11.+Mycobacteria_Nocardia_Actinomyces_2024.pdf

Mycobacteria / Nocardia / Actinomyces Jorge L. Cervantes, M.D., Ph.D. Mycobacteria CDC Mycobacteria GENERAL INFORMATION Cause chronic infections These infections can spread to other sites within the body Major human pathogens are: Mycobacterium tuberculosis M....

Mycobacteria / Nocardia / Actinomyces Jorge L. Cervantes, M.D., Ph.D. Mycobacteria CDC Mycobacteria GENERAL INFORMATION Cause chronic infections These infections can spread to other sites within the body Major human pathogens are: Mycobacterium tuberculosis M. leprae M. avium complex (MAC) M. avium M. intracellulare Mycobacteria MORPHOLOGY Thin rods Don’t stain well by Gram method Stained using the acid-fast method → Acid fast positive Does not form spores Non-motile  Structurally similar to Gram + with a cytoplasmic membrane and peptidoglycan Cell wall contains mycolic acid which has a waxy consistency and is hydrophobic Allows cell to adhere to each other Protect against detergents, drugs and desiccation Cell wall also contains lipoarabamannan (LAM) which is structurally/functionally similar to LPS Mycobacteria PHYSIOLOGY Obligate aerobes Slow growth, 8-10 days for visible colonies Grow in filaments due to a molecule in the wall referred to as cord factor Talaro – Foundations in Microbiology, 10th Ed. McGraw-Hill Education Mycobacterium tuberculosis CDC  Tuberculosis In U.S. - 2023: 2.9 per 100,000 persons EPIDEMIOLOGY WHO estimates that there are ~ 2 billion people in the world infected with M. tuberculosis with 30 million of those having active disease TUBERCULOSIS Transmission: Respiratory droplets Ingestion of milk from TB-cows (rare – due to pasteurization) Abraded skin (rare) Divided into categories: Primary Latent Secondary (reactivation) Extrapulmonary/Disseminated Tuberculosis PATHOGENESIS Initial infection of inhaled bacteria Can manifest within few weeks or years Intracellular growth – inside alveolar macrophages Nester’s Microbiology – A Human Perspective, 9th Ed. McGraw-Hill Education Inhibit the fusion of the lysosome with the phagosome th Tuberculosis PATHOGENESIS Granuloma formation Reactivation Hides bacteria from host Lymphocytes outside with macrophages containing bacteria inside Latent tuberculosis Latent TB Not all mycobacteria die Go into latency/dormant state Low oxygen prevents bacterial multiplication Balcells E, et al. Microbial Pathogenesis 2019 Tuberculosis PATHOGENESIS Reactivation Reactivation Immunity waning, diabetes, age, malnutrition, AIDS, alcoholism Granulomas spread Granulomas rupture, spreading bacteria to Latent TB other parts of the lungs Large areas of necrosis known as tuberculous cavity Immune system can’t keep bacteria under control Balcells E, et al. Microbial Pathogenesis 2019 Tuberculosis CLINICAL MANIFESTATIONS Cavitary lesions Gradual wasting of the body Ulcers on gingiva Periodontal Manifestations of Local and Systemic Diseases, 1st Ed. Springer Talaro – Foundations in Microbiology, 10th Ed. McGraw-Hill Education EXTRAPULMONARY TUBERCULOSIS Bacteria can travel via the blood and lymph to sites beyond the lung Mouth, kidney, meninges, bones, GI tract, liver, spleen, skin More common in immunocompromised patients Tuberculosis What’s the drawback of culturing the sputum? DIAGNOSIS A fluorescent acid-fast stain Sputum acid-fast stain or culture Tuberculin/Mantoux Test PPD is injected beneath the skin and “read” 48-72 hours later to see if a hard induration has developed due to a reaction of the immune response Talaro – Foundations in Microbiology, 10th Ed. McGraw-Hill Education CDC Active Tuberculosis DIAGNOSIS Chest x-ray IGRA (interferon-gamma release assays) More sensitive than PPD ELISA to determine presence of IFN-γ CDC Tuberculosis TREATMENT Multiple antibiotics for extended periods (months) Combination of antibiotics and duration depends of the form of TB and strain susceptibility MDR-TB: resistant to isoniazid and rifampin CDC XDR-TB: resistant to isoniazid, rifampin, fluoroquinolones Anti-TB agents. From left to right: and at least 1 of the 4 injectable anti-TB drugs (streptomycin, isoniazid, rifampin, pyrazinamide, and ethambutol amikacin, kanamycin, or capreomycin) FDA approved in 2019 pretomanid in combination with bedaquiline and linezolid for treatment of XDR-TB strains Tuberculosis PREVENTION Vaccine: BCG (Bacille Calmette-Guérin) Live attenuated strain of Mycobacterium bovis Forbes 2020 Not used in the U.S. Used in developing countries to protect children against disseminated forms of TB Does not protect against pulmonary TB M. avium complex (MAC) MAC Infections caused by M. intracellulare and M. avium Pathogens found in water and soil Patients with HIV/AIDS: disseminated disease and focal lymphadenitis Immunocompetent patients: pulmonary infection Nocardia Nocardia GENERAL INFORMATION Gram + bacilli that grow in branched/filament formation Cell wall contains intermediate-length mycolic acid Partially/weakly acid fast Survive in phagocytes Obligate aerobe and saprophytic 2 important human pathogens in this genus: N. asteroides N. brasiliensis Acid-fast stain Nocardia EPIDEMIOLOGY Found in soil worldwide Transmission: Inhalation of aerosolized bacteria from soil (pulmonary) Injection from prick/skin trauma (cutaneous) Eye trauma Tends to remain localized in healthy patients Can spread to many parts of the body in those with weak immune systems Nocardiosis Nocardiosis can be acute, chronic, or relapsing Most of cases of nocardiosis present as Pulmonary infection (bronchopneumonia) Cough, fever, difficulty breathing Nodule and cavities in the lung with acute Nocardial pneumonia inflammation Dissemination to the brain can occur Nodules Cavity Nocardia CLINICAL MANIFESTATIONS Cellulitis Nocardial abscess in the Keratitis right occipital lobe Brain abscess Nocardia brasiliensis mycetoma Nocardia DIAGNOSIS AND TREATMENT Diagnosis: Gram stain or culture from purulent skin lesions or sputum Treatment: Tests for antibiotic sensitivity Trimethoprim-sulfamethoxazole is the Drug of Choice Actinomyces Actinomyces Molar tooth colony morphology CHARACTERISTICS Gram + elongated, filamentous rods Obligate anaerobe or microaerophilic Produce sulfur granules in pus and tissues Textbook of Diagnostic Microbiology, 5th Ed. Saunders Actinomyces EPIDEMIOLOGY Several species within this genus are normal oral flora and are a major component of dental plaque, particularly at the gingival crevice Associated with root surface caries, and their numbers increase during gingivitis Species isolated in the oral cavity include: A. israelii, A. naeslundii, A. odontolyticus, A. oris, A. meyeri, A. georgiae , A. gerencseriae, Actinomyces EPIDEMIOLOGY Normal flora of the GI tract, mouth, and female genital tract Opportunistic pathogen causing chronic, slowly developing infections They are highly adapted to live on mucosal surfaces, but do not cause disease unless they get into deeper tissues with lower O2 levels Periodontal disease The critical step in the development of Tooth extraction actinomycosis is disruption of the mucosal barrier Trauma to mouth/jaw Actinomyces israelii “Early colonizer” in plaque biofilms Interacts with Fusobacterium nucleatum, Prevotella loesheii and Capnocytophaga gingivalis Actinomyces naeslundii “Early colonizer” in plaque biofilms with many interactions Marsh and Martin's Oral Microbiology, 6th Ed. Elsevier Actinomycosis Oral-cervicofacial actinomycosis Most common form Sulfur granules Periodontal Manifestations of Local and Systemic Angle of the jaw is generally involved Murray - Medical Microbiology, 8th Ed. Elsevier Diseases, 1st Ed. Springer Can develop due to poor oral hygiene, Lesion tooth extraction, or trauma Draining sinus tract, pyogenic lesion, Immune cells submandibular swelling, abscess Can spread to contiguous tissues Bacteria Fouad - Endodontic Microbiology, 2nd Ed. Wiley-Blackwell Actinomyces Chronic Pelvic Inflammatory Disease Intrauterine devices Actinomyces israelii has also been found in cervical smears of women using intrauterine contraceptive devices Eubacterium 34 Eubacterium GENERAL INFORMATION Gram-variable rods or filaments Obligate anaerobe Many strains are asaccharolytic E. saburreum E. saphenum E. yurii E. minutum E. infirmum E. nodatum E. sulci E. brachy Eubacterium ROLE IN THE ORAL CAVITY Isolated from plaque biofilms and calculus Implicated in caries, periodontal disease and dentoalveolar abscesses but role unclear Comprise over 50% of the anaerobes of periodontal pocket E. yurii is involved in “corn-cob” Samaranayake - Essential Microbiology for Dentistry, 5th Ed. Elsevier formation in dental plaque