Transcript MDR/XDR Tuberculosis and Atypical Mycobacterial Disease

MDR/XDR Tuberculosis and Atypical
Mycobacterial Disease
Increasing Role for Surgery, Relearning Old Lessons
John D. Mitchell, M.D.
Professor and Chief
Section of General Thoracic Surgery
Davis Endowed Chair in Thoracic Surgery
University of Colorado School of Medicine
Consultant, National Jewish Health
AATS Postgraduate Course, April 26th, 2015
No relevant financial relationships to disclose.
Case Presentation: XDR+ Tuberculosis
History
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38 yo male Armenian immigrant
Lived in Russia 2001-2005; last visit 4 years prior
No known history in Russian Prison System
Ankylosing Spondylitis, prior GSW to abdomen
Alcoholic, smoker 1.5 packs/day
History of recurrent pneumonias, AFB (-)
July 2013: Started on Remicade for AS, INH for LTBI
Dec 2013: Fevers, productive cough; AFB (+)
Diagnosed with drug resistant TB
Case Presentation: XDR+ Tuberculosis
Initial Drug Regimen
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PZA 1500 mg po qday
Moxifloxacin 600 mg po qday
PAS 4 gm po bid
Linezolid 600 mg po qday
Ethionamide 250 mg qAM, 500 mg qPM
Cycloserine 250 mg po bid
Capreomycin 750 mg (12 mg/kg) IV qMon-Fri
Meropenem 2 gm IV q8h
Augmentin 500 mg po bid
Case Presentation: XDR+ Tuberculosis
Drug Sensitivity Testing (CDC)
Case Presentation: XDR+ Tuberculosis
Revised Drug Regimen
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Linezolid 600 mg IV q24h
Cycloserine 250 mg po bid
Imipenem 1 gm IV q12h
Moxifloxacin 800 mg IV q24h
PAS 6 gm po bid
Bedaquiline 400 mg po qday
Clofazimine 100 mg po qday
Case Presentation: XDR+ Tuberculosis
Treatment Course
• Eventually rendered sputum culture (-)
• Significant medication toxicities
• Debilitated, malnourished
What is the role of surgery in this patient?
Mycobacterium Tuberculosis
General Principles
• Up to one-third of world’s population infected with
mycobacterium tuberculosis
• Typical treatment regimens for drug-sensitive TB last
6 to 9 months
– INH, rifampin, PZA, ethambutol
– Duration and specific regimen depend on pattern of disease
and drug sensitivities, speed of culture conversion
• Chemotherapy usually curative; use of surgery rare
Worldwide Drug-Sensitive TB Treatment Success
2012
Worldwide Incidence of Tuberculosis
December, 2013
Estimated number
of cases, 2013
All forms of TB
HIV-associated TB
Multidrugresistant TB
9.0 million
(8.6–9.4 million)
Estimated number
of deaths, 2013
1.1 million*
(1.0–1.3 million)
1.1 million
360,000
(1.0–1.2 million)
(310,000–410,000)
480,000
210,000
(350,000-610,000)
(130,000–290,000)
* Excluding deaths attributed to HIV/TB
WHO Global Tuberculosis Report 2014. http://www.who.int/tb/publications/global_report/en/index.html
Multidrug and Extensively Drug Resistant
Tuberculosis
9 million TB cases
Drug Susceptible
Any Drug
Resistance
MDR-TB XDRTB
Resistance to at least isoniazid and rifampin (MDR) plus
resistance to fluoroquinolones and one of the second-line
injectable drugs (amikacin, kanamycin, or capreomycin)
New Diagnostic Tests for MDRTB
Xpert MTB/RIF Assay
• Automated PCR test that
detects TB and rifampin
resistance
• 2 hour turn around time
• Allows Point of Care
diagnosis, treatment
• Funded by Gates
Foundation, NIH
Designing a Treatment Regimen for MDRTB
General Principles
• Early DR-TB detection/prompt initiation of therapy
• Regimens should be based on:
the history of drugs taken by the patient
• drugs and regimens used in the country and
• the prevalence of resistance
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• Regimens should consist ≥ 4 effective drugs
• When possible, once daily dosing is recommended
• Drug dosage should be determined by body weight
WHO Guidelines for the Programmatic Management of Drug-Resistant TB2008
Worldwide MDRTB Treatment Success
2009
WHO Global Tuberculosis Report 2012. http://www.who.int/tb/publications/global_report/en/index.html
Worldwide XDRTB Treatment Success
2011
WHO Global Tuberculosis Report 2014. http://www.who.int/tb/publications/global_report/en/index.html
Drug Resistant Tuberculosis
Predictors of Success and Failure
Success
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Use of pyrazinamide and/or
ethambutol, if susceptible
Use of a fluoroquinolone
Use of > 5 drugs
Sputum conversion by 2 mos
Surgical resection
Failure
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Previous therapy
Number of drugs resistant
Resistance to FQN
Resistance to capreomycin
Presence of cavitation
Low BMI
HIV infection
Poor adherence
Positive cultures at 2-3 mos
XDR-TB
Surgery for MDR-TB, XDR-TB
Factors favoring Surgery
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A pattern of drug-resistance so extensive that it
compromises the likelihood of medical cure
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Localized lung damage (cavitation, destroyed lung) that
might be a focus of persistent disease and/or further
acquired resistance
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Allergies or intolerance to essential medications that
might afford cure
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Lack of access to curative chemotherapy
Surgery for MDR-TB
Current Results
Surgery for MDR-TB
Current Results
Xu HB, et al. J Antimicrob Chemother 2011; 66: 1687–1695
Role of Surgery in MDR-TB
NJH Experience
Odds Ratios for Individual Variables
Favorable
Unfavorable
log OR
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-0.5
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1.5
2
Drug resistance (#) p<0.0001
Current drug suscept. (#)
p=0.0004
p=0.0008
Surgery done
FQN used
Non-extensive disease
p=0.02
p=0.48
Chan ED, et al. AJRCCM 2004:169:1103
Surgery for MDR/XDR-TB
Republic of Georgia
Vashiakidze S et al. Ann Thorac Surg 2013;95:1892
Nontuberculous Mycobacteria (NTM)
• AKA:
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Atypical mycobacteria
Environmental mycobacteria (EM)
Mycobacteria other than tuberculosis (MOTT)
Found in water, soils, food, on surfaces
Resistant to chlorination, disinfectants
Not obligate pathogens
No person to person disease transmission
Nontuberculous Mycobacteria
Comparison with Tuberculosis
AFB (+)
TB
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Person to person transmission
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Reportable disease
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Incidence increasing in US
Significant drug resistance seen
NTM
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Nontuberculous Mycobacteria
Common NTM Species
• Slow growing mycobacteria
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M. avium complex (MAC)
M. kansasii
M. xenopi
M. simiae
• Rapid growing mycobacteria
– M. abscessus
– M. fortuitum
– M. chelonae
Nontuberculous Mycobacteria
Common NTM Species
• Slow growing mycobacteria
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M. avium complex (MAC)
M. kansasii
M. xenopi
M. simiae
• Rapid growing mycobacteria
– M. abscessus
– M. fortuitum
– M. chelonae
Nontuberculous Mycobacteria
Therapy
• Therapy directed in part by susceptibility testing, and
should be continued 12 months after Culture (-)
• MAC: macrolide, rifampin, ethambutol, ± amikacin
• M kansasii: rifampin, ethambutol, INH ± macrolide
• M abscessus: macrolide, amikacin, cefoxitin, imipenum
• Indications for surgery include persistent, focal
(cavitary or bronchiectatic) parenchymal disease after
antimicrobial treatment
Surgery for Pulmonary NTM Disease
Presentation
• Middle-aged females, thin,
Caucasian, nonsmokers, right
middle lobe / lingular disease
• Isolated large, thick-walled
cavitary disease.
• Elderly men, smokers, ETOH
abuse, underlying COPD.
Resembles TB, may progress
to complete lung destruction.
Surgery for Pulmonary NTM Disease
Presentation
• Middle-aged females, thin,
Caucasian, nonsmokers, right
middle lobe / lingular disease
• Isolated large, thick-walled
cavitary disease.
• Elderly men, smokers, ETOH
abuse, underlying COPD.
Resembles TB, may progress
to complete lung destruction.
Surgery for Pulmonary NTM Disease
Presentation
• Middle-aged females, thin,
Caucasian, nonsmokers, right
middle lobe / lingular disease
• Isolated large, thick-walled
cavitary disease.
• Elderly men, smokers, ETOH
abuse, underlying COPD.
Resembles TB, may progress
to complete lung destruction.
Surgery for Pulmonary NTM Disease
Results of Surgical Therapy
• Corpe, 1981: 131 cases, mortality 6.9%, BPF 5.3%,
93% sputum conversion rate
• Nelson, 1998: 28 cases, mortality 7.1%, BPF 3.6%,
complication rate 32%, 88% sputum conversion rate
• Shiraishi, 2002: 21 cases, mortality 0%, complication
rate 29%, sputum conversion 100% → 90% at 2 years
• Mitchell, 2008: 265 cases, mortality 2.6%, complication
rate 18%, BPF 4.2%, 87% sputum conversion rate
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Procedures
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1983-1990
1991-2000
2001Mitchell JD et al Ann Thor Surg 2008;85(6):1887
Surgery for Pulmonary NTM Disease
BPF after Pneumonectomy
Shiraishi, 2010: MDR-TB vs. NTM pneumonectomy
• No operative mortality
• MDR-TB: 22 patients (7 right, 15 left)
– Male 72%, Sputum negative 63%
– BPF rate 4.5% (1 right)
• NTM: 11 patients (7 right, 4 left)
– Female 72%, Sputum negative 9%
– BPF rate 45% (4 right, 1 left)
Shiraishi Y et al. ICVTS 2010;11:429
Lung Resection
Infectious vs. Malignant Lung Disease
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Adhesions
Hypertrophied bronchial circulation
Lymphadenopathy
Dissection in hilum / around vessels
Avoid spillage from cavities
Space vs. no space
Buttressing bronchial stump
Send cultures!
Anatomic complete resection is the goal
Surgery for MDR-TB, XDR-TB
Summary
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Surgical resection in MDR/XDR TB and NTM disease
may lead to improved outcomes in selected cases
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Lung resection and muscle flap use often possible using
modern minimally invasive techniques
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Coordination of care best approached in
multidisciplinary environment
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Resection for infectious lung disease differs from
resection for cancer: experience counts