CME INDIA Presentation by Dr. Pratik Savaj, DNB Medicine, FID/FNB Infectious disease, IDCC Hospital, Surat.

Primum non nocere/First, do no harm

(Disclaimer: Article is not to criticize anyone. Author believes that maximum learning comes from mistakes done. Some famous drug brands have been mentioned just for simplicity, not for promotion. Author can be contacted on mobile if any error – 9429889450.)

CASE 1: What is inappropriate?

• 54/Male
• PUO
• No clear cause found (PET SCAN and bone marrow examination – normal)
• MT test – positive
• ATT   started

Diagnosis – Latent TB

Latent tuberculosis infection (LTBI)

State of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active TB.

What is Anergy phenomenon?

• Absence of the normal immune response to a particular antigen or allergen.
• In active TB, there is immuosupression.
• In active TB → Mostly negative MT test.

Area of induration

MT Vs IGRA

Both are unable to differentiate latent versus active TB infection

Head-to-head studies showed no evidence that one test should be preferred over the other to assess progression to TB disease.

It would be logical to use both tests for screening for optimal sensitivity in detecting LTBI

Learning points

• Positive MT/IGRA → Latent TB (not active TB).
• Do not start AKT only based on positive test.

CASE 2

• 31 Yr. aged/ Female
• 2015 – Detected HIV 1 positive
• 2016 – TDF+FTC+EFV (irregular)
• 2017 – Pulmonary koch’s (completed 9month of AKT – irregular in-between), stopped ART

• Aug 2020 – fever with chills of 5 days
• CBC – 9.2/3700/1,14,000
• HIV VL – 31 lac copies/ml
• CD4 – 118 (10%)

• HRCT Lungs – diffuse ill-defined distributed throughout bilat lungs
• USG abdomen – moderate splenomegaly with multiple hypoechoic lesions
• ATT was started

• No clinical response with AKT of 2 weeks
• Persistent fever and new onset of abdominal pain was started
• CECT CHEST + ABDOMEN

Splenic granulomas necrotic LN in mesentery, upper mid and lower pre and paraaortic and aortocaval region.

Miliary nodules

• Why miliary TB is not responding to AKT?
• What went wrong?

• Laparoscopy guided mesenteric lymph-node biopsy→  only sent for HPE
• HPE →Histoplasmosis
• She was treated with L-AMB f/b intraconazole
• Improved

Miliary pattern

Lesson learnt

CASE 3

• 45 male with Back-pain – 6 month
• MRI LS spine

CT guided biopsy

• MTB detected (Rif resistance not detected)
• Weight – 68kg
• AKT 4 started
• Pain increased
• Came for consultation after 2 months
• What went wrong?

AKT 4 is suitable for 50 kg

Important point

• Give AKT based on actual weight (book by Burke A Cuha)
• If previous weight is unknow → Calculate ideal weight based on height
• Give full dose from beginning

• Current weight is 68 kg
• Actual weight was 74 kg

Case was prescribed AKT like this

• R-cinex 300/600 1-0-0
• R-cin 150 1-0-0
• Solonex DT 100 1-0-0
• PZA 1000mg 0-1-0
• PZA 750mg 0-0-1
• Ethambutol 600mg 0-0-2

Result

• Clinical + Radiological improvement
• AKT duration – 1 year
• HRZE – 3month
• HRE – 7 months

CASE 4

Routine adding PPI

Lesson learnt

• No PPI
• Rifampicin and INH to be given in fasting phase

CASE 5

Rifampicin kinetics

Other factors – Age, sex, ethinicity, weight, fromulations, GI disorder etc.

Reference: Prerna K Chawla. J Assoc Physicians India. 2016 Aug;64(8):68-72

CASE 6

• 35 yrs. female
• Cervical LN
• No fever or weight loss
• FNAC– HPE – chronic inflammations
• Wait and watch strategy was advised
• What is wrong?

• When this case consulted, asked for total excision biopsy
• GeneXpert – MTB not detected
• HPE – chronic non-specific inflammations
• Bacterial culture – no growth
• TB culture – MTB detected on 42 days
• TB MGIT DST – all drugs sensitive
• Weight based AKT started → Improved

Lesson learnt

• NO FNAC
• Send at least – GeneXpert, TB culture, HPE

CASE 7

• 42 yrs male
• Cervical lymph-node
• Excision biopsy – GeneXpert – MTB detected and (Rifa resistance not detected)
• Weight based AKT started
• Good clinical improvement and after 1 month increase in size and pus discharge

Suspected MDR koch’s

• 2nd line AKT started
• But no improvement
• Why?

Final diagnosis – Paradoxical response

• Culture guided AKT
• Weight based AKT
• 100% adherence
• Initial improvement
• Later worsening – increase size and pus discharge
• Treatment given – switch back to 1st line AKT and naproxen 500mg BD was given for 4 week
• Recovered

Paradoxical response

• Lymph-node Koch’s (inflammations with
• increase pus discharge)
• CNS Koch’s (increase peri-lesional edema)
• Pleural effusion (increase effusion – neutrophilic)

Lesson learnt

Rule out paradoxical response before labeling MDR koch’s

CASE 8

• 21 /M, engineer student had sports injury (ACL rupture)
• Arthroscopic repair was done
• After 1 month – pain and swelling
• Intra op tissue Gene xpert – MTB not detected
• Bacterial culture – No growth
• HPE – granulomatous inflammations

AKT 4 was started

• No improvement
• Persistent clinical deterioration
• ID opinion was taken Debridement and removal of screw

Final diagnosis – NTM infection (Nontuberculous mycobacteria)

Septic arthroscopic post arthroscopic surgery

• Post arthroscopic or laparoscopic procedure
• AFB positive + GeneXpert – negative
• Granulomatous inflammations

Which procedure commonly associated with NTM infections?

Treatment

• One Aminiglycoside (Amikacin preferred) – 2 week
• One macrolide (Clarithromycin preferred) – 6 month
• With one drug with good susceptibility (Our data showed good susceptibility with linezolid) – 6 month
• Other drug can be used are – Minocycline, TMP-SMX, clofazimne, tigecycline

Why more nosocomial?

• NTM has been isolated from man-made water systems
• NTM frequently exist within biofilms that coat internal surface pipes and fixtures of water distribution systems and storage tank
• Highest rates of NTM colonization in potable water systems are found in hospitals and hemodialysis and dental offices
• Use of colonized aqueous solutions and inadequate sterilization or disinfection of surgical equipment
• Multiuse topical anesthetic spray
• Contamination in microbiology and pathology laboratories has also resulted in pseudo-outbreak

Scopy and NTM

• Bronchoscope suction valves and channels are difficult to clean and disinfect, and they become colonized with mycobacteria, which may lead to the transmission of disease to previously uninfected patients
• Damage to the suction channel is hard to detect, and it predisposes to NTM colonization
• Common practice of using tap water for cleaning and putting scope in 2% glutaraldehyde which was used repeatedly and become diluted

Prevention

• Manual precleaning of endoscopes with a neutral detergent prior to disinfection is vital and results in up to a 4-log reduction in number of organisms
• Iodophors may be used to disinfect endoscopes, but longer contact times may be required
• Endoscope disinfection achieved with 2% concentration when contact time is 20 min at 20 degree and manual precleaning and final alcohol rinse performed

Hospital water systems

• Chlorine at high concentrations (1 mg/L) is mycobactericidal, but concentrations of 0.15 mg/L are ineffective
• Temporarily increasing water temperature to
• >70C combined with flushing all faucets and showers was used to control M. xenopi colonization
• Installation of filters or periodic flushing of water systems

CASE 9

• 25 yr old female
• Fever, cough and breathlessness
• HRCT – Milliary Koch’s
• P/h/o Koch’s – Pulmonary Koch’s (defaulter)
• Sputum sent for geneXpert

GeneXpert – MTB detected, Rif.   resistance detected

• What now?
• Which AKT to start
• Which is best 2nd line AKT for our patient

GeneXpert XDR panel

Lesson learnt

• There is no ideal 2nd line AKT
• Start AKT based on GeneXpert XDR panel or LPA and TB culture DST
• Always ask for DST of all anti TB drugs

CASE 10

• 26/F
• Admitted on with fever, increased headache, backache, and diplopia on looking to the left
• 4 month ago – Low grade fever, headache

Multiple REL

Dural enhancement at LS spine

CSF was done

Routine

• Sugar – 89
• Proteins – 321
• Cells – 400, N-23, L – 67
• ADA – 13.2

1st line AKT started with steroids

After 1 month – severe headache, drowsiness

What to do next?

• 2nd line AKT?
• Steroids to restart?

CSF sent for pyrosequencing

Final diagnosis – paradoxical response

• Steroids increased
• Thalidomide added
• Improved

When to ask pyrosequencing?

• Rapid diagnosis of Koch’s with susceptibility
• Discordance between geneXpert and TB culture
• Differentiation between MDR vs PR

CSF pyrosequencing is significantly more sensitive than Xpert MTB/Rif and TBMGIT culture for diagnosing TBM. Additionally, it facilitates early therapeutic decision-making by providing information on XDR-defining mutations.

Reference: Ajbani K, Kazi M, Agrawal U, Jatale R, Soman R, Sunavala A, Shetty A, Rodrigues C. Evaluation of CSF pyrosequencing to diagnose tuberculous meningitis: A retrospective diagnostic accuracy study. Tuberculosis (Edinb). 2021 Jan;126:102048. doi: 10.1016/j.tube.2020.102048. Epub 2021 Jan 2. PMID: 33421910.

Quick Take-Aways

• No treatment based on positive MT or IGRA test
• Miliary nodules is a broad diagnosis
• Dose based on actual weight/ height
• No routine PPI/antacids with AKT
• Individualized AKT better than FDC
• Send precious sample for needed report
• Think about paradoxical response
• All granulomatous inflammations are not TB (think NTM when it is post procedure)
• Design regimen based on genotypic and phenotypic DST
• Use experimental investigations and take help of ID specialist.

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