Brain Abscess Caused by Nocardia: Case Report and Literature Review

Nocardia brain abscess is a rare clinical entity, accounting for 2% of all brain abscesses, associated with high morbidity and amortality rate 3 times higher than brain abscesses caused by other bacteria. Proper investigation and treatment, characterized by a longterm antibiotic therapy, play an important role on the outcome of the patient. The authors describe a case of a patient without neurological comorbidities who developed clinical signs of right occipital lobe impairment and seizures, whose investigation demonstrated brain abscess caused by Nocardia spp. The patient was treated surgically followed by antibiotic therapy with a great outcome after 1 year of follow-up.

A clinical case report of brain abscess caused by Nocardia brasiliensis in a non-immunocompromised patient and a relevant literature review.

BACKGROUND: Brain abscess due to the Nocardia genus is rare and usually found in immunocompromised patients. The most common subtype implicated is Nocardia farcinica while brain abscess due to Nocardia brasiliensis is comparatively rare. Diagnosis of brain abscess is based mainly on bacteriological culture from pus collected at the site of infection, and brain imaging. Stereotaxic aspiration or surgical resection combined with adequate duration of treatment with antibiotics to which the bacteria are sensitive represent effective treatment strategies. CASE PRESENTATION: We report a rare case of brain abscess caused by Nocardia brasiliensis in a non-immunocompromised patient. He admitted to our hospital twice with a headache. Stereotaxic aspiration was performed at the patient's first appointment at the hospital, and a craniotomy was used to excise the lesion during subsequent abscess recurrence. CONCLUSION: Early diagnosis, reasonable surgical intervention, and adequate duration of treatment with effective antibiotics are critical for treating brain abscess.

A novel experimental immunomodulatory therapy against Nocardia brasiliensis in a BALB/c murine model.

BACKGROUND: Mycetoma is recognized as a neglected tropical disease and there are still therapeutic challenges, especially in cases recalcitrant to standard therapy or with high risk of dissemination. Subcultures have been used previously to decrease the virulence of human pathogens. Previous reports have demonstrated that after carrying out 200 subcultures of Nocardia brasiliensis, a decrease in virulence was observed. AIM: To evaluate the effect of attenuated N. brasiliensis strains on the development of lesions in an established mycetoma infection. METHODS: Female 8-12-week-old BALB/c mice were injected with N. brasiliensis suspension to establish a mycetoma. Sixty mice were selected and divided into three groups: two of these groups were inoculated in the dorsum with N. brasiliensis subcultured 200 and 400 times, respectively, while the third group served as control. The thickness of each lesion was measured with calipers every week for 12 weeks. RESULTS: After 12 weeks, we observed that inoculation of 1 × 105 colony-forming units of attenuated N. brasiliensis strains was able to modify the natural history of the infection, with a decrease in the size of the lesions, particularly with P400, compared with the control group (P < 0.01). CONCLUSION: In this experimental evaluation of an immunomodulatory therapy with attenuated N. brasiliensis strains in a murine model, there was a greater stability in the size of the lesion over time in BALB/c mice inoculated with the P400 strain. This treatment could open the possibility of using the attenuated strain as immunomodulatory therapy in patients recalcitrant to standard therapy, with high risk of dissemination or who develop drug-related adverse effects.

High Intraspecific Genetic Diversity of Nocardia brasiliensis, a Pathogen Responsible for Cutaneous Nocardiosis Found in France: Phylogenetic Relationships by Using sod and hsp65 Genes.

This study aims at genetic characterization and phylogenetic relationships of Nocardia brasiliensis focusing by using housekeeping rrs, hsp65, and sodA genes. N. brasiliensis is the species responsible for 80% of cases of actinomycetoma, one form of cutaneous nocardiosis which occurs mainly in tropical regions reaching immunocompetent patients in which the disease can lead to amputation. We analyze 36 indigenous cases of N. brasiliensis that happened in France. Phylogenetic analysis targeting rrs gene showed no robustness at phylogenetic nodes level. However, the use of a concatenation of hsp65 and sodA genes showed that the tested strains surprisingly ranked in 3 well-defined genotypes. Genotypes 2 and 3 were phylogenetically closer to each other and both diverged from genotype 1 sustained by a high bootstrap of 81%. This last genotype hosts all the cases of pulmonary forms (3), the sole cerebral form, and almost all the cases of immunocompromised patients (3 out of 4). Moreover, excepting one of them, all the strains belonging to this group present a susceptibility to imipenem which is not the case in the other genotypes that rarely count among them strains being susceptible to this drug. The haplotype diversity (Hd) of hsp65 (0.927) and sodA (0.885) genes was higher than that of rrs (0.824). For this gene, we obtained 16 polymorphic sites whereas, for hsp65 and sodA genes, up to 27 and 29 were identified, respectively. This study reveals that these two genes have an important genetic discriminatory power for the evaluation of the intraspecies genetic variability of N. brasiliensis and they may be useful for identification purposes at species level. This study also reveals the possible existence of a new species harbored by genotype 1.

Absceso cerebral por Nocardia spp. en pacientes inmunocompetentes: presentación de 2 casos / Cerebral abscess by Nocardia spp. in immunocompetent patients: report of 2 cases

Nocardia corresponde a un género de bacterias gram positivo que puede producir compromiso pulmonar, sistémico y abscesos cerebrales, especialmente en pacientes inmunocomprometidos. La infección cerebral por Nocardia spp es extremadamente infrecuente en pacientes inmunocompetentes, por lo cual se reportan dos casos: caso 1: mujer de 61 años, sana, consulta por cefalea y paresia en hemicuerpo izquierdo. Estudio con TAC y RM de encéfalo demuestran absceso cerebral. Se inició tratamiento con ceftriaxona mas cloxacilina y fue drenado quirúrgicamente. En el cultivo del LCR se aisló Nocardia spp. cambiándose esquema a cotrimoxazol con meropenem por 6 semanas. Caso 2: varón de 72 años, hipertenso y tabáquico crónico. Consultó por cefalea, paresia de extremidad inferior derecha y pérdida de visión de ojo derecho. Estudio con TAC y RM de encéfalo objetiva absceso cerebral parietal izquierdo. Se inició tratamiento con ceftriaxona, metronidazol y vancomicina. Se realizó drenaje quirúrgico. El cultivo de absceso resultó positivo para Nocardia spp, ajustándose esquema a cotrimoxazol y meropenem por 6 semanas. Requirió tratamiento prolongado por presentar lenta regresión clínica e imagenoló- gica.

Nocardia is a gram positive bacterial genus. Is involved in pulmonary, systemic and brain abscess usually in immunocompromised patients. Nocardia spp. brain infection is extremely rare in immunocompetent patients, hereby we report 2 cases: case 1: 61 years old woman, without morbid conditions, consulted for headache and left hemiparesis. Study with CT and MRI of encephalon shows brain abscess. Treatment with ceftriaxone plus cloxacilin and surgical drainage were started. In CSF culture, Nocardia spp. was obtained. Scheme was changed to cotrimoxazole with meropenem to complete 6 weeks. Case 2: male of 72 years old, history of smoking and hypertension. Consulted for headache, paresis of right leg and loss of vision of the right eye. CT and MRI showed left parietal brain abscess. Treatment with ceftriaxone, metronidazole and vancomycin were started. Surgical drainage was performed. Abscess culture was positive for Nocardia spp., adjusting scheme to cotrimoxazole and meropenem for 6 weeks. It required prolonged treatment due to slow imaging and clinical regression.

Genomic Changes Associated with the Loss of Nocardia brasiliensis Virulence in Mice after 200 In Vitro Passages.

Nocardia species, particularly Nocardia brasiliensis, are etiologic agents of mycetoma, a chronic subcutaneous infection. Until now, little has been known about the pathogenic mechanisms involved in nocardial infection. Traditionally, subculture in rich media has been a simple way to induce attenuation. In this work, we report the changes in virulence toward mice and in genomic constitution of N. brasiliensis produced after 200 continuous subcultures in brain heart infusion (BHI) medium (P-200 strain). The ability of the N. brasiliensis P-200 strain to produce experimental infection was tested using BALB/c mice. P-200 was also used to immunize mice to determine whether it could induce resistance against a challenge with a nonsubcultured isolate (P-0). Comparative proteomic analysis between N. brasiliensis P-0 and P-200 was performed by two-dimensional (2-D) electrophoresis, and the genome sequence was obtained through Roche 454 sequence analysis. Virulence in BALB/c mice was completely lost, and BALB/c mice immunized with P-200 bacterial cells were resistant to mycetoma production by the nonsubcultured strain. Whole-genome sequence analysis revealed that P-200 lost a total of 262,913 bp distributed in 19 deleted regions, involving a total of 213 open reading frames (ORFs). The deleted genes included those encoding bacterial virulence factors, e.g., catalase, nitrate reductase enzymes, and a group of mammalian cell entry (MCE) family proteins, which may explain the loss of virulence of the isolate. Thus, completely attenuated N. brasiliensis was obtained after 200 passages in BHI medium, and putative Nocardia virulence genes were identified for the first time.

Osteomielitis femoral crónica por Nocardia / Chronic femoral osteomyelitis due to Nocardia

La osteolielitis por Nocardia es una enfermedad oportunista, y bastante rara según estudios. Se relata un caso de un paciente, su diagnóstico y tratamiento de la misma.

Pyogranulomatous dermatitis and panniculitis due to Nocardia nova in a cat / Dermatite e paniculite piogranulomatosas causadas por Nocardia nova em um gato

Este relato descreve os achados clínicos, patológicos e microbiológicos de uma infecção incomum por Nocardia nova em um gato. Um gato macho, sem raça definida, de 3 anos de idade, apresentou ferida cutânea exsudativa e ulcerada. Amostras da lesão foram coletadas para histopatologia e bacteriologia. Histologicamente, a lesão consistiu de dermatite e paniculite piogranulomatosas associadas a colônias grandes e irregulares de bactérias filamentosas e ramificadas. O cultivo bacteriológico revelou bacilos filamentosos, gram-positivos, parcialmente ácido resistentes, visualizados pelas colorações de Gram e Kinyoun, respectivamente. A identificação da Nocardia novafoi confirmada pelo sequenciamento 16S rDNA e análise filogenética. Este é o primeiro caso de paniculite e dermatite piogranulomatosas em um gato causado por Nocardia nova registrado no Brasil.(AU)

This report describes the clinical, pathological and microbiological findings of an uncommon infection in a cat by Nocardia nova. A 3-year-old male domestic short hair cat with an ulcerated and exudative cutaneous wound was presented for clinical examination. Samples were collected for histopathology and bacteriology diagnosis. Microscopically, the lesion was diagnosed as pyogranulomatous dermatitis and panniculitis with large and irregular colonies of branching filamentous bacterium. Skin bacteriological culture showed gram-positive rods and partially acid-fast branching filaments by gram and kinyoun staining, respectively. The identity of Nocardia nova was confirmed by 16S rDNA sequencing and phylogenetic analysis. This is the first case of pyogranulomatous dermatitis and panniculitis in a cat caused byNocardia nova reported in Brazil.(AU)

Complete genome sequence analysis of Nocardia brasiliensis HUJEG-1 reveals a saprobic lifestyle and the genes needed for human pathogenesis.

Nocardia brasiliensis is an important etiologic agent of mycetoma. These bacteria live as a saprobe in soil or organic material and enter the tissue via minor trauma. Mycetoma is characterized by tumefaction and the production of fistula and abscesses, with no spontaneous cure. By using mass sequencing, we determined the complete genomic nucleotide sequence of the bacteria. According to our data, the genome is a circular chromosome 9,436,348-bp long with 68% G+C content that encodes 8,414 proteins. We observed orthologs for virulence factors, a higher number of genes involved in lipid biosynthesis and catabolism, and gene clusters for the synthesis of bioactive compounds, such as antibiotics, terpenes, and polyketides. An in silico analysis of the sequence supports the conclusion that the bacteria acquired diverse genes by horizontal transfer from other soil bacteria, even from eukaryotic organisms. The genome composition reflects the evolution of bacteria via the acquisition of a large amount of DNA, which allows it to survive in new ecological niches, including humans.

Retnla down-regulation and IL-13-rich environment correlate with inflammation severity in experimental actinomycetoma by Nocardia brasiliensis.

Nocardia brasiliensis (Nb) is a facultative intracellular pathogen that may cause actinomycetoma when immune response is unable to control the pathogenic invasion. We used comparative real-time PCR to evaluate the expression level of molecules indicative of either classical or alternative activation of macrophages, as well as of cytokines involved in macrophage polarization, during the experimental infection in BALB/c mice. We found induction or increased expression of the pro-inflammatory markers csf2/GM-CSF, interferon-gamma, and nos2/iNOS. The expression of Ym1 and IL-13, which are usually related with alternative activation of macrophage, was also increased. However, retnla/FIZZ1 expression decreased sharply during the infection. We concluded that Nb infection induces both a pro-inflammatory and anti-inflammatory environment, in which there is a strong inverse correlation between IL-13 and retnla expression.

Systemic increased immune response to Nocardia brasiliensis co-exists with local immunosuppressive microenvironment.

Human diseases produced by pathogenic actinomycetes are increasing because they may be present as opportunistic infections. Some of these microbes cause systemic infections associated with immunosuppressive conditions, such as chemotherapy for cancer, immunosuppressive therapy for transplant, autoimmune conditions, and AIDS; while others usually cause localized infection in immunocompetent individuals. Other factors related to this increase in incidence are: antibiotic resistance, not well defined taxonomy, and a delay in isolation and identification of the offending microbe. Examples of these infections are systemic disease and brain abscesses produced by Nocardia asteroides or the located disease by Nocardia brasiliensis, named actinomycetoma. During the Pathogenic Actinomycetes Symposium of the 16th International Symposium on Biology of Actinomycetes (ISBA), held in Puerto Vallarta, Mexico, several authors presented recent research on the mechanisms by which N. brasiliensis modulates the immune system to survive in the host and advances in medical treatment of human actinomycetoma. Antibiotics and antimicrobials that are effective against severe actinomycetoma infections with an excellent therapeutic outcome and experimental studies of drugs that show promising bacterial inhibition in vivo and in vitro were presented. Here we demonstrate a systemic strong acquired immune response in humans and experimental mice at the same time of a local dominance of anti inflammatory cytokines environment. The pathogenic mechanisms of some actinomycetes include generation of an immunosuppressive micro environment to evade the protective immune response. This information will be helpful in understanding pathogenesis and to design new drugs for treatment of actinomycetoma.

Nocardia brasiliensis induces an immunosuppressive microenvironment that favors chronic infection in BALB/c mice.

Nocardia brasiliensis is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+ Foxp3+ regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether N. brasiliensis modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between N. brasiliensis immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P < 0.05) in footpad tissue and spleen. Treg subpopulations peaked at days 7 and 15 (P < 0.01) in the footpad and spleen, respectively. Transforming growth factor ß1 (TGF-ß1) and interleuki-10 (IL-10) are cytokines known for their immunosuppressive effects. During early and chronic infections, these cytokines were elevated with increased TGF-ß1 levels from days 3 to 30 (P < 0.01) and sustained IL-10 expression throughout infection compared to uninfected mice. IL-6 production was increased at day 3 (P < 0.01), whereas gamma interferon (IFN-γ), IL-17A, and IL-23 levels were highest at day 15 postinfection (P < 0.01) when a decrease in the bacterial load (>1 log) was also observed (P < 0.05). After these changes, at 30 to 60 days postinfection, IFN-γ production was decreased, whereas the expression of anti-inflammatory cytokines and the bacterial load again increased (P < 0.05). The increment in Treg cells and the related cytokine profile correlated with reduced inflammation at day 15 (P < 0.05) in the footpad. We conclude that N. brasiliensis modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.

Decrease of virulence for BALB/c mice produced by continuous subculturing of Nocardia brasiliensis.

BACKGROUND: Subculturing has been extensively used to attenuate human pathogens. In this work we studied the effect of continuous subculturing of Nocardia brasiliensis HUJEG-1 on virulence in a murine model. METHODS: Nocardia brasiliensis HUJEG-1 was subcultured up to 130 times on brain heart infusion over four years. BALB/c mice were inoculated in the right foot pad with the bacteria subcultured 0, 40, 80, 100 and 130 times (T0, T40, T80 T100 and T130). The induction of resistance was tested by using T130 to inoculate a group of mice followed by challenge with T0 12 weeks later. Biopsies were taken from the newly infected foot-pad and immunostained with antibodies against CD4, CD8 and CD14 in order to analyze the in situ immunological changes. RESULTS: When using T40, T80 T100 and T130 as inoculums we observed lesions in 10, 5, 0 and 0 percent of the animals, respectively, at the end of 12 weeks. In contrast, their controls produced mycetoma in 80, 80, 70 and 60% of the inoculated animals. When studying the protection of T130, we observed a partial resistance to the infection. Immunostaining revealed an intense CD4+ lymphocytic and macrophage infiltrate in healing lesions. CONCLUSIONS: After 130 in vitro passages of N. brasiliensis HUJEG-1 a severe decrease in its virulence was observed. Immunization of BALB/c mice, with these attenuated cells, produced a state of partial resistance to infection with the non-subcultured isolate.

In situ TLR2 and TLR4 expression in a murine model of mycetoma caused by Nocardia brasiliensis.

Actinomycetoma caused by Nocardia brasiliensis is a common disease in tropical regions. This ailment is characterized by a localized chronic inflammation that mainly affects the lower limbs. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, inducing the production of proinflammatory mediators. The role of TLRs in the immune response against N. brasiliensis is unknown. The aim of this work was to locate and quantify in a murine model the expression of TLR2 and TLR4 in the infection site using reverse transcription-PCR and immunohistochemistry. The results showed that TLR2 expression increased in the infected tissue, whereas TLR4 expression decreased. The presence of TLR2 and TLR4 was demonstrated in different cell populations throughout the chronic infectious process. In the early stages of this process, TLR2 was expressed in neutrophils and macrophages in direct contact with the inoculum, whereas TLR4 was observed in mast cells. In the advanced stages of the infection, TLR2 was expressed in foam cells and fibroblasts and was likely associated with bacterial containment, while TLR4 was downregulated, probably resulting in an imbalance between the host immune response and the bacterial load that favoured chronic disease.

Construction of a Nocardia brasiliensis fluorescent plasmid to study Actinomycetoma pathogenicity.

Nocardia brasiliensis, is a bacteria that lives as saprophyte in soil and causes a disease called actinomycetoma in both human and animals. Nocardia brasiliensis is an intracellular, facultative bacterium that replicates and survives within host macrophages. The mechanisms involved in the evasion of the microbicidal actions of macrophages remain unclear. The filamentous growth of N. brasiliensis is resistant to unicellular preparations, leading to inaccurate quantification of bacterial numbers by means of colony forming units (CFU). As successful survival studies with green fluorescent protein (GFP)-expressing bacterial strains have been reported, we constructed a recombinant GFP-expressing strain of N. brasiliensis. The virulence of the modified strain is maintained because it induces mycetoma in BALB/c mice. This new strain can be used for bacterial survival assays using cytometry and to elucidate the pathogenicity mechanisms in Actinomycetoma infection.

Evaluation of the Combined Therapy of DA-7218, a New Oxazolidinone, and Trimethoprim/ Sulfamethoxazole in the Treatment of Experimental Actinomycetoma by Nocardia brasiliensis.

OBJECTIVES: Currently, for actinomycetoma, combined antimicrobial therapy is preferred to the use of a single compound. This is in order to provide a broader-spectrum coverage due to a combinatory or synergistic effect between the drugs, and to decrease the possibility of emergence of natural resistant strains. A new oxazolidinone pro-drug, DA-7218 [(R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl) methyl-disodium-phosphate] (recently re-named TR-701), has shown very good in vitro and in vivo activities against several gram-positive bacteria including Nocardia spp. METHODS: In the present work we evaluated the effect of DA-7218 at two different doses, alone and combined with trimethoprim/ sulfamethoxazole (SXT), in an experimental Nocardia brasiliensis actinomycetoma murine model. We also included a negative and a positive control group (linezolid and saline solution respectively). RESULTS: At the end of the treatment period, we observed a clinically and statistically significant difference among the drug receiving groups (combined, alone and linezolid) and the control group (P=0.004). The difference was higher (P= 0.004) between the groups receiving DA-7218 (25mg/kg) alone or combined with SXT, and the control group (saline solution). CONCLUSIONS: In this work we proved that DA-7218 alone and combined with SXT is effective in the treatment of experimental actinomycetoma by Nocardia brasiliensis and that it could be potentially useful in the treatment of human actinomycetoma.

Efficacy of ciprofloxacin and moxifloxacin against Nocardia brasiliensis in vitro and in an experimental model of actinomycetoma in BALB/c mice.

The efficacy of ciprofloxacin and moxifloxacin against Nocardia brasiliensis was evaluated by applying 25 mg of each drug/kg subcutaneously every 8 h in BALB/c mice infected with N. brasiliensis. A statistically significant difference was observed only with moxifloxacin. A moxifloxacin-trimethoprim-sulfamethoxazole combination was as active as when each compound was used alone.

In situ detection and distribution of inflammatory cytokines during the course of infection with Nocardia brasiliensis.

Actinomycetoma, caused by the intracellular bacterium Nocardia brasiliensis, is characterized by an infiltration of several inflammatory cell populations. To explore aspects of the immune response in the pathogenesis of these bacteria we injected 10(6) CFU in footpads of BALB/c mice. After 1, 2, 3, 4, 7, 30 and 90 days immunohistochemistry was performed to compare presence and distribution of the inflammatory cytokines TNF-alpha, IL-1 beta, IL-6, IFN-gamma, IL-4, IL-10, and TGF-beta. Analysis of serial paraffin tissue sections showed strong participation and differences in distribution of cytokine-producing cells during the course of infection. Several TNF-alpha immunoreactive lymphocytes of the dermis were present during the course of the infection, but absent in the site of inflammation. During the first 4 days, IL-1 beta immunoreactivity was observed in dendritic epidermal cells and in cells surrounding the neutrophils around the grain. In later stages of infection, immunoreactive cells to this cytokine were mainly in the periphery of the microabscesses. Strong immunoreactivity was observed with IL-6 during the course of infection. Some cells in the epidermis and dermis, as well as muscle cells and several cells at the periphery of the microabscesses, showed strong IL-6 immunoreactivity. Cells immunoreactive to IL-4, IL-10, IFN-gamma and TGF-beta were present at the site of infection and, in later stages, in cells at the periphery of the microabscesses. In conclusion a mix of proinflammatory and antiinflammatory cytokines are produced at the same time by host cells. According to their distribution, inflammatory cytokines seems to have different functions during the course of infection with the intracellular bacterium N. brasiliensis.

[Nocardia brasiliensis leg ulcer and nodular lymphangitis in France]. / Ulcère de jambe et lymphangite nodulaire à Nocardia brasiliensis en France métropolitaine.

INTRODUCTION: Nocardia brasiliensis is a very rarely reported cause of chronic phagedenic ulcerations. We report the case of an elderly woman who developed such an infection after falling on her right leg on the road in the Bresse country (an essentially agricultural and bovine-cattle breading region) and developed a chronic phagedenic ulcer secondarily complicated by nodular lymphangitis of the thigh. CASE REPORT: A 75 year-old woman fell on her right leg on the side of the main road outside her hamlet in the Bresse country and secondarily developed a chronique phagedenic ulceration. We first considered her as suffering from pyoderma gangrenosum. A complete scanning only revealed an autoimmune thyroiditis and a rapidly healing gastric ulceration, and none of the treatments, either local or systemic, helped the skin condition to heal. After 3 weeks of application of a local corticoid ointment, the patient developed fever, general malaise, an exacerbation of her wound and an infiltration of the skin round her knee, together with nodular lymphangitic dissemination. A supplementary bacterial swab disclosed massive proliferation of a slow-growing Gram-positive bacillus, which proved to be Nocardia brasiliensis, together with a methicillino-sensitive Staphylococcus aureus. The treatment with sulfamethoxazole-trimetoprim gave a rash after 12 hours and was changed to amoxicillin and clavulanic acid, which rapidly proved to be permanently effective. DISCUSSION: The revelation of this particular slow-growing bacteria is difficult and requires bacterial swabs. Nocardia brasiliensis is relatively rare in primary skin ulcerations and we discuss the reasons why an elderly women should find this bacteria on the road outside her hamlet in the French countryside. This particular infectious condition requires general scanning, to make sure that the primary skin condition does not extend to other organs. We review the therapeutical options for patients who exhibit allergic reactions to the classically effective antibiotic drugs.