Nocardia is a soil-borne strictly aerobic actynomicete with at least 16 species can affect human’s healthy [8]. Nocardia spp. have a predilection for the lungs and brain as foci of infection, particularly in immunocompromised hosts [9].In this case, the patient was a 61-years-old male with no immunodeficiency disease, but he had bronchiectasis, hypertension, coronary heart disease. Multiple lung infections, 11 hospitalizations, and prolonged antibiotic use in the past five years may be key factors in the patient's Nocardia infection
Nocardia farcinica was the most common speciesin Nocardia infection, accounted for 24.5% [10]. Nocardia farcinica is more prone to affect the central nervous system (CNS) than other species [11, 12]. Clinical manifestations of CNS nocardiosis usually result from local effects of granulomas or abscesses in the brain, less commonly in the spinal cord or meninges[11, 12] .The abscess usually can be identified by CT scan or MRI as a ring enhancement at the capsular phase [15],but it need to be distinguish with tumor, cystic or necrotic foci [16]. In our case, after the patient developed symptom of headache, brain abscess was found by MRI examination. Patient underwent minimally invasive surgery for intracranial abscess puncture and suction under CT-guidance, smear staining and bacterial culture were performed on the drainage fluid, and the cultivated colonies were identified as Nocardia farcinica by mass spectrometry.
Nocardia identification can be difficult because of the slowly growing pattern of the germ and low positive rate (colonies usually require at least 48h of incubation although more commonly 3 to 5 days and up to 14 to 21 days), preferably in selective media[17].To Nocardia spp, multiple cerebrospinal fluid (CSF) specimens should be cultured to increase the yield, although it is not uncommon for the bacteria to be recovered only when direct pus is cultured[18] .Certain laboratory techniques like mass spectrometry may help to identify the genus and species. The preferred methods for test of Nocardia are 16S rRNA gene analysis and other molecular techniques, such as restriction fragment length polymorphisms and multilocus sequence analysis. Direct abscess drainage seems to be the best method for collection of samples for microbiological confirmation and antibiotic susceptibility testing [19]. Nocardia pneumonia often requires bronchoscopy or percutaneous lung biopsy, and a detailed history and thorough physical examination should be taken to adequately assess the presence of spread of the lesions. Cranial CT or MRI should be performed if symptoms or signs suggest intracranial involvement .The patient was considered to have a pulmonary infection caused by inhalation of the bacterium through the respiratory tract and a cerebral abscess caused by haematogenous spread to the brain. In our case, the patient's repeated sputum culture and BALF tests showed no bacterial growth. Test was negative in the first percutaneous lung biopsy tissue culture, possibly because no valuable lesion tissue was collected at the biopsy site or the use of antibiotics affected the detection rate. This also suggests that Nocardia is more difficult to identify than more common bacteria. Bacterial grew after 24 hours of culture of puncture fluid, indicated a severe brain infection and suggested that abscess drainage may be good to isolate and culture Nocardia.
Direct smears from surgical samples show gram-positive, beaded, branching filaments that are partially acid-fast, and thus need to be differentiated from mycobacteria. Colonies usually have a chalky white cotton-like appearance because of the abundant aerial filaments. The smell of moist or wet soil is very characteristic of Nocardia spp colonies[5]. Nocardia spp exhibit variable morphologic appearances depending on the species, the incubation conditions and the duration of incubation. In routine culture media, Nocardia spp appear as bacillii with ramifications and sub-ramifications at rightangles that may form coccus in Thioglycolate medium after prolonged incubation [8]. The colonies we obtained from the puncture fluid were positive for Gram staining and weak acid resistance for acid-fast staining (Fig. 3.D-F). The characteristics of bacterial culture and growth (Fig. 3.A-C) are consistent with the above literature reports.
Nocardia farcinica brain abscess has a high mortality rate,as high as 20% in immunocompetent patients and 55% inimmunocompromised 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 [6]. In a study of Nocardia isolated from human samples in France, N. farcinica was the most frequently isolated species in blood cultures and brain abscesses (21/39, 54% and 19/43, 44.2% respectively. In French data, N. farcinica was frequently not susceptible to cefotaxime (80% of the isolates), meropenem (73% of isolates) and aminoglycosides (more than 90%) [20]. Taking into account the inherent resistance of Nocardia farcinica to hird-generation cefalosporins, TMP/SMX’s ability to cross the blood–brain barrier, most authorities recommend TMP/SMX as part of first-line therapy for nocardiosis [21, 22] .Abscesses > 25mm in diameter and that fail to shrink after 4 weeks of antibiotic therapy should be aspirated to confirm the diagnosis regardless of the immune status of the patient [6]. Empiric treatment of cerebral nocardiosis is well established with the use of parenteral TMP/SMX, amikacin, and imipenem-cilastatin[23, 24]. Recently, extended-spectrum fluoroquinolones such as moxifloxacin has been used successfully against N. farcinica cerebral abscess[25]. 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]. The abscesses in our patient’s brain was about 35mm×52mm, far more than 25mm, minimally invasive puncture drainage is of great significance for the identification of pathogenic bacteria and the treatment of patients. After 16 days of treatment with TMP/SMX, the patient's condition was significantly improved, the lesions in lung and head were also significantly reduced, show a good clinical response (Fig. 1C and Fig. 2C). This also suggesting that the lung lesions was caused by Nocardia farcinica.
The patient had recurring lung infections, merge a variety of basic diseases, long-term use of antibiotics, leading to a weakened immune system. When the patient was identified with Nocardia infection, the lung lesions and brain abscesses were very severe, which also affected the patient's prognosis. After two months of continuous antibiotic treatment, the patient suddenly developed dyspnea, an acute outbreak of pulmonary fungal infection (Fig. 1D), after routine use of antifungal drug, the disease deteriorated and oxygen saturation decreased, eventually resulting in death from ARDS.
In conclusion, brain abscess can be caused by Nocardia farcinica in non-immunocompromised individuals and it is rarely occurs in clinical. In our case, although the patient's condition improved after targeted antibiotic treatment (TMP/SMX), due to lots of basic diseases and long-term use of antibiotics, the central nervous system symptoms appeared lately and delayed diagnosis, the patient eventually died. For pneumonia of unknown cause, a variety of technical means should be used to determine the pathogen as soon as possible, take targeted treatment, pay attention to the examination of the brain and other organs. Minimally invasive puncture drainage is of great significance for the diagnosis and treatment of Nocardia brain abscess. Because the treatment of Nocardia brain abscess requires long-term use of antibiotics, we should pay attention to the changes of patients' immunity and avoid infection with other pathogens, especially fungi. Early diagnosis and targeted antibiotic treatment are critical for Nocardia brain abscess treatment and prognosis.