ANAEROBIC ORGANISMS,ANAEROBIC ORGANISMS,DIPHTHERIA, MYCOBACTERIA DIPHTHERIA, MYCOBACTERIA & TREPONEMA IN ENT& TREPONEMA IN ENT

Dr. Ramesh Parajuli, MSDr. Ramesh Parajuli, MS

Otorhinolaryngology, Head & Neck Surgery

Chitwan Medical College Teaching Hospital, Bharatpur-10, Chitwan, Nepal

Corynebacterium DiphtheriaeCorynebacterium DiphtheriaeAerobic, Gram-positive rod, Aerobic, Gram-positive rod, non spore forming, non motilenon spore forming, non motile

Club shaped, palisades (v or l Club shaped, palisades (v or l shaped) or “shaped) or “Chinese letter”- Chinese letter”- tellurite medium(D)tellurite medium(D)

Granules-loeffler’s medium(SGranules-loeffler’s medium(S))

2 phenotypes- toxigenic(tox+ ve) and non 2 phenotypes- toxigenic(tox+ ve) and non toxigenic(tox-ve)toxigenic(tox-ve)

Diphtheria-nasopharyngeal & skin infection caused Diphtheria-nasopharyngeal & skin infection caused by c.diphtheriaeby c.diphtheriae

Toxigenic:pharyngeal diphtheriaToxigenic:pharyngeal diphtheria

Non-toxigenic:cutaneous diphtheriaNon-toxigenic:cutaneous diphtheria

Lysogenic conversion by bacteriophage ‘tox’ geneLysogenic conversion by bacteriophage ‘tox’ gene

3 strains: Gravis , 3 strains: Gravis , Intermedius & MitisIntermedius & Mitis

Gravis and intermedius Gravis and intermedius types-higher mortalitytypes-higher mortality

CornebacteriumCornebacterium

ulcerans:- infected by ulcerans:- infected by bacteriophagebacteriophage diphtheria like diphtheria like presentationpresentation

Mechanism of action of Diphtheria Mechanism of action of Diphtheria ToxinToxin

PathologyPathology Tonsil Necrosis - initial Tonsil Necrosis - initial lesionlesion

Characterstic Characterstic pseudomembrane pseudomembrane formation: (necrotic tissue + formation: (necrotic tissue + bacteria+ fibrinous exudate)bacteria+ fibrinous exudate)

Early removal - Bleeding, Early removal - Bleeding, easy separation later easy separation later

Bull neck: Cellulitis & Bull neck: Cellulitis & Cervical lymphadenopathyCervical lymphadenopathy

Bull-neck appearance

Transmission: Transmission: aerosol(resp.droplet)aerosol(resp.droplet)

Incubation period:3-4 daysIncubation period:3-4 days

ToxemiaToxemia

Mechanical complications: Mechanical complications: pseudomembranepseudomembrane

Systemic effects:Systemic effects:

toxintoxin

Clinical FeaturesClinical Features

Age : Rare over 10 yearsAge : Rare over 10 years

Malaise ,Sore throat and Malaise ,Sore throat and PyrexiaPyrexia

Membrane over the Membrane over the Faucial pillarsFaucial pillars

Progressive Dysphagia Progressive Dysphagia and Toxemiaand Toxemia

Inspiratory Stridor and Inspiratory Stridor and Barking coughBarking cough

Cough – Paroxysmal and Cough – Paroxysmal and ExhaustingExhausting

DeathDeath

-Acute airway obstruction-Acute airway obstruction

-circulatory failure-circulatory failure

Acute Toxic MyocarditisAcute Toxic Myocarditiscardiac cardiac dysfunctiondysfunction

-2-2ndnd week week

Peripheral NeuropathyPeripheral Neuropathy

--Recurrent laryngeal nerve palsyRecurrent laryngeal nerve palsy

-Palatal Paralysis most common-Palatal Paralysis most common

-Presents with nasal regurgitation -Presents with nasal regurgitation & hyper nasal speech& hyper nasal speech

Differential DiagnosisDifferential Diagnosis

Foreign bodyForeign body

Infectious MononucleosisInfectious Mononucleosis

Peritonsillar AbscessPeritonsillar Abscess

Retropharyngeal AbscessRetropharyngeal Abscess

Differential Diagnosis Differential Diagnosis cont.cont.

Streptococcal Streptococcal pharyngitispharyngitis

Vincent’s anginaVincent’s angina

ThrushThrush

Post-tonsillectomy Post-tonsillectomy faucial membranesfaucial membranes

Leukemia and Leukemia and agranulocytosisagranulocytosis

ManagementManagement

Airway :Airway :

-Removal of Laryngeal -Removal of Laryngeal MembraneMembrane

-Humidification-Humidification

-0xygen therapy-0xygen therapy

- ET intubation or - ET intubation or TracheostomyTracheostomy

-Systemic Steroids : Reduce need -Systemic Steroids : Reduce need for airway intervention for airway intervention

ManagementManagement

Benzyl Benzyl Penicillin :600mgx Penicillin :600mgx i.v.x 6 hourlyi.v.x 6 hourly

Diptheria AntitoxinDiptheria Antitoxin

10,000-1,00,000 units 10,000-1,00,000 units (Depending upon (Depending upon severity)severity)

Bed rest – 2 to Bed rest – 2 to 4 weeks until 4 weeks until danger of danger of myocarditis is myocarditis is overover

Vaccination: Vaccination: DPTDPT

Diptheroids (Coryneforms)Diptheroids (Coryneforms)

Nondiphtherial corynebacteriaNondiphtherial corynebacteria

Colonisers or contaminants –invasive Colonisers or contaminants –invasive disease in immunocompromiseddisease in immunocompromised

C.pseudodipthericum –pharynx ,skinC.pseudodipthericum –pharynx ,skin

-C.xerosis – skin ,nasopharynx & conjunctiva-C.xerosis – skin ,nasopharynx & conjunctiva

C.Auris – EAC, C.striatum – ant.Nares ,skin C.Auris – EAC, C.striatum – ant.Nares ,skin

Anaerobic OrganismsAnaerobic OrganismsMost are commensals- Most are commensals- harmlessharmless

eg saliva,gingival scrappingeg saliva,gingival scrappingSites- skin, mouth, Sites- skin, mouth, nasopharynx, upper nasopharynx, upper respiratory tractrespiratory tractConditions favored- Conditions favored- Decreased oxidation-Decreased oxidation-reduction potential eg. reduction potential eg. Trauma, Tissue destruction, Trauma, Tissue destruction, foreign body, malnutrition.foreign body, malnutrition.

ClassificationClassificationGram-negative rods: Gram-negative rods: BacteroidesBacteroides [e.g. [e.g. B. B. fragilisfragilis],],Fusobacterium, prevotella, Fusobacterium, prevotella, porphyromonasporphyromonas

Gram-positive rods: Gram-positive rods: ActinomycesActinomyces,clostridium,,clostridium,EubacteriumEubacterium, , BifidobacteriumBifidobacterium,,PropionibacteriumPropionibacterium

Gram-positive cocci: Gram-positive cocci: PeptostreptococcusPeptostreptococcus and and PeptococcusPeptococcus

Gram-negative cocci: Gram-negative cocci: VeillonellaVeillonella

IMPORTANT ANAEROBESIMPORTANT ANAEROBESBacteroides-Bacteroides-

B. fragilis- most frequently isolated B. fragilis- most frequently isolated Resistant to beta lactamsResistant to beta lactams

Prevotella: newly named & previously Bacteroides Prevotella: newly named & previously Bacteroides

B. melaninogenicus (Recently Prevotella B. melaninogenicus (Recently Prevotella melaninogenicus )- black, brown colonies Major melaninogenicus )- black, brown colonies Major group in oral flora.group in oral flora.Peptostreptococcus- Peptostreptococcus-

-Normal flora of skin ,mucus membrane -Normal flora of skin ,mucus membrane Species- P. micros, P. anaerobius P. magnus Species- P. micros, P. anaerobius P. magnus

(abscess)(abscess)

Peptococcus Peptococcus

FusobacteriumFusobacterium

Clostridium - spore formingClostridium - spore forming Gas gangrene, food poisoning, tetanus, colitisGas gangrene, food poisoning, tetanus, colitis

Cl. Perfringens- Toxin- hemolytic- dermonecrotic, Cl. Perfringens- Toxin- hemolytic- dermonecrotic, Phospholipase c, LecithinasePhospholipase c, Lecithinase

Wound contamination- cellulitis- myositisWound contamination- cellulitis- myositis gas gas gangrene.gangrene.

Infection due to anaerobes- mostly polymicrobialInfection due to anaerobes- mostly polymicrobial

Abscess cavity or necrotic tissueAbscess cavity or necrotic tissue

Failure of abscess to yield organism on routine Failure of abscess to yield organism on routine cultureculture clue for anaerobic organism clue for anaerobic organism

Abscess in deeper body tissueAbscess in deeper body tissue

Putrid smelling infection site or dischargePutrid smelling infection site or discharge

Acute Necrotizing Ulcerative Acute Necrotizing Ulcerative Gingivitis(ANUG)/ Trench Mouth/Vincent’s Gingivitis(ANUG)/ Trench Mouth/Vincent’s

StomatitisStomatitis

-Etiology. :Fusobacterium -Etiology. :Fusobacterium Nucleatum, Borrelia Nucleatum, Borrelia VincentiVincenti

- Tender bleeding gums, - Tender bleeding gums, foul breathe &bad tastefoul breathe &bad taste

-Gingival mucosa esp. -Gingival mucosa esp. papilla-ulcerated& papilla-ulcerated& covered with grey covered with grey exudateexudate

-Fever, Cervical -Fever, Cervical lymphadenopathy & lymphadenopathy & leucocytosisleucocytosis

Acute Necrotizing Ulcerative Acute Necrotizing Ulcerative Mucositis / Noma/Cancrum OrisMucositis / Noma/Cancrum Oris

Usually a/w ulcerative Usually a/w ulcerative gingivitisgingivitis

Anaerobes esp. Anaerobes esp. B.porphyromonas B.porphyromonas

Rapid tissue Rapid tissue destructiondestructionteeth fall teeth fall outoutbone/whole bone/whole mandible sloughmandible slough

Heal leaving disfiguring Heal leaving disfiguring defectdefect

Acute Necrotizing infection of PharynxAcute Necrotizing infection of Pharynx

Usu.a/w ulcerative Usu.a/w ulcerative gingivitisgingivitis

C/F:fever,sore throat,foul C/F:fever,sore throat,foul breath,bad breath,bad taste,sensation of chokingtaste,sensation of choking

O/E: Greyish membrane O/E: Greyish membrane over Tonsillar pillars that over Tonsillar pillars that peel easilypeel easily

Lymphadenopathy & Lymphadenopathy & LeucocytosisLeucocytosis

May spread to larynxMay spread to larynx

PeriPharyngeal spacePeriPharyngeal space infection infection

Peritonsillar abscessPeritonsillar abscess- Complication of Tonsillitis or Complication of Tonsillitis or

De novoDe novo- Mixed flora containing both Mixed flora containing both

Anaerobes & GABHSAnaerobes & GABHS- Association between Association between

Periodontal disease (source Periodontal disease (source of anaerobic organism) and of anaerobic organism) and PTA. PTA.

- Ludwig’s Angina Ludwig’s Angina

Actinomycosis Actinomycosis

Member of normal oral flora-Member of normal oral flora-gingival crevicesgingival crevices

G+ve, anaerobic,branching G+ve, anaerobic,branching rodsrods

A.israelii-most common. A.israelii-most common. A.naeslundii, A.naeslundii, A.odontolyticus,A.viscous etcA.odontolyticus,A.viscous etc

Disruption of mucosal Disruption of mucosal barrierbarrierlocal infectionlocal infectionslowly slowly progressiveprogressivechronic phase chronic phase with single or multiple indurated with single or multiple indurated lesionslesions

Trauma, F.B. poor oral hygieneTrauma, F.B. poor oral hygiene

Chronic granulomatous Chronic granulomatous infectioninfection

Firm indurated mass- central necrosis with Firm indurated mass- central necrosis with fibrotic ‘wooden wall’(neutrophils & sulfur fibrotic ‘wooden wall’(neutrophils & sulfur granules)granules)

Multiple sinus tract which discharge pusMultiple sinus tract which discharge pus

Usu. angle of jaw involvedUsu. angle of jaw involved

Sulphur granules-characteristicSulphur granules-characteristic

D/D- Malignancy or Granulomatous D/D- Malignancy or Granulomatous diseasedisease

Any mass lesion or relapsing infection in Any mass lesion or relapsing infection in head & neck regionhead & neck regionrule out rule out actinomycosisactinomycosis

Sinusitis &OtitisSinusitis &OtitisAnaerobes implicated in (0-88)% of CRS Anaerobes implicated in (0-88)% of CRS (Doyle, Ramadan, Brook)(Doyle, Ramadan, Brook)

anaerobes in CRS (0 to 52%)(Harrison 17anaerobes in CRS (0 to 52%)(Harrison 17thth edn.)edn.)

Peptostreptococcus, Fusobacterium & P. Peptostreptococcus, Fusobacterium & P. acnesacnes

COM COM - Anaerobes in Upto 50% cases Anaerobes in Upto 50% cases - B.fragilis in upto 28% cases of COMB.fragilis in upto 28% cases of COM

Complications of Anaerobic Complications of Anaerobic Head & Neck InfectionHead & Neck Infection

Continuous spreadContinuous spread- Craniad: Osteomyelitis of skull /mandible or Craniad: Osteomyelitis of skull /mandible or

intracranial complications(brain intracranial complications(brain abscess,subdural empyema)abscess,subdural empyema)

- Caudal :Mediastinitis or Pleuropulmonary Caudal :Mediastinitis or Pleuropulmonary infectioninfection

- Hematogenous disseminationHematogenous dissemination- Lemierre’s Syndrome- Lemierre’s Syndrome- Fusobacterium necrophorumFusobacterium necrophorum

Approach to the patients Approach to the patients

Harmless commensals, disease proximity Harmless commensals, disease proximity to mucosal site colonisedto mucosal site colonised

Site of lower oxidation-reduction potentialSite of lower oxidation-reduction potential

Polymicrobial naturePolymicrobial nature

Negative culture Negative culture ‘clue’‘clue’

Foul or putrid infection site or discharge Foul or putrid infection site or discharge diagnosticdiagnostic

Diagnosis Diagnosis

3 critical steps 3 critical steps

1.1. Proper specimen Proper specimen collectioncollection

2.2. Rapid transport Rapid transport preferably in anaerobic preferably in anaerobic mediamedia

3.3. Proper handling of Proper handling of specimen by the labspecimen by the lab

Specimen collectionSpecimen collection

Sterile body fluid – blood, Sterile body fluid – blood, pleural, peritoneal fluid,CSF pleural, peritoneal fluid,CSF and aspirates or biopsies from and aspirates or biopsies from normally sterile sitesnormally sterile sites

Specimen unacceptable: Specimen unacceptable: expectorated sputum ,nasal expectorated sputum ,nasal tracheal suction, bronchoscopy tracheal suction, bronchoscopy specimen,voided urine & specimen,voided urine & faeces faeces

Ways of eliminating oxygen gasWays of eliminating oxygen gas

Gas pac jarGas pac jar : - : - Contains a Contains a packet of sodium packet of sodium borohydride, sodium borohydride, sodium bicarbonate & citric acid.bicarbonate & citric acid.

- Addition of water causes - Addition of water causes production of H2, CO2 gas & production of H2, CO2 gas & displaces air (and thus displaces air (and thus oxygen).oxygen).

Gas exchange jar : Air in the Gas exchange jar : Air in the jar is replaced with O2-free jar is replaced with O2-free gas (from a tank).gas (from a tank).

Glove box: Glove box: Box is filled with Box is filled with anaerobic (O2-free) anaerobic (O2-free) gas ,usually a mixture of H2 gas ,usually a mixture of H2 and CO2.and CO2.

-Positive pressure -Positive pressure keeps O2 outkeeps O2 out

TreatmentTreatment

Surgical drainage (most Surgical drainage (most circumstances) + antimicrobialscircumstances) + antimicrobials

DOC: Penicillin GDOC: Penicillin G

For Beta –lactamase producing For Beta –lactamase producing Bacteroides and PrevotellaBacteroides and Prevotella

-Clindamycin (DOC infections above -Clindamycin (DOC infections above diaphragm) & Metronidazolediaphragm) & Metronidazole

Mycobacterium TuberculosisMycobacterium Tuberculosis

Rod shaped, obligate Rod shaped, obligate aerobes ,slow growingaerobes ,slow growing

Acid-fast – high content Acid-fast – high content of mycolic acidof mycolic acid

Low cell wall Low cell wall permeability to permeability to antibioticsantibiotics

No exotoxin nor No exotoxin nor endotoxinendotoxin

Damage done by Damage done by immune system (CMI)immune system (CMI)

Tuberculin(surface Tuberculin(surface protein) along with protein) along with mycolic acidmycolic aciddelayed delayed type hypersensitivity & type hypersensitivity & CMICMI

Nasal TuberculosisNasal Tuberculosis

ROUTES OF ROUTES OF SPREADSPREAD

- Direct inoculation: - Direct inoculation: Nose Pricking or Nose Pricking or Finger nail TraumaFinger nail Trauma

- Droplet Spread: - Droplet Spread: Coughing, Sneezing Coughing, Sneezing

- Haematogenous - Haematogenous disseminationdissemination

3 FORMS3 FORMS

1. Nodular1. Nodular

2.Ulcerative2.Ulcerative

3.Sinus Granuloma3.Sinus Granuloma

1.Nodular 1.Nodular

Begins in VestibuleBegins in Vestibule

APPLE JELLY NODULE APPLE JELLY NODULE

Untreated-scar and deformityUntreated-scar and deformity

2.Ulcerative form2.Ulcerative form

Usually cartilaginous septum or inferior Turbinate Usually cartilaginous septum or inferior Turbinate

Septal Perforation Septal Perforation

3.Sinus granuloma3.Sinus granuloma

Isolated sinus involvement without any sign and symptoms Isolated sinus involvement without any sign and symptoms in the nose.in the nose.

Unilateral , Maxillary Sinus- usuallyUnilateral , Maxillary Sinus- usually

Tuberculous Otitis MediaTuberculous Otitis MediaIncidence < 1% COM Incidence < 1% COM Spread: Insuffalation via E.tube, Spread: Insuffalation via E.tube, Hematogenous, contiguousHematogenous, contiguousPresentation:Presentation:

-Chronic Otorrhoea-Chronic Otorrhoea -Hearing loss (moderate to severe -Hearing loss (moderate to severe

CHL, mixed)CHL, mixed) -Dizziness-Dizziness

O/EO/E

Multiple perforations (hall mark)- Multiple perforations (hall mark)- later coalesce into a single large later coalesce into a single large perforationperforation

Abundant Abundant pale granulationpale granulation tissue - characteristic tissue - characteristic

Handle of Malleus- denuded Handle of Malleus- denuded

Middle ear mucosa- paleMiddle ear mucosa- pale

Complications:Complications:

-Profound SNHL-Profound SNHL

-Facial n. palsy-Facial n. palsy

Diagnosis-HPE Diagnosis-HPE

- ME Mucosal biopsy & Aural polpectomy - ME Mucosal biopsy & Aural polpectomy specimen positive in 30% & 35% specimen positive in 30% & 35% respectivelyrespectively

- Management:Management: - ATT- ATT

- Mastoidectomy- Mastoidectomy

Tuberculous Cervical AdenitisTuberculous Cervical Adenitis

Most common Cause of LN Most common Cause of LN swelling in neckswelling in neckChildren & young adultsChildren & young adultsPrimary foci – usually tonsilsPrimary foci – usually tonsils90% single LN group usually 90% single LN group usually Deep Jugular chainDeep Jugular chainStages:Stages:

Stage of Lymphadenitis Stage of Lymphadenitis Stage of Periadenitis including Stage of Periadenitis including

“collar stud” “collar stud” abscessabscess Stage of sinus formation Stage of sinus formation

Differential diagnosisDifferential diagnosis

1.Persistent Generalised Lymphadenopathy(PGL)1.Persistent Generalised Lymphadenopathy(PGL)

2.Lymphoma2.Lymphoma

3.Kaposi’s Sarcoma3.Kaposi’s Sarcoma

4.Carcinomatious Metastasis4.Carcinomatious Metastasis

5.Sarcoidosis 5.Sarcoidosis

6.Drug Reaction(eg.Phenytoin)6.Drug Reaction(eg.Phenytoin)

Diagnosis:Diagnosis:- Tuberculin skin test, Tuberculin skin test, - FNAC-70%sensitivityFNAC-70%sensitivity- LN excisional biopsy-LN excisional biopsy-

80% sensitivity 80% sensitivity

- Treatment: ATT+ Treatment: ATT+ excision of LNexcision of LN

Oropharyngeal TuberculosisOropharyngeal TuberculosisSecondary to coughing Secondary to coughing heavily of infected sputumheavily of infected sputum

Oral lesion – not commonOral lesion – not common

-Ulceration :dorsum of tongue-Ulceration :dorsum of tongue

-Painless , -Painless , irregular ,granulating floorirregular ,granulating floor

Pharynx-not commonPharynx-not common- Site of primary infection Site of primary infection

(Tonsils, Adenoids)(Tonsils, Adenoids)

Mycobacterial infection of the Mycobacterial infection of the Salivary glandsSalivary glands

Etiology.: atypical or NTMEtiology.: atypical or NTM

Parotid, submandibular glandsParotid, submandibular glands

Presentation :Presentation : -Children age group 3 – 4 years-Children age group 3 – 4 years

-Painless mass in neck or face-Painless mass in neck or face-Skin breakdown &sinus -Skin breakdown &sinus formationformation

TB Esophagitis:TB Esophagitis:-swallowed sputum or direct -swallowed sputum or direct

spread from adjacent LNspread from adjacent LN

-stricture,fistula, mucosal -stricture,fistula, mucosal irregularitiesirregularities

Granulomatous Granulomatous cheilitis- cheilitis- rarerare

TB LarynxTB Larynx

Nearly always a Nearly always a complication of advance complication of advance cavitatory PTBcavitatory PTB

C/F:C/F:

-Dysphonia-Dysphonia

-Pain on swallowing & -Pain on swallowing & speakingspeaking

-Otalgia-Otalgia

O/EO/E

-Predominantly posterior -Predominantly posterior 1/31/3rdrd of glottis of glottis

-Diffuse redness & -Diffuse redness & edemaedema

-Ulcerations-Ulcerations

Diagnosis:Diagnosis:

-Biopsy of laryngeal -Biopsy of laryngeal tissuetissue

TreatmentTreatment

-Securing airway-Securing airway

-ATT-ATT

ComplicationsComplications

- Stenosis- Stenosis

- Vocal cord fixation- Vocal cord fixation

DIAGNOSISDIAGNOSISSpecimen Specimen

1.1.Sputum- 3 early morning specimenSputum- 3 early morning specimen2.2.Swab- larynx / gastric aspirateSwab- larynx / gastric aspirate3.3.Tissue biopsy :Tissue biopsy :

AFB Microscopy: -Low sensitivity (40 -60)%AFB Microscopy: -Low sensitivity (40 -60)%Culture- definite diagnosisCulture- definite diagnosis

- Lowenstein- Jensen medium: 4 to 8 - Lowenstein- Jensen medium: 4 to 8 weeksweeksBACTEC media –growth 2 weeksBACTEC media –growth 2 weeksDNA amplification/ PCR : allows diagnosis in DNA amplification/ PCR : allows diagnosis in several hoursseveral hours

RadiologyRadiology

Tuberculin skin test- Tuberculin skin test-

Mantoux test, zone of induration after 48- 72 hrMantoux test, zone of induration after 48- 72 hr

TB Skin TestTB Skin Test

Mycobacterium tuberculosis bacteria using bacteria using

acid-fast acid-fast Ziehl-Neelsen stain. .

Colonies of Colonies of M. tuberculosisM. tuberculosis growing on mediagrowing on media

Histopathologic appearance Histopathologic appearance

TB on AFB smearTB on AFB smear

TREATMENT & PREVENTIONTREATMENT & PREVENTION

BCG vaccinationBCG vaccination

ChemotherapyChemotherapy

11STST Line Treatment Line TreatmentRifampicin – Dose- 10mg/kg body wt.Rifampicin – Dose- 10mg/kg body wt.

Isoniazid – Dose-5mg/kg,Administer vitamin B6Isoniazid – Dose-5mg/kg,Administer vitamin B6

Pyrazinamide –25mg/kgPyrazinamide –25mg/kg

Ethambutol – 15mg/kgEthambutol – 15mg/kg

Streptomycin -15mg/kgStreptomycin -15mg/kg

22NDND LINE TREATMENT OR NEWER DRUGS LINE TREATMENT OR NEWER DRUGS

AMINOGLYCOSIDES: Capreomycin,amikacin,kanamicinAMINOGLYCOSIDES: Capreomycin,amikacin,kanamicin

THIOAMIDES: Ethionamide,prothionamideTHIOAMIDES: Ethionamide,prothionamide

PAS(Para-Aminosalicyclic acid)PAS(Para-Aminosalicyclic acid)

CYCLOSERINE (or trizidone)CYCLOSERINE (or trizidone)

FLUOROQUINOLONES-FLUOROQUINOLONES-ofloxacin,ciprofloxacin,sparfloxacin ofloxacin,ciprofloxacin,sparfloxacin &Gatifloxacin,Sparfloxacin-latest(improved activity)&Gatifloxacin,Sparfloxacin-latest(improved activity)

Rifabutin, RifamycinRifabutin, Rifamycin

ThiocetazoneThiocetazone

Rifapentine- latest one 600mg/weeklyRifapentine- latest one 600mg/weekly

Macrolide- clarithromycin. Macrolide- clarithromycin.

Linezolide :Oxazolidinone antibioticLinezolide :Oxazolidinone antibiotic

MDR- MDR- TB TB MDR suspected :MDR suspected :

-History of irregular multi-drug therapy and sputum -History of irregular multi-drug therapy and sputum remaining positive remaining positive

-No good response in a smear positive case put -No good response in a smear positive case put on standard re-treatment regimen. on standard re-treatment regimen. - Sputum - Sputum C/S test C/S test

Causes:Causes:

- inappropriate regimen ,non compliance,interruption of drug - inappropriate regimen ,non compliance,interruption of drug supply,lack of diagnosis and free treatmentsupply,lack of diagnosis and free treatment

XDR-TBXDR-TB

Extensively drug resistant TB:TB that has developed Extensively drug resistant TB:TB that has developed resistance to at least rifampicin & isoniazid as well as to resistance to at least rifampicin & isoniazid as well as to any member of the quinolone family & at least one of the any member of the quinolone family & at least one of the following 2following 2ndnd line anti-TB injectable drugs: line anti-TB injectable drugs: kanamycin,capreomycin or amikacinkanamycin,capreomycin or amikacin

(Global Task Force on XDR-(Global Task Force on XDR-TB,WHO,2006)TB,WHO,2006)

11STST line drug misused, mismanaged line drug misused, mismanaged MDR- TB MDR- TB

22NDND line drug misused, mismanaged line drug misused, mismanaged XDR-TB XDR-TB

POTENTIAL NEWER THERAPIES FOR POTENTIAL NEWER THERAPIES FOR TUBERCULOSISTUBERCULOSIS

Protein kinase inhibitors: pyridomycin, Rifadine Protein kinase inhibitors: pyridomycin, Rifadine

Pyridine analogues like NAD (Nicotinamide adenine Pyridine analogues like NAD (Nicotinamide adenine dinucleotide) and Streptolydigin which inhibits initiation dinucleotide) and Streptolydigin which inhibits initiation of RNA synthesis. of RNA synthesis.

Cytokine Immunotherapy: IL-2- subcutaneous low Cytokine Immunotherapy: IL-2- subcutaneous low dose for patients with active tuberculosis to augment dose for patients with active tuberculosis to augment the immune cell response. the immune cell response. IFN Gammatherapy by aerosol to accelerate IFN Gammatherapy by aerosol to accelerate M.tuberculosis M.tuberculosis killing. killing.

Interleukin-12: for restoring impaired cellular immune Interleukin-12: for restoring impaired cellular immune function in AIDS and tuberculosis. function in AIDS and tuberculosis.

Recent Advances in the Recent Advances in the Diagnosis & Management of Diagnosis & Management of Tuberculosis:Tuberculosis:

1.BACTEC TM 460-liquid culture method1.BACTEC TM 460-liquid culture methoddetects detects radiolabeled CO2 releasedradiolabeled CO2 released

2.MGIT(mycobacterial growth indicator tube)2.MGIT(mycobacterial growth indicator tube)3.PCR3.PCR4.PA-824 :a nitroimidazopyran compound related to 4.PA-824 :a nitroimidazopyran compound related to

metronidazole activity against both slow &rapidly metronidazole activity against both slow &rapidly dividing mycobact.dividing mycobact.may enter human testing may enter human testing soonsoon

5.Rifacinna 5.Rifacinna

6.Benzofuro(2,3-b) quinolone derivative6.Benzofuro(2,3-b) quinolone derivative

7.Interferon gamma release assay(IGRAs)-mtb-7.Interferon gamma release assay(IGRAs)-mtb-specific antigens,ESAT-6 & CFP-10specific antigens,ESAT-6 & CFP-10

8.Dipiperidines8.Dipiperidines

9.Multiplex SNaphot technique-identification of 9.Multiplex SNaphot technique-identification of diff.species of mycobacteriadiff.species of mycobacteria

10.R207910(TMC207)-a lead compound10.R207910(TMC207)-a lead compound

Atypical MycobacteriaAtypical Mycobacteria

Mycobacteria other than M.tuberculosis & M.bovisMycobacteria other than M.tuberculosis & M.bovis

Mycobacteria Other Than Tuberculosis(MOTTS)=Non Mycobacteria Other Than Tuberculosis(MOTTS)=Non Tuberculous MycobacteriaTuberculous MycobacteriaOppurtunistic infection in human beingsOppurtunistic infection in human beingsNon contagiousNon contagious4 groups-based on pigment production & rate of growth4 groups-based on pigment production & rate of growth

1. 1. Photochromogens – yellow orange colonies in light Photochromogens – yellow orange colonies in light eg.M.kansasii , M. marinumeg.M.kansasii , M. marinum

2. Scotochromogens –pigment in dark eg. M scrofulaceum2. Scotochromogens –pigment in dark eg. M scrofulaceum3. Nonchromogens –no pigments,eg.MAC3. Nonchromogens –no pigments,eg.MAC4. Rapid growers –eg M.Fortuitum ,M. chelonei4. Rapid growers –eg M.Fortuitum ,M. chelonei

Mycobacterium LepraeMycobacterium Leprae

Hansen (1868)-first bacterial pathogen of Hansen (1868)-first bacterial pathogen of humans to be describedhumans to be described

Acid fast rodAcid fast rod

Obligate intracellular-can’t be cultured in Obligate intracellular-can’t be cultured in vitro, but in mouse footpadvitro, but in mouse footpad

Optimum temp.growth-less than body Optimum temp.growth-less than body temptemp preference for skin, mucosa & preference for skin, mucosa & superficial nervesuperficial nerve

Transmission- nasal discharge Transmission- nasal discharge

Both Humoral & cellular Both Humoral & cellular immune responseimmune response

Clinically- Chronic Clinically- Chronic granulomatous diseasegranulomatous diseaseskin, skin, peripheral nerve & nasal peripheral nerve & nasal mucosamucosa

ENT PRESENTATIONENT PRESENTATIONEarly involvement of nasal mucosaEarly involvement of nasal mucosaNasal obstruction ,crust formation & blood stained Nasal obstruction ,crust formation & blood stained discharge. discharge.

Atrophic rhinitis, Cartilaginous perforation & Dorsal Atrophic rhinitis, Cartilaginous perforation & Dorsal saddling –late saddling –late

Nasopharynx to oropharynx- Granulomatous lesion, Nasopharynx to oropharynx- Granulomatous lesion, ulcers, healing with fibrosisulcers, healing with fibrosis

Larynx- lesion like TB & SyphilisLarynx- lesion like TB & Syphilis - Supraglottic- mainly epiglottis, aryepiglottic folds- Supraglottic- mainly epiglottis, aryepiglottic folds

-Epiglottis : hollow rod, mucosa studded with tiny -Epiglottis : hollow rod, mucosa studded with tiny nodules- laryngeal stenosis & airway obstructionnodules- laryngeal stenosis & airway obstruction..

TuberculoidTuberculoid LepromatousLepromatous

Cell mediated Cell mediated immune immune systemsystem

Strong CMIStrong CMI Weak CMIWeak CMI

Lepromine Lepromine skin testskin test

++ __

No. of No. of organismorganism

LowLow HighHigh

No. of lesion & No. of lesion & symptomssymptoms

Fewer lesions, Fewer lesions, Macular, nerve Macular, nerve enlargement, enlargement, paresthesiaparesthesia

Numerous lesions- nodular, Numerous lesions- nodular, loss of eyebrows, loss of eyebrows, destruction of nasal septum, destruction of nasal septum, parasthesia, Leonine faciesparasthesia, Leonine facies

Diagnosis:Diagnosis:

Punch biopsy, Punch biopsy, nasal scrapings, nasal scrapings,

skin lesionsskin lesions

& ear lobules& ear lobules

Form Form of of LeprosLeprosy y

WHO Recommended RegimenWHO Recommended Regimen(1982)(1982)

TubercTuberculoiduloid(paucib(paucibacillary)acillary)

Dapsone-100 mg/d,Dapsone-100 mg/d,unsupervised)unsupervised) + +Rifampin-600 mg/month,Rifampin-600 mg/month,supervised for 6 monthssupervised for 6 months

LepromLepromatousatous(multiba(multibacillary)cillary)

Dapsone-100 mg/d+Dapsone-100 mg/d+clofazimine -50mg/d, unsupervised;clofazimine -50mg/d, unsupervised; rifampin-rifampin-600 mg + 600 mg + clofazimine-clofazimine-300 300 mg monthly (supervised)mg monthly (supervised)for 1–2 yearsfor 1–2 years

TREPONEMATREPONEMA

trepos=turn, nema= threadtrepos=turn, nema= thread

Spiral, round or pointed endsSpiral, round or pointed ends

Member of genera SpirochetesMember of genera Spirochetes

subspecies:subspecies:

1.Pallidum- venereal Syphilis1.Pallidum- venereal Syphilis

2.Endemicum - endemic Syphilis 2.Endemicum - endemic Syphilis (bejel)(bejel)

3.Pertenue- Yaws3.Pertenue- Yaws

4.Carateum-4.Carateum- PintaPinta

Treponema PallidumTreponema PallidumThin walled spiral organismThin walled spiral organism

Motile : endoflagella(axial Motile : endoflagella(axial filaments)filaments)

Thin not reliably seen in gram Thin not reliably seen in gram stain,stain,

darkfield microscopy or darkfield microscopy or immunofluorescenceimmunofluorescence

Not grown on bacteriologic media Not grown on bacteriologic media or cell cultureor cell culture

Stages of syphilisStages of syphilis

Nasal SyphilisNasal Syphilis

Primary Syphilis Primary Syphilis

- External nose or Vestibule- External nose or Vestibule

-chancre-rare-chancre-rare

-Self limiting disappears in -Self limiting disappears in 6-10 weeks6-10 weeks

-contagious-contagious

Secondary SyphilisSecondary Syphilis

Most infectiousMost infectious

MUCOUS PATCHES ON THE TONGUE OF A PATIENT WITH SECONDARY SYPHILIS

Tertiary SyphilisTertiary Syphilis

Most common stage of Most common stage of nasal syphilisnasal syphilis

Bony portion of Nasal Bony portion of Nasal Septum Septum

Gumma –pathognomicGumma –pathognomic

punched out ulcerpunched out ulcer

Congenital SyphilisCongenital SyphilisEARLY:EARLY:

first 3mos of life,manifest first 3mos of life,manifest as snufflesas snufflesnasal nasal discharge purulentdischarge purulent

LATE:manifest at pubertyLATE:manifest at puberty

gummatous lesion gummatous lesion destroys nasal structure,destroys nasal structure,

Keratitis,deafness,hutchisoKeratitis,deafness,hutchison’s teethn’s teeth

Syphilitic PharyngitisSyphilitic Pharyngitis

May be congenital or acquired by sexual May be congenital or acquired by sexual intercourseintercourse

Secondary stage most likelySecondary stage most likely

incidence rising– Mainly in HIV positiveincidence rising– Mainly in HIV positive

Primary SyphilisPrimary SyphilisExtragenital sites : lips, Extragenital sites : lips, tongue, buccal mucosa tongue, buccal mucosa and tonsilsand tonsils

Begins as a Papule, Begins as a Papule, breaks down to form a breaks down to form a painless ulcer with painless ulcer with indurated margin indurated margin (chancre)(chancre)

Non tender cervical Non tender cervical lymphadenopathylymphadenopathy

Spontaneous healingSpontaneous healing

Secondary Syphilis Secondary Syphilis -is infectious-is infectious

Hyperemia and inflammation of Hyperemia and inflammation of pharynx and soft palatepharynx and soft palate

Snail Track ulcer :-Oral Snail Track ulcer :-Oral cavity and oropharnyxcavity and oropharnyx

-Ulcerated leison covered with -Ulcerated leison covered with

greyish white membranegreyish white membrane

which when scraped has which when scraped has pink base pink base with with no bleeding.no bleeding.

Tertiary SyphilisTertiary Syphilis

Typically painless .Typically painless .

No lymphadenopathy unless secondary No lymphadenopathy unless secondary infection.infection.

GUMMA are characterstic.GUMMA are characterstic.

- Seen in Hard palate, Nasal - Seen in Hard palate, Nasal septum ,Tonsil ,PPW or larynx.septum ,Tonsil ,PPW or larynx.

VDRL may be negativeVDRL may be negative

EAREAR- TM perforation, granular middle - TM perforation, granular middle ear, COM- if super infection.ear, COM- if super infection.

-Infection mimic TB.-Infection mimic TB.

-Inner ear: Hennebert’s sign , -Inner ear: Hennebert’s sign , Tullio’signTullio’sign

-SNHL, Vertigo, Endolymphatic -SNHL, Vertigo, Endolymphatic hydrops- Fibrous adhesion bet. hydrops- Fibrous adhesion bet. Stapes foot-plate & Labyrinth.Stapes foot-plate & Labyrinth.

Syphilis LarynxSyphilis Larynx

Rarely involvedRarely involved

Secondary & Tertiary more commonSecondary & Tertiary more common

Hoarseness & Dysphagia – commonHoarseness & Dysphagia – common

O/EO/E

- Epiglottis & Aryepiglottic folds - Epiglottis & Aryepiglottic folds principally involvedprincipally involved

DiagnosisDiagnosis1.Immunoflurorescence or dark field microscopy1.Immunoflurorescence or dark field microscopy

2. Biopsy:2. Biopsy:

3.Serology:3.Serology:

Non-treponemal antibody tests:VDRL,RPR,ARTNon-treponemal antibody tests:VDRL,RPR,ART

For screening and treatment follow upFor screening and treatment follow up

Treponema specific antibody tests:for Treponema specific antibody tests:for confirmation,usu.remains positive for life,confirmation,usu.remains positive for life,

FTA-ABS test,TPHAFTA-ABS test,TPHA

Stage of SyphilisStage of Syphilis TreatmentTreatment

Primary, secondary, or earlyPrimary, secondary, or earlylatentlatent

Penicillin G benzathine (singlePenicillin G benzathine (singledose of 2.4 mU IM)dose of 2.4 mU IM)

Late latent (or latent of Late latent (or latent of uncertainuncertainduration), cardiovascular, orduration), cardiovascular, orbenign tertiarybenign tertiary

benzathine Penicillin Gbenzathine Penicillin G(2.4 mU IM weekly for 3 weeks)(2.4 mU IM weekly for 3 weeks)Procain penicillin- 1.2mu for 20 Procain penicillin- 1.2mu for 20 days.days.

Alternative drugsAlternative drugs Doxycycline- 100mg bd/ 15 daysDoxycycline- 100mg bd/ 15 daysErythromycin- 500mg qid for 15 Erythromycin- 500mg qid for 15 days.days.Ceftriaxone1gm/ im/ 7-15 daysCeftriaxone1gm/ im/ 7-15 days

THANK YOUTHANK YOU