We report the case of an 85-year-old female patient who suffered from disseminated Nocardia asteroides infection complicated by a cerebral abscess. Treatment with amikacin for 2 weeks and ceftriaxone for 6 weeks led to complete recovery, and there was no recurrence of disease over a follow-up period of 12 months after therapy. The use of ceftriaxone in combination with amikacin might significantly shorten the duration of treatment for patients with disseminated nocardiosis. This combination of antibiotics merits further investigation with use of a larger sample of patient

Bodmer, T.

Garlando, F.

Lee, C.

Pirovino, M.

Zimmerli, W.

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1039NOTESuccessful Treatment of Disseminated Nocardiosis Complicated by CerebralAbscess with Ceftriaxone and Amikacin: Case ReportF. Garlando, T. Bodmer, C. Lee, W. Zimmerli,and M. PirovinoFrom the Department ofMedicine. Kantonsspital Olten; the InstituteofMedical Microbiology and Immunology. Kantonsspital St. Gallen;and the Division ofInfectious Diseases. Department ofMedicine,University Hospital, Basel, SwitzerlandWe report the case of an 85-year-old female patient who suffered from disseminated Nocardiaasteroides infection complicated by a cerebral abscess. Treatment with amikacin for 2 weeks andceftriaxone for 6 weeks led to complete recovery, and there was no recurrence of disease over afollow-up period of 12 months after therapy. The use ofceftriaxone in combination with amika-cin might significantly shorten the duration of treatment for patients with disseminated nocar-diosis. This combination of antibiotics merits further investigation with use of a larger sample ofpatients.Sulfonamides or trimethoprim-sulfamethoxazole is givenas standard therapy for disseminated nocardiosis [1-3]. How-ever, primary resistance to sulfonamides is well known [1,4,5], late relapses are frequent [4, 6], and prolonged treatmentis often required. Therefore, therapeutic alternatives areneeded. In view of their good in vitro activity against speciesof Nocardia. ceftriaxone and cefuroxime seem especiallypromising [5, 7]. Amikacin is another drug with excellentefficacy in vitro [5], in animal models [8], and in treatment ofhuman disease [4, 9]. Good clinical results have been ob-served with the synergistic combination of cefuroxime andamikacin [4].We report the case of a patient with disseminated nocar-diosis complicated by cerebral abscess who was successfullytreated with ceftriaxone for 6 weeks and amikacin for 2weeks.An 85-year-old female patient was admitted to the hospi-tal because of arthralgias and multiple skin lesions. On ad-mission, the patient was afebrile; physical examination re-vealed multiple nodular reddish lesions on the left thigh andthe lower abdomen that were painful and measured up to1.5 em.Laboratory analysis revealed mild leukocytosis (whiteblood cell count, 15.1 X 109/L) with 40% neutrophils and arelative lymphopenia of 10%. The Multi-Merieux skin test(Institut Merieux, Lyon, France) revealed complete anergy.Microscopic examination ofpus obtained by puncture ofoneof the cutaneous lesions showed polymorphonuclear leuko-cytes without bacteria. Over the next 24 hours, further skinReceived 24 March 1992; revised 2 June 1992.Reprints or correspondence: Dr. M. Pirovino, Medizinische Klinik, Kan-tonsspital, CH-4600 Olten, Switzerland.Clinical Infectious Diseases 1992;15:1039-40© 1992 by The University of Chicago. All rights reserved.1058-4838/92/1506-0015$02.00lesions appeared and signs of peritoneal irritation were ob-served. A repeated puncture of a cutaneous lesion revealeddelicate, beaded, branching gram-positive filaments. Micro-scopic examination of the sputum showed the same microor-ganisms.A presumptive clinical diagnosis of actinomycosis wasmade, and 20 million units of iv penicillin G were adminis-tered daily. Because of generalized seizures that were as-sumed to be due to CNS toxicity associated with the use ofpenicillin, the treatment was changed to amoxicillin. On day8 of treatment, a left-sided hemiparesis appeared. The com-puted tomography (CT) scan revealed a right-sided ring-en-hancing hemispheric lesion suggestive of an abscess (figure1). The lumbar puncture showed a normal cell count and aslightly elevated level of protein (56.8 mg/dL).In the meantime, culture of a sample obtained by cutane-ous aspiration revealed N. asteroides that was resistant to tri-methoprim-sulfamethoxazole and produced penicillinase.Antibiotic treatment was changed to iv amikacin (MIC, 0.12JLg/mL) and iv ceftriaxone (MIC, 8 JLg/mL) (for microdilu-tion method, see [10]). In vitro testing showed that the com-bination ofceftriaxone and amikacin did not have synergisticpotential. During treatment with amikacin (200 mg b.i.d. iv),a peak serum concentration of 13.6 mg/L and trough con-centrations of 2.3-5.5 mg/L were measured.Ceftriaxone was administered in a total daily dose of 4 g(divided in two doses). With this treatment, the patient'sneurological deficits were markedly reduced; thus, therapywith amikacin was stopped after 14 days. Therapy with cef-triaxone was continued for 6 weeks. After 4 weeks of ther-apy, a second CT scan showed a marked regression of thelesion; a third CT scan ofthe brain 2 weeks after terminationof treatment revealed no evidence of a persisting abscess.Clinically, the patient showed no residual neurological defi-cits, and the skin changes as well as the signs of peritonealirritation had disappeared.1040 Garlando et al. CID 1992; 15 (December)Figure 1. A CT scan taken at the beginning of antibiotic treat-ment revealing a right-sided parietal brain abscess with multilocu-lar ring enhancement and edema.Disseminated nocardiosis has a poor prognosis, with a mor-tality rate of 7%-44% [2, II, 12]. Treatment of nocardialbrain abscesses with sulfonamides is usually recommendedfor up to I year [2]. Furthermore, since primary resistanceand late relapses occur, alternative regimens are required.Among the various antibiotics tested, ceftriaxone, cefurox-ime, and cefotaxime showed good in vitro activity againstNocardia [5]. Cefuroxime and amikacin have been shown tokill Nocardia synergistically in vitro [4], thus providing a ra-tional basis for their clinical use.In the murine model, cerebral nocardiosis responds betterto amikacin than to trimethoprim-sulfamethoxazole [8].However, these data should be interpreted with caution: con-centrations ofthese drugs achieved in the CSF ofhumans arelower than those achieved in the brains of mice [13-15];further problems result from the large variability of concen-trations observed in the CSF ofhumans and the poor correla-tion between the concentrations measured in CSF and thosein cerebral tissue [14, IS]. Considering that the concentra-tion of amikacin achieved in the CSF of humans is 10%-15%of that achieved in serum [12], a CNS effect can be antici-pated with isolates of Nocardia that require a low MIC forinhibition; such an effect has been shown in our case, inwhich the MIC of amikacin was 0.12 p,g/mL and serumconcentrations of amikacin were between 2.3 mg/L and13.6 mg/L.Our patient had an excellent response to therapy with cef-triaxone and amikacin. The neurological deficits disap-peared after 3 weeks of treatment, a finding that correlatedwith the radiological evidence of regression after 4 weeks oftreatment and the complete normalization of the computedtomogram 4 weeks later. On the basis of the low MIC (0.12p,g/mL) ofamikacin and the relatively high MIC of ceftriax-one (8 p,g/mL) in our case, we assume that amikacin had amajor effect on the CNS manifestation. The possibility ofsynergism in vivo cannot be excluded despite its absence invitro. The early institution of adequate antibiotic treatmentmay have been critical. The use ofcombination therapy withamikacin and ceftriaxone for patients with disseminated no-cardiosis merits further investigation.ReferencesI. Wallace RJ Jr, Septimus EJ, Williams TW Jr, et al. Use of trimetho-prim-sulfarnethoxazole for treatment of infections due to Nocardia.Rev Infect Dis 1982;4:315-25.2. Wilson JP, Turner HR, Kirchner KA, Chapman SW. Nocardial infec-tion in renal transplant recipients. Medicine (Baltimore) 1989;68:38-57.3. Berkey P, Bodey GP. Nocardial infection in patients with neoplasticdisease. Rev Infect Dis 1989;11:407-12.4. Goldstein FW, Hautefort B, Acar JF. Amikacin-containing regimensfor treatment ofnocardiosis in immunocompromised patients. Eur JClin Microbiol Infect Dis 1987;6: 198-200.5. Dewsnup DH, Wright DN. In vitro susceptibility ofNocardia asteroidesto 25 antimicrobial agents. Antimicrob Agents Chemother 1984;25: 165-7.6. Stamm AM, McFall DW, Dismukes WE. Failure of sulfonarnides andtrimethoprim in the treatment of nocardiosis. Arch Intern Med1983; 143:383-5.7. Gombert ME. Susceptibility of Nocardia asteroides to various antibi-otics, including newer ,B-Iactams, trimethoprim-sulfamethoxazole,amikacin and x-formimidoyl thienamycin. Antimicrob Agents Che-mother 1982;21: 1011-2.8. Gombert ME, Aulicino TM, Du Bouchet L, Silverman GE, SheinbaumWM. Therapy of experimental cerebral nocardiosis with imipenem,amikacin, trimethoprim-sulfamethoxazole, and minocycline. Anti-microb Agents Chemother 1986;30:270-3.9. Meier B, Metzger U, Muller F, Siegenthaler W, Luthy R. Successfultreatment of a pancreatic Nocardia asteroides abscess with amikacinand surgical drainage. Antimicrob Agents Chemother 1986;29: 150-1.10. Lorian V. Antibiotics in laboratory medicine. 2nd ed. Baltimore: Wil-liams & Wilkins, 1986.11. Beaman BL, Burnside J, Edwards B, Causey W. Nocardial infections inthe United States, 1972-1974. J Infect Dis 1976;134:286-9.12. Palmer DL, Harvey RL, Wheeler JK. Diagnostic and therapeutic con-siderations in Nocardia asteroides infection. Medicine (Baltimore)1974;53:391-401.13. Yow MD. An overview of pediatric experience with amikacin. Am JMed 1977;62:954-8.14. Richards ML, Prince RA, Kenulay KA, Johnson JA, Lefrock JL. Anti-microbial penetration into cerebrospinal fluid. Drug Intelligence andClinical Pharmacy 1981;15:341-68.15. Yogev R, Kolling WM. Intraventricular levels ofamikacin after intrave-nous administration. Antimicrob Agents Chemother 1981;20:583-6.

Successful Treatment of Disseminated Nocardiosis Complicated by Cerebral Abscess with Ceftriaxone and Amikacin: Case Report

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