Atypical Mycobacterium

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Mycobacterial Diseases

Tuberculosis can infect

Immunocompromised and competent Immunocompromised (TB-like, non-TB-like) Immunocompetent (rare, syndromes)

Atypical Mycobacteria can infect

Atypical Mycobacteria still can infect

Other Mycobacteria

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Nontuberculous Mycobacteria

1954 Runyon first NTM classification >100 NTM species Other names

Mycobacteria other than tuberculosis (MOTT) Atypical Environmental Opportunistic

Variable pathogenicity and geographic regions 40% cause diseases in human Immunosuppressed host
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MYCOBACTERIA what they can

Cause

Mycobacteria tuberculosis Mycobacteria kansasii

Ghon complex in primary TB (middle lobe Chronic pulmonary disease similar to classic TB except it is noninfectious and has less or apical lower lobe) disseminated diseases extrapulmonary or Secondarypatients have disseminated disease 15% of TB in apical portion of upper lobes Disseminated disease in the immunocompromised and patients with late stage AIDS Tuberculous effusions - mature Mycobacteria marinum lymphocytes Superficial granulomatous skin infection (swimming pool or fish tank granulomas) involving Mycobacteria avium-intracellular in contact with poorly chlorinated fresh water traumatized skin of the extremities High incidence in AIDS patients and of ulcers up the arm along the lymphatics) Sporotrichosis-like lesions (chain elderly women

Mycobacteria simiae cultures Sepsis and positive blood

common Pulmonary disease in humans AIDS: fever of scrofulaceum Mycobacteria unknown origin and weight loss common; pulmonary disease Scrofula---unilateral painless lymphadenitis, involving lymph nodes high in the neck in healthy uncommon children Immunocompetent hosts or elderly: pulmonary disease common Most common AFB involving bone marrow Rare human infections

Mycobacteria gordonae

Mycobacteria szulgi

Rare human infections

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MYCOBACTERIA what they can Cause

Mycobacteria fortuitum/chelonae Mycobacteria haemophilum complex Painful subcutaneous nodules, swellings and ulcers progressing into abscesses and draining

fistulas Skin infections with draining abscesses Disseminated disease in AIDS patients May have involvement of lungs, bone, CNS, and prosthetic heart valves, and Mycobacteria xenopi disseminated disease TB-like with post-surgical Rare infection in AIDS patients and immunocompetent hosts Associatedpulmonary disease;wound, needle injections, renal transplant Mycobacteria paratuberculosis recipients Associated with Crohns disease Sporotrichosis-like lesions (chain of ulcers Mycobacteria bovis up the arm along the lymphatics) in immunocompromised hosts Typical produces TB in cattle, but may infect humans Mycobacteria ulcerans to that caused by M. tuberculosis Human disease similar Bairnsdale (Buruli) ulcer---a with BCG chemo of bladder cancer Urinary bladder infections painless boil or lump in skin of extremities at the site of previous trauma, developing into a shallow non-healing ulcer with a necrotic base (Tropical disease)

Mycobacterium leprae

Most usual presentation: numbness in the earlobes or nose Several varieties:

Lepromatous leprosy Tuberculoid leprosy

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Dr.T.V.Rao MD

Atypical Mycobacterium

Investigations have defined >100 facultative saprophytes and entities that are acid-fast mycobacteria but do not cause tuberculosis or leprosy. These mycobacteria or atypical mycobacteria (ATM) exist in almost all habitats.
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Nontuberculous Mycobacteria

Water, soil, food and animals Does not spread from person to another Relatively resistant to chlorination and ozonization Outbreak and Pseudo-outbreak in the hospital HIV and dialysis patients Improve laboratory methods reporting MAC 40%,rapidly growing 10%,15% unknown,25% M.gordonae,2.5% M.kansasii(MW USA and UK) and 1% M.xenopi (Ontario)
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Runyon classifies Atypical Mycobacterium

1959, botanist Ernest Runyon put these human disease-associated bacteria into four groups (Runyon classification Photochromogens, which develop pigments in or after being exposed to light. Examples include M. kansasii, M. simiae and M. marinum. Scotochromogens, which become pigmented in darkness. Examples include M. scrofulaceum and M. szulgai
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Runyon classifies Atypical Mycobacterium

Non-chromogens, which includes a group of prevalent opportunistic pathogens called M. avium complex (MAC). Other examples are M. ulcerans, M. xenopi, M. malmoense, M. terrae, M. haemophilum and M. genavense Rapid growers include four well recognized pathogenic rapidly growing non-chromogenic species: M. chelonae, M. abscessus, M. fortuitum and M. peregrinum. Other examples cause disease rarely, such as M. smegmatis and M. flavescens.
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Atypical mycobacteria may cause

Atypical mycobacteria may cause many different types of infections such as septic arthritis, abscesses and skin and bone infection. They may also affect the lungs, gastrointestinal tract, lymphatic system and other parts of the body
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Atypical Mycobacterium are

Unclassified Anonymous Non tuberculosis mycobacterium Present in soil, water, Causes opportunistic infections in AIDS
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Groups of Atypical Mycobacterium

Group 1 - Photochromogens (eg, Mycobacterium kansasii, M marinum, Mycobacterium simiae) Group 2 - Scotochromogens (eg, Mycobacterium scrofulaceum, Mycobacterium szulgai, Mycobacterium gordonae) Group 3 - Nonphotochromogens (eg, Mycobacterium malmoense, Mycobacterium xenopi, M aviumintracellulare) Group 4 - Fast growers (3-5 d) (eg, Mycobacterium fortuitum, Mycobacterium chelonae, Mycobacterium abscessus) M chelonae is an atypical fast-growing mycobacteria that is a rare cause of human infection.
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Group I - Photochromogens
Non pigmented in the dark When young culture exposed to light for 1 hour and reincubated for at 24-48 a yellow orange pigment is produced Slow growing are M kansasii.infects Volves M.marinum M simiae M asiacticum Present in tap water, second most common infection after M.aviumintracellulare

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Photochromogens

M.marinum causes warty skin lesions Causes swimming pool granulomas Poor growth at 37 c Negative by nitrate test Others M simiae M asiacticum

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Group II Scotochromogens

Pigmented colonies even in the dark M.scrofulaceium, causes scrofula ( cervical adenitis in children ) M. gordonae Present in tap water Scotochromogens Contaminates clinical specimens Fail to hydrolyses urea

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M scrofulaceum

M scrofulaceum is a slow-growing atypical mycobacteria that is found in environmental water sources, tap water, and the human respiratory tract. It causes scrofula, a granulomatous cervical adenitis in children and pulmonary disease in adults. It is usually unilateral. Few reports of it causing skin disease exist.
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Group III- Non Photochromogens

Do not form pigment even on exposure to light like tubercle bacilli M. avium, M. intracellare M.xenopi Mostly occurs as opportunistic infection Called MAI complex
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Mycobacterium avium-intracellulare

Mycobacterium avium-intracellulare frequently affects AIDS patients and causes lung disease. Mycobacterium marinum cause skin infections and is also responsible for swimming pool granuloma. Mycobacterium ulcerans cause skin infections. Mycobacterium kansasii causes lung disease
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Mycobacterium avium complex

Mycobacterium avium complex (MAC) consists of two species M avium and M intrac ellulare. Because these species are difficult to differentiate, they a re also collectively referred to Dr.T.V.Rao MD MD Dr.T.V.Rao as Mycobacterium

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Mycobacterium avium-intracellulare

Also known as MAC (Mycobacterium avium complex) Most common non-tuberculous mycobacterial infection associated with AIDS Symptoms include fever, swollen lymph nodes, diarrhoea, fatigue, weight loss and shortness of breath May develop into pulmonary MAC
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Mycobacterium avium-intracellulare

Disseminated M avium complex (MAC) disease is most commonly diagnosed using culture of blood and bone marrow or other normally sterile tissues or body fluids. Other ancillary studies, such as acid-fast bacilli smear or radiographic imaging of the abdomen or mediastinum for detection of lymphadenopathy, may provide supportive diagnosis information.
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M avium and AIDS

M avium is the isolate in more than 95% of patients with AIDS who develop MAC infections, M intracellulare is responsible for 40% of such infections in immunocompetent patients. MAC is the most common cause of infection by nontuberculous mycobacteria (NTM) in patients with AIDS.
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M avium and AIDS

M. avium-intracellulare (MAC or MAI) is a rare cause of lung disease in otherwise healthy humans but a frequent cause of infection among those whose resistance has been lowered by another disorder (opportunistic infection). According to some experts, MAC infection is an almost inevitable complication of HIV.
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Causes

Lymphadenopathy Pulmonary lesions Disseminated disease Patients with AIDS are predisposed M. malmoense Causes pulmonary disease M. xenopi Contaminates water taps

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Atypical mycobacterium is it common ? NO

The rate of atypical mycobacterial infections is rare, but it is increasing as the AIDS population grows. Populations at risk include individuals who have lung disease and weakened immune system
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Symptoms No typical Manifestations

Fever Weight loss Enlarged lymph glands Diarrhea Sweating, excessive -- night sweats Fatigue General discomfort, uneasiness or ill feeling (malaise) Cough Shortness of breath (dyspnea) Skin lesions Joint pain Bone pain
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Type IV- Rapid growers

Heterogeneous group Rapid growers Grows in < 7 days Grows at 37 25 Present Photochromogens Scotochrogens Non Photochromogens
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Mycobacterium marinum

Also known as fish tank granulomas Uncommon infection that occurs most often in people with recreational or occupational exposure to contaminated freshwater or saltwater Usually a single lump or pustule that breaks down to form a crusty sore or abscess Other lumps may occur around the initial lesion, particularly along the lines of lymphatic drainage (sporotrichoid forms) Most often affects elbows, knees, feet, knuckles or fingers Multiple lesions and widespread disease may occur in immunocompromised patients Rarely causes red, swollen and tender joints
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Mycobacterium ulcerans

Also known as Buruli ulcers Infection most common in Central and West Africa around areas of lush vegetation and swamps but may also occur in Australia Solitary, painless and sometimes itchy nodule of 1-2 cm develops about 7-14 days after infection through broken skin Over one to two months the nodule may break down to form a shallow ulcer that spreads rapidly and may involve up to 15% of the patient's skin surface Severe infections may destroy blood vessels, nerves, and invade bone
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Buruli ulcer

Buruli ulcer is a chronic ulcerative skin disease, caused by M ulcerans, that mostly affects the limbs. The lack of acute inflammatory response is typical and is likely due to an immunosuppressive toxin called mycolactone, which is produced by mycobacteria. Buruli ulcer mainly affects children living in humid areas of the tropical rain forest..
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Mycobacterium chelonae

Worldwide distribution: found in tap water and other water sources May cause lung disease, joint infection, eye disease and other organ infections May result in non-healing wound, subcutaneous nodule or abscess Immunosuppression may cause disseminated lesions throughout the body
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Cutaneous Infections Produced by other Atypical Mycobacterium

M. kansasii M. haemophilum M. scrofulaceum M. szulgai M. gordonae M. avium-intracellulare complex M. fortuitum M. abscessus M. chelonae
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Other species infecting skin

Two are common pathogens M. ulcerans M. marinum Causes skin infections, and causes granulomatoous lesions Systemic infections regional lymph nodes.

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Mycobacterium marinum infection

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Mycobacterium marinum infection

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Mycobacterium marinum infection

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Mycobacterium marinum infection

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Atypical mycobacterial lesion

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M.ulcerans

Uganda - Buruli ulcer Few weeks indolent ulcers Edge contain large number of bacilli Grows on L J medium in 4 to 8 weeks Grows between 30 to 33 c , But not at 23 or at 37 c Produces toxins inflamation and necrosis.

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M.marinum

Infects cold blooded animals Papules, indolent ulcers Swimming pool granulomas Undergoes spontaneous healing Bacilli are scanty Two weeks at 30 c Low grade Tuberculin reaction
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Diagnosis

Need to demonstrate organisms by: special stains cultures PCR

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We Miss the Diagnosis of Atypical Mycobacterium on many occasions ?

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Diagnosis of NTM

A positive AFB smear combined with negative MTB-PCR denotes infection with NTM DNA-DNA hybridization for the M.avium-complex 16S rDNA-sequencing remain the gold standard in sophisticated species diagnosis of cultured NTM
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Laboratory Diagnosis

Rapid Growers Days in broth and < 1 week in solid media M.abscessus M.chelonae M.fortutum

Slow Growers 1-2 weeks in broth and 2-4 weeks in solid media M.avium M.kansasii M.scrofulaceum M.ulcerans M.xenopi M.gordonae

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Special Diagnostic Problems

M.marinum lower temperature required M.haemophilum lower temperature required and iron need to be added M.ulcerans lower temperature required M.genavense very slow growth in broth DNA probes for MAC, M. kansasii and M. gordonae available Identification and sensitivity
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Tissue Biopsy Issue Report With RCC

Necr otizin g? Gran ulom as?

AFB Stain s?

Cultu re Sent ?

FFPE PCR with Sequencing/ Prior to biopsy (via discussion with clinicians or from the history) Issue consistent report

Hos t?
Consider Other diagnoses

you may have a high suspicion of mycobacterial disease (or simply infection NOS). This is usually because of some particular host factor (e.g., history of TB, iatrogenic immunosuppression, AIDs, malignancy, classic associations, mononeuropathy not from US, clinical Buruli ulcer, etc). In these situations, despite the fact that granulomas are missing (or lack necrosis if present), it is prudent to order AFB stains to rule out these organisms. If a patient is a perfectly normal host with no clinical reason to suspect a mycobacterial infection, other diagnosis (including other infections) should be considered (this branch, of course, takes you back into the rest of surgical pathology).

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Need for better Diagnostic Methods Laboratory Studies

Organisms from blood, biopsy material, bone marrow, and stools grow on routine bacterial media, but growth is best achieved using selective mycobacterial media, such as a Lowenstein-Jensen medium or Middle brook Nucleic acid hybridization probes using target sequences or ribosomal RNA are available for rapid identification of clinical isolates.
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Better diagnosis of Atypical Mycobacterial Infections

The anti- NTM drug susceptibility patterns often typical for the species. Therefore, the correct and exact species identification is a key issue for clinical NTM isolation.

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Routine Laboratory Methods are not adequate for Diagnosis

Atypical Mycobacterial infection is not diagnosed on routine bacteriological screening of sputum or bronchial washings and the instigation of investigation to identify an NTM species may be prompted by the suggestion of the radiologist based on imaging feature alone.

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Treating Atypical Mycobacterial Infections

Treatment of atypical mycobacterial infections depends upon the infecting organism and the severity of the infection. In most cases a course of antibiotics is necessary. These include rifampicin, Ethambutol, isoniazid, minocycline, ciprofloxacin, clarithromycin, azithromycin and cotrimoxazole. Usually treatment consists of a combination of drugs. Some points to consider when treating atypical mycobacterial infections

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Nontuberculous Mycobacterial Disease

Principles of Treatment of NTM Disease 1. Patients should be carefully evaluated to determine the significance of an NTM isolate. The presence of the organism in a sterile site or repeatedly from airway secretions in association with a compatible clinical and radiologic picture confirms the diagnosis. 2. Treatment of rapidly growing mycobacteria should be guided by in vitro susceptibilities. Other drug susceptibility testing is not standardized.
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Nontuberculous Mycobacterial Disease

3. Treatment should usually combine at least two drugs of proven efficacy. 4. Contact follow-up is not necessary since NTM are not transmitted from person to person. 5. Duration of therapy has not been determined; in general, 6-12 months is required following negative cultures.
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Nontuberculous Mycobacterial Disease

6. In soft tissue infections, because of rapidly growing mycobacteria, a combination of debridement and treatment with antimicrobials is recommended. For selection of antimicrobial agents, consultation with the laboratory should be undertaken regarding the reliability of in vitro testing.
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Theraputic options in Atypical Mycobacterial Infections

MAC Clarithromycin or azithromycin + ethambutol+Rifampin M. xenopi Rifampin+Ethambiotol +INH M. kansasii Rifampin + Ethambutol M. malmoense Rifampin or Ethambutol M. marinum Rifampin or Clarithromycin + Ethambutol 2-3 months Rapid growers doxycycline, amikacin, imipenem, quinolones, sulfonamides, cefoxitin, clarithromycin
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Treatment of atypical mycobacterial infection

Mycobacterium marinum species are often resistant to isoniazid. Treatment with other antibiotics should be for at least two months. Mycobacterium kansasii should be treated for at least 18 months. Mycobacterium chelonae is best treated by clarithromycin in combination with another agent, Sometimes surgical excision is the best approach.
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