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Disseminated Nocardia brasiliensis infection: an unusual complication of immunosuppressive treatment for childhood dermatomyositis.

The use of steroids combined with cytotoxic drugs has increased in the last decade. The concomitant increase of opportunistic infections has contributed significantly to morbidity and mortality of patients treated with immunosuppressive agents. We describe a child with dermatomyositis who developed disseminated Nocardia brasiliensis infection while receiving steroids and methotrexate. Infectious etiology was established by gram stain. The patient was treated successfully. Disseminated Nocardia brasiliensis infection is rare with a high reported mortality. Diagnosis may be delayed secondary to insidious onset, similarity of clinical manifestations to other pathogens and slow growth in routine culture media. Nocardia should be considered early in the evaluation of infection in patients treated with immunosuppressive agents.

Adolescent↗

[Nocardia mastitis in cattle. 1. Clinical observations and diagnosis in 7 particular cases].

Lately reports of nocardial mastitis have been increasing. Therefore the clinical aspects of 7 individual cases were investigated. Pathologic-anatomical changes of the udder were registered and bacteriological examination of tissue and milk probes were performed. All of the cows had a mastitis during previous lactation periods which had to be treated with antibiotics. The infected quarters recovered in no cases. Shortly after parturition 6 cows had a severe acute mastitis. The cows were treated intramammarily and parenterally with various antibiotics during several days. The infected quarter became indurated and strongly enlarged. These changes were not influenced by therapy, and the cows lost weight. 14 days after the outbreak of the illness, all 6 cows were culled. One cow had a chronic Nocardia mastitis with involution of the affected quarter. Though treated several times, this cow did not recover either. The histopathological examination of the affected quarters revealed an acute to chronic, necrotic to granulomatous mastitis. Nocardia asteroides was histologically and bacteriologically proven to be the causative agent. The reason for the frequent infections with Nocardia and the way of infection is not clear yet. Therapy with antibiotics brought no recovery in any cases. The infected cows should be removed from the herd or culled.

Animals↗

Nocardia asteroides keratitis associated with extended-wear soft contact lenses.

Chronic unilateral keratitis developed in a 34-year-old woman who wore extended-wear contact lenses. A clinical response was not obtained until Nocardia asteroides was correctly identified as the causal agent. The response to 30% sulfacetamide was dramatic. We review the clinical presentation of Nocardia keratitis and recommendations for management. Use of corticosteroids should be avoided in Nocardia keratitis. This opportunistic organism should be considered in patients who wear contact lenses in whom infectious keratitis develops.

Adult↗

Nocardia asteroides sepsis of the knee.

Nocardia asteroides as an infecting agent has been an increasingly identified pathogen in humans, especially in immunosuppressed hosts. The Nocardia organisms as a cause of septic arthritis have been very unusual and in all previously reported cases have occurred in immunosuppressed patients. This is a report of two additional patients, one of whom has had no history of immunosuppression either before infection or subsequent to treatment and resolution of the infection. The second is a case of a questionably immunosuppressed patient with Nocardia asteroides septic arthritis. These cases reemphasize the importance of performing not only the most common aerobic and anaerobic bacterial cultures but also fungal and acid-fast bacilli cultures for early identification of less common organisms and for the initiation of appropriate therapy.

Adult↗

Trimethoprim-sulfamethoxazole therapy for Nocardia infections.

The optimal therapy for infections due to Nocardia species has not been established. To assess the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX), we reviewed the records of 19 patients with Nocardia infections seen at Duke University Medical Center, Durham, NC, who were treated with this drug, either alone or in combination with other antibiotics or a surgical procedure. Underlying diseases or therapy causing immunosuppression were present in all but five cases. Sites of involvement were lung (ten of 19), wound (two of 19), and brain (two of 19); five of 19 patients had disseminated disease. The mean duration of therapy was 7.2 months. Overall cure or improvement was achieved in 89% (17/19) of cases; 80% of patients with disseminated disease and 60% of those with CNS involvement recovered. This experience, and accumulated clinical evidence in the literature, indicates that TMP-SMX should be considered the therapeutic drug of choice in infections due to Nocardia species.

Administration, Oral↗

Nocardia species from bronchopulmonary infections and mycetomas.

350 specimens comprising sputum, bronchial aspirate, pleural fluid, pus and biopsy material were investigated for the presence of Nocardia spp. by the paraffin bait technique. Nocardia spp. were isolated in 15 of them. The physiological and morphological characteristics of the organisms and the use of paraffin baiting, a selective technique for isolating Nocardia spp. from clinical specimens, are discussed.

Adult↗

Detection of antigen in Nocardia caviae cross-reacting with mycobacterial antigen No. 21 in M. leprae using a lepromatous leprosy serum pool as antibody reagent.

Eighteen strains of nocardia, representing five different species, were studied in crossed immunoelectrophoresis against a lepromatous leprosy serum pool for the presence of antigen No. 21. This mycobacterial antigen shows antigenic heterogeneity with species specific antigenic determinants defined in Mycobacterium leprae. All four strains of N. caviae were found to share antigen No. 21 determinants with mucobacteria. All other strains of nocardia were negative in these direct immunoprecipitation tests. When compared with M. leprae antigen No. 21, the N. caviae antigen gave a reaction of partial identify in the same way as all strains of other mycobacteria tested previously, ii.e., with spurring by the M. leprae antigen. There was a reaction of complete identity between N. caviae and M. avium-intracellulare and M. smegmatis, respectively, with the lepromatous leprosy serum pool used as the antibody source. The results suggest that N. caviae antigen No. 21 is more closely related to the corresponding antigen of the genus Mycobacterium than to the antigen No. 21 equivalent of other nocardia species tested.

Antigens, Bacterial↗

Prevalence of Nocardia species in the soil of Patiala area.

Five hundred soil samples were examined for Nocardia species in Patiala area by using paraffin bait technique. Forty (8 per cent) yielded Nocardia species. All the forty isolates identified as Nocardia asteroides were pathogenic to white mice.

Animals↗

Optimization studies of components in enzymatic cholesterol reagents containing cholesterol oxidase from Nocardia erythropolis, Streptomyces sp, or Pseudomonas fluorescens.

Although enzymatic methods for serum cholesterol determination are widely used in clinical laboratories, little is known about the optimization of each component in enzymatic reagents. We investigated the optimal components in the reagents containing cholesterol oxidase isolated from Nocardia erythropolis, Streptomyces sp, or Pseudomonas fluorescens. The optimal components in the reagents are: cholesterol oxidase 250 (Nocardia erythropolis), 250 (Streptomyces sp), or 300 (Pseudomonas fluorescens) U/L, cholesterol esterase 200 U/L, peroxidase 10,000 U/L, sodium cholate 3 mmol/L, 4-aminoantipyrine 0.5 mmol/L, phenol 20 mmol/L, Triton X-100 2 mL/L, and phosphate buffer, pH 7.0. Lower reaction sensitivity and lower cholesterol linearity, < 18.1 mmol/L (700 mg/dL), could be obtained by using lower components than those suggested above. Pseudomonas fluorescens were an improper source for cholesterol oxidase; either Nocardia erythropolis or Streptomyces was suitable cholesterol oxidase. We prefer using Streptomyces sp cholesterol oxidase because of its economical cost and longest reagent stability. Sodium cholate must be included in the enzymatic reagent to prevent turbidity. However, sodium cholate of > 5 mmol/ L will suppress the reaction resulting in low cholesterol linearity.

Ampyrone↗

The timing of exposure of mononuclear phagocytes to recombinant interferon gamma and recombinant tumor necrosis factor alpha alters interactions with Nocardia asteroides.

Nocardia asteroides modulates phagocyte function and grows within macrophages. Because interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) have been shown to activate macrophages to kill a variety of microorganisms, the effects of IFN-gamma and TNF-alpha on the activation of murine macrophages and human monocytes to kill nocardiae were studied. It was found that macrophages or monocytes treated with either IFN-gamma, TNF-alpha, or lipopolysaccharide as a secondary signal did not demonstrate increased microbicidal activity against N. asteroides even though these phagocytes were effective at killing the fungus Coccidioides immitis and the protozoan Toxoplasma gondii. Preincubation of phagocytes for 24 h with these compounds resulted in an enhancement of nocardial growth. In contrast, coincubation of these factors with the nocardiae and mononuclear cells during phagocytosis resulted in inhibition of nocardial growth even though this bacterium was not killed. Therefore, the specific timing of the exposure of the phagocyte in vitro to IFN-gamma or TNF-alpha has a significant effect on its ability to alter nocardial growth.

Colony Count, Microbial↗

Improved purification of steroid 1:2-dehydrogenase from Nocardia opaca and partial characterization of its cloned gene sequence.

We have purified a steroid-inducible 1:2-dehydrogenase from Nocardia opaca. The final enzyme preparation was purified 120-fold with a recovery of 38%. The N-terminal amino acid sequence was determined to be: Met-Gln-Asp-Trp-Thr-Ser-Glu-(Cys)-Asp-Val-Leu-Val-Val-Gly-. From the genomic library of Nocardia opaca in the plasmid pUC19, a clone designated as pSTD23 containing a 0.9 kb KpnI-PstI fragment was found to hybridize with an oligonucleotide probe corresponding to the first six amino acids from the N-terminal of the purified protein. The nucleotide sequence of the upstream region and a part of the structural domain were determined. The sequence of the first 56 amino acids of the steroid 1:2-dehydrogenase from Nocardia opaca as deduced from its gene sequence showed a 58% homology with the corresponding gene from Pseudomonas testosteroni, and the conservative sequences in the FAD-binding domain were also determined.

Amino Acid Sequence↗

Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions.

Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected. Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines. A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice, yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca fractions and monokines might be mediated by activated peritoneal macrophages.

Adjuvants, Immunologic↗

Light and electron microscopic studies on experimental nocardia-toxicosis in mice.

An exotoxin (HS-6) produced by Nocardia otitidiscaviarum isolated from certain lesions of cutaneous nocardiosis of a male 82-year-old patient induced severe injuries in the pancreas, liver, stomach, small intestine, heart, thymus and kidney of male ICR mice. Mice given Nocardia-free preparation of HS-6 at a dose of 1 mg/kg of body weight developed several autophagic vacuoles in the pancreas and liver within 20 min after the i.p. injection. Thereafter, the autophagic vacuoles increased in number and size with time. About 24 hr after the administration of HS-6, the liver showed marked accumulation of fat droplets in the cytoplasm of the hepatocytes. Although they contained abundant autophagic vacuoles in the regions of RER, there were no lipomatoses in the acinar cells of the pancreas, those of the chief cells and smooth muscle cells of the stomach, Paneth cells, goblet cells, smooth muscle cells of the small intestine, and plasma cells in the digestive tract. Biochemical examinations revealed that HS-6 had no significant effect on the protein synthesis of reticulocytes. Inoculation of the Nocardia into the mouse peritoneal cavities caused marked granulomatoses in the pancreas, liver and regional lymph nodes, but did not develop autophagic vacuoles in RER regions of these organs.

Aged↗

Nocardia brain abscess mimicking brain tumour in immunocompetent patients: report of two cases and review of the literature.

Nocardia brain abscess is a rare intracranial lesion and has been reported in immunocompromised patients. An optimal treatment approach has not been established. However, early diagnosis and appropriate antimicrobial therapy are very important factors for a good outcome. We report two unusual cases of Nocardia brain abscess simulating brain tumour in immunocompetent patients. One of the cases was presumed to be a primary brain tumour and the other a metastatic brain tumour. They underwent surgical gross total resection. After Nocardia asteroides was seen on Gram's stain and subsequently identified by culture, appropriate antibiotic therapy was initiated.

Adolescent↗

The first isolation of Nocardia nova from an HIV-1 infected individual in Japan.

Nocardia species are opportunistic pathogens of immunocompromised patients. We report a case of Nocardia nova infection complicating Pneumocystis carinii pneumonia (PCP) in an HIV-1 infected individual. A 27-year-old man with hemophilia A was admitted on October 17, 2000, with fever and dyspnea. CD4 cell counts were 5/microl on admission. Prophylaxis against PCP was administered by inhalation of pentamidine isethionate because he was allergic to sulfamethoxazole-trimethoprim (SMZ-TMP). He was diagnosed with PCP from chest X-ray and bronchoalveolar lavage. The sputum obtained for culture on admission was positive for Gram-positive branching rods; the organism was later identified as Nocardia nova. He died from respiratory failure on November 7, 2000. Although PCP might be a principal factor in respiratory failure, this case shows the need to consider pulmonary nocardiosis as a cause of respiratory illness in patients with advanced HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Nocardia gamkensis sp. nov.

A novel actinomycete, strain CZH20(T), was isolated from a soil sample taken from the banks of the Gamka River in the Swartberg Nature Reserve, Western Cape Province, South Africa. Strain CZH20(T) was identified as a member of the genus Nocardia by a polyphasic approach. Strain CZH20(T) could be differentiated from other members of the genus Nocardia on the basis of physiology and 16S-rRNA gene sequence analysis. It exhibited weak antibiosis against Mycobacterium aurum A+. Organic solvent extracts of the culture filtrate and mycelial mass of CZH20(T) exhibited moderate antibiotic activity against Mycobacterium smegmatis LR222 and Mycobacterium tuberculosis H37Rv. The name Nocardia gamkensis is proposed, with the type strain CZH20(T) (=DSM 44956(T) =NRRL B-24450(T)).

Molecular Sequence Data↗

Major structural features of the cell wall arabinogalactans of Mycobacterium, Rhodococcus, and Nocardia spp.

The cell wall arabinogalactans of strains of Mycobacterium, Rhodococcus, and Nocardia were per-O-methylated, partially hydrolyzed with acid, and the resulting oligosaccharides were reduced and per-O-ethylated to yield per-O-alkylated oligoglycosyl alditol fragments. Analyses of these fragments by gas chromatography-mass spectrometry and of the intact solubilized polysaccharides by 1H and 13C NMR revealed the major structural features of the different arabinogalactans from representatives of the different genera. All of the mycobacterial products contained a homogalactan segment of alternating 5-linked alpha-galactofuranosyl (Galf) and 6-linked beta-Galf residues. The arabinan segment consisted of three major domains, linear 5-linked alpha-arabinofuranosyl (Araf) residues and branched (3-->5)-linked Araf units substituted with either 5-linked Araf or the disaccharide beta-Araf-(1-->2)-alpha-Araf at both branched positions. The recognition of these features in in vivo grown Mycobacterium leprae is an important development. The arabinan from strains of Nocardia contains a nonreducing-end motif composed of the linear trisaccharide, beta-Araf-(1-->2)-alpha-Araf-(1-->5)-Araf, attached to linear 5-linked alpha-Araf units. The galactan segment of the arabinogalactan of Nocardia sp. is composed of linear 5-linked beta-Galf units substituted in part at O-6 with terminal beta-glucosyl units. The two representative strains of Rhodococcus also differed in the composition of the galactan moiety; in addition to the 5-linked Galf, 2- and 3-linked beta-Galf units are present. The reducing end of the galactans, and therefore, apparently, of the entire arabinogalactans from all species from all genera, are apparently composed of the unit, rhamnosyl-(1-->3)-N-acetyl-glucosamine, which, in turn, is apparently attached to peptidoglycan via phosphodiester linkage.

Actinomycetales↗

Bioconversion of steroid glycosides by Nocardia restricta.

The bioconversion of steroid alkaloid tomatine by Nocardia restricta yields the conjugate with lactic acid. We studied the bioconversion of some steroid glycosides without a nitrogen atom in the molecule to determine the effect of the nitrogen atom. The glycosides were of three different types: sterol glycosides, bufadienolide rhamnoside and steroid saponine. The results of bioconversions showed that Nocardia restricta converts steroid glycosides differently according to the sugar bound to the steroid aglycone. It can be concluded that in the absence of a nitrogen atom in the steroid molecule no conjugation with lactic acid by Nocardia restricta occurs.

Alkaloids↗