California TB Controllers Association Case Conference

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California TB Controllers AssociationCase
Conference

• Antonino Catanzaro, M.D.
• Professor of Medicine,UC San Diego
• John Renner, M.D.
• Professor of Radiology, UC San Diego
• Mark Tracy, M.D.
• Kathleen Moser, M.D.
• Nickolas Toth, M.D.
• Tim Rodwell, M.D.

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Case 1 The Fence Jumper

• 47 y/o Latin American Man referred to TB clinic
  for evaluation of gross hematuria
• Episodic, painless, gross hematuria for 5 months
• ROS
• Episodic, dry cough for 2 weeks
• Episodic fevers
• Chronic, diffuse abdominal pain
• 30 pound weight loss over one year
• PMH
• Cirrhosis diagnosis 1997
• Hospitalization for ascites in 2006
• Open reduction Internal fixation right ankle in
  2000

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Case 1The Fence Jumper

• Physical Exam
• Weight-85.5 kg.
• Used cane to ambulate due to chronic right ankle
  pain
• Abdomen-RUQ tender without mass or organomegaly
• No physical findings suggestive of chronic liver
  disease
• Genital-normal
• TST-20mm.

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Case 1The Fence Jumper

• LFTs-normal
• PT and INR-normal
• CBC and platelets-normal
• Urinalysis-Protein 3, WBC-30-40, RBC-20-25
• Sputum
• AFB smear negative x 3
• MTDs positive
• Urine
• AFB
• INH, Rifampin, Ethambutol initiated

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Case 1The Fence Jumper
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Case 1The Fence Jumper Follow up at 2 weeks

• M. tuberculosis complex identified in cultures of
  the sputum, urine, and stool
• Pure cultures for antibiotic susceptibility
  studies delayed
• Mutations associated with INH resistance not
  detected
• Mutations associated with Rifampin resistance not
  detected

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Case 1The Fence Jumper 2 month follow up

• M. Bovis identified susceptible to INH and
  Rifampin
• Ethambutol stopped INH and Rifampin continued
  for another 7 months
• Patient seen by orthopedic surgeon who recommends
  ankle arthroplasty

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Case 1The Fence Jumper
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Case 1The Fence Jumper
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Case 1The Fence Jumper 2005
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Case 1The Fence Jumper 2006
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Case 1An Example of disease due to M. bovis
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Case 1An Example of disease due to M. bovis
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Case 1The Fence Jumper

• Since 2000
• 450 to 500 migrants have died each year as a
  direct consequence of an attempted illegal entry
  along the U.S./Mexico border
• LAST decade
• 180 mile stretch of fence
• increased from 8-10 feet to 18-20 feet
• Coincident
• UC San Diego Level-1 Trauma Center
• observed a marked increase in the number of
  undocumented immigrants admitted with injuries
  related to falls or jumping from the US-Mexico
  border fence
• Between 2000 and 2006
• 186 fence jumpers were treated at UCSD for
  serious trauma
• five sustaining fatal injuries

Personal Communications Dr Linda Hill
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Case 1The Fence Jumper

• Discussion

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Case 2A Class B1 Alien (TB, active,
noninfectious)

• AB. is a 69 years old Filipina woman who arrived
  in the USA on 10/09/06 from the Philippines.
• History
• First episode of active TB diagnosed in 2001
• Treated with injections multiple medications
  names unknown
• The injections were discontinued after one month
  she stopped the pills after two months.
• Second episode of active TB diagnosed in 2005.
• Treatment was the standard six month regimen by
  DOT.
• Family History
• Her parents sister also had  active TB.

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Case 2A Class B1 Alien (TB, active,
noninfectious)

• Upon arrival in October 2006 patient presented _at_
  our clinic
• She was an elderly cachectic frail individual
  who was not in acute pain.
• Three sputa were collected which showed 1 AFB
  smears on all three slides, confirmed by
  Ziehl-Neelsen.

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Case 2A Class B1 Alien (TB, active,
noninfectious)

• CXR showed emphysematous lung fields with
  extensive scarring of the upper lobes a streak
  of atelectasis was noted in the RML These
  findings were essentially unchanged when compared
  to the foreign films..

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Case 2A Class B1 Alien (TB, active,
noninfectious)

• Standard 4-drug regimen was initiated.
• Preliminary cultures were reported by the Public
  Health Lab "an organism has been isolated
  resembling M. TB-complex

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Case 2A Class B1 Alien (TB, active,
noninfectious)

• A week later the patient returned to the Clinic
  co/of NV,
• She appeared acutely ill. Her bilirubin was
  slightly elevated
• EKG demonstrated premature ventricular
  contractions.
• INH RFM were stopped
• the patient remained on home isolation.
• Compazine was prescribed to control nausea.

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Case 2A Class B1 Alien (TB, active,
noninfectious)

• Pt. returned a week later feeling much better,
• A new set of AFB smears were negative she was
  taken off isolation
• Pt. returned a week later asking permission to
  attend her sister's funeral in her native country
  during Thanksgiving. Request was granted..

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Case 2A Class B1 Alien (TB, active,
noninfectious)

• The culture specimen was forwarded to the State
  Laboratory for further analysis.
• DNA test for of M. TB complex negative
• molecular beacon
• Accuprobe for MTB Complex also negative
• The new set of cultures grew out M.
  Chelonea/Absessus Complex..

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Non tuberculous mycobacteriaAtypical Mycobacetia

• Runyon classification based on colonial
  morphology
  out of date
• Group I
• Photo chromogen
• Group II
• Scoto chromogen
• Group III
• Non chromogen
• Group IV
• Rapid growers

• Species based on DNA sequencing gt150 species
• More common NTMs
• M avium intracellulare complex MAC
• M. kansasii
• M. abcessus
• M. fortuitum
• M. cheloni
• Rapid growing mycobacteria (RGM)
• Less Common Organisms
• M gordonae
• M. malmoense
• M. simiae
• M. szulgai
• M. smegmatis
• M. xenopi
• M. celatum
• M. marinum
• M. grnavense
• etc

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INFECTION vs DISEASE due to NTM
NTM 1.8/100,000

• Frequency of disease when NTM isolated
• 45
• 75
• 18

• Relative frequency of isolation NTM
• M avium intracellulare complex 61
• M. kansasii 10
• M. fortuitum/cheloni complex 19
• Less Common Organisms 10
• M gordonae
• M. malmoense
• M. simiae
• M. szulgai
• M. smegmatis
• M. xenopi

Good JID 1980 1982 OBrien ARRD 1987
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M. abscessus

• Skin soft tissue or bone
• Usually follows trauma or surgery
• Purple nodules
• Pulmonary
• 80 of RGM
• Risk factors
• gt60 years old
• Caucasian
• Female
• non smokers
• Prior mycobacterial disease
• Bonchiectasis
• Radiology
• Multilobar
• Patchy
• Reticulonodular
• With upper lobe preponderance
• Cavitation in 15

• Treatment
• Resistant to RIPE
• Must do sensitivity testing
• Sensitive
• Clarithromycin 99
• Amikacin 90
• Cefoxitin 70
• Imipenem 50
• Extrapulmonary Disease
• Clari 1000 or azithro 250
• Amikacin IV Rx daily or even 3/wk after 3 weeks
• Cefoxitin or imipenem
• Minimum 4 mos
• 6 mos for bone
• Surgery if feasible
• Pulmonary Disease
• There is no cure
• Best hope to control symptoms
• May give periodic rounds of Rx as above

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Case 2A Class B1 Alien (TB, active,
noninfectious)

• Upon returning to the USA after Thanksgiving the
  patient presented with cough, fever extreme
  prostration.
• TB drugs were stopped the patient was sent to
  the E.R.,
• She was treated with IV Amicacin Cefoxitin,
  which  was continued on home IV therapy using
  PICC for  M. Chelonea bronchietasis.

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Case 2A Class B1 Alien (TB, active,
noninfectious)

• Pt suffered drug toxicity
• She has sustained a significant hearing loss
• dosages had to be adjusted
• oral Clarythromycin was added to the regimen.
• May of 2007
• she has reliably converted therapy was stopped
• Recent follow up
• Pt is surviving but quite sick.

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• Discussion

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Case 3 The Eloeser Case

• 40 yo male with history of IV drug use/crystal
  meth, Type II diabetic
• Feb 8, 2005
• Presented to govt health center in Mexicali with
  productive cough, fever, malaise x 7 months
• AFB 3 (no culture, no CXR)
• Started Rifater (IRP) Ethambutol, self
  administered.
• April 7, 2005
• AFB negative, gained 4 lbs, reduced sx
• Changed to Rifinah (IR) EMB, self-administered
• June 1, 2005
• AFB 1
• Placed on Rifater EMB Streptomycin
• Rifinah EMB after 2-3 months
• Self-administered, except injectable given at the
  local health center
• Smear negative by June 30, 2005
• November 15, 2005

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Case 4 The Eloeser Case

• January 9, 2006 (2 months later)
• Returned to local health center with productive
  cough, fever, 4 lb weight loss, SOB
• 3, no culture
• February 2006
• HIV negative
• Rifater EMB Strep restarted (SAT)
• March 2006 specimen sent to Tijuana Hospital lab
  for cx/DST
• June 2006
• DSTs from March specimen
• Resistant to I, R, S Sensitive to EMB
  Not tested to PZA
• Regimen changed to Rifater EMB Cipro
  Amikacin twice weekly
• Pt had to buy the Cipro (30/8 tab)
  
• ? July Oct 2006 remained smear positive
  

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MS 10/2006
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MS

• November 28 2006
• Presented to the emergency room
• R-sided empyema
• Drainage/chest tube
• Sputum smear negative and fluid smear negative,
  no culture TB treatment considered completed
  (Feb Nov, 2006 10 months)

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MS 11/2006
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MS 12/18/06
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MS 12/19/2006
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1/2007
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MS 1/11/2007
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Case 4 The Eloeser Case

• December 2006
• Seen at the hospital as an outpt, Smear
• DST sent to Imperial County Public Health Lab
• No growth, beacon showed IR mutations
• Jan May 2007 Increased symptoms, Rifater
  Amikacin x 2 months, Proth/PZA/Cipro/Kana for 4
  days
• June 2007
• Increasingly symptomatic, 20 lb weight loss
• 2/27/07 specimen sent to San Diego County PHL
  reported
• S INH (0.4), EMB, CAP, Levo, Strep.
• R INH (0.1), RIF, PZA, Ethio
• S (from National Jewish) Cyclo, PAS, Kanamycin
• Admitted to the hospital, Eloesser procedure
  performed

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Case 4 The Eloeser Case
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Case 4 The Eloeser Case
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MS 2-19-07
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Date reported as June 2007
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Case 4 The Eloeser Case
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Case 4 The Eloeser Case

• August 27, 2007 (97 kg)
• 4 smear
• Started EMB 1400mg (15mg/kg), Cycloserine 250mg
  twice a day, PAS 4gm BID, Moxi 400mg, Kanamycin
  1000mg (AK 1000mg 12-07)
• Oct 07 PAS level 19.7 (10-60mcg/ml), Cyclo
  level25.6 (20-35)
• Bacteriology
• Sept 07 4 culture positive
• Oct 07 4 culture positive
• Dec 07 4 culture positive
• Resistant to INH 0.1, Rif, EMB, Ethio Sens to
  INH 0.4, PZA, Capreo, Levo
• Jan 17 08 Smear neg, culture neg at 5 wks
• Feb 19 08 Smear negative
• Jan 2008 (86 kg)
• ?EMB 1800mg, ?PAS 8gms qam ?4gms qpm,
• ?Moxi 600mg, Cyclo 500mg, AK 1000mg

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MS 2-15-08
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Questions

• Comments on surgery
• What is the best treatment regimen at this point?
  
• What doses?
• How long to maintain injectable?
• D/C EMB?
• Start PZA?
• Start INH at what dose?

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Case 4 Internacional Medical Care

• 25 y/o Latina adult female
• Patient lives and works in San Diego area
• Presented to her physician in Tijuana June 2006
• Chronic, dry cough
• Anorexia
• 10 pound weight loss
• Chest x-ray abnormal

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Case 1 Internacional Medical Care

• AFB smear positive
• Diagnosed with TB
• On 6/27 started
• Ethambutol 1200 mg Q noon
• Rifater 4 tablets QD
• Rifater INH xxx mg
• Rifampin xxxxmg
• PZA xxxx mg
• Patient placed on home isolation

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Case 4 Internacional Medical Care

• Patient has been let go by employer after the
  Tijuana physician explained to the employer her
  need to be off from work for one month
• Since she was no longer employed she lost her
  employer provided health insurance

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Case 4 Internacional Medical Care in San Diego

• Symptoms resolved
• No previous TB treatment
• Family History noteworthy
• Aunt had TB diagnosis and treatment 1998
• This patient was not identified as contact
• Chest x-ray

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Case 1 Internacional Medical Care

• CXR

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Case 4 Internacional Medical Care in San Diego

• INH, Rifampin, Ethambutol, PZA continued
• HIV negative
• Sputum AFB 2

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Case 4 Internacional Medical Care in San Diego

• M. tuberculosis positive culture susceptible to
  INH, Rifampin, PZA
• Completed two months of HRZ then
• Continued with four months of HR
• Genetic match with her aunts organism