBacillary Peliosis in Human Immunodeficiency Viruspatient had never sought medical attention. He had had close contactInfectionwith cats until recently. One month before admission, he was hospital-ized because of low-grade fever, blurred vision in the right eye,Bartonella henselae and Bartonella quintana are agents recog-dysarthria, and right hemiparesis. A CT scan of the brain revealednized to be responsible for bacillary angiomatosis (BA) and bacil-multiple small hypodense lesions distributed throughout both hemi-lary parenchymal peliosis (BPP), two diseases characterized byspheres, with no enhancement after administration of iv contrast.unique vascular lesions affecting almost exclusively patients whoResults of CSF testing were normal. His serum was positive forare severely immunocompromised by HIV [1]. Histologic findingsantitoxoplasmic IgG antibodies at a titer of 1:300, and he had a CD4/in BA consist of lobular proliferations of small blood vesselscell count of 41/mm3. The patient rejected a cerebral biopsy. Hecoated by enlarged endothelial cells. Although BA is most fre-became clinically stable and was discharged while receiving treatmentquently found localized to the skin [1, 2], involvement of virtuallywith pyrimethamine and sulfadiazine.every organ system has been reported [1]. Pathologic findings in

Six days after discharge, he was readmitted to the hospital becauseBPP include dilated capillaries and blood-filled cavernous (pelio-of fever, widespread abdominal pain, vomiting, and anorexia. Ontic) spaces involving the liver and spleen [1, 3]. We report aphysical examination, the patient appeared severely ill, with a tempera-case of an HIV-infected patient with massive hemoperitoneum andture of 38.57C, diffuse abdominal tenderness, and marked hepatomeg-hypovolemic shock as the main manifestation of hepatic BPP,aly. Neurological findings remained unchanged in relation to thosecomplications not previously reported in this entity.observed in the previous admission. The following laboratory valuesA 29-year-old man, seropositive for HIV, was admitted to thewere noted: alkaline phosphatase, 2,774 U/L (normal range, 91–258hospital because of fever and abdominal pain. The patient had aU/L); lactate dehydrogenase, 570 U/L (normal range, 230–460 U/L);WBCs, 1.8 1 109/L; neutrophils, 1.2 1 109/L; platelets, 28.8 1109/L; hemoglobin, 124 g/L. Bilirubin, aspartate aminotransferase, and

Reprints or correspondence: Dr. Fernando Lozano, Seccion de Enfermedades alanine aminotransferase levels were normal, as was a chest radio-Infecciosas, Hospital Universitario de Valme, Carretera de Cadiz, 41014- graph. An abdominal CT scan revealed important liver enlargement,Seville, Spain ([email protected]).

with a small hypodense lesion in the right hepatic lobe, and mildClinical Infectious Diseases 1999;28:911–2 spleen enlargement. On the second hospital day, the patient developedq 1999 by the Infectious Diseases Society of America. All rights reserved.1058–4838/99/2804–0040$03.00 hypovolemic shock and abdominal distension. His hemoglobin level

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912 Brief Reports CID 1999;28 (April)

fell to 64 g/L. Results of a panel of coagulation tests were normal. possible BA of the CNS [8], the emergence of the skin lesions justafter beginning treatment with erythromycin, and treatment failureAn emergency laparotomy was done, revealing large amounts of blood

in the abdominal cavity, with diffuse bleeding from the liver surface, with azithromycin. It is of interest that azithromycin has proved effi-cacious in cases of BA in patients with AIDS [9].without evidence of any other bleeding lesion in the peritoneum or in

any other organs. Histopathologic study of a liver biopsy sample This case report highlights the need for including BPP and BAin the differential diagnosis for HIV-infected patients with feverrevealed the presence of extensive fibrous areas in the portal spaces,

with proliferation of dilated capillaries, in association with extravasated and abdominal pain [2], bleeding disorders [4, 5], or CNS lesions[8]. Likewise, this case of spontaneous hemoperitoneum points outerythrocytes and siderophages. Infiltrates of polymorphonuclear cells

with foci of karyorrhexis could be seen associated with hematosinophi- the actual risk of hepatic hemorrhage in BPP. Theoretically, sucha complication would be more probable if a percutaneous biopsylic clumps containing small bacillary organisms revealed by Warthin-

Starry staining. The titer of IgG antibodies to B. henselae in serum of the liver were done, thus suggesting the selection of a differentdiagnostic specimen in these patients whenever possible [1, 5].was 1:64, determined by an indirect immunofluorescent antibody test

(MRL Diagnostics, Cypress, CA). An MRI scan of the brain revealedmultiple small rounded lesions distributed throughout both brain hemi- Fernando Lozano, Juan E. Corzo, Eva M. Leon,spheres and the right hemicerebellum. Blood cultures and cultures Carmen Rufo, Ana Loza, and Jesus M. Gomez-Mateosof biopsy specimens were negative, including specific cultures for Departments of Infectious Diseases, Pathology, and Intensive Care,

Hospital Universitario de Valme, Seville, SpainBartonella species and mycobacteria. Treatment with intravenouserythromycin was begun at a dosage of 1,000 mg q6h. Shortly afterinitiation of therapy, multiple red dome-shaped vascular papules could Referencesbe seen on the skin surface of all four of the patient’s limbs. Histopath- 1. Koehler JE, Tappero JW. AIDS commentary: bacillary angiomatosis andologic evaluation of the biopsy specimen obtained from one of these bacillary peliosis in patients infected with human immunodeficiency vi-lesions showed proliferation of small blood vessels, with protuberant rus. Clin Infect Dis 1993;17:612–24.endothelial cells and mixed inflammatory infiltrate, in addition to the 2. Mohle-Boetani JC, Koehler JE, Berger TG, et al. Bacillary angiomatosis and

bacillary peliosis in patients infected with human immunodeficiency virus:presence of multiple clumps of bacillary organisms demonstrable byclinical characteristics in a case-control study. Clin Infect Dis 1996;22:794–Warthin-Starry staining. On the following days, the patient became800.afebrile, abdominal pain vanished, and skin lesions improved. Fifteen

3. Perkocha LA, Geaghan SM, Yen TSB, et al. Clinical and pathologicaldays later, intravenous erythromycin was changed to oral azithromycinfeatures of bacillary peliosis hepatis in association with human immuno-(500 mg b.i.d.), but fever resumed. A new change to oral doxycyclinedeficiency virus infection. N Engl J Med 1990;323:1581–6.

(100 mg b.i.d.) was made, and the patient became afebrile again.4. Koehler JE, Cederberg L. Intra-abdominal mass associated with gastrointes-

Follow-up of the patient while he was being treated with doxycycline, tinal hemorrhage: a new manifestation of bacillary angiomatosis. Gastro-stavudine, lamivudine, and indinavir was satisfactory. enterology 1995;109:2011–4.

The clinical picture of this case report was typical of BPP: fever, 5. Huh YB, Rose S, Schoen RE, Hunt S, Whitcomb DC, Finkelstein S. Colonicabdominal pain, hepatosplenomegaly, increased levels of alkaline bacillary angiomatosis. Ann Intern Med 1996;124:735–6.

6. Cockerell CJ, Whitlow MA, Webster GF, Friedman-Kien AE. Epithelioid angio-phosphatase, and thrombocytopenia [2, 3]. The most impressive mani-matosis: a distinct vascular disorder in patients with the acquired immunode-festation, however, was a massive hemoperitoneum with hypovolemicficiency syndrome or AIDS-related complex. Lancet 1987;2:654–6.shock. Although BPP and BA are vascular lesions known to cause

7. Steeper TA, Rosenstein H, Weiser J, Inampudi S, Snover DC. Bacillary epitheli-bleeding (e.g., hemorrhages of the gastrointestinal tract [4, 5]), andoid angiomatosis involving the liver, spleen, and skin in an AIDS patientthe peritoneum may be involved [6], severe intraperitoneal bleedingwith concurrent Kaposi’s sarcoma. Am J Clin Pathol 1992;97:713–8.

has not yet been reported. The histologic findings in our case differ8. Spach DH, Panther LA, Thorning DR, Dunn JE, Plorde JJ, Miller RA.

from those in classical BPP in the lack of true peliotic spaces, in the Intracerebral bacillary angiomatosis in a patient infected with humanportal localization of the lesions, and in the presence of a fibrous immunodeficiency virus. Ann Intern Med 1992;116:740–2.background, all features previously described [7]. Likewise, other re- 9. Guerra LG, Neira CJ, Boman D, et al. Rapid response of AIDS-related

bacillary angiomatosis to azithromycin. Clin Infect Dis 1993;17:264–6.markable peculiarities of the reported case were its clinical onset as

Often, no etiologic agent can be identified, and persistent fever isPersistent Fever as the Only Manifestation of Chronicinterpreted as being due to HIV-1 [1]. We report here the case ofCoxsackievirus B4 Infection in the Brain of a Humanan HIV-1-infected child, in whom persistent fever was the onlyImmunodeficiency Virus Type 1–Infected Childsymptom of chronic coxsackievirus B4 infection in the brain, pre-

Children with perinatal HIV-1 infection frequently have long- ceding by several months the appearance of neurological signs.lasting fever. This fever may be sustained by secondary infections. A perinatally HIV-1-infected child at 3 months of age developed

diffuse lymphadenopathy, hepatosplenomegaly, diarrhea, and fail-ure to thrive. Zidovudine therapy resulted in recovery from diar-

Reprints or correspondence: Prof. P.-A. Tovo, Department of Pediatrics, rhea and a marked weight gain. During the following 4 years, hisUniversity of Turin, Piazza Polonia 94, 10126 Turin, Italy (tovo@pediatria. general condition and growth remained satisfactory, despite theunito.it).

progressive decrease in number of CD4/ cells (723 1 106

Clinical Infectious Diseases 1999;28:912–3 cells/L at 2 years, 38 1 106 cells/L at 4 years). After the identifica-q 1999 by the Infectious Diseases Society of America. All rights reserved.1058–4838/99/2804–0041$03.00 tion of a genotype mutation associated with zidovudine resistance,

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at 4 years his therapy was changed to didanosine. Five months progressively worsened until he became comatose, and the childdied 6 weeks after the beginning of neurological disturbances.later, the child began having recurrent diarrhea with weight loss,

leading to an overt wasting syndrome at 5 years of age. Combined According to the U.S. Centers for Disease Control and Preven-tion indications [1], persistent fever is considered a typical HIV-therapy with zalcitabine and saquinavir did not result in any clinical

or immunological improvement. At 512 years, after a relatively 1-associated clinical manifestation in infected children. However,

symptom-free period, he developed remittent fever unresponsive doubts arise as to whether HIV-1 by itself can cause fever. Feverto broad-spectrum antibiotics. No signs of sepsis or localized infec- does not manifest in subjects with high virus loads but mild immu-tion were found. Abdominal echography and chest radiography nodeficiency, whereas it does in patients with severe immunosup-were normal. His WBC count was 4.5 1 109/L and his C-reactive pression [3] who are thus at high risk for secondary infections.protein level was õ3 mg/L. Repeated cultures for bacteria, fungi, Common infections may have an atypical presentation and an un-viruses, and protozoa from blood, stool, and urine were negative; usual course in immunocompromised subjects. Agammaglobulin-serological tests for infectious agents were unremarkable. After 35 emic patients may develop chronic enterovirus meningoencephali-days of fever, CSF analysis revealed the following values: WBCs, tis with an indolent course [2]. HIV-1-infected children have a60 1 106/L (70% mononuclear cells); protein, 74 mg/dL; and significant humoral immunodeficiency, which may account for theglucose, 51 mg/dL. Cultures from CSF, including those for entero- chronic coxsackievirus B4 meningoencephalitis in our patient.viruses, were negative. Coxsackievirus B4 was detected by a PCR Chronic viral infections in the brain without neurological distur-assay; the virus was not found in stool and throat washings either bances for prolonged periods may be more frequent than is usuallyby culture or by PCR. Electroencephalography showed mild dif- thought in children with HIV-1 infection. Another of our patientsfuse aspecific abnormalities, and a cranial CT scan showed mild recovered from measles, but the persistence of the virus in hisdilatation of subarachnoid spaces. brain led to subacute meningoencephalitis 2 months later [4].

Transient or long-lasting effects of high doses of intravenous In conclusion, in HIV-1-infected children with unexplained fe-immunoglobulins have been reported in agammaglobulinemic chil- ver, targeted investigations for viral infections in the brain shoulddren with chronic enterovirus meningoencephalitis [2]. Intravenous be considered, even in the absence of neurological signs.immunoglobulin (1 g/kg; Endobulin; Immuno, Vienna) and thymo-poietin (25 mg; Timunox; Cilag, Schaffhausen, Switzerland) were E. Palomba and P.-A. Tovoinfused on each of 6 consecutive days, twice a week for 1 month, Department of Pediatrics, University of Turin, Turin, Italyand then every 10 days for another month. Fever disappearedwithin 5 days of starting therapy. One month later, however, cox-

Referencessackievirus B4 was still detected by PCR in CSF, together with

1. Centers for Disease Control and Prevention. 1994 revised classificationincreased protein levels and WBC count. After 2 months with nosystem for human immunodeficiency virus infection in children less thansymptoms, the patient’s fever reappeared and was unresponsive to13 years of age. MMWR Morb Mortal Wkly Rep 1994;43:1–10.previous treatments on a daily basis. Two weeks later, neurological

2. Misbah SA, Spickett GP, Ryba PCJ, et al. Chronic enteroviral meningoen-signs developed: apathy and involvement of oculomotor nerves,cephalitis in agammaglobulinemia: case report and literature review. J

with diplopia, vertigo, and convergent strabismus alternated withClin Immunol 1992;12:266–70

vertical nystagmus. Cerebellar-type tremors of the hands, ataxia, 3. Tovo PA, de Martino M, Gabiano C, et al. Prognostic factors and survivaland dysarthria appeared, followed by global incoordination, gener- in children with perinatal HIV-1 infection. Lancet 1992;339:1249–53.alized hypotonia, hyporeflexia, and drowsiness. Electroencepha- 4. Vigliano P, Boffi P, Giordana MT, et al. Subacute measles encephalitis inlography showed diffuse abnormalities prevalent in the left tempo- a boy with perinatal HIV-1 infection. Dev Med Child Neurol 1995;37:

1117–19.rooccipital region. The patient’s symptoms and consciousness level

number of CD4/ T lymphocytes; however, vaccination of HIV-Postexposure Rabies Vaccination in Patients Infectedinfected persons with these antigens may induce a normal antibodywith Human Immunodeficiency Virusresponse when undertaken early in the disease [4–6]. AlthoughHIV-infected persons require special consideration because of con-In general, symptomatic HIV-infected children and adults havecern that their response to vaccine may be abnormal, the vaccina-suboptimal immunologic responses to several commonly used vac-tion of HIV-infected persons against tetanus, diphtheria, pertussis,cines [1–5]. Previous studies demonstrated impaired formation ofpoliomyelitis, hepatitis B, influenza, and pneumococcal disease

antibodies to T lymphocyte–dependent antigens (such as diphthe-has been recommended [7].

ria, tetanus, poliovirus, and influenza vaccines) in relation to theThere is little doubt that postexposure rabies vaccination pre-

vents deaths in persons who are exposed to rabies, so it differsfrom other immunizations in that it represents treatment for a fataldisease. Because the aim of postexposure rabies vaccination is to

This study was approved by the ethics committee of the authors’ institution. induce protective immunity, as measured by neutralizing antibod-Reprints or correspondence: Dr. Terapong Tantawichien, Division of Infec- ies to rabies virus, as quickly as possible, we have been concerned

tious Diseases, Department of Medicine, Chulalongkorn University Hospital,whether the World Health Organization (WHO)–recommendedRama IV Road, Bangkok, Thailand 10330.postexposure treatment regimens provide protecting neutralizing

Clinical Infectious Diseases 1999;28:913–4antibodies in HIV-infected persons exposed to rabies [8]. A pro-q 1999 by the Infectious Diseases Society of America. All rights reserved.

1058–4838/99/2804–0042$03.00 spective study of the neutralizing antibody responses to rabies virus

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1,124/mL) treated in the same manner (data not shown). Thispreliminary study demonstrated that HIV-infected persons withlow CD4/ T lymphocyte counts have an impaired (primary) anti-body response after receipt of tissue culture rabies vaccines asrecommended by WHO. We recommend that it is necessary tocheck titers of neutralizing antibody to rabies virus in HIV-infectedpatients after postexposure rabies vaccination with tissue culturerabies vaccine. Higher doses or more frequent booster injectionsmay be considered for HIV-infected patients; however, the re-sponse to higher doses of rabies vaccine and the persistence ofneutralizing antibodies in these patients have not been evaluated.Recently, we decided to double the dose of tissue culture rabiesvaccine in HIV-infected persons exposed to rabies. This practiceat our institution is needed to determine whether this will resultin an adequate neutralizing antibody response.

Wipaporn Jaijaroensup, Terapong Tantawichien,Pakamatz Khawplod, Saowaluck Tepsumethanon,Figure 1. Titers of neutralizing antibody to rabies virus before and

and Henry Wildeafter postexposure rabies vaccination in HIV-infected persons withCD4/ T lymphocyte counts of £300/mL (range, 111–250/mL) (X) The Queen Saovabha Memorial Institute, Thai Red Cross Society, andand ú300/mL (range, 316–950/mL) (O). Division of Infectious Diseases, Department of Medicine, Chulalongkorn

University Hospital, Bangkok, Thailand

Referencesin HIV-infected patients after postexposure rabies vaccination was

1. Borkowsky W, Steele CJ, Grubman S, Moore T, La Russa P, Krasinski K.conducted. We identified nine HIV-infected patients without active Antibody responses to bacterial toxoids in children infected with theopportunistic infections, who presented with possible or proven human immunodeficiency virus. J Pediatr 1987;110:563–6.rabies exposure (all except one had severe exposure, WHO cate- 2. Ochs HD, Junker AK, Collier AC, Virant FS, Handsfield HH, Wedwoodgory III) [8]. CD4/ T lymphocyte counts were determined in ve- RJ. Abnormal antibody responses in patients with persistent generalized

lymphadenopathy. J Clin Immunol 1988;8:57–63.nous blood collected from all HIV-infected patients before vacci-3. Barbi M, Bardare M, Luraschi C, Zehender G, Clerici Schoeller M, Ferrarisnation (day 0). They were given the WHO-approved Thai Red

G. Antibody response to inactivated polio vaccine (E-IPV) in childrenCross multisite intradermal postexposure vaccine regimen (2-2-2-born to HIV positive mothers. Eur J Epidemiol 1992;8:211–6.0-1-1, TRC-ID) with purified Vero cell rabies vaccine (Verorab;

4. Kroon FP, van Dissel JT, de Jong JC, Furth R. Antibody response toPasteur Merieux, Connaught, France; batch L0316 and K0185;influenza, tetanus, and pneumococcal vaccines in HIV-seropositive indi-

potency, 8.8 and 8.9 IU/mL). All except one received purifiedviduals in relation to the number of CD4/ lymphocytes. AIDS 1994;8:

equine rabies immune globulin (Institut Pasteur Diagnostics, 469–76.Marnes-la-Coquette, France; batch L 5174; potency, 247 IU/mL, 5. Vardinon N, Handsher R, Burke M, Zacut V, Yust I. Poliovirus vaccination40 IU/kg). Titers of neutralizing antibody to rabies virus were responses in human immunodeficiency virus–infected patients: correla-determined by the method of Smith et al. [9] before vaccination tion with T4 cell counts. J Infect Dis 1990;162:234–41.

6. Kroon FP, van Dissel JT, Labadie J, van Loon AM, Furth R. Antibodyand on days 7, 14, 28, and 90 thereafter. This study was approvedresponse to diphtheria, tetanus, and poliomyelitis vaccines in relationby the ethics committee of this institution.to the number of CD4/ T lymphocytes in adults infected with humanWe found that none of the HIV-infected patients died of rabiesimmunodeficiency virus. Clin Infect Dis 1995;21:1197–203.during the following 6–12 months. Five HIV-infected patients

7. 1997 USPHS/IDSA guidelines for the prevention of opportunistic infectionswith low CD4/ T lymphocyte counts of £300/mL (range, 111–in persons infected with human immunodeficiency virus: disease-specific

250/mL) had a poor or even nondetectable neutralizing antibodyrecommendations. Clin Infect Dis 1997;25(suppl 3):S133–335.

response to vaccination (figure 1). However, four HIV-infected 8. World Health Organization Expert Committee on Rabies. Eighth report.patients with CD4/ T lymphocyte counts of ú300/mL (range, World Health Organ Tech Rep Ser 1992;824.316–950/mL) had neutralizing antibody titers well above the mini- 9. Smith JS, Yager PA, Baer GM. A rapid reproducible test for detection ofmal WHO-recommended level of 0.5 IU/mL, as did nine HIV- rabies neutralizing antibodies. In: Laboratory techniques in rabies. Ge-

neva: World Health Organization, 1997:181–92.seronegative patients (CD4/ T lymphocyte count range, 554–

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Successful Treatment of Multiple CerebralHistoplasmomas with Itraconazole

Amphotericin B has been suggested as the treatment of choicefor cerebral histoplasmomas, but it is effective in only about halfof cases [1]. In the review by Wheat et al. [1], no cases of cerebralhistoplasmomas resolved without antifungal therapy, and only twowere treated with azoles. I am unaware of previous reports ofitraconazole use for CNS histoplasmosis.

A 53-year-old woman with a history of type II diabetes mellituspresented with a 3-week history of confusion, dysarthria, right-sided weakness, left-sided eyelid ptosis, weakness of gaze to theright, right-sided hyperreflexia, and left-sided neglect. She deniedhaving chills or sweats and was afebrile.

Four months earlier, she had had a platelet count of 5,000/mm3

and was treated with corticosteroids and intravenous immunoglob-ulin for idiopathic immune thrombocytopenia. During that time,she had a brief febrile illness; a bone marrow examination revealednoncaseating granulomas, and a chest radiograph showed increasedinterstitial markings. Her platelet count, fever, and chest radio-graph returned to normal after a few days, and corticosteroid treat-ment was tapered and then discontinued 3 weeks before her neuro-logical symptoms began.

Figure 1. Post–gadolinium contrast T1-weighted axial cerebralAt the time of her neurological symptoms, an MRI scan revealed MRI in a 53-year-old patient with cerebral histoplasmomas.

numerous lesions (diameter, õ1 cm) of the grey and white matterof the frontal, parietal, and occipital lobes and lesions within themidbrain and brain stem (figure 1). The lesions enhanced after

revealed a decrease in the number and size of the lesions and inintravenous injection of gadolinium, and some had surrounding

the surrounding edema. She continued to receive itraconazole foredema. An abdominal CT scan showed the left adrenal to be 3.4

1 year. Another MRI scan done 4 months after discontinuation of1 3.9 cm with a hypodense center and hyperdense rim. A chesttherapy revealed no change from the scan at the end of therapy.

radiograph was normal. A fine-needle adrenal aspirate showedMore than 2.5 years after discontinuing therapy, the patient re-

nondiagnostic results. On CSF testing, the following values weremains asymptomatic.

noted: glucose, 52 mg/dL; protein, 61 mg/dL; RBCs, 0/mm3;The patient described had evidence of cerebral histoplasmomas,

WBCs, 1/mm3 (100% mononuclear). Bone marrow and CSF cul-despite the lack of a brain biopsy. H. capsulatum was found in

tures were negative. The Histoplasma capsulatum polysaccharidethe adrenal gland, antibodies to H. capsulatum were present in

antigen level in serum was 0.5 U and in CSF was 0.7 U. TheCSF, and the lesions and symptoms responded to antifungal ther-

patient was negative for IgG antibodies to Echinococcus speciesapy. Negative cultures of CSF and a negative result on CSF his-

and HIV and IgM antibodies to Toxoplasma species in serum. Hertoplasma polysaccharide antigen testing are observed in about half

serum was positive for IgG antibodies to Toxoplasma species, butof cases of CNS histoplasmosis [1]. It is likely that her disease

the ratio of Toxoplasma IgG antibodies to total IgG was twofoldwas related to the immunosuppressive effects of the corticoste-

greater in serum than in CSF. Her titer of complement fixationroids, despite discontinuation of corticosteroids 3 weeks before

antibody to H. capsulatum in CSF was 1:2 for the mycelial antigenher neurological symptoms began.

and 1:4 for the yeast antigen. An open adrenal biopsy revealedTwo cases of cerebral histoplasmomas have been successfully

extensive necrosis, granulomatous inflammation, and organismstreated with ketoconazole after relapse following therapy with in-

consistent with histoplasmosis. Culture of adrenal tissue yieldedtravenous amphotericin B [2, 3]. There has also been a report of

H. capsulatum.treatment failure with ketoconazole therapy for cerebral histoplas-

The patient refused therapy with amphotericin B. She beganmomas [4]. Ketoconazole has been associated with treatment fail-

receiving itraconazole, 200 mg three times daily for 3 days, fol-ures in immunocompromised patients with histoplasmosis and has

lowed by 200 mg twice daily. Her neurological signs and symp-poor penetration into CSF [1]. Two reported cases of CNS histo-

toms improved over the next 3 months, and repeat MRI scansplasmosis have been treated with fluconazole, which crosses theblood-brain barrier, but the length of follow-up was short [5, 6].Fluconazole is associated with treatment failures and relapses inboth immunocompetent and immunocompromised patients with

Reprints or correspondence: Dr. David M. Bamberger, Red 4 Unit, Univer- histoplasmosis and is less active than itraconazole against H. cap-sity of Missouri–Kansas City School of Medicine, 2411 Holmes Street, Kansas

sulatum in vitro [7].City, Missouri 64108 ([email protected]).Itraconazole is more active than ketoconazole or fluconazole in

Clinical Infectious Diseases 1999;28:915–6non-CNS histoplasmosis [7, 8]. In animal models, concentrationsq 1999 by the Infectious Diseases Society of America. All rights reserved.

1058–4838/99/2804–0043$03.00 of itraconazole in CSF are negligible, but concentrations in brain

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3. Goodpasture HC, Hershberger RE, Barnett AM, Peterie JD. Treatment oftissue exceed those in plasma, which may explain itraconazole’scentral nervous system fungal infection with ketoconazole. Arch Internutility in cases of cryptococcal and coccidioidal meningitis andMed 1985;145:879–80.cerebral aspergillosis [8–10]. Itraconazole use should be consid-

4. Walpole HT, Gregory DW. Cerebral histoplasmosis. South Med J 1987;ered for cerebral histoplasmomas, especially in patients who cannot80:1575–7.

tolerate treatment with amphotericin B or who have amphotericin 5. Rivera IV, Curless RG, Indacochea FJ, Scott GB. Chronic progressiveB treatment failure. CNS histoplasmosis presenting in childhood: response to fluconazole

therapy. Pediatr Neurol 1992;8:151–3.6. Tiraboschi I, Casas Parera I, Pikielny R, Scattini G, Micheli F. ChronicDavid M. Bamberger

Histoplasma capsulatum infection of the central nervous system suc-University of Missouri–Kansas City School of Medicine,

cessfully treated with fluconazole. Eur Neurol 1992;32:70–3.Kansas City, Missouri

7. Wheat J, MaWhinney S, Hafner R, et al. Treatment of histoplasmosis withfluconazole in patients with acquired immunodeficiency syndrome. AmJ Med 1997;103:223–32.References

8. Dismukes WE, Bradsher RW, Cloud GC, et al. Itraconazole therapy for1. Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum blastomycosis and histoplasmosis. Am J Med 1992;93:489–97.

infections of the central nervous system. A clinical review. Medicine 9. Heykants JM, Van Peer A, Van de Velde P, et al. The clinical pharmacoki-1990;69:244–60. netics of itraconazole: an overview. Mycoses 1989;32(suppl 1):67–87.

2. Craven PC, Graybill JR, Jorgensen JH, Dismukes WE, Levine BE. High- 10. Sanchez C, Mauri E, Dalmau D, Quintana S, Aparicio A, Garau J. Treat-dose ketoconazole for treatment of fungal infections of the central ner- ment of cerebral aspergillosis with itraconazole: do high doses improve

the prognosis? Clin Infect Dis 1995;21:1485–7.vous system. Ann Intern Med 1983;98:160–7.

increased, and CSF analysis revealed 27,900 cells/mm3 (95% poly-Successful Treatment of Ventriculitis Due tomorphonuclear cells), and cultures of CSF yielded A. baumannii.Carbapenem-Resistant Acinetobacter baumannii withMeropenem was discontinued, and intraventricular tobramycin (10Intraventricular Colistin Sulfomethate Sodiummg/12 h), intravenous tobramycin (5 mg/kg once a day), and intrave-nous sulbactam (2 g/6 h) were then initiated. On day 19, because CSFOver the past 2 decades, Acinetobacter baumannii has devel-cultures remained positive, the ventriculostomy tube was replaced andoped one of the most alarming patterns of antibiotic resistanceintraventricular tobramycin was switched to intraventricular colisti-ever observed [1]. Nowadays, since an increasing proportion ofmethate sodium (5 mg/12 h), intravenous tobramycin was maintained,isolates are resistant to all antibiotics tested routinely, therapy isand intravenous sulbactam was discontinued. Intraventricular colistina serious challenge [2]. Beginning in 1992, a large outbreak duewas administered in a 5-mL solution of saline serum through theto multiresistant A. baumannii was noted in our 1,000-bed tertiaryventriculostomy tube after previous extraction of 5 mL of CSF, andteaching hospital, causing considerable imipenem overuse [3]. Inthereafter, the drainage was interrupted for 3 hours. On day 21, cul-January 1997, two clones resistant to carbapenems emerged: clonetures of CSF were negative and remained so until colistin sulfometh-D, moderately resistant to imipenem (MICs, 4–16 mg/L) and to-ate sodium therapy was ended on day 39, when a ventriculoperitonealbramycin (MIC, 8 mg/L) and susceptible only to sulbactam andshunt was inserted. During therapy, CSF bactericidal titers at 3 hourspolymyxins (MICs, £4 mg/L), and clone E, highly resistant toafter colistin sulfomethate sodium administration (peak) were 1/2,imipenem and sulbactam (MICs, ú256 mg/L), moderately resis-and before doses were administered (trough), titers ranged fromtant to tobramycin (MIC, 8 mg/L), and susceptible only to poly-õ1/2 to 1/4. Similarly, CSF bacteriostatic titers at peak were 1/8 andmyxins. Since then, five patients have developed catheter-associ-at trough ranged from 1/4 to 1/16. Levels of tobramycin in CSF variedated ventriculitis due to carbapenem-resistant A. baumannii strainsfrom 7.9 mg/L (peak) to 0.7 mg/L (trough). No adverse reactions were(table 1). Of these five patients, three died of their infection afterdocumented during therapy. On day 82, the patient was alert withreceiving inadequate therapy (patients 1–3). The other two are, tospontaneous mobilization of the extremities, but he died suddenly ofour knowledge, the first reported to date who survived after treat-cardiac arrest. Postmortem examination ruled out ventriculitis, andment with intraventricular colistin sulfomethate sodium (patientscultures of CSF were negative for A. baumannii.4 and 5).

Patient 5 was a 34-year-old woman who required an externalPatient 4 was a 16-year-old boy who underwent surgery and theventriculostomy tube because of subarachnoid hemorrhage withinsertion of an external ventriculostomy tube for continuous drainagehydrocephalus. The catheter was removed 6 days after insertion;because of hemangioblastoma of the fourth ventricle. On day 7 afterhowever, 24 hours later, the patient developed high fever andsurgery, meropenem at 2 g/8 h was started empirically to treat hisneurological symptoms worsened, with purulent secretion from thefever, although CSF cultures had been sterile. On day 16, his fevercatheter insertion site. CSF obtained through a new ventriculardrainage site was cloudy, showing 2,000 cells/mm3 (95% polymor-phonuclear cells) and short gram-negative rods on gram stain.

Reprints or correspondence: Dr. P. Fernandez-Viladrich, Infectious Disease Cultures from the purulent secretion and CSF yielded A. bauman-Service, Hospital de Bellvitge, 08907 L’Hospitalet de Llobregat, Barcelona, nii. Intraventricular colistimethate sodium (5 mg/12 h), givenSpain.

following the above-mentioned procedures, and intravenous tobra-Clinical Infectious Diseases 1999;28:916–7 mycin (4 mg/kg once a day) were administrated without com-q 1999 by the Infectious Diseases Society of America. All rights reserved.1058–4838/99/2804–0044$03.00 plications. Although a rapid decrease in the bacterial count in CSF

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Table 1. Clinical characteristics of the five patients with carbapenem-resistant Acinetobacter baumannii ventriculitis.

Antibiotic treatment

Patient Surgery/ Intrathecal Intravenous Infectionno. Age/sex Underlying condition ventricular tube* Clone colistin† antibiotics† outcome‡

1 47/F Subarachnoid hemorrhage No/yes (7) E No Mer (2) / Tm (2) Died (2)2 61/F Ependymoma Yes/yes (11) E No Sulb (7) / Tm (7) Died (7)3 64/M Epidermoid tumor Yes/yes (21) E No No Died (1)4 16/M Hemangioblastoma Yes/yes (16) D Yes (19) Sulb (3) / Tm (19) Cured§

5 34/F Subarachnoid hemorrhage No/yes (7) E Yes (17) Tm (17) Cured

NOTE. Mer Å meropenem; Sulb Å sulbactam; Tm Å tobramycin.* Parentheses indicate the days from catheter insertion to diagnosis of infection.† Parentheses indicate the days of treatment.‡ Parentheses indicate the days from diagnosis of infection to death.§ The patient died of a noninfectious cause, 66 days after treatment ended.

was observed, cultures of CSF remained positive through the fifth In view of these results, search for new therapeutic strategies isurgently needed for the treatment of CNS infections due today of therapy. Dosages of colistin sulfomethate sodium were then

increased to 10 mg/12 h, and 24 hours later, cultures of CSF A. baumannii that is resistant to carbapenems. In the meantime,intraventricular colistimethate sodium may be life-saving in cir-yielded negative results (CSF peak bactericidal and bacteriostatic

titers were õ1/2 and 1/16, respectively). Cultures of CSF contin- cumstances in which there are no other options.ued to be negative until day 30 of the patient’s stay in the intensivecare unit (6 days after the end of colistin sulfomethate sodium

P. Fernandez-Viladrich, X. Corbella, L. Corral, F. Tubau,therapy), when a ventriculoperitoneal shunt was inserted. Twoand A. Mateumonths later, the patient was discharged from the unit, remaining

Departments of Infectious Diseases, Intensive Medicine, andwell after 4 months of follow-up.Microbiology, Hospital de Bellvitge, University of Barcelona,Carbapenems are considered the treatment of choice in severe

Barcelona, SpainA. baumannii infections; however, no antibiotic alternatives havebeen defined for cases of infection due to carbapenem-resistantstrains. Therapy in these patients is severely threatened and cur-

Referencesrently limited to sulbactam or polymyxins [4–6]. In patients withmeningitis, although there are some scattered experiences of the 1. Bergogne-Berezin E, Towner KJ. Acinetobacter spp. as nosocomial patho-use of the sulbactam/ampicillin combination with encouraging re- gens: microbiological, clinical, and epidemiological features. Clin Micro-sults [7], the efficacy of this antibiotic could not be guaranteed biol Rev 1996;9:148–65.

2. Go ES, Urban C, Burns J, et al. Clinical and molecular epidemiology ofagainst our A. baumannii strains (MICs of sulbactam ranged fromAcinetobacter infections sensitive only to polymyxin B and sulbactam.4 to ú256 mg/L) [6]. Furthermore, even though all of our carba-Lancet 1994;344:1329–32.penem-resistant A. baumannii clones are considered to be uni-

3. Corbella X, Pujol M, Ayats J, et al. Relevance of digestive tract colonizationformly susceptible to polymyxins (MICs, £4 mg/L), desirablein the epidemiology of multiresistant Acinetobacter baumannii. Clin In-concentrations of polymyxins could be difficult to attain in CSFfect Dis 1996;23:329–34.after parenteral doses [8].

4. Urban C, Go E, Mariano N, et al. Effect of sulbactam on infections causedThese observations led us to reconsider some scanty but classical

by imipenem-resistant Acinetobacter calcoaceticus biotype anitratus. Jexperiences in which intraventricular polymyxins were used in the Infect Dis 1993;167:448–51.treatment of gram-negative meningitis to achieve better therapeutic 5. Wood CA, Reboli AC. Infections caused by imipenem-resistant A. calcoace-ranges [9]. In our experience, the clinical and bacteriological response ticus biotype anitratus. J Infect Dis 1993;168:1602–3.after intraventricular colistin sulfomethate sodium was favorable in 6. Corbella X, Ariza J, Ardanuy C, et al. Efficacy of sulbactam alone and in

combination with ampicillin in nosocomial infections caused by multire-the two patients treated, although in patient 5, higher doses weresistant Acinetobacter baumannii. J Antimicrob Chemother 1998;42:793–required because of delayed CSF sterilization. Since levels of tobra-802.mycin in CSF after intravenous tobramycin administration did not

7. Jimenez-MejıB as ME, Pachon J, Becerril B, Palomino-Nicas J, RodrıB guez-reach the MICs, we considered the antimicrobial activity documentedCobacho A, Revuelta M. Treatment of multi-resistant Acinetobacter bau-in the CSF to be only that exhibited by colistimethate sodium. Al-mannii meningitis with ampicillin/sulbactam. Clin Infect Dis 1997;24:though the bactericidal titers found were low, it is difficult to evaluate932–5.

the extent to which these microbiological results really reflect clinical8. Polymyxins. In: Kucers A, Crowe S, Graysson ML, Hoy J, eds. The use

efficacy in these patients with continuous CSF drainage, in whom of antibiotics. 5th ed. Oxford, England: Butterworth-Heineman, 1997:CSF pharmacokinetics are variable. Nevertheless, these results may be 667–75.in accordance with the previous knowledge that colistin sulfomethate 9. Clifford HE, Stewart GT. Intraventricular administration of a new derivativesodium can show lesser bactericidal activity in vivo than in vitro of polymyxin B in meningitis due to Ps. pyocyanea. Lancet 1961;2:

798–9.against some gram-negative rods [8].

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contamination [6]. In contrast, patients with systemic lupus erythe-Adult Pneumococcal Cellulitis: Case Report and Reviewmatosus, nephrotic syndrome, and hematologic disorders, includ-ing multiple myeloma and macroglobulinemia, commonly presentStreptococcus pneumoniae is an infrequent cause of skin infec-with face and neck cellulitis [1–4, 7]. Pharyngeal colonization hastions in adults. Prior reports describe facial cellulitis in childrenbeen postulated to be the initiating event for facial cellulitis be-with hypogammaglobulinemia and hemoglobinopathy and incause of the proximity to the respiratory tract [1]. The age distribu-adults with connective tissue disorders [1, 2]. We report a case oftion correlated with the patient’s underlying disease. The male-to-pneumococcal cellulitis and bacteremia in an alcoholic patient withfemale ratio was Ç2:1.diabetes and discuss this disease in adult patients.

Pneumococcal cellulitis was universally associated with bacter-A 71-year-old man with a history of alcohol abuse presentedemia [2–5, 7]. Penicillin was typically the drug of choice. Thuswith fever and a 4-week history of intermittent and progressivefar, only one reported case was due to penicillin-resistant S. pneu-pain in the right lower extremity associated with skin discoloration.moniae [7]. The role of pneumococcal vaccination is difficult toHe denied any history of trauma or respiratory illness. He had notascertain, since administration was not reported and most patientspreviously received polyvalent pneumococcal vaccination.would be expected to have a poor antibody response.On admission, the patient was febrile to 387C, lethargic, and

Suppurative complications were common, and surgical interven-confused. Bullae, a violaceous hue, and multiple areas of desqua-tion was required in many cases [2–4, 6]. Procedures includedmation were noted on the right foot and lower leg. The lower legdebridement, fasciectomy, amputation, and skin grafting. Mortalitywas warm and tender, whereas the foot was cold and pulseless.was Ç15% [1–6].Significant laboratory values included the following: leukocytes,

In summary, pneumococcal skin infections represent two dis-30,500/mm3, and creatine phosphokinase, 295 U/L. A chest roent-tinctive clinical syndromes: facial cellulitis in persons with sys-genogram was unremarkable. Cultures of blood yielded S. pneu-temic lupus erythematosus and hematologic disorders and limbmoniae.cellulitis in persons with diabetes and substance abuse. Blood-The patient underwent a below-knee amputation. Histopatho-stream invasion, tissue necrosis, and suppurative complications arelogic evaluation revealed diffuse polymorphonuclear infiltration ofcommon. Thus, a clinician should have a high degree of suspicionthe soft tissue, gram-positive diplococci, and acute thrombophlebi-of pneumococcal cellulitis for patients who present with cellulitistis with acute inflammatory infiltrates of arterial adventitia consis-associated with bullae and violaceous color, to allow for the initia-tent with cellulitis. The patient was treated with vancomycin. Hetion of early, aggressive management.underwent a subsequent above-knee amputation because of poor

stump healing.Jorge P. Parada and Joel N. MaslowPneumococcal cellulitis is rare, with Ç30 cases reported in the

Department of Medicine, Cook County Hospital, Chicago, Illinois, andEnglish-language literature. Descriptions range from localized ery-the Department of Medicine, Boston University School of Medicine, andthema to violaceous or brawny skin discoloration and bullae forma-

the Veterans Affairs Medical Center, Boston, Massachusettstion [2–4]. It has been postulated that a toxin may mediate someaspects of local tissue inflammation [2, 3]. The majority of patients

Referenceshad underlying chronic illnesses or were immunocompromised bydrug or alcohol abuse [2–5]. 1. Hill MD, Karsh J. Invasive soft tissue infections with Streptococcus pneu-

There appear to be two distinct clinical syndromes of pneumo- moniae in patients with systemic lupus erythematosus: case report andcoccal cellulitis. The first is cellulitis of the limbs that is associated review of the literature. Arthritis Rheum 1997;40:1716–9.with a history of ethanol abuse, injection drugs, and diabetes melli- 2. Lawler MT, Crowe HM, Quintiliani R. Cellulitis due to Streptococcus

pneumoniae: case report and review. Clin Infect Dis 1992;14:247–50.tus [1, 2, 6]. These patients are at higher risk for limb trauma,3. Peters NS, Eykyn SJ, Rudd AG. Pneumococcal cellulitis: a rare manifesta-which may serve as the portal of entry of bacteria. The practice by

tion of pneumococcaemia in adults. J Infect 1989;19:57–9.some injection drug users of blowing through syringes to establish4. Varghese R, Melo JC, Chun C-H, Raff MJ. Erysipelas-like syndrome causedpatency before injection may increase the risk for pneumococcal

by Streptococcus pneumoniae. South Med J 1979;72:757–8.5. Hinnen RM, Trachtenbarg DE, Miller MA, Coon JJ. Streptococcus pneu-

moniae cellulitis. IMJ Ill Med J 1986;170:84–6.6. Lewis RJ, Richmond AS, McGrory JP. Diplococcus pneumoniae cellulitisReprints or correspondence: Dr. Joel N. Maslow, VA Medical Center

in drug addicts. JAMA 1975;232:54–5.(151), 150 South Huntington Avenue, Boston, Massachusetts 021307. Souweine B, Mom T, Bret L, Klisnick A, Baguet J-C, Gilain L. Cellulitis([email protected]).

due to Streptococcus pneumoniae with diminished susceptibility to peni-Clinical Infectious Diseases 1999;28:918

cillin in an immunocompromised patient. Scand J Infect Dis 1997;29:q 1999 by the Infectious Diseases Society of America. All rights reserved.1058–4838/99/2804–0045$03.00 518–9.

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Recrudescence of Cutaneous Mycobacterium haemophilumLesions Following Tetanus Immunization

Mycobacterium haemophilum is increasingly recognized as acause of cutaneous, joint, and pulmonary infections in immuno-compromised hosts [1, 2]. We describe a patient with HIV infectionand cutaneous lesions due to M. haemophilum who experiencedan unusual reaction to a routinely administered tetanus vaccine.

In August 1996, a 51-year-old homosexual man was diagnosedwith Pneumocystis carinii pneumonia and treated successfully withtrimethoprim-sulfamethoxazole (TMP-SMZ). He declined formalHIV testing, choosing instead to travel in search of nontraditionalhealing strategies. While in Thailand in April 1997, he noted thesubacute onset of tender, erythematous nodules on his extremities.He returned to the United States and presented to the hospital,where he reported intermittent fevers and weight loss. Physicalexamination revealed a temperature of 39.07C, temporal wasting,and oral candidiasis. There were multiple violaceous, tender, andfluctuant nodules on his legs (figure 1). A chest radiograph wasnormal. The WBC count was 3,000/mm3, and testing for antibodyto HIV was positive. The absolute CD4 count was 4/mm3, and theplasma HIV RNA was 432,000 copies/mL.

Aspirates from skin lesions were heavily laden with acid-fastbacilli. The patient was initially treated with isoniazid, rifampin,ethambutol, and pyrazinamide until DNA probes ruled out Myco-bacterium tuberculosis. Specimens subcultured on chocolate agarat 307C yielded growth after 1 month. Gas-liquid chromatographicanalysis of the cell-wall fatty acids produced a pattern consistentwith M. haemophilum, and the patient was treated with clarithro-mycin, TMP-SMZ, rifabutin, and ciprofloxacin. He also receivedthe antiretroviral medications stavudine, lamivudine, and nelfi-navir. By July 1997, the lesions were greatly improved; his CD4count had risen to 64/mm3, and plasma HIV RNA was undetect- Figure 1. Skin lesions caused by Mycobacterium haemophilum inable. As part of a routine clinic visit, he was given an intramuscular a 51-year-old HIV-infected man.injection of tetanus toxoid. Within 1 day, he noted the rapid recur-rence of the nodular lesions on his legs. Aspirates of these lesions1 week later again revealed many acid-fast bacilli. However,

of M. haemophilum and the absence of viable organisms from theplasma HIV RNA remained undetectable, and the CD4 count was

recurrent lesions, it is unlikely that this recrudescence represented95/mm3. The patient was observed while taking the same regimen

resurgence of infection. Rather, this case illustrates a previouslyof antiretroviral and antimycobacterial medications, and after sev-

unrecognized effect of tetanus vaccination in the setting of im-eral weeks the lesions again slowly resolved. Cultures from the

mune-system restoration.second aspirate remained negative.

The phenomenon of inflammatory reactions resulting fromM. haemophilum has been reported as a cause of lymphadenitis

newly competent immune cells has been recognized in HIV-in otherwise healthy children, and is now recognized as a pathogen

infected patients since the advent of potent antiretroviral therapy,of immunocompromised adults [1, 2]. Because of the organism’s

and has been particularly noted with mycobacterial infections [4].propensity for growth at reduced temperatures, skin lesions are

In the case presented here, the combined medication regimen ini-usually found on the extremities. Optimal treatment is unknown,

tially resulted in successful treatment of both mycobacterial andand the prognosis appears to be closely linked to the degree of

HIV infections. The return of functional CD4 cells is supportedunderlying immunosuppression [1–3]. The rapid recrudescence of

by the near resolution of the M. haemophilum skin lesions, which tosuch skin lesions has not been reported. Given the slow growth

date has been rare in AIDS patients [3]. However, the vaccinationprovided a sudden immune stimulus, presumably secondary toCD4-cell activation by the T-cell dependent tetanus toxoid. Theresulting skin lesions, although now sterile, were no less dramatic.

Reprints or correspondence: Dr. Carol Ann Huff, Department of General The transient increase in HIV viral load that can be seen followingInternal Medicine, Johns Hopkins Outpatient Center, Room 7143, 601 North

tetanus vaccination [5, 6] was likely mitigated by antiretroviralCaroline Street, Baltimore, Maryland 21287.therapy. Despite the temporary setback, the combination therapy

Clinical Infectious Diseases 1999;28:919–20again proved to be successful, with no detrimental effect on CD4q 1999 by the Infectious Diseases Society of America. All rights reserved.

1058–4838/99/2804–0046$03.00 count or HIV viral load. Tetanus, and perhaps other vaccines,

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2. Straus WL, Ostroff SM, Jernigan DB, et al. Clinical and epidemiologicalwhile still of great benefit in preventive health care, should alsocharacteristics of Mycobacterium haemophilum, an emerging pathogenbe recognized as nonspecific immune activators. Practitioners whoin immunocompromised patients. Ann Intern Med 1994;120:118–25.are treating HIV-infected patients should be aware of such acute

3. Dever LL, Martin JW, Seaworth B, Jorgensen JH. Varied presentations andstimuli and the immune reconstitution syndrome.responses to treatment of infections caused by Mycobacterium haemophi-lum in patients with AIDS. Clin Infect Dis 1992;14:1195–200.Michael K. Gibson, Stephen A. Villano, Carol Ann Huff,

4. Race EM, Adelson-Mitty J, Kriegel GR, et al. Focal mycobacterial lymphad-and Joseph Cofrancescoenitis following initiation of protease-inhibitor therapy in patients with

Divisions of Internal Medicine and Infectious Diseases, Johns Hopkinsadvanced HIV-1 disease. Lancet 1998;351:252–5.

University School of Medicine, Baltimore, Maryland5. Stanley SK, Ostrowski MA, Justement JS, et al. Effect of immunization

with a common recall antigen on viral expression in patients infectedReferences

with human immunodeficiency virus type 1. N Engl J Med 1996;334:1222–30.1. Saubolle MA, Kiehn TE, White MH, Rudinsky MF, Armstrong D. Myco-

6. Staprans SI, Hamilton BL, Follansbee SE, et al. Activation of virus replica-bacterium haemophilum: microbiology and expanding clinical and geo-tion after vaccination of HIV-1-infected individuals. J Exp Med 1995;graphic spectra of disease in humans. Clin Microbiol Rev 1996;9:

435–47. 182:1727–37.

8, she had severe neutropenia (WBCs, 0.9 1 109/L; neutrophils,Severe Neutropenia During Therapy for Concurrent0.05 1 109/L), an axial temperature of 39.67C, and her conditionPrimary Human Immunodeficiency Virus andwas deteriorating. Antiretroviral therapy was discontinued, andCytomegalovirus Infectionsempirical treatment for sepsis syndrome was started with ceftizox-ime and tobramycin. The CD4/ lymphocyte count was 0.180 1

Treatment of primary HIV infection with antiretrovirals is based 109/L on day 9. An esophagogastroscopy done on day 17 revealedon theoretical rationale, limited clinical trial data, and the opinions a necrotic esophageal ulcer (1 cm by 10 cm). CMV and HIV wereof experts. We describe a patient with concurrent primary HIV-1 cultured from biopsy material. Neither staining nor culture showedand cytomegalovirus (CMV) infections who had severe neutro- evidence of fungal etiology. CMV inclusion bodies could not bepenia while receiving antiretroviral therapy. identified. Ganciclovir was started and the retrosternal pain quickly

Serologies for antibodies to CMV and HIV and testing to deter- abated.mine plasma HIV RNA viral load (Amplicor HIV Monitor Test, On day 15, the patient’s WBC count was 3.5 1 109/L (neutro-Roche Diagnostic Systems, Branchburg, NJ) were done with use phils, 0.361 109/L) and her plasma HIV RNA viral load was 5,700of commercial kits. A search was performed on MEDLINE and copies/mL; zidovudine (600 mg/d) was restarted. Lamivudine (300AIDSLINE through November 1997 for concurrent acute/primary mg/d) was added on day 17. Because of the declining neutrophilinfections with HIV and CMV. Additional cases were identified count (0.13 1 109/L), therapy with zidovudine was replaced byby manual searches. that with stavudine (80 mg/d) on day 19. The neutrophil count

A previously healthy, 32-year-old woman was hospitalized (day increased to 1.51 109/L and the CD4/ lymphocyte count to 0.6071) because of fever of 12 days’ duration, headache, skin rash, and 1 109/L by day 25, when saquinavir (1,800 mg/d) was added. Theenlarged cervical lymph nodes. She had been prescribed acyclovir patient tolerated stavudine, lamivudine, and saquinavir and wasfor suspected genital herpes infection 9 days earlier. Her history discharged to her home. On day 54, her WBC count was 4.9 1revealed two episodes of condom-protected heterosexual inter- 109/L (neutrophils, 2.6 1 109/L), CD4/ lymphocyte count wascourse 2 weeks before the fever. She had been HIV-negative 4

0.640 1 109/L, and her plasma HIV RNA viral load was 2,200months earlier, and she denied other possible exposures to HIV

copies/mL. A serology for antibodies to HIV showed strong reac-thereafter. On hospital day 1, serologies for antibodies to HIV

tions to gp 41 and gp 120, but no reaction to p34. A serologyshowed a distinct reaction to envelope protein gp 41 and weak

for IgG antibodies to CMV was positive. Esophagogastroscopyreactions to envelope protein gp 120 and to protein p 17, the plasma

findings were within normal limits.HIV RNA viral load was 480,000 copies/mL, and a serology for

The cause of neutropenia in our patient was probably multifacto-antibodies to CMV was negative. On day 3, her WBC count was

rial; antiretroviral agents, two acute viral infections, and sepsis may3.6 1 109/L (neutrophils, 1.1 1 109/L), hemoglobin level was 127

have contributed to neutropenia. There was no definite histologicalg/L, and her platelet count was 188 1 109/L. On day 5, therapy

proof for CMV causing the esophageal ulcer, but positive culturewith zidovudine (600 mg/d), lamivudine (300 mg/d), and indinavir

from biopsy material, CMV seroconversion, and response to gan-(2,400 mg/d) was instituted, and fluconazole and famotidine were

ciclovir supported this diagnosis.started for oral thrush and retrosternal pain, respectively. On dayTen cases of HIV and CMV primary coinfections have been

described. In general, HIV infection seemed to progress rapidly,as measured by the decline in CD4 cell counts. Several patientshad complications during the primary disease. One patient had

Reprints or correspondence: Dr. Matti Ristola, Aurora Hospital, P.O. Box CMV and toxoplasma retinitis 5 months after the primary infec-348, FIN-00029 HYKS, Finland.

tion [1]. He died 2 months later of lymphoma. Other complica-Clinical Infectious Diseases 1999;28:920–1 tions included pancytopenia, hepatitis, and pericarditis [2],q 1999 by the Infectious Diseases Society of America. All rights reserved.1058–4838/99/2804–0047$03.00 CMV colitis [3], and CMV encephalitis [4]. Only one of the

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Referencespreviously described patients was distinctly neutropenic (0.151 109/L) during the primary infection [2]. In vitro studies have

1. Walsh MB, Calabrese LH. Rapid progression of HIV-1 infection to AIDS.suggested possible mechanisms for interactions between HIV

Clev Clin J Med 1992;59:637–9.and CMV including increased expression of both HIV and CMV 2. Schindler JM, Neftel KA. Simultaneous primary infection with HIV andin coinfected cell lines, or in cells infected by CMV; induction CMV leading to severe pancytopenia, hepatitis, nephritis, perimyocar-of Fc receptors on cells to facilitate the entry of HIV immune ditis, myositis, and alopecia totalis. Klin Wochenschr 1990;68:237–40.complexes; or expression of a protein that can be used as a co- 3. Gupta KK. Acute immunosuppression with HIV seroconversion [letter]. N

Engl J Med 1993;328:288–9.receptor for HIV entry [5–7].4. Berger DS, Bucher G, Nowak JA, Gomatos PJ. Acute primary humanSerious adverse events during antiretroviral treatment of acute

immunodeficiency virus type 1 infection in a patient with concomitantHIV infection have not been previously reported. We emphasizecytomegalovirus encephalitis. Clin Infect Dis 1996;23:66–70.the role of concomitant pathogens that may modify symptoms and

5. Skolnik PR, Kosloff BR, Hirsch MS. Bidirectional interactions betweenpotentially affect the prognosis of HIV disease.human immunodeficiency virus type I and cytomegalovirus. J Infect Dis1988;157:508–14.

6. McKeating JA, Griffiths PD, Weiss RA. HIV susceptibility conferred toJussi Sutinen, Matti Ristola, Jukka Suni, Hannu Nuutinen, human fibroblasts by cytomegalovirus-induced Fc receptor. Nature 1990;

and Juhani Lahdevirta 343:659–61.Divisions of Infectious Diseases and Gastroenterology, Department of 7. Pleskoff O, Treboute C, Brelot A, et al. Identification of a chemokine

Medicine, and Division of Virology, HD Laboratories, Helsinki receptor encoded by human cytomegalovirus as a cofactor for HIV-1entry. Science 1997;276:1874–8.University Central Hospital, Helsinki, Finland

continued for 56 days. Oral maintenance treatment (ofloxacin, 800Melioidosis Brain and Lung Abscess After Travel to Srimg per day) was administered for 8 months. The patient’s clinicalLankacondition improved and the radiological evolution of the pulmo-nary and brain lesions was favorable. The patient had no recrudes-Melioidosis is an infection caused by the soil and water bacte-cence of melioidosis during 2 years of follow-up.rium Burkholderia pseudomallei. Melioidosis is endemic in

This case of melioidosis is intriguing because of its clinicalSoutheast Asia and Northeast Australia [1]. Occasionally tour-presentation and geographic origin. The disease was acquiredists who have traveled for a limited period in an area of endemic-by a tourist who traveled in a region that was considered nonen-ity, such as the northern part of Thailand, may develop meli-demic [1]. Indeed, only very few cases of melioidosis have beenoidosis [2]. Herein, we describe a patient who had acutereported from the Indian subcontinent or Sri Lanka, despitemelioidosis, with necrotizing pneumonia and a brain abscess,similarities in geographic location, weather, and environmental

that occurred after travel to Sri Lanka, a region that was consid-conditions with Southeast Asian countries. Melioidosis may,

ered nonendemic [1].however, be underdiagnosed because of difficulties in cultur-

A 66-year-old man with a negative medical history traveled ining the causative microorganism or may be misdiagnosed as

Sri Lanka for 15 days. He returned to Europe 2 days before theplague [3].

onset of fever (temperature, 397C) and headache. He was treatedThe common clinical presentations of acute melioidosis are sep-

initially with paracetamol. Ten days after onset of symptoms, the sis and pneumonia. Neurological involvement is infrequent [4].patient was admitted to the hospital because of persisting fever Only one other case of melioidosis brain abscess acquired duringand increasing stupor and disorientation. There was no nuchal travel has recently been described [5]. The patient we describe,rigidity. A CT scan of the head revealed a frontal lobe mass. A with multiple organ involvement, was treated with ceftazidimechest radiograph and CT scan showed an infiltrate with central followed by a prolonged maintenance treatment with ofloxacin.necrosis in the right upper pulmonary lobe. Direct microscopy of Ceftazidime has been shown to halve the mortality rate of acutea specimen obtained by CT-guided aspiration of the pulmonary melioidosis and has become first-choice antibiotic for treatment oflesion revealed polymorphonuclear WBCs; there were no bacteria severe melioidosis [6, 7]. Fluoroquinolones have been used forevident on gram-staining of the aspirate. Culture of the aspirate treatment of melioidosis, but recent experience indicates that pri-yielded B. pseudomallei. The strain was susceptible to ceftazidime mary treatment failures and relapses are more frequent than with(MIC, 1.0 mg/L), imipenem (MIC, 0.09 mg/L), and ciprofloxacin a conventional antibiotic combination [8]. The main reasons for(MIC, 0.5 mg/L). Serology for B. pseudomallei (agglutination these failures may be the marginal in vitro activity against mostassay) performed at the Pasteur Institute (Paris), showed a titer of isolates of B. pseudomallei and the emergence of resistance during1:320. Antibiotic treatment with ceftazidime (2 g iv t.i.d.) was treatment. The favorable response of our patient may be due to

the lower MIC, the higher dose of the fluoroquinolone, and a longerprimary treatment with ceftazidime compared to the experience inthe literature.

Reprints or correspondence: Dr. W. E. Peetermans, Department of Internal In conclusion, we described a patient with acute pulmonary andMedicine, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium

neurological melioidosis acquired during travel in Sri Lanka, a([email protected]).region that was considered nonendemic. Ceftazidime monotherapy

Clinical Infectious Diseases 1999;28:921–2followed by long-term maintenance treatment with ofloxacin re-q 1999 by the Infectious Diseases Society of America. All rights reserved.

1058–4838/99/2804–0048$03.00 sulted in complete cure.

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4. Woods ML, Currie BJ, Howard DM, et al. Neurological melioidosis: sevenWilly E. Peetermans, Eric Van Wijngaerden,cases from the Northern Territory of Australia. Clin Infect Dis 1992;15:Johan Van Eldere, and Jan Verhaegen163–9.Departments of Internal Medicine and of Microbiology and

5. Padiglione A, Ferris N, Fuller A, Spelman D. Brain abscesses caused byImmunology, University Hospital Leuven, Leuven, BelgiumBurkholderia pseudomallei. J Infect 1998;36:335–7.

6. Suputtamongkol Y, Rachanuwong A, Chaowagul W, et al. Ceftazidimeversus amoxicillin/clavulanate in the treatment of severe melioidosis.Clin Infect Dis 1994;19:846–53.References

7. Sookpranee M, Boonma P, Susaengrat W, Bhuripanyo K, Punyagupta S.1. Dance DAB. Melioidosis: the tip of the iceberg? Clin Microbiol Rev 1991; Multicenter prospective randomized trial comparing ceftazidime plus co-

4:52–60. trimoxazole with chloramphenicol plus doxycycline and co-trimoxazole2. Sauerwein RW, Lammers JW, Horrevorts AM. Ceftazidime monotherapy for treatment of severe melioidosis. Antimicrob Agents Chemother 1992;

for pulmonary melioidosis in a traveler returning from Thailand. Chest 36:158–62.1992;101:555–7. 8. Chaowagul W, Suputtamongkol Y, Smith MD, White NJ. Oral fluoroquino-

3. Dance DAB, Sanders D, Pitt TL, Speller DCE. Burkholderia pseudomallei lones for maintenance treatment of melioidosis. Trans R Soc Trop MedHyg 1997;91:599–601.and Indian plague-like illness. Lancet 1995;346:904–5.

Candida (Torulopsis) glabrata: A New Pathogen Found inan Empyema

A 75-year-old man presented to the emergency department be-cause of epigastric pain, nausea, and vomiting after consumingdinner. On initial presentation he was afebrile. He had diffuseabdominal tenderness with guarding. His physical examinationfindings were otherwise normal. The WBC count was normal withno left shift. His chest radiograph revealed a small left-lower-lobe infiltrate, for which he was started on intravenous ampicillin/sulbactam. An abdominal series revealed no evidence of obstruc-tion. An exploratory laparotomy showed no significant pathology.Within 24 hours following the operation, a closed chest-tube thora-costomy was performed because of the development of an ex-panding massive left pleural effusion with compression atelectasis.Microscopic evaluation of a pleural-fluid specimen revealed a Figure 1. A 75-year-old man with empyema due to Candida (Toru-yeast-like organism, and culture of the pleural fluid yielded Can- lopsis) glabrata demonstrating budding yeast cells (arrows) (Go-dida (Torulopsis) glabrata. mori’s methenamine silver stain, magnification1100, oil immersion).

The patient was treated initially with intravenous fluconazole,1,200 mg over 3 days, for a presumed systemic candidal infectionwhile awaiting the final identification of the yeast. Therapy withfluconazole was discontinued when the organism was identified, to HIV was negative. Immunoglobulin assay studies revealed aand then therapy with intravenous amphotericin B was begun. mild decrease in IgA and IgG. The patient was anergic on skinVideo-assisted thoracoscopy revealed a multiloculated fluid collec- testing with controls. He received a total dose of 1,260 mg oftion with massive fibrinous pleuritis and an entrapped lung. The amphotericin B. Despite intense treatment, he died of persistentpatient underwent a left thoracotomy, intrapleural instillation of empyema and polymicrobial sepsis. The family declined an au-streptokinase, open drainage, left lung decortication, and open lung topsy.biopsy of the left lower lobe and left lingulae, as well as a left The patient we described represents the first reported case ofpleural biopsy. Gram staining of the biopsy specimens and empy- pleural empyema associated with C. glabrata. His presentationema (figure 1) revealed a yeast-like organism, and cultures yielded is interesting, as others have also reported infection due toC. glabrata. Blood cultures were positive once for C. glabrata C. glabrata with an initial presentation of gastroenteritis [1].and three times for Staphylococcus aureus, for which the patient Although the upper airway is an important portal of entry forwas treated with intravenous vancomycin. A serology for antibody Candida species, pneumonia due to Torulopsis species is very

rare [1, 2]. Several cases of pneumonia due to Torulopsis speciesassociated with fungemia have been reported, but the pulmonaryinfection was not believed to be the etiology of the fungemia

Reprints or correspondence: Dr. Brenda A. El-Shiekh, Mercy Health Partners [3]. Although studies suggest that C. glabrata is an organism ofFamily Practice Residency Program, 2127 Jefferson Avenue, Toledo, Ohio low virulence, C. glabrata accounts for Ç7% of all nosocomial43624.

fungal infections [4]. Underlying disease and coexisting bacte-Clinical Infectious Diseases 1999;28:922–3 rial infection are the most important factors responsible forq 1999 by the Infectious Diseases Society of America. All rights reserved.1058–4838/99/2804–0049$03.00 death [5].

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ReferencesIn summary, empyema due to C. glabrata has not beenreported previously. Early diagnosis and appropriate treat- 1. Srivastava S, Kleiman G, Manthous CA. Torulopsis pneumonia. A casement of infections due to Torulopsis species with prompt, ade- report and review of the literature. Chest 1996;110:858–61.

2. Stone H, Kolb L, Currie C, Geheber C, Cuzzell J. Candida sepsis: pathogen-quate drainage of an empyema will reduce morbidity and mor-esis and principles of treatment. Ann Surg 1974;179:697–711.tality.

3. Berkowitz I, Robboy S, Karchme A, Kunz L. Torulopsis glabratafungemia—a clinical pathological study. Medicine (Baltimore) 1979;58:430–40.

Vasanthi Chandrasekaran, Brenda A. El-Shiekh, and 4. Henderson V, Hirela E. Emerging and re-emerging microbial threats. Noso-Camille A. Karaffa comial fungal infections. Arch Surg 1996;131:330–7.

Mercy Health Partners Family Practice Residency Program, 5. Marshall J, Christou N, Meakins J. The gastrointestinal tract: the ‘undrainedabscess’ of multiple organ failure. Ann Surg 1993;218:111–9.Toledo, Ohio

Gas Gangrene in an Immunocompromised Girl Due to aClostridium ramosum Infection

Clostridia are gram-positive, spore-forming anaerobic rods. Anumber of Clostridium species that are normally present in thecommensal flora of the human intestine may cause infections.Severe infection of soft tissue results in gas gangrene or myo-necrosis. Such infections occur after traumatic injuries as well asspontaneously. Spontaneous nontraumatic gas gangrene is eitherlocally associated with an intraabdominal focus or a distant spreadof infection. These infections occur mainly in immunocomprom-ised hosts. Clostridium septicum is the Clostridium species isolatedmost frequently in nontraumatic gas gangrene in patients withmalignancies of the gastrointestinal tract and leukemia, and inchildren with cyclic neutropenia [1, 2]. In patients colonized with

Figure 1. Radiograph of the thorax of an 11-year-old immunocom-C. septicum, it appears that neutropenia predisposes to the develop-promised patient with an infection due to Clostridium ramosum. Inter-ment of bacteremia. Clostridium ramosum is one of the Clostrid-stitial emphysema is seen in the right axilla (black arrow) and theium species that is often isolated from stool samples of children,superior mediastinum (white arrows).but has been associated only rarely with severe infections or bacter-

emia [3, 4]. The number of cultures positive for C. ramosum isprobably underestimated. The organism can easily be missed in

ture of 40.57C, a pulse rate of 160 beats/min, and a blood pressureanaerobic cultures, because it usually stains gram-negative instead

of 80/45 mm Hg. A chest radiograph revealed no signs of pulmo-of gram-positive, and the typical terminally located spores are

nary infection or congestion, but showed an interstitial emphysemasometimes hard to detect. We describe a lethal septic episode in

in the right axilla and the superior mediastinum (figure 1). Thisan immunocompromised child with spontaneous gas gangrene and

finding was confirmed by ultrasonography. Laboratory findingscultures of blood yielding C. ramosum and Candida albicans.

showed leukocytopenia (WBC count, 100 1 106/L), thrombocyto-An 11-year-old girl had been receiving chemotherapy for several

penia (platelet count, 12 1 109/L), and anemia (hemoglobin level,weeks because of the recurrence of a common acute lymphatic

4.1 mmol/L). There was diffuse intravascular coagulation (partialleukemia and was in a neutropenic phase (WBC count, 200 1

thromboplastin time, ú40 sec; activated partial thromboplastin106/L). While at home, she developed a severe mucositis, and her

time, ú150 sec). The sodium level was 128 mmol/L, potassiumcondition deteriorated in the days before she was admitted to the

level was 6.9 mmol/L, total bilirubin level was 750 mmol/L, andhospital. She had fever, chills, myalgia, loss of appetite, and wa-

lactate level was 11.6 mmol/L.tery, bloody diarrhea. Physical examination at admission revealed

Only one blood culture set (anaerobic/aerobic) could be ob-a sick, somnolent, dyspneic girl with yellow sclerae and several

tained. In both bottles, microbial growth was noted after 24 hours.greenish necrotic ulcers on the tongue. Her face and neck were

Gram staining of the anaerobic bottle specimen demonstratedswollen with palpable crepitations of the skin. She had a tempera-

gram-negative rods with typical terminal spores. Subculture onblood agar plates yielded growth only anaerobically after 48 hours.The isolate was nonmotile, unable to produce indole, and able toferment maltose, salicine, lactose, sucrose, and mannitol, and was,

Reprints or correspondence: Dr. E. R. van der Vorm, Academic Medical therefore, identified as C. ramosum. Antibiotic susceptibility testsCenter, L1-104, P.O. Box 22660, 1100 DD Amsterdam, the Netherlands (e.r.

showed that the isolate was susceptible to penicillin. Candida [email protected]).cans was isolated from the aerobic bottle. A culture of the oropha-

Clinical Infectious Diseases 1999;28:923–4ryngeal swab yielded a few colonies of C. albicans. No otherq 1999 by the Infectious Diseases Society of America. All rights reserved.

1058–4838/99/2804–0050$03.00 specimens were available for culture.

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In the pediatric intensive care unit, the girl was treated for septic that may facilitate mucosal penetration [9]. The (oral) mucositisin our patient—a common feature in patients treated with chemo-shock. Vancomycin (40 mg/kg), gentamicin (6 mg/kg), ceftazidimetherapy—was most likely the portal of entry and may have en-(100 mg/kg), and dexamethasone (stress doses) were administeredhanced intravascular invasion with C. ramosum and probably alsointravenously, and she received circulatory and respiratory support.with C. albicans. Whether the fungemia due to C. albicans playedIn spite of maximal treatment she died within 1 hour of admission.a role in the fatal outcome of the acute infection in this patientThe presumptive diagnosis was spontaneous gas gangrene withremains unclear.circulatory failure. The diagnosis could not be confirmed because

autopsy was not permitted.E. R. van der Vorm, I. A. von Rosenstiel, L. Spanjaard, andTo our knowledge, we have described the first case of a fatal

J. Dankertinfection due to C. ramosum in a child with leukemia and chemo-Departments of Medical Microbiology and Pediatrics, Academictherapeutic-induced neutropenia. A number of the ú80 known

Medical Center, Amsterdam, the Netherlandsclostridial species have been isolated from soft-tissue infections.They are frequently part of polymicrobial cultures and can act

Referencessynergistically with other pathogens, thereby worsening the clini-

1. Collier PE, Diamand DC, Young JC. Nontraumatic Clostridium septicumcal outcome. Underlying illnesses such as cancer are believed togangreneous myonecrosis. Dis Colon Rectum 1983;26:703–4.

facilitate the development of clostridial infections. Our patient2. Bratton SL, Krane EJ, Park JR, Burchette S. Clostridium septicum infections

presented with spontaneous gas gangrene. This disorder has been in children. Pediatr Infect Dis J 1992;11:569–75.reported in patients with colon cancer and leukemia and other 3. Brook I. Clostridial infection in children. J Med Microbiol 1995;42:forms of neutropenia. C. septicum is the Clostridium species most 78–82.

4. Stark PL, Lee A. Clostridia isolated from the feces of infants during thefrequently isolated from blood cultures and intraabdominal speci-first year of life. J Pediatr 1982;100:362–5.mens in these patients [1, 2]. C. ramosum has been cultured from

5. Langdale LA, Rice CL, Brown N. Emphysematous pyelonephritis in agastrointestinal abscesses and ear infections. Since many otherxanthogranulomatous kidney. An unusual cause of pneumoperitoneum.Clostridium species and non-clostridial bacteria are often presentArch Surg 1988;123:377–9.

in such infections, it is difficult to assess the pathogenic role of6. Muakkassa WF, Mohanty PK, Kipreous B, Lee HM, Goldman MH. Left

C. ramosum. On the other hand, there have been a few reports of ventricular mass with septic (Clostridium ramosum) arterial emboli in aunusual infections with C. ramosum as the sole microorganism renal allograft patient: report of a case and review of the literature.isolated [5, 6]. Bacteremia has been described and is occasionally Transplant Proc 1983;15:1715–9.

7. Gorbach SL, Thadepalli H. Isolation of Clostridium in human infections:found in leukemic patients [7].evaluation of 114 cases. J Infect Dis 1975;131(suppl 1):S81–5.In healthy persons, C. albicans is frequently isolated from gas-

8. Odds FC, Kibbler CC, Walker E, Bhamra A, Prentice HG, Noone P. Car-trointestinal tract specimens as part of the normal flora. Fifty toriage of Candida species and C. albicans biotypes in patients undergoingseventy percent of the stool and throat specimens from immuno-chemotherapy or bone marrow transplantation for haematological dis-

compromised patients show colonization with C. albicans [8].ease. J Clin Path 1989;42:1259–66.

The finding of a blood specimen positive for C. ramosum in the 9. Kobayashi K, Fujiyama Y, Hagiwara K, Kondoh H. Resistance of normalpresence of gas gangrene in the neck and thorax implicates a serum IgA and secretory IgA to bacterial IgA proteases: evidence for thepathogenic role for C. ramosum in this patient with severe neutro- presence of enzyme-neutralizing antibodies in both serum and secretory

IgA, and also in serum IgG. Microbiol Immunol 1987;31:1097–106.penia. C. ramosum is able to produce IgA1 and IgA2 proteases

A 45-year-old male marine electrician presented with a progres-Disseminated Papulopustular Eruption Due tosively spreading papulopustular eruption. The first lesions had ap-Mycobacterium fortuitum in an Immunocompetent Patientpeared 2 months earlier on the right arm and had persisted despitelocal disinfection. Gradually, the other arm, the trunk, and the neckCutaneous infections due to atypical mycobacteria are wellhad become involved (figure 1). There was no pruritus or fever.known. However, the frequency of rapidly growing mycobacteriaOral antibiotics were administered (oxacillin, 2 g per day for 1is probably underestimated. Cutaneous or soft-tissue infections areweek, followed by pristinamycin, 3 g per day for 2 weeks) withthe most frequent human diseases caused by these microorganisms.no improvement. There was no history of previous surgery, trauma,The lesions are usually nodular, ulcerative, or cellulitic. To ouror injection. The clinical examination did not reveal lymph node

knowledge, we describe the first case of a disseminated papulopus-involvement or hepatosplenomegaly. Blood cell count, lympho-

tular eruption due to Mycobacterium fortuitum without associatedcytic phenotyping, profile of ion concentration, hepatic and renal

systemic infection in an immunocompetent patient.function, as well as chest radiographs and abdominal ultrasonogra-phy were normal. A serology for antibodies to HIV was negative.Cultures of two different specimens from two pustules obtainedat 2-week intervals both yielded mycobacteria within 5 days. The

Reprints or correspondence: Dr. Desruelles Francois, CHU de Nice, Hopital strain presented characteristics of M. fortuitum group [1]: coloniesde l’Archet 2, Service de Dermatologie, 151 Rte de St-Antoine de Ginestiere-

were nonphotochromogenic, grew on MacConkey agar, and wereBP 3079-06202 Nice Cedex 3, France ([email protected]).positive for nitrate, iron uptake, and arylsulfatase. As determined

Clinical Infectious Diseases 1999;28:924–5by the Etest method (AB BIODISK, Solna, Sweden), the strainq 1999 by the Infectious Diseases Society of America. All rights reserved.

1058–4838/99/2804–0051$03.00 was susceptible to clarithromycin, ciprofloxacin, and minocycline

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neous lesions may also follow a systemic infection. Immunocom-petent patients develop cellulitic, nodular, or ulcerative lesions.Extensive necrosis and abscess formation are more often encoun-tered in immunocompromised patients. A satellite pathologiclymph node is generally noted.

To our knowledge, only one case of maculopapular eruptiondue to a rapidly growing mycobacterium has been reported, accom-panied by disseminated infection, which was not observed in ourcase [5]. Therefore, we have described the first case of profusepapulopustular eruption due to M. fortuitum, without systemicinvolvement, occurring in an immunocompetent patient. The par-ticular occupational context (a marine electrician often exposed tomicrotraumas in stagnant water) probably explains this kind oferuption with its particular disseminated variety. The partial regres-sion of the lesions after 2 months of bi-antimicrobial therapy couldbe explained by a lower sensitivity of the microorganism in vivothan in vitro. Alternatively, the partial efficacy of the treatmentFigure 1. Papulopustular eruption of the neck, trunk, and arm of acould be related to insufficient skin protection of the patient during45-year-old man due to Mycobacterium fortuitum.his work activities.

The spectrum of primitive cutaneous lesions due to M. fortuitumin immunocompetent patients should be extended to disseminatedand resistant to rifampin. Histological evaluation of a skin biopsypapulopustular eruptions.specimen showed an inflammatory infiltrate without tuberculoid

granuloma. Doxycycline (200 mg/day) and clarithromycin (3T. Passeron, F. Desruelles, T. Fosse, M. Weiller, C. Perrin,g/day) were administered. Two months later, the cutaneous lesions

J. Ph. Lacour, and J. P. Ortonnehad only partially regressed; ciprofloxacin, 1 g/day, was added toDepartments of Dermatology, Bacteriology, and Pathology, Hopital dethe previous regimen. Because the patient continued his usual

l’Archet, Nice, Francework, he was asked to protect his skin while working in stagnantwater. Three months after the beginning of the treatment, the le-

Referencessions had improved. However, further follow-up is necessary.The mycobacteria of Runyon group IV are rapidly growing 1. Nolte FS, Metchoek B. Mycobacterium. In: Murray PR, Baron EJ, Pfaller

MA, Tenover FC, Yolken RH, eds. Manual of clinical microbiology. 6thmycobacteria. The time required for growth is 3 to 7 days at 257Ced. Washington, DC: ASM Press, 1995:400–37.to 407C on routine bacteriologic media [2]. In this group, only

2. Wallace RJ Jr. The clinical presentation, diagnosis and therapy of cutaneousM. fortuitum and Mycobacterium chelonae are considered to beand pulmonary infections due to the rapidly growing mycobacteria M.pathogenic for humans. Rapid growers are found in soil, dust, andfortuitum & M. chelonei. Clin Chest Med 1989;10:419–29.water [3, 4]. More than 90% of cutaneous diseases caused by

3. Wolinsky E, Rynaerson T. Mycobacterial flora of the soil. Am Rev Respirmycobacteria are due to M. fortuitum and M. chelonae [2, 5];

Dis 1966;94:478.cutaneous infections are the most frequent manifestations. M. for- 4. Kubica GP, Beam RE, Palmer JW. A method for the isolation of unclassifiedtuitum is isolated more often from skin lesions, whereas M. chelo- acid fast bacilli from the soil and water. Am Rev Respir Dis 1966;94:nae is mostly responsible for disseminated infections [5]. The 718–20.organisms gain entry into a host by inoculation into the skin and 5. Wallace RJ, Swenson JM, Silcox VA, et al. Spectrum of disease due to

rapidly growing mycobacteria. Rev Infect Dis 1983;5:657–79.subcutaneous tissues during surgery, trauma, or injections. Cuta-

have been a number of articles describing the detection of toro-Torovirus Gastroenteritis Presenting as Acute Abdomenvirus-like particles in children and adults with gastroenteritis [4–7]. It was further shown in a case-control study that torovirus

Toroviruses are enveloped, positive stranded RNA viruses thatwas definitively associated with hospital-acquired gastroenteritis

are classified as members of the family Coronaviridae [1]. Theyin children [8]. The detection of toroviruses by use of electron

have been shown to be etiologic agents of gastroenteritis in cattle,microscopy has been substantiated by EIAs using antisera to Breda

and a porcine torovirus has recently been reported [2, 3]. Therevirus, a bovine torovirus, and by immunospecific and molecularapproaches [5, 7]. Herein we describe two patients who presentedwith gastroenteritis as well as with signs of acute surgical abdo-men. In both patients, the detection of torovirus in the stool speci-

Reprints or correspondence: Dr. Martin Petric, Virology, Department of mens was the only finding implicating an etiologic agent. To ourPediatric Laboratory Medicine, The Hospital for Sick Children, 555 University

knowledge, we describe the first cases of torovirus associated withAvenue, Toronto, Ontario, Canada, M5G 1X8 ([email protected]).symptoms and signs of peritonitis.

Clinical Infectious Diseases 1999;28:925–6Patient 1 was a 9-year-old girl with familial Mediterranean feverq 1999 by the Infectious Diseases Society of America. All rights reserved.

1058–4838/99/2804–0052$03.00 (FMF), diagnosed at 21/2 years of age [9], that was well controlled

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with daily colchicine therapy. She presented with a 1-day history Torovirus has been reported in association with human gastroen-teritis [6, 8]. These studies showed that the virus can be detected inof fever (temperature, to 397C) that resolved the following day,

when she developed recurrent bouts of severe colicky abdominal stool specimens of symptomatic patients by use of electron micros-copy and ELISA. Torovirus has recently been shown to be a rela-pain, each lasting 30 to 60 minutes; she was pain free between

the episodes. Accompanying the abdominal pain were vomiting tively common agent of diarrhea [6, 8]. Clinically, torovirus-inducedgastroenteritis is similar to other types of viral gastroenteritis andand loose watery stools without frank or occult blood. On physical

examination, she was afebrile and looked well except during the presents with abdominal pain associated with vomiting and diarrhea;fever may be present at the onset. The disease is self-limited andpainful abdominal attacks when she was in significant distress.

The abdominal examination revealed generalized tenderness, with resolves within several days, although shedding of the virus maycontinue for weeks, particularly in immunocompromised hosts [8].involuntary guarding, positive rebound sign, and reduced peristal-

tic sounds. There was no hepatosplenomegaly. The remainder of Torovirus was the principal identifiable cause of nosocomial diarrheain immunocompromised patients and in this regard patient 2, whomthe physical examination findings were within normal limits. This

patient was not considered to be having an episode of FMF, since we have described, was immunosuppressed [8]. An antibody re-sponse to the virus develops in more than one-half of the patients;the clinical presentation differed from those during her previous

attacks. She was afebrile and the pain was intermittent and not however, serology for torovirus was not performed on the abovepatients while they were hospitalized.consistent as in patients with FMF [9].

The results of the following laboratory tests were normal or The two patients described herein are unique in their clinicalfeatures. Both presented initially with common, nonspecific clini-negative: CBC with differential and platelet count, erythrocyte

sedimentation rate, electrolyte levels, renal and liver function tests, cal features, namely fever, vomiting, and abdominal pain followedby diarrhea, but then developed severe abdominal pain and acuteserum amylase level, and urinalysis. Abdominal and chest radio-

graphs were within normal limits. Abdominal ultrasonography re- peritoneal signs. To our knowledge, these signs have not beenpreviously reported in conjunction with a torovirus infection. Thevealed free peritoneal fluid. WBCs were seen on microscopic ex-

amination of the stool. Stool cultures were negative for bacteria thorough investigations excluded other etiologies of acute abdo-men, as no bacterial or other etiologic agent was found, and theand Clostridium difficile cytotoxin. Electron microscopic examina-

tion of the stool revealed torovirus. The patient was treated with fact that both patients recovered completely in 2–3 days withconservative treatment alone suggests that this illness was consis-bowel rest, intravenous fluids, and intravenous meperidine until

her symptoms resolved 3 days later. Repeated examination for tent with a torovirus infection [8].Awareness that torovirus may be associated with acute abdomentorovirus in stool 1 month later was negative, and the patient has

remained well. is important. More clinical data are needed to further describe thepathogenesis and the clinical features of this potentially commonPatient 2 was a 15-year-old boy who had had severe systemic-

onset juvenile rheumatoid arthritis since age 4. His medications at and important pathogen.the time of presentation included prednisone, 15 mg a day alternat-

Yosef Uziel, Ronald M. Laxer, and Martin Petricing with 5 mg a day; indomethacin, 25 mg t.i.d.; ranitidine, 150

Division of Rheumatology, Departments of Pediatrics, and Medicine,mg b.i.d.; and methotrexate, 12.5 mg subcutaneously once weekly.

and Pediatric Laboratory Medicine, The Hospital for Sick Children,He was admitted because of dehydration following 3 days of vom- University of Toronto, Toronto, Ontario, Canadaiting and diarrhea, but he was afebrile. His condition improved

Referencesafter receiving intravenous fluids, but on the 7th day after onsetof symptoms, he suddenly developed severe colicky abdominal 1. Cavanagh D. Nidovirales: a new order comprising Coronaviridae and Arteri-

viridae. Arch Virol 1997;142:629–33.pain and fever (temperature, to 397C). At physical examination he2. Woode GN, Reed DE, Runnels PL, Herrig MA, Hill T. Studies with anwas in moderate distress. The abdominal examination revealed

unclassified virus isolated from diarrheic calves. Vet Microbiol 1982;7:diffuse tenderness, guarding and rebound; there were no peristaltic221–40.sounds. Other than for multiple joint deformities, the remainder

3. Kroneman A, Cornelissen LAHM, Horzinek MC, DeGroot RJ, Egberinkof the physical examination findings were within normal limits.

HF. Identification and characterization of a porcine torovirus. J VirolLaboratory studies revealed the following values: hemoglobin, 76 1998;72:3507–11.g/L; WBCs, 19.2 1 109/L (increased from 10.6 1 109/L the previ- 4. Beards GM, Hall C, Green J, Flewett TH, Lamouliatte F, Du Pasquier P.ous day) with a normal differential; and platelets, 740 1 103/L. An enveloped virus in stools of children and adults with gastroenteritisThe results of the renal and liver function studies, serum amylase that resembles the Breda virus of calves. Lancet 1984;12:1050–2.

5. Koopmans M, Petric M, Glass RI, Monroe SS. Enzyme-linked immunosor-level, and the urinalysis were normal, as was the chest radiograph.bent assay reactivity of torovirus-like particles in fecal specimens fromAn abdominal radiograph revealed a distended stomach and bowelhumans with diarrhea. J Clin Microbiol 1993;31:2738–44.loops. Abdominal ultrasonography revealed fluid-filled bowel

6. Koopmans MP, Goosen ES, Lima AA, et al. Association of torovirus withloops with minimal free abdominal fluid in the cul-de-sac.acute and persistent diarrhea in children. Pediatr Infect Dis J 1997;16:The stool culture was negative for bacteria and parasites and504–7.for C. difficile cytotoxin. Torovirus particles were detected in stool

7. Duckmanton L, Luan B, Devenish J, Tellier R, Petric M. Characterizationby use of electron microscopy. The patient was treated with bowel

of torovirus from human fecal specimens. Virology 1997;239:158–68.rest and triple antibiotic therapy (ampicillin, gentamicin, and met- 8. Jamieson FB, Wang EE, Bain C, Good J, Duckmanton L, Petric M. Humanronidazole) until the confirmation of negative bacterial cultures, torovirus: a new nosocomial gastrointestinal pathogen. J Infect Dis 1998;and he recovered gradually in 3 days. Torovirus was detected in 178:1263–9.the repeated stool examination by electron microscopy 2 weeks 9. Gedalia A, Adar A, Gorodischer R. Familial Mediterranean fever in chil-

dren. J Rheumatol 1992;19(suppl 35):1–9.later, but could not be detected 1 month after presentation.

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species and a PCR assay for intracellular Ehrlichia antigen wereAutoimmune Thrombocytopenia Associated with Borrelianegative. Repeated blood smear staining showed no evidence forburgdorferiintraerythrocytic babesiosis. Serological tests were all negative forhepatitis A, B, and C viruses; influenza and parainfluenza viruses;

The association of borreliosis and thrombocytopenia remains anadenovirus; flavivirus causing seasonal tickborne meningoenceph-

issue of controversy [1, 2]. In a recent review, Nadelman andalitis; Chlamydia; herpes simplex virus; cytomegalovirus; parvovi-

Wormser [3] proposed that thrombocytopenia is not characteristicrus B19; Epstein-Barr virus; and HIV. There was no immunopatho-

of Lyme borreliosis per se but suggestive of coinfection with spe-logical evidence for connective tissue disease. Histological

cies of Babesia or Ehrlichia. The few cases of thrombocytopeniaevaluation of an iliac crest bone marrow trephine showed hyperpla-

associated with borreliosis appear to have been transient, remedia-sia of megakaryocytes but no other abnormalities.

ble by antibiotic therapy, and a consequence of decreased thrombo-Glycoprotein-specific ELISA showed IgG binding to patient and

poiesis [4]. We describe a patient in whom borreliosis triggereddonor platelet glycoprotein IIb/IIIa, allowing the diagnosis of auto-

an autoimmune thrombocytopenia in the absence of coinfectionimmune thrombocytopenia. Cross-reactivity between Borrelia-

with Babesia or Ehrlichia species.specific IgG antibodies and platelets was excluded, since the acid

A previously healthy 49-year-old woman from a rural area ineluate of the patient’s platelets containing IgG antibodies did not

the German state of Baden-Wurttemberg was admitted for evalua-bind to Borrelia-specific proteins in the immunoblot. Furthermore,

tion of a 6-month history of recurrent episodes of fever, malaise,incubation of the patient’s serum with donor platelets failed to

and arthralgia. Easy bruising was not reported. In response todecrease Borrelia-specific IgG levels.

specific questioning, the patient recalled a ring-shaped migratingOur patient presented with a history and symptoms typical of

rash and a tick bite on the upper trunk 18 months previously.Lyme borreliosis, confirmed by serological tests. The acute infec-

Except for occasional acetaminophen tablets, she had not takention probably dates back to one and one-half years ago. Since

any medication. Two years previously, a routine platelet count ofthen, she had developed an autoimmune thrombocytopenia without

220 1 109/L had been recorded by the general practitioner. Physi-evidence of bleeding. Before the Borrelia infection, platelet counts

cal examination was essentially unrevealing. Laboratory evaluationhad been normal. Since we can exclude a causal relationship with

revealed the following significant values: WBCs, 7.21 109/L (94%drugs and other infectious organisms, in particular Ehrlichia and

neutrophils); platelets, 20 1 109/L; and C-reactive protein, 2.0Babesia species, we propose that the borrelia infection triggered

mg/dL. The first documented platelet count of below 100 1the autoimmune thrombocytopenia in this patient.

109/L had occurred 6 months earlier.ELISA (Enzygnost Borreliosis, Behring Diagnostics, Marburg, Norbert Stefan, Susanne Elsner, Martina Schnaidt,

Germany) showed IgG antibodies to Borrelia burgdorferi (710 Dorothee Wernet, and Michael StumvollU/mL; normal, õ10 U/mL). Western blot analysis confirmed IgG Medizinische Klinik, Abteilung fur Medizinische Mikrobiologie,binding to a Borrelia-specific protein at 18 kDa and 39 kDa, and Abteilung fur Transfusionsmedizin der Universitat Tubingen, Tubingen,IgM binding to a 41-kDa protein (Recom Blot, Microgen, Munich). GermanyImmunofluorescence testing of serum for antibodies to Ehrlichia

References

1. Nadelman RB, Strle F, Horowitz HW, Agger WA, Wormser GP. Leukope-nia, thrombocytopenia, and Lyme borreliosis: is there an association?Clin Infect Dis 1997;24:1027–9.Reprints or correspondence: Dr. Michael Stumvoll, Medizinische Klinik der

2. Peter O, Gubler J, Gunthard HF. Reply. Clin Infect Dis 1997;24:1028–9.Universitat, Otfried-Muller-Str. 10, 72076 Tubingen, Germany.3. Nadelman RB, Wormser GP. Lyme borreliosis. Lancet 1998;352:557–65.

Clinical Infectious Diseases 1999;28:9274. Ballard HS, Bottino G, Bottino J. The association of thrombocytopaeniaq 1999 by the Infectious Diseases Society of America. All rights reserved.

1058–4838/99/2804–0053$03.00 and Lyme disease. Postgrad Med J 1994;70:285–7.

tean, ranging from benign soft-tissue abscesses to a rapidlyArabinose-Positive Burkholderia pseudomallei Infection inprogressive fatal septicemia [2]. Two distinct types of B. pseu-Humans: Case Reportdomallei strains, differentiated by their ability to utilize the sugarL-arabinose as a sole energy source for growth into Ara0 and Ara/

Burkholderia pseudomallei is the causative organism of meli- B. pseudomallei, are found in the environment [3]. The strains areoidosis. The disease is endemic in the tropics, especially in north- similar in morphology and antigenicity, but are genetically differ-eastern Thailand [1]. Clinical presentations of melioidosis are pro- ent [4]. Both types have been commonly isolated from the soil

and water in northeastern Thailand [3]. Theú2,500 strains isolatedfrom human cases of melioidosis in Thailand to date have all beenAra0 B. pseudomallei [3]. Thus it appears that Ara/ B. pseudomal-

Reprints or correspondence: Dr. Yupin Suputtamongkol, Department of lei strains have been previously found exclusively in the environ-Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok ment. To our knowledge, Ara/ B. pseudomallei has never before10700, Thailand ([email protected]).

been isolated from patients with melioidosis. We describe hereinClinical Infectious Diseases 1999;28:927–8 the first case of human melioidosis caused by an Ara/ B. pseu-q 1999 by the Infectious Diseases Society of America. All rights reserved.1058–4838/99/2804–0054$03.00 domallei.

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A 16-year-old man was admitted to Srisaket Hospital (Thailand) of a very heavy inoculation at the time of his accident. The Pseu-domonas species strain, which was grown from his blood culture,20 minutes after a motorcycle accident, with blunt trauma to the

abdomen and compound fractures of the right femur and right was not available for further identification and might also beB. pseudomallei. Thus, Ara/ B. pseudomallei can also be patho-tibia. Physical examination at admission revealed a temperature

of 377C, a blood pressure of 130/80 mm Hg, a pulse rate of genic to humans, as shown in this patient.90/min, a respiratory rate of 32/min, and marked tenderness at theepigastrium. An emergency laparotomy revealed a rupture of the Nimit Lertpatanasuwan, Kridsada Sermsri,duodenum, and the leakage site was repaired. The compound frac- Anantachoke Petkaseam, Suwanna Trakulsomboon,ture of his right leg was associated with severe soft-tissue and Visanu Thamlikitkul, and Yupin Suputtamongkolvascular injuries. An above-the-knee amputation of that leg was Departments of Medicine, Orthopedics, and Surgery, Srisaket Hospital,

Srisaket, and Division of Infectious Diseases and Tropical Medicine,carried out 5 days later.Department of Medicine, Faculty of Medicine Siriraj Hospital, MahidolThe patient was febrile and clinically septic after admission.

University, Bangkok, ThailandHowever, his condition gradually improved with intravenous clox-acillin and gentamicin treatment and supportive ventilation for 2

Referencesweeks. During the third week, he again developed a high fever.Cultures of blood obtained at this time yielded Pseudomonas spe- 1. Chaowagul W, White NJ, Dance DAB, et al. Melioidosis: a major causecies, and cultures of purulent material from the amputation site of community-acquired septicemia in northeastern Thailand. J Infect Dis

1989;159:890–9.yielded B. pseudomallei. The patient’s therapy was switched to2. White NJ, Dance DA, Chaowagul W, Wattanagoon Y, Wuthiekanun V,that with ceftazidime, and then to a combination of cefoperazone/

Pitakwatchara N. Halving of mortality of severe melioidosis by ceftazi-sulbactam because the hospital pharmacy ran out of ceftazidime.dime. Lancet 1989;2:697–701.He was afebrile after 17 days of parenteral treatment, and dis-

3. Wuthiekanun V, Smith MD, Dance DAB, Walsh AL, Pitt TL, White NJ.charged with oral co-trimoxazole and doxycycline therapy for aBiochemical characteristics of clinical and environmental isolates of

total course of 20 weeks. The B. pseudomallei strains isolated fromBurkholderia pseudomallei. J Med Microbiol 1996;45:408–12.

his wound were identified on the bases of the characteristic colonial 4. Trakulsomboon S, Dance DAB, Smith MD, White NJ, Pitt TL. Ribotypemorphology on a differential agar, positive oxidase reaction, and differences between clinical and environmental isolates of Burkholderiaresistance to colistin and gentamicin, and confirmed by a biochemi- pseudomallei. J Med Microbiol 1997;46:565–70.cal profile based on the results of API-2ONE (bioMerieux, Marcy 5. Dance DAB, Wuthiekanun V, Naigowit P, White NJ. Identification of Pseu-

domonas pseudomallei in clinical practice: use of simple screening testsl’Etoile, France) [5]. Arabinose utilization was determined byand API 2ONE. J Clin Pathol 1989;42:645–8.growth on minimal salt agar [6] containing L-arabinose (0.2%).

6. Clowes RC, Hayes W, eds. Experiments in microbiological genetics. Ox-This extended biochemical testing confirmed that the strain wasford, England: Blackwell Scientific Publications, 1968:184–92.an Ara/ B. pseudomallei.

7. Smith MD, Angus BJ, Wuthiekanun V, White NJ. Arabinose assimilationIn the murine model, there was a striking difference in virulencedefines a nonvirulent biotype of Burkholderia pseudomallei. Infect Im-

between Ara0 and Ara/ B. pseudomallei [7]. The ability to assimi-mun 1997;65:4319–21.

late L-arabinose was found to be more strongly associated with 8. Hasse A, Smith-Vaughan H, Melder A, et al. Subdivision of Burkholderiavirulence than was ribotype group [4, 8]. Ara/ B. pseudomallei is pseudomallei ribotypes into multiple types by random amplified polymor-currently defined as a nonvirulent strain [7]. The acquisition of phic DNA analysis provides new insights into epidemiology. J Clin Mi-

crobiol 1995;33:1687–90.B. pseudomallei infection in this patient was most likely the result

species [1, 3]. However, the recovery of anaerobic bacteria is rarelyAerobic and Anaerobic Microbiology of Mycotic Aorticreported [3–6], as generally, most previous studies did not useAneurysmproper methods for transportation and recovery of these organisms.Herein we review the 5-year experience of our hospital in theIdentification of the organisms infecting aortic aneurysms isrecovery of aerobic and anaerobic bacteria for cases of MAA.important, as these organisms can cause local and systemic infec-

Specimens included in the analysis were collected from patientstion [1], and can contaminate vascular prostheses [2]. Various

with MAA who were hospitalized at the Navy Hospital inorganisms have been found in mycotic aortic aneurysms (MAAs),

Bethesda, Maryland, between June 1987 and June 1992. Includedincluding gram-positive aerobic bacteria such as Staphylococcus in the analysis were only those patients whose specimens wereaureus and gram-negative aerobic bacteria such as Salmonella submitted for recovery of aerobic and anaerobic bacteria that

showed bacterial growth and whose medical records were availablefor review. Eight cases of MAA had positive cultures. Six of thepatients were male, and their ages ranged from 59 to 82 years (table

The opinions and assertions contained herein are the private ones of the 1). Specimens for cultures were obtained during repair surgery, byauthors and are not to be construed as official or reflecting the views of the

swabbing a portion of the intramural thrombus or the aneurysmalU.S. Department of the Navy or the U.S. Naval Service at large.wall. The swab was placed into anaerobic transport media (Port-A-Reprints or correspondence: Dr. Itzhak Brook, POB 70412, Chevy Chase,Cul, Baltimore Biological Laboratories, Cockeysville, MD), sent toMaryland 20813-0412 ([email protected]).the microbiology laboratory, and inoculated within 2 hours ofClinical Infectious Diseases 1999;28:928–9collection. Anaerobic and aerobic bacteria were identified as de-q 1999 by the Infectious Diseases Society of America. All rights reserved.

1058–4838/99/2804–0055$03.00 scribed previously [7]. Blood samples for culture were obtained

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Table 1. Features of eight patients with mycotic aortic aneurysm from Navy Hospital in Maryland.

Case no./ Location of Clinicalage (y)/sex aneurysm Associated conditions manifestations MAA culture results Surgery Outcome

1/69/M Infrarenal Atherosclerosis Fever, leukocytosis, Staphylococcus aureus* In situ graft Survivedback pain

2/75/M Infrarenal Diabetes Fever, leukocytosis Staphylococcus epidermidis In situ graft Survived3/81/M Infrarenal Atherosclerosis, urinary Fever, back pain Escherichia coli* Resection Died

tract infection Klebsiella pneumoniae4/78/F Supraceliac Atherosclerosis Leukocytosis S. aureus, Drainage abscess Survived

Peptostreptococcusmicros

5/65/M Distal abdomen Gallstones, Fever, leukocytosis Salmonella enteritidis Resection Survivedatherosclerosis

6/73/M Distal abdomen Abdominal abscess, Leukocytosis, Bacteroides fragilis,* In situ graft Bleeding, diedatherosclerosis abdominal pain Peptostreptococcus

prevotii7/59/F Distal abdomen Colonic cancer Fever, abdominal Clostridium perfringens* In situ graft Died

pain8/82/M Descending thorax Atherosclerosis, Leukocytosis Proprionibacterium acnes Resection Survived

diabetes

NOTE. MAA Å mycotic aortic aneurysm.* Similar organisms isolated from the blood.

from all patients and were inoculated into two bottles, one support- The true incidence of recovery of anaerobes in MAA could notbe calculated from our study because of its retrospective natureive of aerobic growth and the other of anaerobic growth.and because we included only specimens that were cultured forMicrobiology. Eleven organisms, six facultatively aerobic andboth aerobic and anaerobic bacteria. The true prevalence of thesefive anaerobic, were isolated from the eight patients included inorganisms in MAA has yet to be investigated by prospective stud-the study (table 1). Aerobic organisms were isolated in only fouries. This is of particular importance, since these organisms arecases, anaerobic organisms in only three, and mixed aerobic andoften resistant to the antimicrobials used to treat these infections.anaerobic bacteria in one. Polymicrobial infection was present

in three (patients 3, 4, and 6). The predominant bacteria wereStaphylococcus species (3 isolates), Enterobacteriaceae (2), and

Itzhak Brook and Edith H. FrazierPeptostreptococcus species (2). Organisms similar to the ones re-Department of Infectious Diseases, Navy Hospital, Bethesda, Marylandcovered from the MAA were isolated from the blood of four pa-

tients. These included one isolate each of S. aureus, Escherichiacoli, Bacteroides fragilis, and Clostridium perfringens (table 1).

ReferencesClinical Manifestations. Systemic signs of infection, as evi-denced by fever and leukocytosis, were present in most patients. 1. Gomes MN, Choyke PL, Wallace RB. Infected aortic aneurysms. A chang-

ing entity. Ann Surg 1992;215:435–42.Localized pain was present in four (table 1). Associated conditions2. Ilgenfritz FM, Jordan FT. Microbiological monitoring of aortic aneurysm wallwere present in all cases: atherosclerosis in six; diabetes in two; and

and contents during aneurysmectomy. Arch Surg 1988;123:506–8.urinary tract infection, gallstones, abdominal abscess, and colonic3. Anderson CB, Butcher HR, Ballinger WF. Mycotic aneurysms. Arch Surgcancer in one each. In situ grafts were placed in four cases, resec-

1974;109:712–6.tion of the MAA was done in three, and abscess drainage in one.4. Reddy DJ, Lee RE, Oh HK. Suprarenal mycotic aortic aneurysm: surgical

Three of the patients died.management and follow up. J Vasc Surg 1986;3:917–20.

This report highlights the importance of anaerobic bacteria in 5. Jewkes AJ, Black J. Infection of an abdominal aortic aneurysm from anMAA. The recovery of these organisms is not surprising, given the appendix abscess. J Cardiovasc Surg 1989;30:870–2.proximity of the aorta to the gastrointestinal tract, where anaerobes 6. Hurley L, Howe K. Mycotic aortic aneurysm infected by Clostridiumpredominate and reach 1012 organisms per gram of stool, outnum- septicum—a case history. Angiology 1991;42:585–9.

7. Brook I. Role of anaerobic bacteria in aortofemoral graft infection. Surgerybering aerobic organisms in a ratio of 1,000–10,000 to one [7]. The1988;104:843–5.enteric source of these organisms is supported by the recovery of

8. van der Vliet JA, Kouwenberg PP, Muytjens HL, Barendregt WB, BollEnterobacteriaceae, B. fragilis, and C. perfringens, which normallyAP, Buskens FG. Relevance of bacterial cultures of abdominal aorticcolonize the gut. B. fragilis, Peptostreptococcus species, and Propion-aneurysm contents. Surgery 1996;119:129–32.ibacterium acnes were recovered from infected aortofemoral and

9. McIlroy MA, Reddy D, Markowitz N, Saravolatz LD. Infected false aneu-aortic grafts [7, 8], from MAA [3–6], and from femoral artery aneu-

rysms of the femoral artery in intravenous drug addicts. Rev Infect Disrysms in intravenous drug addicts [9]. Although the recovery of 1989;11:578–85.anaerobic bacteria from MAA is rare, it is possible that the incidence 10. Brown SL, Busuttil RW, Baker JD, Machleder HI, Moore WS, Barkerof these microorganisms is higher than reported, given that the per- WF. Bacteriologic and surgical determinants of survival in patients with

mycotic aneurysms. J Vasc Surg 1984;1:541–7.centage of negative cultures for MAA is generally ú25% [10].

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fungemia in a non-immunocompromised patient without bowelFungemia Due to Saccharomyces Species in a Patientdisease who was receiving high doses of enteral Ultra-Levure. AsTreated with Enteral Saccharomyces boulardiiis true for the other reported cases, the primary identification ofthe Saccharomyces species was incorrect, with the usual confusion

As a pharmaceutical biotherapeutic agent, Saccharomyces boul- between S. boulardii and S. cerevisiae [1, 2, 5].ardii has been used for years outside of the United States to treat Given that S. boulardii may be initially misidentified as S. cere-diarrhea [1] and is considered to be safe. Nevertheless, serious visiae, it is likely that S. boulardii is responsible for saccharomycesside effects can occur. fungemia in patients receiving enteral Ultra-Levure. High doses

A 78-year-old immunocompetent woman was admitted to the of Ultra-Levure associated with antibiotics effective against anaer-intensive care unit because of an acute exacerbation of chronic obes, bowel diseases, and/or immunodeficiency seem to be riskobstructive pulmonary disease. Current treatment consisted of anti- factors for such fungemia; our observation suggests that fungemiabiotics (amoxicillin/clavulanic acid), mechanical ventilation, and due to Saccharomyces species can also occur in immunocompetententeral feeding via a gastric tube. On hospital day 12, diarrhea hosts without bowel disease. Enteral S. boulardii is widely usedappeared. Investigation for stool pathogens was negative; lopera- in the prevention or treatment of diarrhea; therefore, physiciansmide and S. boulardii (Ultra-Levure, 1.5 g/day [Biocodex, Mon- must be aware of the possibility of potentially serious side effects.trouge, France]) were administered via the gastric tube (day 13) The reported occurrence of such side effects is infrequent at pres-for 15 days. On day 18, antibiotic therapy was changed to that with ent, and no current guidelines exist for their treatment.ceftazidime and ciprofloxacin because of a nosocomial pulmonaryinfection. On day 34, the temperature was elevated to 397C and M. Niault, F. Thomas, J. Prost, F. Hojjat Ansari, andthe WBC count was 8,600/mm3. From day 34 to day 37, seven P. Kalfoncultures of blood were positive for Saccharomyces species; the Service de Reanimation Polyvalente and Service de Biologie, Hopital

des Diaconesses, Paris, Franceorganism was initially identified as Saccharomyces cerevisiae andlater as S. boulardii. Cultures of arterial and venous catheters

Referencesremoved on day 35 were negative. A colonoscopy was normal1. McFarland LV. Saccharomyces boulardii is not Saccharomyces cerevisiae.and no parasites were found in the stool. Complete recovery was

Clin Infect Dis 1996;22:200–1.observed after fluconazole therapy for 15 days.2. Chia JK. Reply. Clin Infect Dis 1996;22:200–2.Routine identification of Saccharomyces species often fails to3. Grillot R, Lebeau B, Gouillet-Fleuret A, Chouraqui JP, Andrini P. Overseas

distinguish S. boulardii from S. cerevisiae [1, 2]. Fungemia dueand imported fungal infections. The 30th anniversary of La Societe Fran-

to Saccharomyces species has already been reported in patients caise de Mycologie Medicale (Institut Pasteur, Paris), 21–22 Novemberreceiving high enteral dosages of Ultra-Levure. Transfer of Sac- 1986.charomyces species from an affected bowel (e.g., ischemic or in- 4. Zunic P, Lacotte J, Pegoix M, et al. Ultra-Levure Saccharomyces boulardiiflammatory) appears to be the primary origin of these fungemias lyophilise; Dossier de pharmacovigilance: dossier UL 9201-Caen-adulte

male 33 ans. Therapie 1991;46:497–501.[3–7], especially when antibiotics effective against anaerobes are5. Boucaud C, Berrada K, Bouletreau P. Septicemie a Saccharomyces boular-given [5–9]; in other cases, infected catheters have been implicated

dii apres administration orale d’Ultra-Levure. Reanimation Urgencesas the source of infection [6]. Patients who develop fungemia1996;5:665.due to Saccharomyces species are generally immunocompromised

6. Force G, Aznar C, Marguet F, Polomeni P, Bouchet R, Manicacci M.(e.g., patients with AIDS and patients receiving corticosteroid ther-Saccharomyces fungemia in AIDS patients after treatment for chronic

apy) [3–8]. In all reported cases, therapy has consisted of support-diarrhea [abstract no 304]. The 5th European Conference on Clinical

ive care, anti-fungal drugs, and the cessation of Ultra-Levure. To Aspects and Treatment of HIV Infection (Copenhagen, Denmark), 26–our knowledge, we have described the first case of S. boulardii 29 September, 1995.

7. Viggiano M, Badetti C, Bernini V, Garabedian M, Manelli JC. Fongemiea Saccharomyces boulardii chez un brule grave. Ann Fr Anesth Reanim1995;14:356–8.

8. Pletincx M, Legein J, Vandenplas Y. Fungemia with Saccharomyces boular-Reprints or correspondence: Dr. Frank Thomas, Service de Reanimationdii in a 1 year old girl with protracted diarrhea. J Pediatr GastroenterolPolyvalente, Hopital des Diaconesses, 18 rue du Sergent Bauchat, 75012 Paris,Nutr 1995;21:113–5.France.

9. Wells CL, Maddaus MA, Reynolds CM, Jechorek RP, Simmons RL. RoleClinical Infectious Diseases 1999;28:930

of anaerobic flora in the translocation of aerobic and facultative anaerobicq 1999 by the Infectious Diseases Society of America. All rights reserved.1058–4838/99/2804–0056$03.00 bacteria. Infect Immun 1987;55:2689–94.

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of detectable CSF HIV RNA after 2 weeks. Foscarnet was thenFoscarnet Activity on Human Immunodeficiency Viruscontinued for 3 months at maintenance doses (100 mg/[kgrd]).Type 1 in the Central Nervous SystemCSF and plasma viral loads remained undetectable.

To improve the quality of life for our patient, we decided toFoscarnet, a reverse transcriptase inhibitor, has been shown to interrupt foscarnet administration without modifying the rest of

decrease HIV-1 replication in vitro [1, 2]. Recently, reports of two the treatment. A lumbar puncture performed 2 weeks later showedstudies about the effects of this antiviral agent on HIV replication a detectable HIV RNA viral load at 3 log10 copies/mL. A thirdin vivo were published [3, 4]. Both investigators observed signifi- episode of mental dysfunction, associated with an important risecant reductions of HIV plasma viral loads in patients who were in CSF viral load (5.1 log10 RNA HIV copies/mL), occurred 6treated with foscarnet. Herein, we report an observation that foscar- weeks after stopping foscarnet. Therapy was switched to that withnet is also active in the CNS when used to treat HIV encephalo- new drugs available at this time, abacavir, nevirapine, and nelfi-pathy-related symptoms. navir, with successful clinical and virological response.

A 55-year-old HIV-1-infected man with a Burkitt’s lymphoma Foscarnet has been shown to penetrate the blood-brain barrierwas treated with indinavir (800 mg t.i.d.) and saquinavir (400 mg [5]. In our patient, foscarnet was highly effective in reducing theb.i.d.). Therapy with this combination of two protease inhibitors CSF HIV viral load and neurological symptoms, and this effectwas started during multidrug chemotherapy for his lymphoma to was sustained throughout the 3 months of therapy. The CSF HIVavoid myelotoxicity induced by nucleoside analogs. Since the RNA load rebounded 2 weeks after cessation of therapy, and clini-platelet count remained low (30,000/mm3) and plasma HIV viral cal symptoms reappeared a few weeks later.load was undetectable, antiretroviral therapy was not modified after The CNS is a protected compartment, known to be difficult tocompletion of the antineoplastic treatment, which led to complete reach, since antiretroviral drugs like protease inhibitors do notremission. The CD4/ cell count was 150/mm3. cross the blood-brain barrier efficiently. This phenomenon is illus-

The patient works as a translator. Six months after beginning trated in the case we described, given the occurrence of neurologi-therapy with protease inhibitors, he experienced a first episode of cal symptoms associated with a high CSF viral load despite unde-somnolence, lack of concentration, and inability to work. Brain tectable HIV RNA in plasma. In our patient, clinical evolutionCT scan and MRI showed no abnormalities. A CSF specimen paralleled changes in CSF HIV RNA, indicating that high CSFcontained 3 lymphocytes/mm3 and protein levels were normal. viral loads can be a marker of HIV encephalopathy. Our observa-Microscopic examination and cultures of CSF were negative for tion suggests that foscarnet might be helpful for the treatmentbacteria, parasites, and fungi. A search for neoplastic cells and of HIV-associated mental deterioration in cases of resistance orcryptococcal antigen was negative. A PCR assay of CSF was intolerance to all antiretroviral drugs known to be active innegative for herpes simplex virus types 1 and 2, cytomegalovirus the CNS.(CMV), JC virus, and Toxoplasma gondii. The CSF HIV viral loadwas 4.23 log10 HIV RNA copies/mL, whereas the plasma viral Marie-Luce Delforge, Claire-Michele Farber,load was still undetectable. Zidovudine at low doses (100 mg t.i.d.) Frederic De Leener, Jean-Marc Caroyer,was added to the treatment. After 2 weeks, the patient regained Corinne Liesnard, and Jean-Paul Van Voorenhis fluency in six languages, and CSF HIV viral load levels de- Virology and AIDS Reference Laboratory, Immunodeficiencies Unit, andcreased to 2.77 log10 HIV RNA copies/mL. Neurology Department, Hopital Erasme, Universite Libre de Bruxelles,

Brussels, BelgiumThree months later, a lumbar puncture was performed becauseof recurrent drowsiness. An HIV RNA viral load of 4.36 log10

Referencescopies/mL was detected in an otherwise normal CSF specimen. A1. Eriksson BF, Schinazi RF. Combinations of 3*-azido-3*-deoxythymidinePCR assay of CSF for CMV was negative. Tests for CMV antigen

(zidovudine) and phosphonoformate (foscarnet) against human immuno-remained negative. Lamivudine (150 mg b.i.d.) was added to thedeficiency virus type 1 and cytomegalovirus replication in vitro. Antimi-therapeutic regimen, but no clinical improvement was noted aftercrob Agents Chemother 1989;33:663–9.10 days. Stavudine was not proposed, as the patient previously

2. Koshida R, Vrang L, Gilljam G, Harmenberg J, Oberg B, Wahren B. Inhibi-had a severe peripheral neuropathy induced by this antiretroviral

tion of human immunodeficiency virus in vitro by combinations of 3*-agent. Therapy with intravenous foscarnet (100 mg/kg b.i.d.) was azido-3*-deoxythymidine and foscarnet. Antimicrob Agents Chemotherstarted, leading to complete linguistic recovery and disappearance 1989;33:778–80.

3. Devianne-Garrigue I, Pellegrin I, Denisi R, et al. Foscarnet decreases HIV-1 plasma load. J Acquir Immune Defic Syndr Hum Retrovirol 1998;18:46–50.

4. Bergdahl S, Jacobsson B, Moberg L, Sonneborg A. Pronounced anti-HIV-Reprints or correspondence: Dr. M-L Delforge, Virology and AIDS Refer-1 activity of foscarnet in patients without cytomegalovirus infection. Jence Laboratory, Hopital Erasme, Route de Lennik 808, B-1070 Brussels,Acquir Immune Defic Syndr Hum Retrovirol 1998;18:51–3.Belgium ([email protected]).

5. Raffi F, Taburet AM, Ghaleh B, Huart A, Singlas E. Penetration of foscarnetClinical Infectious Diseases 1999;28:931

into cerebrospinal fluid of AIDS patients. Antimicrob Agents Chemotherq 1999 by the Infectious Diseases Society of America. All rights reserved.1058–4838/99/2804–0057$03.00 1993;37:1777–80.

/ 9c64$$ap73 03-16-99 08:25:44 cida UC: CID

gas gangrene in an immunocompromised girl due to a clostridium ramosum infection

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