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First human case of nocardiosis was reported in 1890 by Eppinger. Dr.T.V.Rao MD 2 What are Nocardia : What are Nocardia Nocardia is a genus of weakly staining Gram-positive, catalase-positive, rod-shaped bacteria. It forms partially acid-fast beaded branching filaments (acting as fungi, but being truly bacteria). It has a total of 85 species. Some species are non-pathogenic while others are responsible for nocardiosis. Dr.T.V.Rao MD 3 Nocardia : Nocardia Genus : aerobic Actinomyctes G+ branching filamentous bacteria Subgroup: aerobic nocardiform actinomycetes -Mycobacterium -Corynebacterium -Nocardia -Rhodococcus -Gordona -Tsukamurella Dr.T.V.Rao MD 4 Nocardia :ECOLOGY& EPIDEMIOLOGY : Nocardia :ECOLOGY& EPIDEMIOLOGY Ubiquitous environmental saprophyte Soil, organic matter, water Tropical and subtropical regions :Mexico, Central and South America, Africa and India Dr.T.V.Rao MD 5 Nocardia is present as commensal In Humans : Nocardia is present as commensal In Humans Nocardia are found worldwide in soil that is rich with organic matter. In addition, Nocardia are oral microflora found in healthy gingiva as well as periodontal pockets. Most Nocardia infections are acquired by inhalation of the bacteria or through traumatic introduction. Dr.T.V.Rao MD 6 Other Species of Nocardia : Other Species of Nocardia Gram-positive bacteria. On microscopy have branching filamentous cells. The more common human pathogen are Nocardia asteroids sensu stricto, Nocardia farcinica, Nocardia nova, Nocardia brasiliensis, Nocardia pseudobrasiliensis, Nocardia otitidiscaviarum, and Nocardia transvalensis Dr.T.V.Rao MD 7 Microbiology : Microbiology Branching, beaded, filamentous bacteria Can cause "Sulfur granules" like actinomycosis, in nocardial mycetomas. Stains acid fast in tissue unlike the Actinomyces. Dr.T.V.Rao MD 8 Nocardia :ECOLOGY& EPIDEMIOLOGY : Nocardia :ECOLOGY& EPIDEMIOLOGY The risk of pulmonary or disseminated disease *deficient cell-mediated * -Alcoholism -Diabetes -Lymphoma -Transplantation -Glucocorticoid therapy -AIDS CD4+ < 250 Transmission Inhalation Skin General approach to Diagnose the Infection with Nocardia : General approach to Diagnose the Infection with Nocardia Bronchial wash specimens sent to laboratory were to be examined microscopically by gram stain. If numerous gram positive branching bacilli were observed raising suspicion of Nocardia. A partial acid-fast stain will confirm suspicions that the organism was indeed partially acid-fast and consistent with Nocardia. Gram stain results and presumptive diagnosis were to be reported Dr.T.V.Rao MD 10 Microscopy and Culturing essential for establishing Diagnosis : Microscopy and Culturing essential for establishing Diagnosis Dr.T.V.Rao MD 11 Transmission : Transmission Pulmonary, disseminated and CNS infections are acquired through inhalation; primary cutaneous disease is acquired through inoculation of the skin. Rarely, nosocomial postsurgical transmission occurs. Dr.T.V.Rao MD 12 Risk Factors : Risk Factors Immunocompromised: 60% of all reported nocardiosis is associated with preexisting immune dysfunction. Organ transplantation, hematologic malignancy, alcoholism, steroid use, diabetes, acquired immunodeficiency syndrome (AIDS). Patients with chronic pulmonary disorders, especially, pulmonary alveolar proteinosis, Given its ubiquity in the environment and the increasing numbers of poor hosts, this organism should become increasingly common. Dr.T.V.Rao MD 13 Virulence Factors : Virulence Factors Virulent strains are relatively resistant to neutrophil-mediated killing. Organisms in the logarithmic growth phase are more toxic to macrophages. Inhibit Phagosome-lysosome fusion more successfully in vitro, which gives rise to L-forms, which can survive in macrophages for days L-forms have been found human and animal infections and perhaps account for treatment failure. Virulence Factors : Virulence Factors The inability to be killed my normal white cells takes on additional significance in the immunoincompetant who have WBC dysfunction that tips the battle between host and pathogen in favor of the Nocardia. Patients with CGD have increased risk for Nocardia infections, a double whammy where the patients cannot generate an oxidative burst and some strains have the ability to make superoxide dismutase, Virulence Factors : Virulence Factors There are species tissue tropism's: N. asteroides complex including N. farcinica cause 80% of noncutaneous invasive disease and for most systemic and CNS disease. N. brasiliensis: cutaneous and lymphocutaneous disease. N. pseudobrasiliensis: systemic infections, including the CNS. N. transvalensis and N. otitidiscavarium: Noncutaneous disease Clinical presentation of Nocardia : Clinical presentation of Nocardia Overall, 80% of nocardiosis cases present as invasive pulmonary infection, disseminated infection, or brain abscess; 20% present as cellulitis. Pulmonary infection commonly presents with fever, cough, or chest pain. Central nervous system (CNS) symptoms include headache, lethargy, confusion, seizures, or sudden onset of neurologic deficit. Dr.T.V.Rao MD 17 Clinical Syndromes: mucocutaneous : Clinical Syndromes: mucocutaneous Can occur after minor trauma and animal or insect bites; may also colonize open wounds. Often in normal hosts. Misdiagnosis common. N. brasiliensis commonly causes a progressive cutaneous and lymphocutaneous (sporotrichoid) disease. presents as an ascending nodules N. asteroides more commonly causes self-limited infection. Dr.T.V.Rao MD 18 CLINICAL MANIFESTATIONS: Main form : CLINICAL MANIFESTATIONS: Main form Lymphocutaneous syndrome Pulmonary :Pneumonia CNS : Brain abscess Disseminated disease CNS Eyes (particularly the retina Keratitis), Skin& subcutaneous Kidneys, Joints, bone Heart Dr.T.V.Rao MD 19 Nocardial actinomycetoma swelling, multiple sinus tracts, : Nocardial actinomycetoma swelling, multiple sinus tracts, Dr.T.V.Rao MD 20 Clinical Syndromes: Mucocutaneous : Clinical Syndromes: Mucocutaneous Mycetoma: a chronic progressive, destructive disease, occurring days to months after inoculation located distally on the limbs (classically the foot) and presents with Suppurative granulomata progressive fibrosis and necrosis sinus formation and destruction of adjacent structures, macroscopically visible infective granules Mimics fungal mycetoma and actinomycetomata (due to actinomycete). Dr.T.V.Rao MD 21 Lymphocutaneous syndrome : Lymphocutaneous syndrome Ubiquitous in soil inoculation injuries, Insect and animal bites contaminated abrasions N. brasiliensis : most common N. asteroides : self-limited Because initial response Rx as staphylococcus underdiagnosed Mycetoma Days to months ,typical:distal limb -Cellulitis -Lymphocutaneous syndrome -Actinomycetoma Dr.T.V.Rao MD 22 Clinical Syndromes: pulmonary : Clinical Syndromes: pulmonary Clinical Presentations: endobronchial inflammatory masses pneumonia lung abscess, cavitary disease empyema pneumonia (often progressive in HIV) it can invade through surrounding tissues like actinomycosis Dr.T.V.Rao MD 23 Pulmonary disease : Pulmonary disease Pneumonia Subacute(more acute in immunosuppressed) Cough** Small amounts of thick, purulent sputum Fever, anorexia, weight loss, malaise Endobronchial inflammatory mass Lung abscess Cavitary disease Inadequate therapy Progressive fibrotic diseaseฆ Cerebral imaging, should be performed in all cases of pulmonary and disseminated nocardiosis Dr.T.V.Rao MD 24 CNS : Brain abscess : CNS : Brain abscess Insidious presentations : mistaken for neoplasia !!! Granulomatous , abscesses Cerebral cortex, basal ganglia and midbrain*** Less commonly: spinal cord or meninges. Brain tissue diagnosis in pulmonary nocardiosis : not necessary However, cerebral biopsy: considered early in immunocompromised Dr.T.V.Rao MD 25 Nocardiosis can manifest in any region : Nocardiosis can manifest in any region Local findings associated with metastatic abscesses may be present at almost any site but are typically in the lower extremities. The combination of pneumonia and lower-extremity abscess is particularly suggestive of nocardiosis, although this is not seen exclusively in nocardiosis. Patients with brain abscess may present with altered mental status, personality changes, or various localizing neurologic findings. Dr.T.V.Rao MD 26 LABORATORY DIAGNOSIS : LABORATORY DIAGNOSIS Gram-positive, beaded, branching filaments usually weak acid fast+ve . Standard blood culture :48 hrs. to several wks., but typical = 3 to 5 days Colonization of sputum :underlying pulmonary dz + not receiving steroid therapy no specific therapy Susceptibility testing -Deep-seated /disseminated dz. fail initial therapy -Relapse after therapy -Alternatives to sulfonamides are being considered Dr.T.V.Rao MD 27 Culturing of Nocardia : Culturing of Nocardia Plate culture of the bacteria Nocardia asteroides grown on 7H10 agar plates at 37° C. Photo courtesy CDC/Dr.William Kaplan Dr.T.V.Rao MD 28 Specific Methods in Diagnosis : Specific Methods in Diagnosis specimens with mixed flora can over grow the Nocardia colonies Selective media may increase yield: Thayer-Martin agar with antibiotics paraffin agar. Buffered charcoal-yeast extract (BCYE) medium Decontamination methods used for mycobacterial culture kill Nocardia and may decrease culture yield. Dr.T.V.Rao MD 29 Diagnosis : Diagnosis Slow growing, Nocardia may take from 48 hours to several weeks. typical colonies are buff or pigmented waxy cerebriform colonies and/or as chalky white and are usually seen from 3 to 5 days. biochemical testing and antibiotic resistance patterns can differentiate some species, but PCR83,84 and 16S rRNA sequencing are the most reliable for giving a precise spp. Dr.T.V.Rao MD 30 Treatment : Treatment I&D depending of the location reversal of immunosuppression sulfas the mainstay of therapy, but susceptibilities vary; for example N. farcinica usually resistant to third generation cephalosporins sulfonamide mono therapy in immuno competent or severe disease has a 50% mortality rate in vitro sensitivity and resistance does not predict in vivo response send for susceptibility testing is reasonable Dr.T.V.Rao MD 31 Treatment : Treatment Long-term antibiotic therapy (usually with sulphonamides) for 6 months to a year (or longer depending on the individual and the parts of the body involved) is needed to treat Nocardia. Frequently, chronic suppressive therapy (long-term, low-dose antibiotic therapy) is needed. Dr.T.V.Rao MD 32 MANAGEMENTMedication : MANAGEMENTMedication TMP-SMX :currently preferred :drugs in serum:CSF = 1:20 :high MICs good therapeutic responses -General:5-10 mg/kgTMP & 25-50 mg/kgSMX divide2- 4times -Cerebral abscesses,severe,disseminated,AIDS :15 mg/kg TMP and 75 mg/kg SMX) -Cutaneous infection: 5 mg/kg/day (TMP) + DB Dr.T.V.Rao MD 33 Treatment: duration : Treatment: duration Expect a clinical response in 3 - 10 days Duration is until cure. Often 3-6 months total treatment. Cutaneous disease usually is cured in a month or two Non CNS disease is usually treated for 6 months; CNS disease is treated for a year. Relapses can occur up to a year after stopping therapy; AIDS patient and perhaps other immuno incompetent should be maintained on lifelong suppressive TMP/SULFA Epidemiology : Epidemiology Nocardia is everywhere in the environment: soil, organic matter, and water. Human infection usually occurs from minor trauma and direct inoculation of the skin or soft tissues or by inhalation. It is also a common animal infection Outbreaks in oncology and transplant wards and surgical wounds have occurred from fomites, hospital construction with resultant contaminated dust, and health care worker hands. Dr.T.V.Rao MD 35 Slide 36: Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World Email email@example.com Dr.T.V.Rao MD 36 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.