Atypical Mycobacterium (2)

7/31/2019 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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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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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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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.

T ti At i l


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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.

N t b l M b t i l


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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.

N t b l M b t i l


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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.

Th ti ti i At i l


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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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Atypical Mycobacterium (2)

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