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Nocardia species as an etiologic agent in Parkinson's disease: serological testing in a case-control study.

To test the hypothesis that Nocardia spp. may be an etiologic factor in Parkinson's disease (PD), we used a serodiagnostic panel to determine if PD patients had antibodies specific for Nocardia spp. To validate the serological test panel, sera from healthy volunteers and from patients with culture-proven nocardiosis (n = 307) were compared in part 1 of the study. The sensitivity of the panel was 88% for detection of culture-proven nocardial infections, and specificity was 85% (excluding cross-reactive leprosy cases). In part 2, no difference in seropositivity was found when PD patients were compared with their age- and gender-matched controls (n = 140). We found a high exposure rate of humans to nocardial antigens, especially among men and older individuals. Our results offer no support to the hypothesis that Nocardia spp. are causative in PD; however, it is possible that serological testing may not be optimal for detection of nocardial central nervous system infection.

Antibodies, Bacterial↗

Nocardia thyroiditis: unusual location of infection.

Nocardia asteroides complex is an important opportunistic agent in immunocompromised hosts. Usually, primary pulmonary infection occurs and is followed by dissemination of the pathogen to the central nervous system and soft tissues. As described in the literature, almost every organ can be infected, but to our knowledge, Nocardia has been described as a pathogen responsible for thyroid abscess in only one report, which was published in 1993. The present report is the second case report of Nocardia thyroiditis. The patient was under immunosuppressor treatment following a combined liver-kidney transplant and presented with a preexisting nodular goiter which was probably a predisposing factor to the start and development of the thyroid infection.

Abscess↗

Identification of medically relevant Nocardia species with an abbreviated battery of tests.

Identification of Nocardia to the species level is useful for predicting antimicrobial susceptibility patterns and defining the pathogenicity and geographic distribution of these organisms. We sought to develop an identification method which was accurate, timely, and employed tests which would be readily available in most clinical laboratories. We evaluated the API 20C AUX yeast identification system as well as several biochemical tests and Kirby-Bauer susceptibility patterns for the identification of 75 isolates encompassing the 8 medically relevant Nocardia species. There were few biochemical reactions that were sufficiently unique for species identification; of note, N. nova were positive for arylsulfatase, N. farcinica were positive for opacification of Middlebrook 7H11 agar, and N. brasiliensis and N. pseudobrasiliensis were the only species capable of liquefying gelatin. API 20C sugar assimilation patterns were unique for N. transvalensis, N. asteroides IV, and N. brevicatena. There was overlap among the assimilation patterns for the other species. Species-specific patterns of susceptibility to gentamicin, tobramycin, amikacin, and erythromycin were obtained for N. nova, N. farcinica, and N. brevicatena, while there was overlap among the susceptibility patterns for the other isolates. No single method could identify all Nocardia isolates to the species level; therefore, a combination of methods was necessary. An algorithm utilizing antibiotic susceptibility patterns, citrate utilization, acetamide utilization, and assimilation of inositol and adonitol accurately identified all isolates. The algorithm was expanded to include infrequent drug susceptibility patterns which have been reported in the literature but which were not seen in this study.

Algorithms↗

Nocardia veterana, a new emerging pathogen.

Nocardia veterana is a newly described species named after the veteran's hospital where it was first isolated. This initial type strain was not thought to be clinically significant. We describe three cases of pulmonary disease attributable to N. veterana: two cases in patients presenting with multiple pulmonary nodules in a setting of immunocompromise and one case of exacerbation of chronic pulmonary disease. The isolates were susceptible to ampicillin, imipenem, gentamicin, amikacin, and trimethoprim-sulfamethoxazole and had reduced susceptibilities to ceftriaxone, cefotaxime, minocycline, and ciprofloxacin. The MICs of amoxicillin-clavulanate were higher than that of ampicillin alone, and the bacteria produced a beta-lactamase detectable only after induction with clavulanic acid. Phenotypically, the isolates could not be characterized beyond the Nocardia genus level. All three isolates were definitively identified as N. veterana by PCR and sequencing of the 16S rRNA gene. On the basis of their susceptibility and restriction enzyme analysis profiles, our findings indicate that they could potentially be misidentified as N. nova. These cases illustrate the pathogenic potential of this newly described species and emphasize the importance of accurate identification of Nocardia isolates to the species level by integrated use of phenotypic and genotypic methods.

Adult↗

Multiple copies of the 16S rRNA gene in Nocardia nova isolates and implications for sequence-based identification procedures.

Molecular investigation of two Nocardia patient isolates showed unusual restriction fragment length polymorphism patterns with restriction endonuclease assays (REA) using an amplified portion of the 16S rRNA gene. Patterns typical of Nocardia nova were obtained with REA of an amplified portion of the 65-kDa heat shock protein gene. Subsequent sequence analysis of the 16S rRNA gene regions of these isolates showed the presence of ambiguous bases within an expected restriction endonuclease recognition site which were not able to be resolved on repeat testing. Cloning of amplified regions of the 16S rRNA genes and subsequent sequencing of the resulting clones from the two patient isolates showed three different 16S rRNA gene sequences which corresponded to sequences found in N. nova, a molecular variant of N. nova, and a previously undescribed sequence. Hybridization studies using a DNA probe corresponding to an 89-bp conserved region of the 16S rRNA gene confirmed the presence of at least two copies of the 16S rRNA gene in the N. nova type strain, in a patient isolate identical to the molecular variant of N. nova, and in the two other patient isolates. All isolates were found to belong to the species N. nova as determined by DNA-DNA hybridization. Because minimal variation has been found in the 16S rRNA gene sequences of different species of Nocardia, those laboratories employing molecular methods for identification of these species must be aware of the potential identification complications that may be caused by the presence of differing 16S rRNA genes in the same isolate.

Bacterial Proteins↗

Brain abscess caused by Nocardia cyriacigeorgica in a patient with human immunodeficiency virus infection.

Nocardia cyriacigeorgica is a recently characterized species within the genus of Nocardia. We report a brain abscess, following a primary pulmonary colonization, due to this species in a human immunodeficiency virus-infected patient. This case confirms that isolation of Nocardia in sputum is associated with a high risk of disseminated infection in immunocompromised patients.

AIDS-Related Opportunistic Infections↗

Endogenous Nocardia asteroides endophthalmitis in a patient with systemic lupus erythematosus.

We report a case of endogenous Nocardia endophthalmitis in a patient with systemic lupus erythematosus (SLE). He developed a parafoveal lesion in the right fundus while on systemic corticosteroid and antibiotic treatment. Initially we suspected a fungal origin and treated him with antifungal drugs. The intraocular disease progressed without improvement and advanced to the vitreous cavity. Nocardia asteroides was found in a specimen obtained at pars plana vitrectomy and was also cultured from the same specimen. The intraocular infection was controlled by antibacterial drugs, though the visual acuity of the right eye was reduced to only light perception owing to heavy vitreous opacity and secondary cataract. This case is the first report of endogenous Nocardia endophthalmitis in Japan and also the first case of this disease reported from outside the United States of America.

Adult↗

Chronic granulomatous pleuritis caused by nocardia: PCR based diagnosis by nocardial 16S rDNA in pathological specimens.

Nocardiosis is an uncommon infection caused by the aerobic actinomycete nocardia. Identification of the pathogen is essential for the definitive diagnosis and for an effective treatment. This report describes a case of chronic granulomatous pleuritis caused by nocardia. A 59 year old Japanese man had a history of repeated pyothorax. Right pleural decortication and thoracic drainage were performed. Microbiological examinations of the drained fluid failed to identify a pathogen. Pathological examinations revealed Gram positive filamentous and branching bacilli in the granulomatous lesion of the pleura. Sequencing of the 971 bp 16S ribosomal DNA extracted and amplified from paraffin wax embedded sections identified the microorganism as Nocardia sp. IFM 0860. The patient received sulfamethoxazol/trimethoprim and minocycline. Although the presence of a brain abscess was disclosed by systemic examination, the clinical course has been favourable. In this patient, polymerase chain reaction analysis of 16S ribosomal DNA in pathological specimens was useful in making an accurate diagnosis of nocardiosis and in determining the appropriate treatment.

DNA, Bacterial↗

Molecular diagnosis of fatal Nocardia farcinica pneumonia in an HIV-negative patient.

Nocardiosis is a rare and potentially life-threatening infection caused by several species of the Nocardia genus. Most cases occur in immunocompromised patients, and a delay in establishing the diagnosis is common due to the non-specific clinical presentations and the difficulty in cultivating Nocardia. Although the majority of pulmonary nocardiosis cases are caused by Nocardia asteroides, cases of human infection due to N. farcinica are increasingly diagnosed due to recent developments in taxonomy and diagnostic methods. N. farcinica is a separate species from N. asteroides and appears to be more virulent and resistant to antibiotics. Herein, we describe the case of a 65-year-old HIV-negative immunocompromised patient with a fulminant bilateral pulmonary nocardiosis while on empirical treatment with trimethoprim/sulfamethoxazole and imipenem. Post-mortem diagnosis of N. farcinica infection was performed by means of DNA amplification and sequencing of the 65-kDa bacterial heat shock protein.

Aged↗

Studies on corynebacterial precipitinogens common to Mycobacteria, Nocardiae and rhodochrous.

Ten strains of Corynebacterium were analyzed by means of the comparative immunodiffusion technique employing reference precipitation systems from strains of Mycobacterium, Nocardia and the rhodochrous taxon. The test strains had precipitinogens in common with the reference strains. Two of the intergenerical cross-reacting precipitinogens revealed were labelled x and y. Two other precipitinogens (alpha,beta), earlier found to be common for strains of mycobacteria, nocardiae, and rhodochrous, were not demonstrated in the corynebacterial strains, thus indicating a qualitative or quantitative serological difference between Corynebacterium and the other taxa. It was furthermore shown that the corynebacterial preparations reacted with antisera against ribosomal 30S fractions from mycobacteria. Common precipitinogens in ribosomal preparations from mycobacteria, nocardiae, rhodochrous, and corynebacteria are discussed.

Antigens↗

Cardiac tamponade due to Nocardia asteroides.

Pericarditis with hemodynamic compromise is a rare manifestation of infection with Nocardia asteroides. To our knowledge, only six cases have been reported previously. In contrast to other cases of pericardial disease due to Nocardia, culture of the pericardial fluid in our case was negative while culture of pericardial tissue led to the diagnosis. Surgical intervention and appropriate antibiotic therapy are essential in the treatment of Nocardia pericarditis.

Cardiac Tamponade↗

Nocardia otitidiscaviarum (GAM-5) induces parkinsonian-like alterations in mouse.

Parkinson's disease, a major neurodegenerative disorder in humans whose etiology is unknown, may be associated with some environmental factors. Nocardia otitidiscaviarum (GAM-5) isolated from a patient with an actinomycetoma produced signs similar to Parkinson's disease following iv injection into NMRI mice. NMRI mice were infected intravenously with a non-lethal dose of 5 x 10(6) colony forming units of N. otitidiscaviarum (GAM-5). Fourteen days after bacterial infection, most of the 60 mice injected exhibited parkinsonian features characterized by vertical head tremor, akinesia/bradykinesia, flexed posture and postural instability. There was a peak of nocardial growth in the brain during the first 24 h followed by a decrease, so that by 14 days nocardiae could no longer be cultured. At 24 h after infection, Gram staining showed nocardiae in neurons in the substantia nigra and occasionally in the brain parenchyma in the frontal and parietal cortex. At 21 days post-infection, tyrosine hydroxylase immunolabeling showed a 58% reduction of tyrosine hydroxylase in the substantia nigra, and a 35% reduction of tyrosine hydroxylase in the ventral tegmental region. Dopamine levels were reduced from 110 +/- 32.5 to 58 +/- 16.5 ng/mg protein (47.2% reduction) in brain from infected mice exhibiting impaired movements, whereas serotonin levels were unchanged (191 +/- 44 protein in control and 175 +/- 39 ng/mg protein in injected mice). At later times, intraneuronal inclusion bodies were observed in the substantia nigra. Our observations emphasize the need for further studies of the potential association between Parkinson's disease or parkinsonism-like disease and exposure to various nocardial species.

Animals↗

Nocardia asteroides-infected aneurysm of the aorta: case report and review of the literature.

Infected aneurysms of the aorta were first described as a result of septic emboli or contiguous spread from bacterial endocarditis and are usually caused by Staphylococcus or Salmonella species. We report a case of Nocardia-associated infected aneurysm of the native suprarenal aorta in an immunocompromised host. Surgical management consisted of placement of an interposition cryopreserved aortic homograft. Nocardia asteroides was identified on a microbiology specimen of the aorta and both microbiology and pathology specimens of the splenic tissue. To the best of our knowledge, this represents the first carefully documented, unique case of a Nocardia-infected aneurysm treated with homograft interposition. In addition, pathologic and microbiologic data are included from the postmortem examination 10 months later.

Aneurysm, Infected↗

Nocardia endophthalmitis following uncomplicated phacoemulsification and implantation of a posterior chamber intraocular lens.

A patient developed endophthalmitis 15 days after uncomplicated cataract extraction. Excised infectious material sequestered in the capsular bag revealed Nocardia on culture. She required multiple intravitreal injections of Amikacin and dexamethasone, pars plana vitrectomies with explantation of the lens, and chronic topical and oral sulfonamide antibiotics to control the infection. Clinicians should also consider Nocardia when the suspicion of fungal endophthalmitis is entertained, as Nocardia are resistant to antifungals, but respond to intravitreal amikacin and chronic topical and oral sulfonamides.

Aged↗

[Nocardia asteroides infection in a patient with systemic lupus erythematosus].

Nocardia asteroides infection are unusually observed in systemic Lupus erithematous (SLE) patients. They are generally associated to steroidal and immunosuppressive therapy. We report a 24 years old female with SLE diagnosed in 1994 who developed a severe preeclampsia in her first pregnancy requiring emergency caesarean section. Post partum acute renal failure and type IV lupus nephropathy were treated with hemodialysis, methylprednisolone, cyclophosphamide and prednisone. Three months later, while she was receiving the fourth cyclophosphamide dose, she presented with a pleuro pneumonia and occipital abscess, both caused by Nocardia asteroides. She was treated with cotrimoxazole + cefixime and pleural decortication was required. Five months later, she developed Meningitis caused by Nocardia asteroides and hydrocephalus. She was treated with ceftriaxone, vancomycin, cotrimoxazole and ventricular shunting procedure. Two months later, a retroperitoneal abscess was diagnosed and surgically drained but the patient died, due to a methicillin-resistant Staphylococcus aureus septicemia.

Adult↗

Seven cases of human nocardiosis caused by Nocardia farcinica.

Twelve nocardia strains isolated from Danish human patients have been examined and compared with reference strains of Nocardia asteroides and N. farcinica using Tsukamura's (1969) simple method of identification. Seven of these strains, recovered from human lesions compatible with nocardioisis, were identified as N. farcinica. These investigations suggest that N. farcinica could be a more common cause of human nocardiosis in Denmark than N. asteroides and other nocardias. N. farcinica might also be the cause of human nocardiosis in other countries.

Culture Media↗

[Nocardia otitidiscaviarum, cutaneous infection in a patient receiving long-term corticosteroid treatment].

A 62-year-old man, under long-term corticosteroid therapy for pigeon breeder's disease, was admitted to endocrinology disease department for cutaneous abscess on back, limbs and scalp. Culture of various bacteriological samples (cutaneous abscess, blood culture) isolated Nocardia otitidiscaviarum. The patient was treated by trimethoprime-sulfametoxazole during several weeks with abscess disappearance. Our laboratory quickly identificatied a bacteria belonging to the Nocardia genus, with simple technique, later confirmed by a specialized laboratory (Pr. Boiron Claude Bernard University Lyon I) with identification of Nocardia otitidiscaviarum. The proof of pulmonary nocardiosis could not be established despite the existente of several risk factors. Prognosis is poor for immunocompromised patients, but the secondary cutaneous dissemination phase presented a favourable evolution under antibiotic therapy.

Adrenal Cortex Hormones↗

Thigh abscess due to Nocardia farcinica.

Nocardia farcinica is an uncommon cause of nocardiosis and usually infects immunocompromised individuals. We describe a patient with Hodgkin's disease and a thigh abscess due to N. farcinica. To the best of our knowledge, this has never been reported before in the English literature. It is important to recognize this complication, because a delay in diagnosis may result in widespread dissemination. Unless initially suspected, culture and identification will be delayed, as selective media for isolating Nocardia are not routinely used in most clinical laboratories. It is also important to differentiate N. farcinica from other Nocardia species due to its resistance to many antibiotics that are routinely used to treat abscesses, including cephalosporins. A case report along with literature review is presented in an effort to stress the importance of including this pathogen in the differential diagnosis of immunocompromised patients with abscesses.

Abscess↗