Nocardia farcinica Brain Abscess: Epidemiology,Pathophysiology,and Literature Review

Abstract

Background:

Infections caused by Nocardia farcinica are potentially lethal because of the organism's tendency to disseminate and resist antibiotics. Central nervous system involvement has been documented in 30% of infections caused N. farcinica.

Methods:

Case report and review of the literature.

Results:

A case of primary brain abscess caused by N. farcinica, identified by 16SrRNA sequencing, is presented, and 39 cases reported previously in the literature are reviewed. Our patient underwent a neuronavigation-guided right frontal craniotomy and was treated with trimethoprim/sulfamethoxazole and amoxicillin-clavulanic acid for 12 mo. He showed marginal improvement in his prior left hemiparesis at the last review 14 months later.

Conclusion:

Cases of N. farcinica infections are being reported increasingly because of recent changes in taxonomy and diagnostic methodology. This change in epidemiology has implications for therapy because of the organism's pathogenicity and natural resistance to multiple antimicrobial agents, including third-generation cephalosporins. Any delay in starting appropriate antibiotic therapy can have adverse consequences.

Nocardiosis is a localized or disseminated infection caused by an aerobic actinomycete that is soil-borne with a worldwide distribution. There are at least 50 recognized species in the genus Nocardia [1], and approximately 16 species have been implicated in human infections, with N. asteroides being the predominant one [2,3]. Nocardia asteroides complex includes N. asteroides sensu stricto, N. farcinica, N. cyriacigeorgica, N. nova, and N. abscessus. Nocardia farcinica has recently been redefined as a separate species, distinct from N. asteroides, and was first isolated from a case of bovine farcy in 1888 by Nocard. Classically, it causes bovine nocardiosis.

Nocardiosis presents most commonly as pulmonary disease, which may be followed by dissemination to multiple sites by hematologic spread. Among the various etiologic agents of brain abscess, Nocardia accounts only for 2% and usually occurs in patients with predisposing conditions [4]. Central nervous system (CNS) infection is present in one-third of the cases of nocardiosis and is attributable mostly to hematogenous dissemination. The portals of entry of Nocardia are respiratory tract, surgery, or traumatic skin injuries [5 –8]. In the majority of cases, nocardiosis is acquired through inhalation, with the lung being the most commonly involved organ. Disseminated disease is defined as the presence of lesions in two or more organs [5] and occurs in males three times as often as in females [9,10]. Most cases of CNS disease are considered disseminated infection by most clinicians, as it is presumed that underlying lung foci exist whether identified or not [11,12]. Nocardia farcinica characteristically is resistant to multiple antibacterial agents, including third-generation cephalosporins [8,13,14]. Studies have shown a high mortality rate (31%) when empiric antibiotic therapy was inappropriate, whereas the mortality rate was as low as 10% when nocardiosis was diagnosed and treated correctly [15].

We describe a case of primary brain abscess caused by N. farcinica, identified by 16SrRNA sequencing, in a patient with chronic demyelinating neuropathy who was on steroid therapy with no clinical or radiologic features of pulmonary nocardiosis. The patient was treated successfully with surgical excision and oral trimethoprim/sulfamethaoxazole (TMP/SMX) and amoxicillin/clavulanic acid.

Case Report

A 58-year old male with chronic demyelinating polyradiculopathy, who was receiving oral corticosteroids, presented with a two-week history of left hemiparesis with weakness of the right lower limb, tremors of both upper limbs, and a recent onset of slurring of speech. There was no history of headache, loss of consciousness, or convulsions. He had undergone a coronary artery bypass graft one year previously. Physical examination revealed flaccid left-sided hemiplegia with minimal weakness in the right lower limb, brisk deep tendon reflexes, and bilateral extensor plantar reflexes. Cerebellar signs and nuchal rigidity were absent. Examination of the sensory system was unremarkable.

A magnetic resonance imaging (MRI) scan of the brain revealed a well-defined T₁ hypointense and T₂ hyperintense lesion measuring 32×43×28 mm in the right corona radiata, extending to the superior and middle frontal gyri with smooth peripheral ring enhancement and mild perilesional white matter edema. Two small daughter cysts were attached to its lateral wall (Fig. 1A, B). Spectroscopy showed elevated lipid and lactate concentrations indicating a possibility of cerebral abscess. Multi-detector computed tomography scans of his chest and abdomen were unremarkable. Blood investigations were normal, with a white blood cell count of 8,260/mcL, hemoglobin 12.2 g/dL, and a platelet count of 140,000/mcL.

FIG. 1.

Gadolinium-enhanced T₁-weighted magnetic resonance scans demonstrate lesion measuring 32×43×28 mm in right corona radiata and superior and middle frontal gyri, with smooth peripheral rim enhancement and mild perilesional edema. Two small daughter cysts are seen attached to lateral wall.

The patient underwent a neuronavigation-guided right frontal craniotomy. The lesion was reached through a small cortical incision in the precentral region. A thick-walled cavity containing purulent material was encountered. The necrotic contents were drained, and the capsule was excised. He recovered well from the procedure, although left hemiparesis persisted at discharge.

Microbiologic examination of the pus revealed gram-positive branching bacilli that were partially acid-fast and were identified presumptively as Nocardia spp. After 96 h of incubation, aerobic cultures of the pus grew pale-orange, dry, cerebriform colonies on sheep blood agar and Lowenstein-Jensen medium. Gram staining demonstrated numerous thin-branching, filamentous, and beaded bacteria, which were partially acid-fast. The isolate was identified presumptively as N. asteroides complex on the basis of urease production and colony morphology.

Partial sequencing of the polymerase chain reaction (PCR) product was performed using the BigDye Terminator Cycle sequencing kit (Applied Biosystems, a division of Life Technologies, Grand Island, NY) and analyzed on an ABI PRISM 310 Genetic Analyzer (Applied Biosystems). The sequence of the 16S rRNA gene showed 100% homology with that of the type strain N. farcinica ATCC 3318 (GenBank No. Z36936.1). Growth at 45°C and 35°C after three days of incubation and opacification of Middlebrooks 7H10 agar, along with 16S rRNA sequencing results, confirmed the identification as N. farcinica (submitted to GenBank as No. JN634065.1) Antibiotic resistance was determined by a disk diffusion test on Mueller Hinton agar after incubation for 36 h at 37°C. The isolate was susceptible to amoxicillin-clavulanic acid, minocycline, imipenem-cilastatin, amikacin, TMP/SMX, and linezolid, and resistant to cefotaxime, tobramycin, and erythromycin.

The patient was treated with TMP/SMX and amoxicillin-clavulanic acid for 12 mo. He showed marginal improvement in his left hemiparesis at the last review 14 mo later. An MRI scan done on followup showed focal gliosis at the site of the brain abscess with no evidence of other lesions (Figs. 2A, 2B).

FIG. 2.

Follow-up coronal gadolinium-enhanced T₂-weighted scan of brain 12 mo after discharge showing focal gliosis at prior site of brain abscess.

Discussion

Nocardia farcinica brain abscess has a high mortality rate, as high as 20% in immunocompetent patients and 55% in immunocompromised patients. These high rates are attributed to the severity of underlying disease, difficulties in identifying the pathogen, and its inherent resistance to antibiotics, leading to inappropriate or late initiation of therapy [4].

The risk of dissemination to the brain is higher for N. farcinica than for other species (from 15% to 30%) associated with high mortality rates [3,8,16]. The isolation of N. farcinica is highly variable among countries. It has been reported to constitute 60.3% of Nocardia isolates in Germany, 44% in Belgium, 35% in Thailand, 27% in Japan, 24% in France, 19% in the U.S., and 14% in Italy [12,17,18].

Nocardia abscesses tend to be multiloculated and poorly encapsulated because of a weak inflammatory response to the organism. The overall mortality rate in multiple abscesses is twice that of patients with solitary abscess (66% vs. 33%) [4]. Abscesses >25 mm in diameter and that fail to shrink after 4 ws of antibiotic therapy should be aspirated to confirm the diagnosis regardless of the immune status of the patient [4]. In fact, the mortality rate among patients undergoing craniotomy (24%) is less than one-half of that among patients undergoing aspiration or drainage alone (50%) [4].

Because of the rarity of brain abscess caused by N. farcinica, we did a MEDLINE search from 1966–2011 and identified 39 additional cases (Table 1). Among 40 cases (including the present one), complete data were available for only 38, of which 83% (n=31) affected male patients. Underlying disease was documented in 31 cases (malignant disease in four, transplanted organ in nine, alcohol/chronic liver disease in five, autoimmune/immunosuppressive therapy in eight, and human immunodeficiency virus (HIV) infection in six patients). The abscess was most commonly located in the parietal region (13 cases) and frontal lobe (n=13), with location in the temporal lobe in four, the occipital region in six, the thalamus in three, and the cerebellum in three cases. Of the 26 cases for which details were available, 34% (n=17) had multiple abscesses. Primary brain abscess was seen in 45% of the cases, whereas among the cases of secondary brain abscess, concomitant pulmonary involvement was seen in 68% (n=5) patients, subcutaneous tissue in 18% (n=4) and muscle, and adrenal in 13.6% (n=3), and kidney involvement in 9% (n=2). Of the 12 patients who died, three were human immunodeficiency virus (HIV) positive, four of them post transplant; two had an autoimmune disorder and were on immunosuppressants; one had chronic liver disease; and two did not have any underlying disease.

Table 1.

Summary of Clinical Characteristics, Antimicrobial Therapy, and Outcome of Previous Reported Cases of Nocardia farcinica Brain Abscess

Author (year)	Age/sex	Predisposing factor(s)	Organs involved/sample for culture	Localization of abscess /number	Treatment	Outcome
Bergström et al. (1966) [26]	49/M	None	Lung, brain, kidney	NA	SSS/CHL/PEN/AMP/STR/TET/ERY/INH	Death
Palmer et al. (1974) [27]	50/M	AIDS, ITP, PCP	Blood, brain, lung, blood, CSF	NA	IMI + AM; CPM + TSX	Death
Dietlein et al. (1988) [17]	43/M	Alcohol abuse	Brain abscess/pus	NA	AMC/AMP AM/AM + IMI	Survived
Krone. (1989) [11]	72/F	None	Brain/pus	NA	MEZ + FCX + AMN; AMN + IMI/MIN	Survived
Miksits et al. (1991) [21]	55/F	Kidney transplant and immunosuppressive therapy	brain abscess/pus (on autopsy)	Right cerebellar/multiple	CTX/PYR + CLI + CAZ/FLX + MET + CIP + PYR + AMB + FLU	Death
Debieuvre et al. (1993) [23]	44/M	None	lung, brain abscess/pleural fluid	NA	IMI + CIP + AM	Death
Miralles et al. (1994) [16]	24/M	HIV	lung, brain, kidney abscesses/ kidney tissue, sputum, CSF	Left thalamus/single	TSX/DOX + CIP	Survived
Bani-Sadr et al. (1995) [28]	72/M	Horton disease, Guillain-Barré syndrome, COPD, steroid therapy	lung, skin, eye, brain/ skin and lung tissue	NA/multiple	IMI + TSX/AMC + PEF	Survived
Bani-Sadr et al. (1995) [28]	60/M	Heart transplant and immunosuppressive therapy	skin and brain abscess, arthritis/ skin tissue	NA/single	AMC + IMI/TSX + PEF	Survived
Farina et al. (1995) [24]	29/M	AIDS, IVDU	brain	NA	NA/death
Farina et al. (1995) [24]	11/M	Astrocytoma	brain	NA	NA/ survived	Survived
Beaman et al. (1995) [29]	NA	CLL	brain abscess/pus	NA	NA
Beaman et al. (1995) [29]	NA	Hodgkin disease	brain abscess/ spinal fluid	NA	NA
Nampoory et al. (1996) [30]	46/M	Kidney transplant and immunosuppressive therapy	Lung, brain/ blood	Bilateral parietal and frontal/multiple	NA	Death
Peters et al. (1996) [2]	64/M	DM, Wegener disease, chronic kidney disease and immunosuppressive therapy	brain, subcutaneous tissue pectoral region & forearm blood/skin lesion culture	Right thalamus, occipital and frontal white matter/multiple	TSX/MIN + SUF	Survived
Minamoto & Sordillo. (1998) [31]	50/M	AIDS, IVDU	lung, brain/ blood, CSF	Cerebellum, thalamus, pons, white matter/multiple	AMP + CTR + AM + TSX/VAN CLI + FLC + AM + CPM	Death
Kontoyiannis et al. (1998) [32]	48/M	Liver transplant& Immunosuppressive therapy	lung, brain/blood, sputum, urine	NA	AMP-Sulb/IMI + AMN + VAN	Death
Malinarne et al. (2002) [33]	62/M	Hypertension, immunocompetent	Brain/pus	Frontoparietal/multiple	TSX, MEM, AK	Survived
Sabuncuoğlu et al. (2004) [3]	58/F	DM	Brain/pus	Left occipitoparietal region/multiple	TSX/AK + CTR	Survived
Lai et al. (2005) [34]	68/M	ESRD, ITP with splenectomy, colon cancer, steroid therapy	Lung, brain/sputum, blood	Left parietal, right temporal/ multiple	SAM; MEM + TSX; TSX	Survived
Viganò et al. (2005) [13]	46/M	HIV	Brain, lung	NA	TMP-SMX	Death
Tatti et.al (2006) [15]	42/M	DM, HTN, Alcohol abuse	Brain/pus	Right parietal/ single	CTR + MTZ/TMP-SMX	Survived
Fihman et al. (2006) [35]	49/M	Kidney transplant, immunosuppressive therapy	Lung, brain/pus	Right parietal lobe/single	IMI + TMP-SMX/MXF	Survived
Shin et al. (2006) [36]	71/F	Chronic liver disease	Adrenal, lung, brain, BAL	Bilateral occipital, left frontal/multiple	IMI + AK + TMP-SMX	Survived
Muñoz et al. (2007) [37]	46/M	HIV	lung, brain, sputum	NA	TMP-SMX	Death
Fellows et al. (2007) [20]	57/M	None	Brain/pus	Right temporal lobe/single	TMP-SMX + IMI/IMI + MXF/MXF	Survived
Kandasamy et al.(2008) [18]	43/M	None	Brain/pus	Left parieto-occipital lobe/single	CTR/TMP-SMX + MXF	Survived
Park et al. (2008) [22]	55/M	Kidney transplant, immunosuppressive therapy	Lung, brain, blood	Bilateral frontal and parietal/multiple	NA	Death
Tachezy et al. (2009) [38]	71/F	HTN	Brain, lung, adrenal/pus	Right frontal parietal region/multiple	CTR + MTZ/TMP-SMX	Survived
Chung et al. (2009) [39]	65/M	Alcoholi abuse	Brain/pus	Right fronto-parietal region/single	CTR/TMP-SMX	Survived
Iannotti et al. (2009) [40]	53/M	None	Lung, brain/ pus	Left temporo-parietal region/single	TMP-SMX/LZ	Survived
Marchan et al. (2009) [41]	69/M	Liver transplant, immunosuppressive therapy	Brain, subcutaneous nodule/pus	Frontal cortex/single	TMP-SMX	Survived
Al-Tawfiq and Al-Khatti (2009) [1]	66/F	Psoriasis, DM, infliximab therapy	Brain, adrenal/pus	Parietal & frontal/multiple	TMP-SMX/LZ	Death
Scharfen et al. (2010) [42]	63/M	Liver transplant, immunosuppressive therapy	Brain, muscle/pus	Right precentral gyrus, left frontal pole and medial occipitotemporal gyrus/multiple	IMI/CTR + AK	Survived
Hara et al. (2011) [43]	52/M	SLE, steroids	Brain, calf muscle/pus (muscle)	Right parietal and temporal/multiple	TMP-SMX + IMI	Survived
Moon et al. (2011) [12]	43/M	Liver transplant, immunosuppressive therapy	Brain/pus	Occipital/multiple	TMP-SMX + CTR	Survived
Izawa et al. (2011) [44]	72/M	None	Brain/pus	NA	PZF	Survived
Izawa et al. (2011) [44]	78/F	Cirrhosis	Brain/pus	NA	PZF + MER + AK + TMP-SMX	Death
Göktay et al. (2011) [45]	19/M	Idiopathic CD4+ T lymphocytopenia	Brain/pus	Cerebellum, frontal/multiple	AMC + CIP	Death
This study (2012)	58/M	Chronic demyelinating poly- radiculopathy, steroid therapy	Brain/pus	Frontal/multiple	TMP-SMX	Survived

NA = data not available; BAL = broncheoalveolar lavage; CLL = chronic lymphatic leukaemia; DM = diabetes mellitus; IVDU = intravenous drug use; ITP = idiopathic thrombocytopenic purpura; ESRD = end-stage renal disease; COPD = chronic obstructive pulmonary disease; SLE = systemic lupus erythematosus; AMB = amphotericin B; AMC = amoxicillin-clavulanic acid; AMX, = amoxicillin; AM = aminoglycoside; AMP = ampicillin, CHL, chloramphenicol; CLI = clindamycin; CLX, cloxacillin; CPM = cefepime; CIP = ciprofloxacin; CTX = cefotaxime; CAZ = ceftazidime, CTR = ceftriaxone; DOX = doxycyline; ERY = erythromycin; FLX, = flucloxacillin; FLU = flucytosine; FLC = fluconazole; GEN = gentamicin; HIV = human immunodeficiency virus; HTN = hypertension; IMI = imipenem-cilastatin; INH = isoniazid; LZ = linezolid; MTZ = metronidazole; MEZ, = MIN = minocycline; MXF = moxifloxacin; PCP = pneumocaptic pneumonia; PEF = pefloxacin; PEN = penicillin; PIP, = piperacillin; PYR, = pyrimethamine;; PZF, = pazufloxacin; SAM = ampicillin-sulbactam; TMP-TSX = sulfamethoxazole; SUF = sulfadiazine; SSS = sulfonamide; STR = streptomycin; TEC = teicoplanin; VAN = vancomycin.

Empiric treatment of cerebral nocardiosis is well established with the use of parenteral TMP/SMX, amikacin, and imipenem-cilastatin [19,20]. Recently, extended-spectrum fluoroquinolones such as moxifloxacin has been used successfully against N. farcinica cerebral abscess [20,21]. Because of its ability to cross the blood–brain barrier, TMP/SMX is the treatment of choice and may be effective even when in vitro studies show resistance [13,23]. An alternative regimen comprising amikacin in combination with imipenem-cilastatin or amoxicillin-clavulanic acid has been suggested in patients with disseminated disease, especially of the central nervous system [24,25], and therapy must be continued for at least 12 months [3]. Our patient was treated with oral TMP-SMX and amoxicillin-clavulanic acid for 12 months with a good clinical response.

Conclusion

Cases of N. farcinica infections are being reported more often because of recent changes in taxonomy and diagnostic methodology. This change in epidemiology has implications for therapy because of the organism's pathogenicity and natural resistance to multiple antimicrobial agents, including third-generation cephalosporins; any delay in starting appropriate antibiotic therapy can have adverse consequences.

Footnotes

Author Disclosure Statement

No conflicting financial interests exist. No funds were provided for this work.

References

Al-Tawfiq

, Al-Khatti

. Disseminated systemic Nocardia farcinica infection complicating alefacept and infliximab therapy in a patient with severe psoriasis. Int J Infect Dis, 2009; 14:153–157.

Peters

, Saubolle

, Costantino

. Disseminated and cerebral infection due to Nocardia farcinica: Diagnosis by blood culture and cure with antibiotics alone. Clin Infect Dis, 1996; 23:1165–1167.

Sabuncuoğlu

, Cibali Açikgo

, Caydere

, et al. Nocardia farcinica brain abscess: A case report and review of the literature. Neurocirugia (Astur), 2004; 15:600–603.

Mamelak

, Obana

, Flaherty

, Rosenblum

. Nocardial brain abscess: Treatment strategies and factors influencing outcome. Neurosurgery, 1994; 35:622–631.

Beaman

, Beama

. Nocardia species: Host–parasite relationships. Clin Microbiol Rev, 1994; 7:213–264.

Boiron

, Provost

, Chevrier

, Dupont

. Review of nocardial infections in France from 1987 to 1990. Eur J Clin Microbiol Infect Dis, 1992; 11:709–714.

Holm

. Seven cases of human nocardiosis caused by Nocardia farcinica. Sabouraudia, 1975; 13:161–169.

Lerner

. Nocardia species. In: Mandel

, Douglas

, Bennet

(eds). Principles and Practice of Infectious Diseases. New York. Churchill Livingstone, 1995:2273–2280.

Kramer

, Uttamchandani

. The radiographic appearance of pulmonary nocardiosis associated with AIDS. Chest, 1990; 98:382–385.

10.

Roth

, Andrees

, Kroppenstedt

, et al. Phylogeny of the genus Nocardia based on reassessed 16S rRNA gene sequences reveals underspeciation and division of strains classified as Nocardia asteroides into three established species and two unnamed taxons. J Clin Microbiol, 2003; 41:851–856.

11.

Krone

, Schaal

, Brawanski

, Schuknecht

. Nocardial cerebral abscess cured with imipenem/amikacin and enucleation. Neurosurg Rev, 1989; 12:333–340.

12.

Moon

, Cho

, Kang

, Kim

. Nocardia brain abscess in a liver transplant recipient. J Korean Neurosurg Soc, 2011; 50:396–398.

13.

Viganò

, Edefonti

, Ferraresso

, et al. Successful medical treatment of multiple brain abscesses due to Nocardia farcinica in a paediatric renal transplant recipient. Pediatr Nephrol, 2005; 20:1186–1188.

14.

Wallace

, Tsukamura

, Brown

, et al. Cefotaxime-resistant Nocardia asteroides strains are isolates of the controversial species Nocardia farcinica. J Clin Microbiol, 1990; 28:2726–2732.

15.

Tatti

, Shieh

, Phillips

. Molecular diagnosis of Nocardia farcinica from a cerebral abscess. Hum Pathol, 2006; 37:1117–1121.

16.

Miralles

. Disseminated Nocardia farcinica infection in an AIDS patient. Eur J Clin Microbiol Infect Dis, 1994; 13:497–500

17.

Dietlein

, Firsching

, Peters

. Therapie eines Hirnabszesses, verursacht durch Nocardia farcinica. Med Klin, 1988; 83:613–614.

18.

Kandasamy

, Iqbal

, Cooke

, Eldridge

. Primary Nocardia farcinica brain abscess with secondary meningitis and ventriculitis in an immunocompetent patient, successfully treated with moxifloxacin. Acta Neurochir, 2008; 150:505–506.

19.

Brown-Elliott

, Brown

, Conville

, Wallace

Jr . Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev, 2006; 19:259–282.

20.

Fellows

, Kalsi

, Martin

. Nocardia farcinica brain abscess in a patient without immunocompromise. Br J Neurosurg, 2007; 21:301–303.

21.

Miksits

, Stoltenburg

, Neumayer

, et al. Disseminated infection of the central nervous system caused by Nocardia farcinica. Nephrol Dial Transplant, 1991; 6:209–214.

22.

Park

, Park

, Kim

, et al. A case of disseminated Nocardia farcinica diagnosed through DNA sequencing in a kidney transplantation patient. Clin Nephrol, 2002; 70:542–545.

23.

Debieuvre

, Dalphin

, Jacoulet

, et al. Infection disséminée due à un germe inhabituel, Nocardia farcinica. Rev Mal Respir, 1993; 10:356–358.

24.

Farina

, Boiron

, Goglio

, Provost

. Human nocardiosis in northern Italy from 1982 to 1992. Northern Italy Collaborative Group on Nocardiosis. Scand J Infect Dis, 1995; 27:23–27.

25.

Lerner

. Nocardiosis. Clin Infect Dis, 1996; 22:891–903.

26.

Bergström

, Edebo

, Fors

, Tegner

. Systemic Nocardia infection. Scand J Respir Dis, 1996; 47:75–84.

27.

Palmer

, Harvey

, Wheeler

. Diagnostic and therapeutic considerations in Nocardia asteroides infection. Medicine, 1974; 53:391–401.

28.

Bani-Sadr

, Hamidou

, Raffi

, et al. Aspects cliniques et bactériologiques des nocardioses: 9 observations. Presse Méd, 1995; 24:1062–1066.

29.

Beaman

, et al. Nocardia, Rhodococcus, Streptomyces, Oerskovia and other actinomycetes of medical importance. In: Murray

, Baron

, Pfaller

, et al. (eds): Manual of Clinical Microbiology. Washington, DC. American Society for Microbiology. 1995:379–399.

30.

Nampoory

MRN

, Khan

, Johny

, et al. Nocardiosis in renal transplant recipients in Kuwait. Nephrol Dial Transplant, 1996; 11:1134–1138.

31.

Minamoto

, Sordillo

. Disseminated nocardiosis in a patient with AIDS: Diagnosis by blood and cerebrospinal fluid cultures. Clin Infect Dis, 1998; 26:242–243.

32.

Kontoyiannis

, Ruoff

, Hooper

. Nocardia bacteremia: Report of 4 cases and review of the literature. Medicine, 1988; 77:255–266.

33.

Malincarne

, Marroni

, Farina

, et al. Primary brain abscess with Nocardia farcinica in an immunocompetent patient. Clin Neurol Neurosurg, 2002; 104:132–135.

34.

Lai

, Lee

, Teng

, et al. Disseminated Nocardia farcinica infection in a uraemia patient with idiopathic thrombocytopeni purpura receiving steroid therapy. J Med Microbiol, 2005; 54:1107–1110.

35.

Fihman

, Berçot

, Mateo

, et al. First successful treatment of Nocardia farcinica brain abscess with moxifloxacin. J Infect, 2006; 52:99–102.

36.

Shin

, Sugawara

, Tsukada

, et al. Successful treatment of disseminated Nocardia farcinica infection in a living-donor liver transplantation recipient. Transpl Infect Dis, 2006; 8:222–225.

37.

Muñoz

, Mirelis

, Aragón

, et al. Clinical and microbiological features of nocardiosis 1997–2003. J Med Microbiol, 2007; 56:545–550.

38.

Tachezy

, Simon

, Ilchmann

, et al. Abscess of adrenal gland caused by disseminated subacute Nocardia farcinica pneumonia: A case report and mini-review of the literature. BMC Infect Dis, 2009; 2:194.

39.

Chung

, Lin

, Hsieh

, et al. Nocardia farcinica brain abscess in an immunocompetent patient treated with antibiotics and two surgical techniques. J Clin Neurosci, 2009; 16:1675–1677.

40.

Iannotti

, Hall

, Procop

, et al. Nocardia farcinica brain abscess in an immunocompetent adult mimicking metastatic brain tumor: Rapid diagnosis by pyrosequencing and successful treatment. Surg Neurol, 2009; 72:74–79.

41.

Marchan

SJG

, Meneu Díaz

, Caso Maestro

, et al. Disseminated nocardiosis: A rare infectious complication following non-heart-beating donor liver transplantation. Transplant Proc, 2009; 41:2495–2497.

42.

Scharfen

Jr , Morávková

, Buncek

, et al. Nocardia farcinica as the causative agent of a brain abscess in a patient with interstitial lung disease. Epidemiol Mikrobiol Imunol, 2010; 59:13–20.

43.

Hara

, Wakui

, Ochiai

. Disseminated Nocardia farcinica infection in a patient with systemic lupus erythematosus. J Med Microbiol, 2011; 60:847–850.

44.

Izawa

, Sakano

, Okumura

, et al. Two cases of Nocardia farcinica brain abscess. No Shinkei Geka, 2011; 39:1167–1172.

45.

Göktay

, Mansur

, Erşahin

, et al. Idiopathic CD4⁺ T lymphocytopenia with epidermodysplasia verruciformis-like skin eruption, Nocardia farcinica brain abscesses and pulmonary tuberculosis: A case report with fatal outcome. J Dermatol, 2011; 38:930–933.