atypical mycobacterium (2)
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Dr.T.V.Rao MD
Atypical
MycobacteriumDr.T.V.Rao MD
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Mycobacterial Diseases
Tuberculosis can infect Immunocompromised and competent
Atypical Mycobacteria can infect Immunocompromised (TB-like, non-TB-like)
Atypical Mycobacteria still can infect Immunocompetent (rare, syndromes)
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 canCause
Mycobacteria tuberculosis Ghon complex in primary TB (middle lobe
or apical lower lobe) Secondary TB in apical portion of upper
lobes Tuberculous effusions - mature
lymphocytes
Mycobacteria avium-intracellular High incidence in AIDS patients and elderly
women Sepsis and positive blood cultures
common AIDS: fever of unknown origin and weight
loss common; pulmonary diseaseuncommon
Immunocompetent hosts or elderly:pulmonary disease common Most common AFB involving bone marrow
Mycobacteria gordonae Rare human infections
Mycobacteria szulgi Rare human infections
Mycobacteria kansasii Chronic pulmonary disease similar to classic TB except it is noninfectious and has less
extrapulmonary or disseminated diseases 15% of patients have disseminated disease Disseminated disease in the immunocompromised and patients with late stage AIDS
Mycobacteria marinum
Superficial granulomatous skin infection (swimming pool or fish tank granulomas) involvingtraumatized skin of the extremities in contact with poorly chlorinated fresh water Sporotrichosis-like lesions (chain of ulcers up the arm along the lymphatics)
Mycobacteria simiae Pulmonary disease in humans
Mycobacteria scrofulaceum Scrofula---unilateral painless lymphadenitis, involving lymph nodes high in the neck in healthy
children
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MYCOBACTERIA what theycan Cause
Mycobacteria fortuitum/chelonaecomplex
Skin infections with draining abscesses May have involvement of lungs, bone,
CNS, and prosthetic heart valves, anddisseminated disease
Associated with post-surgical wound,
needle injections, renal transplantrecipients Sporotrichosis-like lesions (chain of ulcers
up the arm along the lymphatics) inimmunocompromised hosts
Mycobacteria ulcerans Bairnsdale (Buruli) ulcer---a painless
boil or lump in skin of extremities at thesite of previous trauma, developing into a
shallow non-healing ulcer with a necroticbase (Tropical disease)
Mycobacterium leprae Most usual presentation: numbness in the
earlobes or nose Several varieties:
Lepromatous leprosy
Tuberculoid leprosy
Mycobacteria haemophilum Painful subcutaneous nodules, swellings and ulcers progressing into abscesses and draining
fistulas Disseminated disease in AIDS patients
Mycobacteria xenopi TB-like pulmonary disease; Rare infection in AIDS patients and immunocompetent hosts
Mycobacteria paratuberculosis Associated with Crohns disease
Mycobacteria bovis Typical produces TB in cattle, but may infect humans Human disease similar to that caused by M. tuberculosis Urinary bladder infections with BCG chemo of bladder cancer
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Atypical Mycobacterium
Investigations have defined >100facultative saprophytes and
entities that are acid-fastmycobacteria but do not causetuberculosis or leprosy. These
mycobacteria oratypicalmycobacteria (ATM) exist in almostall 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(MWUSA and UK) and 1% M.xenopi (Ontario)
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Runyon classifies AtypicalMycobacterium
1959, botanist Ernest Runyon put thesehuman disease-associated bacteria intofour groups (Runyon classification
Photochromogens, which developpigments in or after being exposed to light.Examples include M. kansasii, M. simiaeand M. marinum.
Scotochromogens, which becomepigmented in darkness. Examples includeM. scrofulaceum and M. szulgai
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Runyon classifies AtypicalMycobacterium
Non-chromogens, which includes a group ofprevalent 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 examplescause disease rarely, such as M. smegmatis andM. flavescens.
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Atypical mycobacteria maycause
Atypical mycobacteria may causemany different types of infections
such as septic arthritis, abscessesand skin and bone infection. Theymay also affect the lungs,
gastrointestinal tract, lymphaticsystem and other parts of thebody
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Atypical Mycobacterium are
Unclassified Anonymous Non tuberculosis
mycobacterium Present in soil,
water,
Causesopportunisticinfections in AIDS
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Groups of AtypicalMycobacterium
Group 1 - Photochromogens (eg, Mycobacteriumkansasii, M marinum, Mycobacterium simiae)
Group 2 - Scotochromogens (eg, Mycobacteriumscrofulaceum, Mycobacterium szulgai, Mycobacteriumgordonae)
Group 3 - Nonphotochromogens (eg, Mycobacteriummalmoense, Mycobacterium xenopi, M avium-intracellulare)
Group 4 - Fast growers (3-5 d) (eg, Mycobacteriumfortuitum, Mycobacterium chelonae, Mycobacterium
abscessus) M chelonaeis 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 orangepigment is produced
Slow growing areM kansasii.infects VolvesM.marinumM simiae
M asiacticumPresent 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 atypicalmycobacteria that is found inenvironmental water sources, tap water,
and the human respiratory tract. It causesscrofula, a granulomatous cervical adenitisin children and pulmonary disease inadults. It is usually unilateral. Few reportsof it causing skin disease exist.
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Group III- Non Photochromogens
Do not form pigment even onexposure 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-intracellularefrequently affects AIDS patients andcauses lung disease.
Mycobacterium marinum cause skininfections and is also responsible forswimming pool granuloma.
Mycobacterium ulcerans cause skin
infections. Mycobacterium kansasiicauses lung
disease
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Mycobacterium avium complex
Mycobacteriumavium complex(MAC) consists oftwo species M
avium and M intracellulare. Becausethese species are
difficult todifferentiate, they are also collectivelyreferred to
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Mycobacterium avium-intracellulare
Also known as MAC (Mycobacteriumavium complex)
Most common non-tuberculous
mycobacterial infection associated withAIDS 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 diagnosedusing culture of blood and bone marrow or
other normally sterile tissues or bodyfluids. Other ancillary studies, such asacid-fast bacilli smear or radiographicimaging of the abdomen or mediastinumfor detection of lymphadenopathy, mayprovide supportive diagnosis information.
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M avium and AIDS
M avium is the isolate in more than 95% ofpatients with AIDS who develop MACinfections, M intracellulare is responsible
for 40% of such infections inimmunocompetent patients. MAC is themost common cause of infection bynontuberculous mycobacteria (NTM) inpatients with AIDS.
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M avium and AIDS
M. avium-intracellulare (MAC or MAI) is arare cause of lung disease in otherwisehealthy humans but a frequent cause of
infection among those whose resistancehas been lowered by another disorder(opportunistic infection). According tosome experts, MAC infection is an almostinevitable 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 itcommon ? NO
The rate of atypical mycobacterialinfections is rare, but it is
increasing as the AIDS populationgrows. Populations at risk includeindividuals who have lung disease
and weakened immune system
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Symptoms
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SymptomsNo 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 contaminatedfreshwater or saltwater
Usually a single lump or pustule that breaks down to forma 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 occurin Australia
Solitary, painless and sometimes itchy nodule of 1-2 cmdevelops about 7-14 days after infection through brokenskin
Over one to two months the nodule may break down toform 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 Mulcerans, that mostlyaffects the limbs. The lack
of acute inflammatoryresponse is typical and islikely due to animmunosuppressive toxincalled mycolactone, whichis produced by
mycobacteria. Buruli ulcermainly affects childrenliving in humid areas ofthe tropical rain forest..
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Mycobacterium chelonae
Worldwide distribution: found in tap waterand 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 causedisseminated lesions throughout the body
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C taneo s Infections Prod ced b other
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Cutaneous Infections Produced by otherAtypical 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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Di i
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Diagnosis
Need to demonstrate organismsby:
special stains cultures PCR
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We Miss the Diagnosis of AtypicalMycobacterium on many occasions ?
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Diagnosis of NTM
A positive AFB smearcombined withnegative MTB-PCRdenotes infectionwith NTM
DNA-DNA hybridizationfor theM.avium-complex
16S rDNA-sequencing remain the
gold standard in sophisticated speciesdiagnosis 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 insolid 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. kansasiiand M.
gordonae available Identification and sensitivity
Tissue Biopsy
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FFPE PCR withSequencing/
Issue consistent report
Necr
otizing?
AFB
Stains?
Cultu
reSent
?
IssueReportWithRCC
Granulom
as?
Host?
ConsiderOtherdiagnoses
Prior to biopsy (via discussion with clinicians or from the history)you may have a high suspicion of mycobacterial disease (or simplyinfection NOS).This is usually because of some particular host factor (e.g., historyof TB, iatrogenic immunosuppression, AIDs, malignancy, classicassociations, mononeuropathy not from US, clinical Buruli ulcer,etc).In these situations, despite the fact that granulomas are missing (orlack necrosis if present), it is prudent to order AFB stains to rule outthese organisms.If a patient is a perfectly normal host with no clinical reason tosuspect a mycobacterial infection, other diagnosis (including otherinfections) should be considered (this branch, of course, takes youback into the rest of surgical pathology).
Need for better Diagnostic Methods
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Need for better Diagnostic MethodsLaboratory Studies
Organisms from blood, biopsy material,bone marrow, and stools grow on routinebacterial media, but growth is bestachieved using selective mycobacterialmedia, such as a Lowenstein-Jensenmedium or Middle brook
Nucleic acid hybridization probes using
target sequences or ribosomal RNA areavailable for rapid identification of clinicalisolates.
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B tt di i f At i l
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Better diagnosis of AtypicalMycobacterial Infections
The anti- NTM drug susceptibilitypatterns often typical for the species.Therefore, the correct and exact
species identification is a key issue forclinical NTM isolation.
R ti L b t M th d
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Routine Laboratory Methods arenot adequate for Diagnosis
Atypical Mycobacterial infection is not diagnosed onroutine bacteriological screening of sputum or bronchialwashings and the instigation of investigation to identify anNTM species may be prompted by the suggestion of theradiologist based on imaging feature alone.
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Treating AtypicalMycobacterial Infections
Treatment of atypical mycobacterial infectionsdepends upon the infecting organism and theseverity of the infection. In most cases a courseof antibiotics is necessary. These includerifampicin, Ethambutol, isoniazid, minocycline,ciprofloxacin, clarithromycin, azithromycin andcotrimoxazole. Usually treatment consists of acombination 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 associationwith a compatible clinical and radiologic pictureconfirms the diagnosis.
2. Treatment of rapidly growing mycobacteria
should be guided by in vitro susceptibilities.Other drug susceptibility testing is notstandardized.
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Nontuberculous MycobacterialDisease
3. Treatment should usually combine atleast two drugs of proven efficacy.
4. Contact follow-up is not necessary since
NTM are not transmitted from person toperson.
5. Duration of therapy has not been
determined; in general, 6-12 months isrequired following negative cultures.
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Nontuberculous MycobacterialDisease
6. In soft tissue infections, because ofrapidly growing mycobacteria, acombination of debridement and treatment
with antimicrobials is recommended. Forselection of antimicrobial agents,consultation with the laboratory should beundertaken regarding the reliability ofinvitro testing.
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Theraputic options in AtypicalMycobacterial Infections
MAC Clarithromycin or azithromycin +ethambutol+Rifampin
M. xenopi Rifampin+Ethambiotol +INH
M. kansasii Rifampin + Ethambutol M. malmoenseRifampin or Ethambutol M. marinum Rifampin or Clarithromycin +
Ethambutol 2-3 months Rapid growersdoxycycline, amikacin,
imipenem, quinolones, sulfonamides, cefoxitin,clarithromycin
Treatment of atypical mycobacterial
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Treatment of atypical mycobacterialinfection
Mycobacterium marinum species are oftenresistant to isoniazid. Treatment with otherantibiotics should be for at least twomonths.
Mycobacterium kansasiishould be treatedfor at least 18 months.
Mycobacterium chelonae is best treated
by clarithromycin in combination withanother agent, Sometimes surgicalexcision is the best approach.
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