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The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission. AIDS CLINICAL ROUNDS
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Cases from the Clinic

Jan 27, 2017

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Page 1: Cases from the Clinic

The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission.

AIDS CLINICAL ROUNDS

Page 2: Cases from the Clinic

Cases%from%the%Clinic%

Darcy%Wooten,%MD,%MS%Health%Sciences%Assistant%Clinical%Professor%

Owen%Clinic%Infec<ous%Diseases%Hospital%Medicine%

%

Page 3: Cases from the Clinic

Financial%disclosures:%None%%Conflicts%of%interest:%None%

Page 4: Cases from the Clinic

HPI%36%yo%man%with%no%PMH%

• %2%weeks%prior,%presented%to%public%health%with%urethral%discharge%%

• %Diagnosed%with%nonJgonococcal%urethri<s%(by%a%“urine%test,”%denied%having%throat/rectal%tes<ng)%and%new%HIV%

• %Treated%with%azithromycin%1g%PO%x1%dose%

• %Referred%to%Owen%Clinic%for%further%care%

• %1%week%prior%to%his%Owen%Clinic%appointment,%reJpresented%to%public%health%with%ongoing%urethral%discharge%and%treated%with%7%days%of%doxycycline%100mg%bid%

Page 5: Cases from the Clinic

Owen%Clinic%Visit%(#1)%At%his%first%Owen%Clinic%visit%(2%weeks%a[er%his%ini<al%symptoms):%

• %Unchanged%urethral%discharge%(thin,%watery,%morning)%

• %Mild%urinary%urgency,%but%NO:%dysuria,%burning,%frequency,%hesitancy,%dribbling,%hematuria%

• %No%tes<cular%pain%or%swelling,%genital%ulcers,%rectal/perirectal%pain,%pelvic%floor%pain,%inguinal%pain%

• %No%abdominal%pain,%nausea,%vomi<ng,%diarrhea,%cons<pa<on,%back%pain,%rash,%eye%symptoms,%or%joint%pain%

• %No%fevers,%chills,%sweats%%

Page 6: Cases from the Clinic

Addi<onal%History%Social%History:%• %%No%tobacco%

• %6%glasses%wine/week%

• %MJ%q%2%weeks;%IN%cocaine%x1,%ecstasy%x2,%no%other%drugs,%no%IVDU%

• %Born%in%San%Diego,%lives%alone%

• %Works%in%So[ware%R&D%

• %No%travel%or%pets%%%

PMH:%• %Per%HPI%

Meds:%• %Azithro%+%Doxy%per%HPI%• %100%%adherent%

%All:%• %NKDA%%%Family%History:%• %Hypertension%

Page 7: Cases from the Clinic

Sexual%History%%• %Sex%with%men%(inser<ve%and%recep<ve%oral%and%anal%sex)%%• %Used%condoms%with%anal%sex,%but%only%during%ejacula<on%%• %No%associated%alcohol%and%substance%use%during%sex%%• %3%partners%in%the%past%3%months%%• %~10J15%life<me%partners,%unknown%HIV/STI%status%of%partners%%• %No%history%of%symptoma<c%STIs%%

• %No%new%partners%since%HIV%diagnosis%

Page 8: Cases from the Clinic

Exam%Normal%vitals%%HEENT:%Sclera%anicteric%and%not%injected,%OP%clear%without%erythema%or%exudates,%no%thrush,%no%LAD%%Cardiac,%Pulm:%Normal%%Abdomen:%So[,%NT,%ND,%+BS,%no%HSM,%no%CVA%tenderness%%GU:%Circumcised,%no%penile%lesions/ulcer,%normal%meatus%without%discharge,%normal%testes,%normal%perirectal%exam,%DRE%normal%without%tenderness,%and%mild,%nonJtender,%mobile%inguinal%LAD%%Skin:%No%rash%%Neuro:%Normal%%

Page 9: Cases from the Clinic

Owen%Clinic:%Plan%• %Ordered%a%UA,%urine%culture,%urine/throat/rectal%GC/CT%PCR,%and%syphilis%EIA%

• %Requested%outside%records%

• %“ReJtreated”%with%Ce[riaxone%250mg%IM%x1%+%Azithro%1g%PO%x1%

• %Ini<al%“HIV%labs”%(CD4,%viral%load,%genotype,%CBC,%CMP,%lipids,%hepa<<s%serologies,%QFN,%HLA%B5701)%

• %Discussed%ARV%op<ons%

• %Follow%up%in%2%weeks%to%start%ART%and%reassess%symptoms%

Page 10: Cases from the Clinic

2%Weeks%Later…%• %Returns%for%follow%up%with%no%change%in%urethral%discharge%• %Improved%for%~1J2%days%a[er%an<bio<cs%but%then%returned%to%baseline%symptoms%

• %No%new%symptoms%or%exam%findings%• %No%new%sexual%partners%since%HIV%diagnosis%

Page 11: Cases from the Clinic

2%Weeks%Later…%• %Returns%for%follow%up%with%no%change%in%urethral%discharge%• %Improved%for%~1J2%days%a[er%an<bio<cs%but%then%returned%to%baseline%symptoms%

%• %No%new%symptoms%or%exam%findings%• %No%new%sexual%partners%since%HIV%diagnosis%

• %WBC:%5.1% % % % %CD4:%375%(29%) %HIV%VL:%10K,%WT%• %Hgb:%15.5% % % % %GC/CT%PCR%x3:%Neg%• %Plt:%196 % % % % %UA:%Normal,%UCx:%Neg%

• %Chem%panel:%Normal% %Hep%A+B:%Immune,%HCV%Ab:%Neg%• %LFTs:%Normal% % % %Syphilis%EIA:%Neg%%%%%%%QFN:%Neg%

Page 12: Cases from the Clinic

Audience%Response%Ques<on%What%would%your%next%steps%in%management%be%for%this%young,%HIV+%man%with%ongoing%urethri<s%despite%mul<ple%rounds%of%an<bio<c%therapy?%%A.  Repeat%treatment%with%ce[riaxone%and%azithromycin%B.  Repeat%treatment%with%azithromycin%1g%PO%x1%C.  Repeat%treatment%with%azithromycin%1.5g%PO%over%5%days%

(500mg%on%day%1%!%250mg%daily%on%days%2J5)%D.  Repeat%treatment%with%moxifloxacin%for%7J14%days%E.  Admit%to%the%hospital%and%retreat%with%broadJspectrum%IV%

an<bio<cs%%%%

Page 13: Cases from the Clinic

Owen%Clinic%Visit%(#2)%• %Sent%urine%for%Urogenital%Ureaplasma%and%Mycoplasma%spp.%PCR%(sendout%to%ARUP)%

• %Treated%with%Moxifloxacin%400mg%PO%daily%x7%days%

• %Started%Stribild%

• %1%week%later:%symptoms%resolved%with%Moxifloxacin%

%

Page 14: Cases from the Clinic

4%Weeks%Later…%%• %ARUP%report:%

• %Ureaplasma-parvum%PCR:%Not%detected%• %Ureaplasma-urealy0cum-PCR:%Not%detected%• %Mycoplasma-hominis-PCR:%Not%detected%• %Mycoplasma-genitalium-PCR:%Detected%

Page 15: Cases from the Clinic

Mycoplasma-genitalium:%%Emerging%Pathogen%

Page 16: Cases from the Clinic

Causes%of%nonJgonococcal%urethri<s%%• %NonJgonococcal%urethri<s%(NGU)%• -Chlamydia-trachoma0s%(25%%of%cases)-

• %Mycoplasma-genitalium%(30%%of%cases)-

• %Trichomonas-vaginalis%(10J25%%of%cases)%

• -Ureaplasma-urealy0cum%(controversial)%

• -HSV-

%

Page 17: Cases from the Clinic

Mycoplasma-Genitalium:"Micro-• %First%described%in%1981%

• %580%kilobase%genome%!%Smallest%freeJliving%bacterium%

• %No%cell%wall;%pear%shape%with%terminal%<p%structure%that%allows%for%adherence%to%and%invasion%epithelial%cells%

• %SlowJgrowing%and%fas<dious%bacterium%%• %Evades%host’s%immune%response%by%1)%an<genic%varia<on%and%2)%immune%modula<on%!%Persistent%infec<on%

• %Secretes%mycoplasmal%toxins%and%H2O2%!%Tissue%destruc<on%

Page 18: Cases from the Clinic

Mycoplasma-Genitalium:%Epi-• %Risk%Factors:%

• %Higher%number%of%sex%partners%• %Younger%age%during%first%intercourse%• %Partner%with%ac<ve%STI%symptoms%• %CoJinfec<on%with%other%STIs%• %Smoking%• %HIV%coJinfec<on%%%%• %Strongest%associa<on%with%nonJgonococcal%urethri<s%in%men%• %Weaker%associa<on%with%cervici<s%and%PID%(conflic<ng%studies)%

Page 19: Cases from the Clinic

Mycoplasma-Genitalium:%Dx-%• %Consider%in%cases%of%NGU%or%cases%of%persistent%urethri<s%despite%therapy%%• %No%FDAJcleared%tests%(NAAT%as%a%sendout%is%available)%

• %NAATs%target%78%bp%region%of%the%adhesion%protein%and%a%517%bp%region%of%the%16S%rRNA%• %Op<mal%specimen%is%unclear%(first%void%urine%in%men,%vaginal%specimen%in%women)%

%

Page 20: Cases from the Clinic

Mycoplasma-Genitalium:%Tx-Doxycycline%%Azithromycin%%Moxifloxacin%

Page 21: Cases from the Clinic

Mycoplasma-Genitalium:%Tx-Doxycycline%• %In-vitro-data%suggests%M.-genitalium-would%be%suscep<ble%

• %Controlled%clinical%trials%show%efficacy%ranging%between%22J45%%

• %Discrepancy%is%unclear%

• %Not%recommended%for%therapy%

Page 22: Cases from the Clinic

Mycoplasma-Genitalium:%Tx-Azithromycin%• %Good%in-vitro-ac<vity%

• %Efficacy%of%Azithromycin%1g%dose%appears%to%be%declining%• %87%%cure%rates%prior%to%2005%vs%71%%a[er%2005%• %85%%cure%rates%prior%to%2009%vs%67%%a[er%2009%

• %Explana<ons:%• %Increase%in%AzithroJresistance%• %Organism%load%

Page 23: Cases from the Clinic

Mycoplasma-Genitalium:%Tx-

Would%an%extended%dose%of%azithromycin%be%more%efficacious%and/or%lead%to%less%resistance?%

%1g%vs%1.5%g%(500mg%x1%+%250mg%x4)%

%%

• %Controlled%trial%1g%vs%1.5g,%efficacy%was%85%%vs%95%%• %Pa<ent%treated%with%1.5g%dose%had%previously%failed%treatment%with%doxy%

Page 24: Cases from the Clinic

Mycoplasma-Genitalium:%Tx-Moxifloxacin%%• %Cipro,%Levo,%and%Ofloxacin%all%have%poor%in-vitro-ac<vity%against%M.-genitalium-as%well%as%poor%clinical%efficacy%

• %Ini<al%cure%rates%with%moxifloxacin%amongst%pa<ents%with%prior%treatment%failure%were%as%high%as%100%%

• %In%Asia,%treatment%failure%is%as%high%as%15J30%%and%is%associated%with%FQ%resistance%

Page 25: Cases from the Clinic

Take%Home%Points%• %Think%about%Mycoplasma-genitalium,%especially%in%pa<ents%with%persistent%urethri<s%

• %ARUP%has%a%panel%which%tests%for:%%

%• %Order%as%“Urine%Lab%Misc.”%and%type%in%“Urogenital%Ureaplasma%and%Mycoplasma%spp.%PCR”%%

• %Treatment%is%challenging%because%of%resistance%• %Azithro%1.5g%or%Moxifloxacin%

%

Ureaplasma-parvum%PCR%Ureaplasma-urealy0cum-PC%Mycoplasma-hominis-PCR%Mycoplasma-genitalium-PCR%

Page 26: Cases from the Clinic
Page 27: Cases from the Clinic

HPI%CC:%Rash%%HPI:%• %31%yo%woman%with%newly%diagnosed%HIV%(CD4%385,%VL%4.5%million)%and%drugJresistant%TB%in%November,%2014%at%Sharp.%%%• %Miliary%pulmonary%disease,%+pleural%effusion,%bone%marrow%biopsy%with%nonJcasea<ng%granulomas.%%

• %11/26/14:%Sputum%AFB%smear%neg,%Cx:%+MTB,%+MTD%PCR%• %11/26/14:%Pleural%fluid%AFB%Smear%neg,%Cx:%+MTB,%+MTD%PCR%• %12/6/14:%Sputum%AFB%smear%neg,%Cx:%+MTB%• %12/7/14:%Sputum%AFB%smear%neg,%Cx:%+MTB%• %Low%level%resistance%to%INH%and%Ethionamide%%

• %Rifabu<n,%Ethambutol,%Pyrazinamide%12/6%–%12/24%

Page 28: Cases from the Clinic

HPI%(cont.)%%• %Absconded%on%12/24/14%

• %%Found%crossing%the%border%from%Mexico%in%June,%2015%

• %%Admiwed%to%Sharp%and%reJstarted%on%Rifabu<n,%Ethambutol,%and%Pyrazinamide%

• %Repeat%sputum%AFB%smears%neg,%cultures%were%posi<ve%for%MTB%%

Page 29: Cases from the Clinic

HPI%(cont.)%%• %Drug%Suscep<bility%Report%(BACTEC%MGIT%960)%• %Isoniazid%0.1%ug/mL:%Resistant%• %Isoniazid%0.4%ug/mL:%Sensi<ve%• %Pyrazinamide%100%ug/mL:%Sensi<ve%• %Ethambutol%5%ug/mL:%Sensi<ve%• %Ethionamide%5.0%ug/mL:%Resistant%• %Capreomycin%3.0%ug/mL:%Sensi<ve%• %Amikacin%1.5%ug/mL:%Sensi<ve%• %Moxifloxacin%0.25%ug/mL:%Sensi<ve%

Page 30: Cases from the Clinic

HPI%(cont.)%%• %Drug%Suscep<bility%Report%(Pyrosequencing)%

DRUG% TARGET% RESULTS% INTERPRETATION%INH% katG% No%muta<on% %

Associated%with%INH%resistance.%%Approximately%2/3%of%isolates%in%inhA%promoter%also%demonstrate%ethionomide%resistance.%

inhA%promoter%

015T%muta7on%

ahpC%promoter%

No%muta<on%

RIF% rpoB% No%muta<on% Suggests%suscep<bility%

AMK,%CAP,%KAN%

rrs% No%muta<on% Suggests%suscep<bility%

Quinolones% gyrA% No%muta<on% Suggests%suscep<bility%%

Page 31: Cases from the Clinic

INH%Resistance%%• %Mechanism%of%INH%vs.%TB%

• %Inhibits%mycolic%acid%synthesis%• %INH%is%ac<vated%by%mycobacterial%catalase%and%then%binds%to%inhA%protein%(involved%in%the%synthesis%of%mycolic%acid)%!%Inhibi<on%of%cell%wall%synthesis%%

• %Muta<ons%in%the%katG%and/or%inhA%genes%account%for%85J90%%of%INH%resistance%

• %Low%level%resistance%=%MIC%>0.1%but%%<1.0%ug/mL%(point%muta<ons)%• %High%level%resistance%=%MIC%>1.0%ug/mL%(major%dele<ons)%

• %7J11%%of%pa<ents%with%TB%in%the%U.S.%have%INH%resistance%

• %Ethionamide%is%an%isonico<nic%acid%deriva<ve%(similar%to%INH)%• %Muta<ons%in%the%inhA%gene%are%also%associated%with%ethionamide%resistance,%but%not%muta<ons%in%the%katG%gene%

Page 32: Cases from the Clinic

HPI%(cont.)%•  3%weeks%into%therapy%she%developed%a%rash%and%her%TB%therapy%was%

stopped.%

•  TB%therapy%reJintroduced%one%drug%at%a%<me;%developed%a%rash%with%rifabu<n%

%•  TB%therapy%stopped%again%%•  Desensi<za<on%to%rifabu<n%%•  TB%therapy%reJini<ated%and%developed%a%rash%to%rifabu<n%again%%•  TB%therapy%change%to%rifampin/EMB/PZA%without%development%of%

rash%

Page 33: Cases from the Clinic

HPI%(cont.)%•  Rifampin/EMB/PZA%con<nued%for%4%weeks%without%

development%of%rash%•  Efavirnez/Truvada%started%•  Discharged%to%SNF%

•  2%weeks%later,%presents%to%Owen%Clinic%with%4%days%of:%•  Diffuse,%pruri<c,%and%burning%rash%on%bilateral%upper%extremi<es,%

then%lower%extremi<es,%then%torso%and%back%•  Started%a%red%papules%that%then%coalesced%into%plaques%•  Bilateral%lower%extremity%edema%(painful)%•  Large,%tender,%right%cervical%lymph%node%•  Fevers%to%102,%tachycardic%to%130%

%

Page 34: Cases from the Clinic

PMH%

• %HIV%(CD4%351,%VL%10%million,%treatmentJnaïve)%• %Disseminated,%drugJresistant%TB%• %Syphilis%(late%latent,%RPR%1:4,%never%treated)%• %Genital%HSV%• %Schizophrenia/ADHD/Bipolar%disorder/Developmental%delay%• %Tobacco%use%• %Methamphetamine%use%• %Severe%calorie%and%protein%malnutri<on%• %s/p%2%CJsec<ons%%

Page 35: Cases from the Clinic

MEDS%•  Efavirenz%800mg%daily%(stopped%2%days%ago)%•  Truvada%1%tab%daily%(stopped%2%days%ago)%

•  Rifampin%600mg%daily%(stopped%2%days%ago)%•  Ethambutol%800mg%daily%(stopped%2%days%ago)%•  Pyrazinamide%1000mg%daily%(stopped%2%days%ago)%

•  Ce<rizine%10mg%daily%•  Hydroxyzine%0.25mg%q%6%

•  Olanzapine%5mg%q%am,%10mg%q%pm%

•  Nysta<n%S+S%

•  Tylenol,%Norco,%Zofran,%Nico<ne%patch,%Metoprolol,%Levothyroxine,%Ferrous%sulfate%

%

Page 36: Cases from the Clinic

Addi<onal%History%

SH:%•  ½%ppd%tobacco%•  No%alcohol%•  Methamphetamine%use%•  WSM,%likely%contracted%HIV%through%exJboyfriend%•  Previously%worked%as%a%pros<tute%in%TJ%•  Originally%from%Texas%

FH:%•  Unknown%

Allergies:%•  Bactrim%!%Rash%•  Rifabu<n%!%Rash%

Page 37: Cases from the Clinic

Exam%%VS:%100.3 %%93/52 % %111 % %19 % %97%%RA%%%GEN:%Cachec<c,%mildly%ill%appearing%HEENT:%Sclera%anicteric,%injected%L%conjunc<va,%PERRL,%MMM,%no%thrush%NODES:%Firm,%tender%3x3%cm%supraclavicular%lymph%node%CHEST:%CTAB%HEART:%Tachy%but%regular,%no%murmurs%ABDOMEN:%So[,%tender%to%palpa<on%in%RUQ%with%hepatomegaly%and%splenomegaly,%no%R/G%EXT:%1+%edema%in%bilateral%lower%extremi<es%SKIN:%Diffuse%blanching,%erythematous%papular%confluent%rash%on%bilateral%UE,%LE,%torso,%worse%on%the%le[%v%right%sparing%face,%palms,%and%soles%NEURO:%A+Ox3,%CN%intact,%normal%gait%

%

Page 38: Cases from the Clinic
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Audience%Response%Ques<on%In%this%young%woman%with%HIV%and%drugJresistant%TB,%with%a%history%of%rash%to%Bactrim%and%Rifabu<n,%a%history%of%syphilis,%and%recently%on%Rifampin/Ethambutol/Pyrazinamide%x7%weeks%and%efavirenz/tenofovir/emtrici<bine%x%2%weeks,%which%of%the%following%is%the%MOST%likely%cause%of%her%rash?%%A.  Rifampin%B.  Ethambutol%C.  Pyrazinamide%D.  Efavirnez%E.  Olanzapine%F.  Undiagnosed%vasculi<s%G.  Syphilis%(it’s%always%syphilis)%

Page 43: Cases from the Clinic

Clinical%Course%%• %Admiwed%to%the%hospital%

• %All%TB%and%HIV%meds%held%

• %Labs%and%imaging%

• %Dermatology%consult%

Page 44: Cases from the Clinic

Labs%%• %WBC:%4.1%(65%%segs/%25%%lymphs/%7%%%mono/%4%%eos)%• %Hgb:%9.6%• %Plt:%199%

• %Cr:%0.44 % %LDH:%159%

• %LFTs:%Normal%(0.21%/%19%/%17%/%117)%

• %UA:%>50%WBCs,%+LE,%neg%Ni,%2+%protein%

• %Syphilis%EIA+,%RPR%1:4%

• %Hep%A,%B,%C:%Neg%

Page 45: Cases from the Clinic

Labs%%• %Blood%cultures:%Neg%

• %AFB%blood%culture:%NGTD%

• %Sputum%AFB%smear/Cx%x3:%Neg/NGTD%

• %Sputum%MTD%PCR:%Neg%

• %Stool%AFB%smear/Cx:%NGTD%%• %Serum%CrAg:%Neg,%Serum%Cocci:%Neg,%Urine%Histo%Ag:%Neg%

• %uCG/CT:%Neg%

Page 46: Cases from the Clinic

CT%Neck%

Page 47: Cases from the Clinic

CT%Chest%

Page 48: Cases from the Clinic

CT%Abdomen/Pelvis%

Page 49: Cases from the Clinic

Dermatology%Consult%%• %Exanthematous%drug%reac<on%

• %Not%clinically%consistent%with%DRESS%or%SJS/TEN%

• %No%biopsy%

Page 50: Cases from the Clinic

Clinical%Course%%• %Rash%resolved%a[er%several%days%off%all%TB%and%HIV%meds%

• %FNA%of%cervical%lymph%node:%• %Path:%Necro<zing%granulomatous%inflamma<on%• %Unable%to%perform%GMS%and%AFB%stains%• %Micro:%AFB%smear%and%culture%nega<ve%

• %Plan%was%made%to%reJintroduce%TB%medica<ons%in%a%stepwise%fashion%and%hold%ARVs%un<l%she%was%able%to%tolerate%2%weeks%of%TB%therapy%

Page 51: Cases from the Clinic

Drug%Rashes%in%Pa<ents%with%HIV%• %%Adverse%drug%reac<ons%are%common%

• %Up%to%80%%of%pa<ents%experience%an%adverse%drug%reac<on%at%some%point%during%therapy%• %Immune%dysregula<on%• %Altered%drug%metabolism%• %Polypharmacy%

• %HIVJinfected%pa<ents%have%a%higher%risk%of%developing%cutaneous%reac<ons%than%the%general%popula<on%

Page 52: Cases from the Clinic

Drug%Rashes%in%Pa<ents%with%HIV%• %%Efavirenz%

• %%Rifabu<n%

• %%Rifampin%

Page 53: Cases from the Clinic

Efavirenz%• %%Usually%a%mild%to%moderate%maculopapular%rash;%typically%treat%through%with%topical%hydrocor<sone%and%an<histamines%

• %Can%occur%in%5J26%%of%pa<ents%(11%)%

• %Median%<me%of%onset%is%11%days;%typically%resolves%a[er%1%month%

• %Pa<ents%with%a%history%of%sulfa%rash%are%more%likely%to%develop%a%rash%to%NNRTIs%than%without%a%sulfa%allergy%

• %Severe%hypersensivity,%DRESS,%and%SJS/TEN%are%rare%but%have%been%reported%%

• %%<1%%

• %Increased%risk%of%rash%associated%with%HLAJDRB101%

Page 54: Cases from the Clinic

Rifabu<n%and%Rifampin%• %Adverse%reac<ons%to%TB%therapy%occur%at%a%higher%frequency%amongst%HIV+%vs%HIVJ%pa<ents%%%

• %Rifabu<n%is%associated%with%rash%in%11%%of%pa<ents%

• %Rifampin%is%associated%with%rash%in%1J5%%of%pa<ents%

• %Severe%rash/hypersensi<vity%is%rare%for%rifabu<n%and%rifampin%

• %CrossJreac<vity:%Of%pa<ents%who%had%a%dermatologic%reac<on%to%rifampin,%23%%developed%a%rash%when%switched%to%rifabu<n%

Page 55: Cases from the Clinic

Clinical%Course%%• %ReJintroduced%the%following%regimen%at%standard%doses%q2%days:%%• %Ethambutol%800mg%daily%(9/2%J%%• %PZA%30mg/kg%daily%(9/4%J%%• %Moxifloxacin%400mg%daily%(9/6%J%• %Rifampin%daily%(9/8J%%

%

Page 56: Cases from the Clinic

Clinical%Course%%• %Tolerated%Rifampin/PZA/EMB/Moxi%for%3%days%

• %Remained%rashJfree%

• %Developed%fevers%(without%sepsis),%leukopenia,%neutropenia,%and%thrombocytopenia.%%Infec<ous%w/u%neg.%HIT%w/u%neg.%

• %RifampinJdependent%an<Jplatelet%an<body%was%sent%out%%

• %Rifampin%was%discon<nued%a[er%5%days%of%ongoing%fevers%and%cytopenias%

%

Page 57: Cases from the Clinic

Clinical%Course%Date% Drugs% Temp% WBC% ANC% PLT%9/7% PEM% 98.0% 4.4% JJ% 265%

9/8% PEM% 97.7% 4.2% JJ% 285%

9/9% RPEM% 99.0% 4.2% JJ% 257%

9/10% RPEM% 101.5% 3.7% JJ% 248%

9/11% RPEM% 102.4% 3.2% JJ% 195%

9/12% RPEM% 102.7% 2.6% 700% 159%

9/13% RPEM% 101.8% 2.6% 800% 146%

9/14% PEM% 102.3% 2.6% 900% 108%

9/15% PEM% 102.5% 2.0% 600% 86%

9/16% PEM% 99.8% 2.0% 600% 71%

9/17% PEM% 97.6% 1.6% 700% 78%

9/18% PEM% 101.2% 2.0% 700% 90%

9/19% PEM% 97.8% 1.4% 200% 108%

Page 58: Cases from the Clinic

Rifampin%Hypersensi<vity%Reac<on%%• %Fever,%headache,%chills,%and%bone%pain%

• %Symptoms%usually%begin%1J2%hours%a[er%medica<on%and%resolve%8J10%hours%later%

• %More%common%with%intermiwent%therapy%and%typically%develops%several%months%into%the%treatment%course%

• %%Can%be%associated%with%leukopenia,%agranulocytosis,%thrombocytopenia,%hemoly<c%anemia,%and%renal%failure%

• %ImmuneJmediated%type%III%hypersensi<vity%%

• %Fever%usually%resolves%3J5%days%a[er%discon<nua<on;%thrombocytopenia%usually%resolved%5J7%days%a[er%discon<nua<on%%

Page 59: Cases from the Clinic

DrugJInduced%Immune%Thrombocytoepnia%with%Rifampin%• %DrugJdependent,%platelet%reac<ve%an<bodies%

• %Bind%to%platelets%or%megakaryocytes%!%cell%destruc<on%or%clearance%

• %Glycoprotein%1b/IX%has%been%iden<fied%as%the%target%for%rifampinJinduced%immune%thrombocytopenia%

• %Tes<ng%for%rifampinJdependent%an<platelet%an<bodies%can%be%done%at%the%Blood%Center%of%Wisconsin%using%flow%cytometry%

• %Sensi<vity%and%specificity%are%not%known%• %False%posi<ves%and%nega<ves%are%possible%• %Not%absolutely%necessary%to%make%the%diagnosis%

Page 60: Cases from the Clinic

%Abciximab%

Carbamazepine%Ce[azadime%Ce[riaxone%Ep<fiba<de%Fentanyl%

%Loracarbef%Naproxen%Phenytoin%Quinidine%Quinine%Rani<dine%

%Rifabu<n%Rifampin%

Sulfamethoxazole%Suramin%

Trimethoprim%Vancomycin%

Page 61: Cases from the Clinic

Audience%Response%Ques<on%Case%Summary:%31%yo%woman%with%HIV%(CD4%350),%and%disseminated,%drugJresistant%TB%(low%level%resistance%to%INH%and%resistance%to%Ethionomide)%currently%being%treated%with%EMB/PZA/Moxi%without%rifampin%because%of%presumed%associated%toxicity.%%She%has%no%respiratory%symptoms.%%What%TB%regimen%would%you%recommend%at%this%point?%%A.  EMB/PZA/Moxi%for%18%(12J24)%mo%B.  EMB/PZA/Moxi/INH%for%18%(12J24)%mo%C.  EMB/PZA/Moxi%for%18%(12J24)%mo%+%Injectable%D.  EMB/PZA/Moxi/Linezolid%for%18%(12J24%mo)%E.  Awempt%reJintroduc<on%of%a%rifamycin%to%EMB/PZA/Moxi%F.  Other%

Page 62: Cases from the Clinic

Thank%you%

Page 63: Cases from the Clinic

References%Falk%L,%Fredlund%H,%Jensen%JS.%Symptoma<c%urethri<s%is%more%prevalent%in%men%infected%with%Mycoplasma%genitalium%than%with%Chlamydia%trachoma<s.%Sex%Transm%Infect%2004;%80:289.%%Towen%PA,%Schwartz%MA,%Sjöström%KE,%et%al.%Associa<on%of%Mycoplasma%genitalium%with%nongonococcal%urethri<s%in%heterosexual%men.%J%Infect%Dis%2001;%183:269.%%TaylorJRobinson%D.%The%Harrison%Lecture.%The%history%and%role%of%Mycoplasma%genitalium%in%sexually%transmiwed%diseases.%Genitourin%Med%1995;%71:1.%%Jensen%JS,%Orsum%R,%Dohn%B,%et%al.%Mycoplasma%genitalium:%a%cause%of%male%urethri<s?%Genitourin%Med%1993;%69:265.%%TaylorJRobinson%D.%Mycoplasma%genitalium%JJ%an%upJdate.%Int%J%STD%AIDS%2002;%13:145.%%Gaydos%C,%Maldeis%NE,%Hardick%A,%et%al.%Mycoplasma%genitalium%as%a%contributor%to%the%mul<ple%e<ologies%of%cervici<s%in%women%awending%sexually%transmiwed%disease%clinics.%Sex%Transm%Dis%2009;%36:598.%Anagrius%C,%Loré%B,%Jensen%JS.%Mycoplasma%genitalium:%prevalence,%clinical%significance,%and%transmission.%Sex%Transm%Infect%2005;%81:458.%%Falk%L,%Fredlund%H,%Jensen%JS.%Signs%and%symptoms%of%urethri<s%and%cervici<s%among%women%with%or%without%Mycoplasma%genitalium%or%Chlamydia%trachoma<s%infec<on.%Sex%Transm%Infect%2005;%81:73.%%Manhart%LE,%Critchlow%CW,%Holmes%KK,%et%al.%Mucopurulent%cervici<s%and%Mycoplasma%genitalium.%J%Infect%Dis%2003;%187:650.%%Møller%BR,%TaylorJRobinson%D,%Furr%PM.%Serological%evidence%implica<ng%Mycoplasma%genitalium%in%pelvic%inflammatory%disease.%Lancet%1984;%1:1102.%%Simms%I,%Eas<ck%K,%Mallinson%H,%et%al.%Associa<ons%between%Mycoplasma%genitalium,%Chlamydia%trachoma<s,%and%pelvic%inflammatory%disease.%Sex%Transm%Infect%2003;%79:154.%

Page 64: Cases from the Clinic

References%World%Health%Organiza<on%(WHO).%Laboratory%XDRJTB%defini<ons.%Geneva:%Mee<ng%of%the%global%XDR%TB%task%force%2006.%%%Velaya<%AA,%Masjedi%MR,%Farnia%P,%et%al.%Emergence%of%new%forms%of%totally%drugJresistant%tuberculosis%bacilli:%super%extensively%drugJresistant%tuberculosis%or%totally%drugJresistant%strains%in%iran.%Chest%2009;%136:420.%%%Udwadia%ZF,%Amale%RA,%Ajbani%KK,%Rodrigues%C.%Totally%drugJresistant%tuberculosis%in%India.%Clin%Infect%Dis%2012;%54:579.%%%World%Health%Organiza<on.%Global%Tuberculosis%Report%2014.%hwp://www.who.int/tb/publica<ons/global_report/en/%(Accessed%on%July%07,%2015).%%%WHO/IUATLD%Global%Project%on%An<JTuberculosis%Drug%Resistance%Surveillance.%An<Jtuberculosis%drug%resistance%in%the%world,%report%no.%4%hwp://www.who.int/tb/features_archive/drsreport_launch_26feb08/en/index.html%(Accessed%on%April%29,%2008).%%%Zignol%M,%van%Gemert%W,%Falzon%D,%et%al.%Surveillance%of%an<Jtuberculosis%drug%resistance%in%the%world:%an%updated%analysis,%2007J2010.%Bull%World%Health%Organ%2012;%90:111.%%%World%Health%Organiza<on%(WHO).%Global%tuberculosis%control:%Epidemiology,%strategy,%financing,%Geneva,%WHO%report%2009.%%%Zhao%Y,%Xu%S,%Wang%L,%et%al.%Na<onal%survey%of%drugJresistant%tuberculosis%in%China.%N%Engl%J%Med%2012;%366:2161.%%%World%Helath%Organiza<on.%Global%tuberculosis%control%2011.%WHO;%Geneva,%2011.%%%Poudel%A,%Nakajima%C,%Fukushima%Y,%et%al.%Molecular%characteriza<on%of%mul<drugJresistant%Mycobacterium%tuberculosis%isolated%in%Nepal.%An<microb%Agents%Chemother%2012;%56:2831%%%

Page 65: Cases from the Clinic

Mycoplasma-Genitalium:%Tx-Azithromycin%Resistance%%• %SNPs%in%region%V%of%the%23S%rRNA%gene%• %Strongly%associated%with%increased%MICs%to%azithro%

Sweden% Japan% Australia%2006% 0%% JJ% JJ%2009% 6%% JJ% 20%%2010% 14%% JJ% JJ%2011% 21%% 0%% JJ%2012% JJ% 0%% 36%%2013% JJ% 29%% JJ%