Intracerebral Nocardia asteroides abscess treated by neurosurgical aspiration and combined therapy with sulfadiazine and cefotaxime C. Jansen*, H . M . E . Fr6nay* * * * * *, W.P. Vandertop* * *, and M . R . Visser* *
Introduction Summary Nocardia asteroides, a gram-positive, branching rod, is a soil bacterium and an opportunistic pathogen, which frequently causes infection in immunocompromised hosts 1. The yearly incidence of Nocardia infections in the United States was estimated to be 500-1000 cases in the early seventies but is increasing2. A primary pulmonary focus is found in 75%-85% of cases of systemic nocardiosis3. Hematogenous dissemination to the central nervous system occurs in 20%-45% 35. Primary nocardiosis of the brain is seen in 7% of all cases 2. The pulmonary infection may be transient or subclinical in man, and may not be recognised. Thirty to 75 percent of patients with systemic or cerebral nocardiosis have underlying malignancies, immunodeficiency states, iatrogenic immunosuppression following organ transplantation, diabetes mellitus, collagen vascular disease, or alcoholism 13,68. The usual CNS manifestation is that of brain abscess formation causing focal signs and symptoms. The mortality rate for intracerebral nocardiosis is 75% to 90% 3'6. Men are affected three times more often as women. We report here a patient with a Nocardia brain abscess which was diagnosed after stereotactic aspiration and primarily treated with sulfadiazine without effect. After additional treatment with cefotaxime his clinical condition gradually improved.
We present a patient with a Nocardia brain abscess who failed to respond to repeated neurosurgical aspiration in combination with sulfadiazine therapy but improved after additional treatment with cefotaxime. Key words: Nocardia asteroides, brain abscess, stereotactic aspiration, sulfadiazine, cefotaxime.
Case report A 33-year-old male with a two week history of headache, nausea and general discomfort was admitted because of simple partial seizures in the right leg and secondary progression to tonicclonic seizures. On neurologic examination, the patient was fully conscious, had a normal body temperature and no signs of nuchal rigidity. There was a mild right hemiparesis with legpredominance. Tendon jerks were brisker on the right side. Plantar reflexes were flexor. Laboratory investigations showed no abnormalities (WBC 6.4 x 106/1, ESR 10 mm). Chest, skull and paranasal sinus X-rays were entirely normal. A CT-scan of the brain showed an area of low density in the left centrum semi-ovale with oedema and rim enhancement after contrast-injection.
Departments of Neurology*, Clinical Microbiology and Laboratory of Infectious diseases* *, and Neurosurgery* * *, University Hospital Utrecht, The Netherlands. National Institute of Public Health and Environmental Protection* * * *, Bilthoven, The Netherlands. Address for correspondence and reprint requests: C. Jansen, Department of Clinical Neurophysiology, St. Antonius Hospital, Box 2500, 3430 EM Nieuwegein, The Netherlands. Accepted 25-1-91 Clin Neurol Neurosurg 1991. Vol. 93-3
253
Cerebral abscess, with unknown offending micro-organism, was diagnosed and the patient was treated empirically with penicillin G 5 million units 6-hourly, chloramphenicol 1 g 8-hourly and phenytoin 100 mg 8-hourly, all intravenously. In the course of one week, his condition worsened and the level of consciousness deteriorated. A repeat CT-scan showed an increased abscess volume. A left parietal burr-hole was made (Dr J.W. van 't Verlaat) and by stereotactic cannulation 2 cc of purulent material was aspirated. Gram stain revealed gram-positive bacilli that appeared acid-fast when stained with the modified Ziehl-Neelsen technique. Cultures grew Nocardia asteroides that was susceptible in vitro to sulfonamides, cefotaxime, ceftriaxone, imipenem and amikacin. From this day on the patient was treated with sulfadiazine 8 g per day orally. Two weeks later, his consciousness deteriorated again and repeat CT-scanning showed a large abscess with marked oedema, compression of the left lateral ventricle and midline shift (Fig. 1). The patient was re-operated (WPV) with aspiration of 9 cc pus through a Fisher cannula. Culture again yielded Nocardia asteroides. Sulfadiazine treatment was increased to 12 g per day. Subsequently, his consciousness improved but the patient complained of severe headache after a few days. There was a right hemiparesis with extensor plantar response. Another CT-scan showed a
marked increase in size and formation of multiple abscesses in the left hemisphere. A third aspiration procedure was carried out (Dr Th.A. Dokkum) and again Nocardia asteroides grew on culture. Cefotaxime 2 g IV. 6-hourly was added to the therapeutic regimen. Following this, the clinical condition gradually improved. Control CT-scan after 2 months showed a marked decrease of abscess volume and cefotaxime therapy was stopped. Another CT-scan 6 months later showed a small hypodense area without contrast enhancement as the only residual sign. Sulfadiazine treatment, 8 g per day, was continued for one year. Twenty-four months after discharge from hospital the patient has a mild paresis of the dorsiflectors of the right foot and simple partial seizures which are treated successfully with carbamazepine. Extensive investigations for predisposing conditions such as systemic diseases, malignancies or immunodificiency remained negative. Discussion
Cerebral abscess due to Nocardia asteroides is often unresponsive to antibiotic therapy given for the empiric management of cerebral abscesses (penicillin, chloramphenicol) 1. Nocardiaceae are variably susceptible to a number of antimicrobial agents. Sulfonamides, including sulfisoxazole and sulfadiazine, are generally regard-
Fig. 1. CT-scan of the brain after intravenous contrast injection showing a large abscess in the left centrum semi-ovale with rim enhancement, edema and midline shift.
254
ed as the most effective agents for treatment because of their penetration and distribution in CSF. The presence of multiple or multiloculated lesions as demonstrated by CT-scan may direct treatment plans. Surgical aspiration or open drainage is the only way to obtain material for culture and a definite diagnosis, although the risk of meningeal seeding of the infection exists3'911. If possible, stereotactic aspiration or enucleation in combination with antibiotic treatment is recommended 1'3,5,12. However, if clinical improvement is observed during antimicrobial therapy, surgery is not necessary, especially when multiple abscesses are present or when a single abscess cannot be treated surgically because of its localisation 13. Stereotactic aspiration or open craniotomy is also indicated for patients with systemic nocardiosis on appropriate therapy who worsen neurologically or show enlargement of the intracerebral lesion on control C T 3 Although sulfonamides are considered to be the drugs of choice for nocardial infections, an additional or alternative therapy may be necessary because of therapeutic failure or allergic reactions6,7,14,15.
Besides sulfonamides the most active antibiotics against Nocardia in vitro are imipenem, cefotaxime, ceftriaxone and amikacin 1619. Cefotaxime is active against many Nocardia strains at clinically achievable serum levels. Good penetration in the central nervous system is another advantage of cefotaxime. This case clearly illustrates that Nocardia cerebral abscesses which do not improve after repeated surgical aspiration and administration of sulfadiazine should be treated with a combination of sulfadiazine and, as it turned out to be effective in our patient, cefotaxime. The optimal duration of therapy for nocardiosis has not yet been established, but relapses after discontinuation of sulfonamides in Nocardia infections have frequently been described, indicating the need for a prolonged sulfadiazine therapy of approximately 12 months.
References 1
LV. Nocardia cerebral abscess: new concepts in diagnosis, management and prognosis. J Ncurol Neurosurg Psychiatry 1979;
2
BEAMAN BL, BURNSIDE J, EDWARDS B~ CAUSEY W.
42:1038-45.
3
We thank Dr M. Rozenberg-Arska for her advice concerning the microbiological aspects of this report, Drs Th.A. Dokkum and Dr J.W. van 't Verlaat who performed the neurosurgical aspirations.
Nocardial Infections in the United States, 1972-1974. J Infect Dis 1976; 134:286-289.
HALL WA~ MARTINEZ AJ~ D U M M E R JS~ LUNSFORD LD, N o -
cardial Brain Abscess: Diagnostic and Therapeutic Use of Stereotactic Aspiration. Surg Neurol 1987; 28:114-8.
Nocardiosis of the central nervous system. J Neurosurg 1954; 11:226-
4
K RU E G E R E G , NORSA L, KENNEY M, PRICE PA.
5
T U R N E R E, WHITBY JL.
33.
6
Nocardial Cerebral Abscess with Systemic Involvement Successfully Treated by Aspiration and Sulphonamides. J Neurosurg 1969; 31:227-9. CURRY WA. Human Nocardiosis: A Clinical Review With Selected Case Reports. Arch Intern Med 1980; 140:818-26.
7
SIMPSON GL~ STINSON E B, E G G E R MJ, REMINGTON JS. N o -
cardial Infections in the Immunocompromised Host: A
Detailed Study in a Defined Population. Rev Infect Dis 1981; 3:492-507. 8
HOEPELMAN IM~ BAKKER LJ~ JESSURUN RFM~ R O Z E N B E R G -
Disseminated Nocardia asteroides infection complicating renal transplantation. Neth J Med 1987; 31:175-182. 9 LIST CF, WILLIAMS JR, BEEMAN CB, PAYNE CA. Nocardiosis with multiloculated cerebeUar abscess: report of a cured case. J Neurosurg 1954; 11:394-8. 10 MUNSLOW RA. Actinomycotic (Nocardia asteroides) brain abscess with recovery: case report. J Neurosurg ARSKA M, VERHOEF J.
1954; 11:399-402. 11 TURNEROA. Brain abscess caused by Nocardia Asteroides. J Neurosurg 1954; 11:312-8. 12
13
Nocardia Asteroides Brain Abscess Successfully Treated by Enucleation. Case Report. J Neurosurg 1969; 30:83-86. WEISS MH, JANE JA.
KIRMANI N, T U A Z O N CU, OCUIN JA~ THOMPSON AM, KRA-
Extensive cerebral nocardiosis cured with antibiotic therapy alone: case report. J NeuMER NC, G E E L H O E D GW.
rosurg 1978; 49:924-8. 14
SMITH PHW, STEINKRAUS G E , HENRICKS BW, MADSON EC.
CNS Nocardiosis. Response to Sulfamethoxazole-Trimethoprim. Arch Neurol 1980; 37:729-30. 15
Nonsurgical Treatment of Cerebral Nocardiosis. Arch Neurol 1983;
NORDEN CW, RUBEN FL, SELKER R.
40:594-5. 16 GOMBERTME. Susceptibility of Nocardia asteroides to
Various Antibiotics, Including Newer Beta-Lactams, Trimethoprim-Sulfa methoxazole, Amikacin, and NForminidoyl Thienamycin. Antimicrob Agents Chemother 1982; 21:1011-1012. 17 BERREYP, MOORED, ROLSTONI~. In Vitro Susceptibilities
18
19
Acknowledgements
BYRNE E , BROPHY BP, P E R R E ~
of Nocardia Species to Newer Antimicrobial Agents. Antimicrob Agents Chemother 1988; 32:1078-1079. WALLACE RJ~ STEELE LC~ SUMTER G , SMITH JM. Antimicrobial Susceptibility Patterns of Nocardia asteroides. Antimicrob Agents Chemother 1988; 32:1776-79. GOMBERT ME, D U B O U C H E T L, AULICINO TM~ B E R K O W l T Z
LB. Antimicrobial synergism in the therapy of experimental nocardiosis. J Antimicrob Chemother 1989; 23:39-43.
255
Introduction Summary Nocardia asteroides, a gram-positive, branching rod, is a soil bacterium and an opportunistic pathogen, which frequently causes infection in immunocompromised hosts 1. The yearly incidence of Nocardia infections in the United States was estimated to be 500-1000 cases in the early seventies but is increasing2. A primary pulmonary focus is found in 75%-85% of cases of systemic nocardiosis3. Hematogenous dissemination to the central nervous system occurs in 20%-45% 35. Primary nocardiosis of the brain is seen in 7% of all cases 2. The pulmonary infection may be transient or subclinical in man, and may not be recognised. Thirty to 75 percent of patients with systemic or cerebral nocardiosis have underlying malignancies, immunodeficiency states, iatrogenic immunosuppression following organ transplantation, diabetes mellitus, collagen vascular disease, or alcoholism 13,68. The usual CNS manifestation is that of brain abscess formation causing focal signs and symptoms. The mortality rate for intracerebral nocardiosis is 75% to 90% 3'6. Men are affected three times more often as women. We report here a patient with a Nocardia brain abscess which was diagnosed after stereotactic aspiration and primarily treated with sulfadiazine without effect. After additional treatment with cefotaxime his clinical condition gradually improved.
We present a patient with a Nocardia brain abscess who failed to respond to repeated neurosurgical aspiration in combination with sulfadiazine therapy but improved after additional treatment with cefotaxime. Key words: Nocardia asteroides, brain abscess, stereotactic aspiration, sulfadiazine, cefotaxime.
Case report A 33-year-old male with a two week history of headache, nausea and general discomfort was admitted because of simple partial seizures in the right leg and secondary progression to tonicclonic seizures. On neurologic examination, the patient was fully conscious, had a normal body temperature and no signs of nuchal rigidity. There was a mild right hemiparesis with legpredominance. Tendon jerks were brisker on the right side. Plantar reflexes were flexor. Laboratory investigations showed no abnormalities (WBC 6.4 x 106/1, ESR 10 mm). Chest, skull and paranasal sinus X-rays were entirely normal. A CT-scan of the brain showed an area of low density in the left centrum semi-ovale with oedema and rim enhancement after contrast-injection.
Departments of Neurology*, Clinical Microbiology and Laboratory of Infectious diseases* *, and Neurosurgery* * *, University Hospital Utrecht, The Netherlands. National Institute of Public Health and Environmental Protection* * * *, Bilthoven, The Netherlands. Address for correspondence and reprint requests: C. Jansen, Department of Clinical Neurophysiology, St. Antonius Hospital, Box 2500, 3430 EM Nieuwegein, The Netherlands. Accepted 25-1-91 Clin Neurol Neurosurg 1991. Vol. 93-3
253
Cerebral abscess, with unknown offending micro-organism, was diagnosed and the patient was treated empirically with penicillin G 5 million units 6-hourly, chloramphenicol 1 g 8-hourly and phenytoin 100 mg 8-hourly, all intravenously. In the course of one week, his condition worsened and the level of consciousness deteriorated. A repeat CT-scan showed an increased abscess volume. A left parietal burr-hole was made (Dr J.W. van 't Verlaat) and by stereotactic cannulation 2 cc of purulent material was aspirated. Gram stain revealed gram-positive bacilli that appeared acid-fast when stained with the modified Ziehl-Neelsen technique. Cultures grew Nocardia asteroides that was susceptible in vitro to sulfonamides, cefotaxime, ceftriaxone, imipenem and amikacin. From this day on the patient was treated with sulfadiazine 8 g per day orally. Two weeks later, his consciousness deteriorated again and repeat CT-scanning showed a large abscess with marked oedema, compression of the left lateral ventricle and midline shift (Fig. 1). The patient was re-operated (WPV) with aspiration of 9 cc pus through a Fisher cannula. Culture again yielded Nocardia asteroides. Sulfadiazine treatment was increased to 12 g per day. Subsequently, his consciousness improved but the patient complained of severe headache after a few days. There was a right hemiparesis with extensor plantar response. Another CT-scan showed a
marked increase in size and formation of multiple abscesses in the left hemisphere. A third aspiration procedure was carried out (Dr Th.A. Dokkum) and again Nocardia asteroides grew on culture. Cefotaxime 2 g IV. 6-hourly was added to the therapeutic regimen. Following this, the clinical condition gradually improved. Control CT-scan after 2 months showed a marked decrease of abscess volume and cefotaxime therapy was stopped. Another CT-scan 6 months later showed a small hypodense area without contrast enhancement as the only residual sign. Sulfadiazine treatment, 8 g per day, was continued for one year. Twenty-four months after discharge from hospital the patient has a mild paresis of the dorsiflectors of the right foot and simple partial seizures which are treated successfully with carbamazepine. Extensive investigations for predisposing conditions such as systemic diseases, malignancies or immunodificiency remained negative. Discussion
Cerebral abscess due to Nocardia asteroides is often unresponsive to antibiotic therapy given for the empiric management of cerebral abscesses (penicillin, chloramphenicol) 1. Nocardiaceae are variably susceptible to a number of antimicrobial agents. Sulfonamides, including sulfisoxazole and sulfadiazine, are generally regard-
Fig. 1. CT-scan of the brain after intravenous contrast injection showing a large abscess in the left centrum semi-ovale with rim enhancement, edema and midline shift.
254
ed as the most effective agents for treatment because of their penetration and distribution in CSF. The presence of multiple or multiloculated lesions as demonstrated by CT-scan may direct treatment plans. Surgical aspiration or open drainage is the only way to obtain material for culture and a definite diagnosis, although the risk of meningeal seeding of the infection exists3'911. If possible, stereotactic aspiration or enucleation in combination with antibiotic treatment is recommended 1'3,5,12. However, if clinical improvement is observed during antimicrobial therapy, surgery is not necessary, especially when multiple abscesses are present or when a single abscess cannot be treated surgically because of its localisation 13. Stereotactic aspiration or open craniotomy is also indicated for patients with systemic nocardiosis on appropriate therapy who worsen neurologically or show enlargement of the intracerebral lesion on control C T 3 Although sulfonamides are considered to be the drugs of choice for nocardial infections, an additional or alternative therapy may be necessary because of therapeutic failure or allergic reactions6,7,14,15.
Besides sulfonamides the most active antibiotics against Nocardia in vitro are imipenem, cefotaxime, ceftriaxone and amikacin 1619. Cefotaxime is active against many Nocardia strains at clinically achievable serum levels. Good penetration in the central nervous system is another advantage of cefotaxime. This case clearly illustrates that Nocardia cerebral abscesses which do not improve after repeated surgical aspiration and administration of sulfadiazine should be treated with a combination of sulfadiazine and, as it turned out to be effective in our patient, cefotaxime. The optimal duration of therapy for nocardiosis has not yet been established, but relapses after discontinuation of sulfonamides in Nocardia infections have frequently been described, indicating the need for a prolonged sulfadiazine therapy of approximately 12 months.
References 1
LV. Nocardia cerebral abscess: new concepts in diagnosis, management and prognosis. J Ncurol Neurosurg Psychiatry 1979;
2
BEAMAN BL, BURNSIDE J, EDWARDS B~ CAUSEY W.
42:1038-45.
3
We thank Dr M. Rozenberg-Arska for her advice concerning the microbiological aspects of this report, Drs Th.A. Dokkum and Dr J.W. van 't Verlaat who performed the neurosurgical aspirations.
Nocardial Infections in the United States, 1972-1974. J Infect Dis 1976; 134:286-289.
HALL WA~ MARTINEZ AJ~ D U M M E R JS~ LUNSFORD LD, N o -
cardial Brain Abscess: Diagnostic and Therapeutic Use of Stereotactic Aspiration. Surg Neurol 1987; 28:114-8.
Nocardiosis of the central nervous system. J Neurosurg 1954; 11:226-
4
K RU E G E R E G , NORSA L, KENNEY M, PRICE PA.
5
T U R N E R E, WHITBY JL.
33.
6
Nocardial Cerebral Abscess with Systemic Involvement Successfully Treated by Aspiration and Sulphonamides. J Neurosurg 1969; 31:227-9. CURRY WA. Human Nocardiosis: A Clinical Review With Selected Case Reports. Arch Intern Med 1980; 140:818-26.
7
SIMPSON GL~ STINSON E B, E G G E R MJ, REMINGTON JS. N o -
cardial Infections in the Immunocompromised Host: A
Detailed Study in a Defined Population. Rev Infect Dis 1981; 3:492-507. 8
HOEPELMAN IM~ BAKKER LJ~ JESSURUN RFM~ R O Z E N B E R G -
Disseminated Nocardia asteroides infection complicating renal transplantation. Neth J Med 1987; 31:175-182. 9 LIST CF, WILLIAMS JR, BEEMAN CB, PAYNE CA. Nocardiosis with multiloculated cerebeUar abscess: report of a cured case. J Neurosurg 1954; 11:394-8. 10 MUNSLOW RA. Actinomycotic (Nocardia asteroides) brain abscess with recovery: case report. J Neurosurg ARSKA M, VERHOEF J.
1954; 11:399-402. 11 TURNEROA. Brain abscess caused by Nocardia Asteroides. J Neurosurg 1954; 11:312-8. 12
13
Nocardia Asteroides Brain Abscess Successfully Treated by Enucleation. Case Report. J Neurosurg 1969; 30:83-86. WEISS MH, JANE JA.
KIRMANI N, T U A Z O N CU, OCUIN JA~ THOMPSON AM, KRA-
Extensive cerebral nocardiosis cured with antibiotic therapy alone: case report. J NeuMER NC, G E E L H O E D GW.
rosurg 1978; 49:924-8. 14
SMITH PHW, STEINKRAUS G E , HENRICKS BW, MADSON EC.
CNS Nocardiosis. Response to Sulfamethoxazole-Trimethoprim. Arch Neurol 1980; 37:729-30. 15
Nonsurgical Treatment of Cerebral Nocardiosis. Arch Neurol 1983;
NORDEN CW, RUBEN FL, SELKER R.
40:594-5. 16 GOMBERTME. Susceptibility of Nocardia asteroides to
Various Antibiotics, Including Newer Beta-Lactams, Trimethoprim-Sulfa methoxazole, Amikacin, and NForminidoyl Thienamycin. Antimicrob Agents Chemother 1982; 21:1011-1012. 17 BERREYP, MOORED, ROLSTONI~. In Vitro Susceptibilities
18
19
Acknowledgements
BYRNE E , BROPHY BP, P E R R E ~
of Nocardia Species to Newer Antimicrobial Agents. Antimicrob Agents Chemother 1988; 32:1078-1079. WALLACE RJ~ STEELE LC~ SUMTER G , SMITH JM. Antimicrobial Susceptibility Patterns of Nocardia asteroides. Antimicrob Agents Chemother 1988; 32:1776-79. GOMBERT ME, D U B O U C H E T L, AULICINO TM~ B E R K O W l T Z
LB. Antimicrobial synergism in the therapy of experimental nocardiosis. J Antimicrob Chemother 1989; 23:39-43.
255
![[Empyema by Nocardia asteroides].](/assets/img/hold.png)
