Non-Tuberculous Mycobacteria Case Reports. Alana Sterkel, PhD University of Wisconsin Hospital and Clinics Nov. 17, 2016

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1 Nn-Tuberculus Mycbacteria Case Reprts Alana Sterkel, PhD University f Wiscnsin Hspital and Clinics Nv. 17, 2016

2 Overview Review f NTM Case 1 Case 2

3 Nn-Tuberculus Mycbacteria Ubiquitus rganisms Fund in sil and water Need t crrelate with clinical picture Opprtunistic infectin Mst patients are immune cmprmised r have preexisting damage Prevalence increasing wrldwide Adjemian et al and CDC Advances in diagnstic technlgy and enhanced cntrl f Tuberculsis has made it clear that ther mycbacteria can cause similar disease

4 Clinical Syndrmes Prgressive pulmnary disease Lymphadenitis Disseminated disease Skin and sft tissue infectins

5 Nn-Tuberculus Mycbacteria Over 125 different species ~40% dcumented t cause disease in humans Park, Chul Min, et al. Kr J Lab Med. 2006

6 Runyn Classificatin Phtchrmgens M. marinum Sctchrmgens M. grdnae Nn-chrmgens M. avium cmplex Rapid grwers (5-7 days) M. frtuitum M. chelnae M. abscessus

7 Case 1 Recalcitrant

8 Patient Histry 52 year ld man presents after a few mnths f prductive cugh and a 40 lb unintentinal weight lss. Asthma and a 2.5 pack/day smking histry. Smked since he was 14 and bth parents died f lung cancer. N significant travel histry, animal expsure, r sick cntacts. N histry f sterids use r ther immune suppressants Otherwise healthy man with remte medical histry f a knee surgery and back surgery mre than 10 years prir.

9 On presentatin Patient feels he is drwning in phlegm Bld seen in sputum n several ccasins Des nt imprve n rutine antibitics Cavitary lesin seen n X- ray Despite a lack f expsure histry he is presumed t have Tb

10 1-3 mnths since presentatin He is started n RIPE therapy Rifampin Isniazid Pyrazinamide Ethambutl Quantifern Gld rdered and sputum cultures sent Quantifern Gld negative Sputum smear psitive fr AFB PCR negative fr Tuberculsis RIPE therapy stpped Sputum culture eventually identifies Mycbacterium szulgai RIPE therapy restarted Referred t UW Hspital fr management

Szulga wh develped the lipid identificatin methd that helped t describe this pathgen.

11 Mycbacterium szulgai Dark Light Unusual cause f disease Very rarely islated frm envirnmental surces Nearly always clinically relevant First described in 1972 by Marks and Jenkins and named after Dr. Szulga wh develped the lipid identificatin methd that helped t describe this pathgen. Clnies are slw grwing days Sctchrmgen at 37 C and phtchrmgen at 25 C Only Mycbacteria t d this Des nt grw at 42 C Phtchrmgen at 25 C Dark Light Sctchrmgen at 37 C Margie Mrgan. Mycbacterilgy 2016 Marks J, Jenkins PA, Tsukamura M. Mycbacterium szulgai a new

12 Mycbacterium szulgai Often present like pulmnary Tuberculsis Seen in wunds less frequently Mst cmmn: upper lbe cavitatin in lder men with sme kind f lung damage Generally susceptible hwever, they tend t be mre resistant t isniazid

13 3 mnths frm presentatin Antimicrbial susceptibility testing is rdered Patient wrked up fr immune defects Negative fr HIV, nrmal T cell cunts, n unusual illness as a child. N apparent immune defect Damage frm heavy smking and asthma? Patient is highly encuraged t quite smking and is given resurces t assist with this. Patient instructed t cntinue antibitics until susceptibilities return

14 CT scan 3 mnths frm presentatin Frnt view Side view Large cavitary lesin n upper right lbe Bttm up view

15 Mycbacterium szulgai susceptibility testing Drug Amikacin Capremycin Ciprflxacin Clarithrmycin Cyclserine Ethambutl Ethinamide Isniazid lw Isniazid high Kanamycin PAS Rifampin Streptmycin lw Streptmycin high Results Resistant Key Intermediate Resistant

16 6 mnths frm presentatin Decreases smking Feeling better Gaining weight Less phlegm Less hemptyses Repeat sputum cultures remain psitive fr M. szulgai

1 year frm presentatin Patient has a heart attack Has stent placement Started n bld thinners Diagnsed with crnary artery disease Repeat sputum

17 1 year frm presentatin Patient has a heart attack Has stent placement Started n bld thinners Diagnsed with crnary artery disease Repeat sputum cultures remain psitive fr M. szulgai Patient indicates he des nt always take his antibitics. Is nt interested in changing his antibitic regimen.

1 year frm presentatin Patient has resumed smking 1.5-2.

18 1 year frm presentatin Patient has resumed smking pack/day Endrses headaches and stmach pain Indicates pr cmpliance with antibitics Persistent infectin and increasing ndularity prmpt discussin f lung lbe resectin Due t bld thinners and recent heart attack surgery is declined Culture remain psitive fr M. szulgai New susceptibilities run

19 Mycbacterium szulgai Susceptibility Testing Drug At presentatin 1 year later Amikacin Capremycin Ciprflxacin Intermediate Clarithrmycin Cyclserine Ethambutl Ethinamide Isniazid lw Resistant Resistant Isniazid high Intermediate Kanamycin Resistant Levflxacin Linezlid Mxiflxacin Oflxacin PAS Resistant Rifampin Streptmycin lw Resistant Streptmycin high Key Intermediate Resistant Increased resistance

20 1.5 years frm presentatin Patient is lst t fllw-up fr a few mnths Patient has truble eating and has wrsening GI discmfrt. Blames antibitics and stps therapy Fr next 6 mnth he intermittently takes his antibitics. Off and n fr abut 4 days at a time when he feels bad Stps again when he feels stmach discmfrt

21 2 years Patient returns t the clinic Clinician stresses the imprtance f antibitics Recmmends changes t therapy t help with tlerance and circumvent new resistance patterns. Patient refuses t change his antibitic regimen Surgery is discussed and declined by the patient Culture remains psitive fr M. szulgai New susceptibilities run

22 Mycbacterium szulgai Susceptibility Testing Drug At presentatin 1 year later 2 years later Amikacin Capremycin Ciprflxacin Intermediate Intermediate Clarithrmycin Cyclserine Ethambutl Ethinamide Isniazid lw Resistant Resistant Isniazid high Intermediate Kanamycin Resistant Levflxacin Intermediate Linezlid Mxiflxacin Oflxacin Resistant PAS Resistant Rifampin Streptmycin lw Resistant Streptmycin high Key Intermediate Resistant Increased resistance

23 2.25 years Patient indicates he stpped taking his antibitics all tgether a few weeks back. He has stpped cming in fr testing. States he understands that stpping treatment may lead t death Patient des nt fllw up with testing r clinic visits

24 3 years frm presentatin Patient presents at ED with wrsening symptms Cugh sputum prductin that is bldy shrtness f breath affecting his ability t wrk Recent diagnsis f COPD and type 2 diabetes Says he has nt taken antibitics fr several mnths

25 Chest CT at 3 years frm presentatin Wrsening cavitary lesin Several ndular frnd-like pacities Patient says he is ready t try fr a cure Restarts antibitics New cultures grw M. abscessus nly Frnt view Bttm up view Side view

26 M. abscessus Rapid grwer (nnchrmgenic) Grwth n bld agar n day 5 M. abscessus cmplex abscessus (cmmn) massiliense (cmmn) blletii (rare) Secnd mst cmmn NTM after MAC First islated frm a knee abscess in 1952 Usually causes skin and sft tissue r pulmnary infectins Fund in water and sil Generally hard t treat One study shwed nly 58% cure after a year f therapy with cmbinatin f IV and ral antibitics Jen K, et al. Am J Respir Crit Care Med Kil-S Lee, et al. J Bacteril Virl. 2008

27 Susceptibility testing M. abscessus M. szulgai Drug Result Drug 1 year later Amikacin Amikacin Augmentin Resistant Capremycin Azithrmycin Ciprflxacin Intermediate Cefxitin Cyclserine Ciprflxacin Resistant Ethambutl Clarithrmycin Ethinamide Clfazimine Isniazid lw Resistant Dxycycline Resistant Isniazid high Intermediate Imipenem Intermediate Kanamycin Resistant Kanamycin Levflxacin Intermediate Linezlid Intermediate Linezlid Mxiflxacin Resistant Mxiflxacin Tigecycline Oflxacin Resistant Tbramycin Intermediate PAS Resistant Trimethprim/sulfa Resistant Rifampin Streptmycin lw Resistant Streptmycin high

28 3.5 years Chrnic cugh 2-3 bld clts a day Recently quit his jb due t chrnic shrtness f breath Quit smking last mnth and has gained 10 lb Underges surgery: Right upper, middle lbes, and invlved ribs resected Discharged hme with a PICC line fr IV antibitics Amikacin, Cefxitin, Rifampin, Ethambutl, and Clarithrmycin

29 Pathlgy 40X 100X 400X 1000X 1000X 1000X

30 M. abscessus susceptibility testing Drug 1st 2nd Amikacin Augmentin Resistant Resistant Azithrmycin Cefepime Resistant Ceftaxime Resistant Cefxitin Intermediate Ceftriaxne Resistant Key Intermediate Resistant Increased resistance Ciprflxacin Resistant Resistant Clarithrmycin Clfazimine Dxycycline Resistant Resistant Gentamicin Intermediate Imipenem Intermediate Intermediate Kanamycin Linezlid Intermediate Resistant Mxiflxacin Resistant Resistant Tigecycline Tbramycin Intermediate Intermediate Trimethprim/sulfa Resistant Resistant

31 One mnth later (~3.5 years) In the next few weeks he feels wrse Fever, chills, vmiting Discntinue his all antibitics including the IV The next day his chest wund pens and large amunt f chunky, disclred, purulent material drains He then feels much better Resumes ral antibitics nly On exam a large amunt f thick purulent material is draining frm his chest tube site IV antibitics restarted Culture grws M. abscessus

32 3.5 years Chest wall thickening Emphysema Tree and bud pacities in remaining right lung Frnt view Side view Bttm up view

33 Tree-in-bud pacities

34 3.75 years Bld draining frm wund site Albumin drpping (1.5 g/dl) White bld cell cunt rising (14 K/uL) Brnchpulmnary fistula identified Underges secnd surgery fr debridement, flap repair and endbrnchial stent placement Albumin

35 One mnth later (~4 years) Wund cntinues t drain pus and bleed. Heavy lifting at hme resulted in sudden large amunt f bleeding. Albumin at 1.1 g/dl in clinic Patient initially refuses t be admitted despite warnings he may have a heart attack Wife cnvinces him t get a transfusin Regular sputum cultures identify new rganism

36 M. peregrinum Nnpigmented Rapid grwer Very rare cause f pulmnary infectins M. frtuitum cmplex Frtuitum, peregrinum, senegalense, setense, septicum, prcinum, hustnense, benickei, brisbanense, newrleansense Case reprts f disease in previusly healthy peple (Nihn Kkyuki Gakkai Zasshi )

37 Tw mnths later (4 years) Salvage therapy recmmended by natinal Jewish amikacin, cefxitin, tigecycline, and clfazimine Imprves initially then represents with air and pus leaking frm chest wund. Underges anther surgery t debride and clse multiple fistulas. New sputum culture results...

38 M. frtuitum Rapid grwer Nn-pigmented Cmmn mycbacterial pathgen Usually in skin and sft tissue infectins Often nscmial Macrlide and cephalsprin resistance is cmmn 4-6 mnths f therapy recmmended

39 Summary M. szulgai M. abscesses M. peregrinum M. frtuitum Slw grwer Rapid grwer Rapid grwer Rapid grwer Rare Cmmn Uncmmn Cmmn Fairly susceptible (except isniazid) Pigment in light nly when grwn at 25 Fairly resistant Fairly susceptible Fairly susceptible N grwth at 45C

40 Case 2 Nn- tuberculus spndylitis

destructin f the disc space and vertebral bdies, results in wedging

41 Ptt s Disease Infectin f the spine with Mycbacterium First described in 1779 by an English surgen named Percivall Ptt Causes destructin f the disc space and vertebral bdies, results in wedging Result in prgressive kyphsis Can lead t neurlgic deficits and severe defrmity

Ptt s Disease Mst cmmn site f mycbacterial stemyelitis Mst cmmn in children and yung adults Befre anti-tuberculsus medicatins mrtality was 20% Likely disseminates frm a

42 Ptt s Disease Mst cmmn site f mycbacterial stemyelitis Mst cmmn in children and yung adults Befre anti-tuberculsus medicatins mrtality was 20% Likely disseminates frm a pulmnary surce Yet, mst patients have n evidence f extra spinal disease Prgnsis is best when treated early Ravindra Kumar Garg and Dilip Singh Smvanshi. J Spinal Crd Med. 2011

1965 Slw grwing Sctchrmgen Optimal grwth at 45 C Nest like clnies

43 Mycbacterium xenpi First islated in 1959 frm skin lesins n an adult female Xenpus laevis (African clawed frg) Recgnized as a pathgen in 1965 Slw grwing Sctchrmgen Optimal grwth at 45 C Nest like clnies Treatment ften requires 2+ years f ethambutl, rifampin and macrlide therapy

STUDY PROTOCOL. Doctor of Pharmacy Student, Faculty of Pharmaceutical Sciences, University of British Columbia,

STUDY PROTOCOL. Doctor of Pharmacy Student, Faculty of Pharmaceutical Sciences, University of British Columbia, Methicillin-Resistant Staphylcccus aureus Infectin in a Tertiary Care Hspital in Rural British Clumbia: A Retrspective Study f Resistance Patterns and Empiric Antibitic Therapy STUDY PROTOCOL Nicle Bruchet,