Opportunistic infections Flashcards

1
Q

When can you stop various maintenance OI treatments?

A
  • CMV retinitis/other CMV disease CD4>100 and undetectable 6 months
  • Toxo maintenance when CD4>200 and VL<20 for 6 months
  • PCP when CD4>200 and 14% for 3 months
  • Crypto fluconazole 200mg can stop when CD4>100 and VL<20 for 3 months
  • MAC treatment when CD4>100, VL<20 and clinically well for at least 3 months
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2
Q

First and second most often occurring cryptococcal serotype in the UK?

A

First: Cryptococcal neoformans grubii (serotype A)
Second: Cryptococcal neoformans gattii

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3
Q

Diagnosis of cryptococcal disease

A
  • All those with positive serum CrAg should have LP after brain imaging
  • A positive CSF Cr-Ag is the most sensitive test
  • Must have manometry when do LP
  • All those with CD4<200 and symptoms of crypto should have the disease excluded
  • A negative test generally excludes disseminated disease although there are isolated reports
  • Serum Cr-Ag can be negative in isolated pulmonary disease so MC+S of pulmonary are required to make a diagnosis
  • A positive CSF Cr-Ag, indian ink stain of CSF or CSF Cryptococcus culture confirms meningitis
  • Blood cultures should always be performed
  • If blood or CSF cultures are positive, isolates can be sent for fungal susceptibility testing
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4
Q

Poor prognostic markers in cryptococcal meningitis

A
  • Blood culture positivity
  • Low white blood cells in CSF (<20cells/ml)
  • High CSF cryptococcal antigen (>1:1024)
  • Confused state
  • Raised ICP
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5
Q

When might you see a false positive Cr-Ag?

A

In the presence of rheumatoid factor, heterophiles antibodies, anti-idiotypic antibodies or Trichosporon asahii (beigelii) infection

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6
Q

Induction therapy for cryptococcal

A
  • Liposomal amphotericin B (Ambisome) and flucytosine
  • (Addition of flucytosine speeds rate of sterilisation of CSF and reduces rate of relapse in those not on ART, but no impact on mortality)
  • Flucytosine associated with haematological toxicity and daily blood counts are required
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7
Q

Management of raised ICP

A

If opening pressure >25mmHg then should be reduced to 20mmHg or to 50% of the initial pressure and then repeated daily until stable

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8
Q

Maintenance therapy for cryptococcal meningitis and when to stop

A
  • After 2 weeks of induction therapy switch to fluconazole 400mg/day for 10 weeks total then reduce to 200mg
  • Can stop the 200mg when CD4>100 and VL<20 for 3 months
  • (An LP after induction and extension of induction therapy can be considered until CSF cultures are negative e.g. in setting of poor prognostic factors or poor initial response)
  • (CSF cryptococcal burden correlates with risk of relapse and mortality)
  • Start ART approx 2 weeks after treatment starts, can consider steroids if IRIS
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9
Q

Management of cryptococcal disease without CNS involvement:

A
  • Always do an LP
  • If CSF negative, isolated pulmonary disease can be treated with fluconazole 400mg OD or if more severe then ambisome then secondary prophylaxis
  • Same for cryptococcaemia
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10
Q

Where do toxo lesion have a predilection for?

A
  • Multiple, ring enhancing lesions at the grey-white matter interface often basal ganglia or thalamus
  • Associated with cerebral oedema and mass effect
  • (If CD4 count low, may not have ring enhancement)
  • (Single, periventricular lesion suggestive PCNSL)
  • (PML tend to involve white matter, rarely contrast enhancing and no mass effect)
  • Can also present with signs of a diffuse encephalitis
  • Rarely can present as a toxo myelitis, caudal equina syndrome
  • Presentations outside CNS include chorioretinitis and pneumonia
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11
Q

Diagnosis of toxoplasma:

A
  • It is now standard practice to treat a patient with CD4<200 and a brain mass lesion with anti-toxo therapy
  • 90% will show good clinical/radiological response within 2 weeks which is good evidence of diagnosis
  • CSF PCR for T.Gondii helps establish diagnosis but is only moderately sensitive (sensitivity of 50%, specificity of >94%)
  • Do G6PD (although sulphadiazine has been shown to be ok in many that are deficient, but any Hb drop should certainly prompt testing)
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12
Q

First line induction therapy for cerebral toxoplasmosis

A
  • Sulphadiazine oral
  • Pyrimethamine
  • Folinic acid
  • For 6 weeks
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13
Q

Second line toxoplasmosis induction therapy:

A
  • Clindamycin, Pyrimethamine, Folinic acid
  • Other alternatives include trimethoprim with sulphamethoxazole OR atovaquone with sulphadiazine or pyrimethamine

Give the above for 6 weeks then lower dose for maintenance
Maintenance can be stopped if CD4>200 and VL UD for 6 months
Steroids if symptoms and signs of raised ICP

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14
Q

Maintenance therapy for toxoplasmosis
(after 6 weeks induction)
(can be stopped when CD4>200 and VL<20 for 6 months)

A
  • Sulphadiazine lower dose
  • Pyrimethamine lower dose
  • Folinic acid 10mg daily
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15
Q

Second line toxoplasmosis maintenance

A
  • Clindamycin
  • Pyrimethamine
  • Folinic acid
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16
Q

First and second line primary toxo prophylaxis

A

First line: Cotrimoxazole 480-960mg daily
Second line: Dapsone 50mg daily with pyrimethamine (50mg/weekly) and folinic acid (15mg/weekly)

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17
Q

Diagnosis of PML

A
  • Lesions are usually bilateral, asymmetric, non enhancing, T2 hyperintense and T1 hypointense
  • Restricted to white matter and no oedema
  • Sharply demarcated as compared to HIVe
  • Pre-ART, JC DNA in CSF had sensitivity of 70-90% and specificity of 92-100% (since introduction ART sensitivity fallen to 50% reflecting reduced viral replication and increased clearance of virus from CSF)
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18
Q

Poor prognostic factors in PML

A
  • Clinical (older age, brainstem involvement, lowered GCS)
  • Viral (high CSF JC VL with delayed clearance with ART)
  • Radiological (early brainstem involvement)
  • Immunological (CD4<100)
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19
Q

Prognosis of PML

A
  • Without ART predicted survival of 10% at 1 year
  • With ART 50% will survive this long
  • Some enter true remission with stabilisation of morbidity and development of atrophy and gliosis on MRI
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20
Q

Seropositivity of CMV

A

50-75%
Most MSM

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21
Q

Major sites of CMV disease

A
  • Retina (accounts for 75%), also GI tract, lung, liver, biliary tract, heart, adrenal glands and nervous system (encephalitis and polyradiculitis)
  • Nervous system disease accounts for <1%
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22
Q

Diagnosis CMV polyradiculitis

A
  • EMG shows axonal neuropathy helping to distinguish from an acute demyelinating polyneuropathy
  • (can present as a lumbosacral polyradiculitis with rapidly progressive, painful, bilateral ascending flaccid paralysis)
  • Positive CSF PCR >80% sensitive and >90% specific
  • Detection of CMV DNA in CSF by PCR correlates well with disease and is not usually due to latent infection, but can also be negative in biopsy proven CMV
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23
Q

Treatment of neurological CMV disease

A
  • Ganciclovir with or without foscarnet
  • ART
  • (prophylaxis not required)
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24
Q

AIDS defining incidence of bacterial pneumonia

A

2 or more episodes in 12 months

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25
Q

Diagnosis of cryptococcal pulmonary disease:

A
  • Usually requires culture of the yeast +/- positive antigen test or staining of the yeast on BAL or pleural fluid
  • Giemsa stain or Indian ink would reveal an encapsulated yeast, calcofluor white with fluorescence microscopy
  • Culture using blood agar or fungal media such as Sabouraud media
  • Biopsy specimens could be stained with fungal stains like Grocott-Gomori methenamine silver
  • Blood cultures or serum CrAg frequently positive suggesting disseminated disease, but may be negative
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26
Q

Predictive factors for PCP

A

Not on ART
Oral thrush or OHL
Weight loss
Not taking septrin
Recurrent bacterial pneumonia
High VL
Previous PCP

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27
Q

First line treatment of PCP

A

Severe = PaO2<9.3
- IV high dose septrin 21 days
- Corticosteroids e.g. 5 days 40mg prep BD, then 5 days 40mg OD then 10 days 20mg OD
Mild-moderate
- PO high dose septrin 21 days

Early use CPAP

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28
Q

Second line treatment for PCP

A

Severe disease:
- Clindamycin and primaquine
- Pentamidine
Mild to moderate:
- As above or trimethoprim + dapsone
- Atovaquone

G6PD should be tested before high dose septrin, dapsone or primaquine

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29
Q

PCP prophylaxis and when to stop

A
  • Septrin 480mg OD where CD4<200 or <14%, - Stop once over these values for 3 months
  • (alternatives include nebulized pentamidine, dapsone plus pyrimethamine)
  • If proven PCP at CD4>200, may consider lifelong
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30
Q

What trial gave evidence to support early ART in PCP and other OI? (But not Tb)

A

ACTG 5164
- RCT, randomised to start ART within 2 weeks Vs more like 6 weeks
- More sick were excluded

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31
Q

Most likely pathogen for a CAP:

A
  • Similar to general population: Strep pneumoniae and haemophilia influenzae
  • Staph aureus has been reported at increased frequency
  • Pseudomonas aeruginosa has been noted more at low CD4
  • Consider gram negative pathogens if develop in hospitalised setting (e.g. pseudomonas, klebsiella, E-coli, acinetobacter)
  • SMART study identified that a structured treatment interruption was associated with increase incidence of bacterial pneumonia
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32
Q

Diagnosis of pulmonary cryptococcus neoformans:

A
  • Symptoms and radiology may be indistinguishable from PCP
  • Sputum/BAL/pleural fluid could be stained with Giemsa stain, India ink or calcofluor white with fluorescence microscopy
  • Cryptococcal antigen can be detected in BAL which is 100% sensitive and 98% specific
  • Yeast can be cultured from BAL or biopsy specimens using blood agar or fungal media like Sabouraud media
  • Bloods specimens can be stained with E.G. Grocott/Gomori methenamine silver
  • Serum CrAG and blood culture frequently positive
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33
Q

Side effects of septrin

A

Rash
Hyperkalaemia
Thrombocytopenia/leukopenia
GI disturbance
Fever
Hepatitis
Anaphylaxis

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34
Q

Treatment of pulmonary cryptococcus neoformans

A
  • Ambisome + flucytosine 2 weeks then 400mg fluconazole for 10 weeks total then 200mg until CD4>100 and VL<20 for 3 months
  • If LP has excluded CNS disease then could treat with fluconazole 400mg OD for 10 weeks then 200mg
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35
Q

Aspergillosis diagnosis:

A
  • Aspergillus spp colonise lung, however if the fungus invades the parenchyma it’s called invasive aspergillosis
  • Can present insidiously
  • Diagnosis combination of radiology and micro: fungal stains such as KOH or Grocott-Gomori methanamine silver
  • Galactomannan test is an enzyme linked assay that detects a cell wall constituent of Aspergillus - false positives can occur e..g in those receiving tazocin
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36
Q

Treatment of aspergillosis:

A

Voriconazole
Ambisome alternative
Caspofungin if significant renal or liver disease

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37
Q

Diagnosis and treatment of CMV pneumonia

A
  • Requires biopsy showing intranuclear viral inclusion or positive immunostaining for CMV antigens plus a compatible syndrome and no alternative cause
  • Treatment:
  • Gancliclovir 21 days
  • Foscarnet or cidofovir are alternatives
38
Q

First line treatment for oral and oesophageal candida

A
  • Oral: fluconazole 100-200mg/day for 7-14 days
  • Oesophageal: 200-400mg/day 14-21 days

Caspofungin or ambisome alternatives

Alternatives for oral candida:
- Nystatin 100,000 units/ml, amphotericin lozenges, clotrimazole pessaries etc

39
Q

Treatment of CMV oesophagitis or colitis

A
  • IV gancliclovir
  • Oral valganciclovir alternative
40
Q

Treatment of HSV oesophagitis

A
  • Aciclovir IV followed by valaciclovir or famciclocvir oral for total for 14 days
41
Q

Who with bacterial diarrhoea should get Abx

A

If CD4<200, or if C diff

42
Q

Treatment of microsporidium

A
  • ART
  • If E. intestinalis then albendazole
43
Q

Treatment of entamoeba histolytica

A
  • Metronidazole high dose 10 days then paromomycin (for luminal infection)
  • (or diloxanide furoate)
44
Q

Strogyloides stercoralis treatment

A
  • Ivermectin
  • (alternative albendazole)
45
Q

Schistosoma treatment

A
  • Praziquantel
46
Q

Stool investigation to look for Microsporidia

A
  • Examination of 3 stools with chromotrope and chemofluorescent stains
47
Q

Treatment of CMV retinitis

A
  • If peripheral disease only then oral valganciclovir 900mg BD induction for 2 weeks, (ganciclovir/foscarnet/cidofovir alternatives)
  • If zone 1 or 2 (more central) part of retina involved then may use adjunctive intraocular ganciclovir or foscarnet
  • Continue valgan 900mg OD until CD4>100

NB all CMV therapies can cause cytopenias, renal toxicity and electrolyte disturbance

48
Q

Treatment of Chagas disease

A

Benznidazole

49
Q

Anti-fungals in pregnancy

A
  • Aim for topical treatment where possible e.g. PV clotrimazole or PO nystatin, avoid fluconazole certainly in first trimester,
  • Ambisome can be used in most cases instead
  • Caspofungin and voriconazole never
50
Q

Treatment of varicella zoster virus

A
  • Primary varicella (chickenpox): IV acyclovir or oral if CD4 ok and uncomplicated disease
  • Zoster: start treatment as soon as possible and continue for at least 7 days until lesions dried
  • > Localised dermatomal zoster: oral acyclovir 800mg 5x day
  • > Severe cutaneous or disseminated or CNS disease admit for IV acyclovir 10-14 days
  • > if resistance or failing then IV foscarnet
51
Q

Which of HSV1 or HSV2 more likely to cause meningitis?

A
  • HSV1 more likely encephalitis
  • HSV2 more likely meningitis
  • > CSF HSV DNA very sensitive and specific although may get false negative in first 72 hours
52
Q

Treatment of HSV encephalitis

A

Acyclovir IV

53
Q

Diagnosis of MAC

A
  • Culture in blood or from bone marrow aspirate
  • Preferred culture method on solid media e.g. Lowenstein-Jenson, middlebrow
  • May see acid fast organisms before cultures are back
54
Q

Treatment of MAC

A
  • Macrolide and ethambutol with or without rifabutin (given when marked symptoms or advanced immunosuppression)
  • Clarithromycin better (max 500mg BD) than azithro however azithro has fewer DDI and better tolerated
55
Q

How long to continue MAC treatment?

A
  • Stable on ART with low VL, CD4>100 for at least 3 months and clinical response (asymptomatic and negative blood cultures) for at least 3 motnhs
56
Q

If patient not responding to MAC treatment in 4-8 weeks what to do?

A
  • Construct a new regimen out of e.g. rifabutin, linezolid, oflox, levoflox, moxiflox, amikacin
  • Most would continue ethabutol as it facilitates the penetration of other agents into the mycobacteria
57
Q

MAC prophylaxis

A
  • Consider if CD4<50
  • Azithromycin 1250mg weekly (can stop when VL<20 and CD>50 for at least 3 months)
58
Q

Mycobacterium kansasii treatment

A
  • Rifamycin is key (rifampicin or rifabutin) then ethambutol, isoniazide + pyridoxine
  • RIE
59
Q

Diagnosis of malaria

A
  • Thick film to diagnose malaria and estimate % parasitaemia
  • Thin film- for speciation
  • +/- rapid diagnostic antigen test
60
Q

Treatment of uncomplicated falciparum malaria

A
  • Artemether-lumefantrine (Riamet) (PIs might decrease levels but can still give)
  • Alternatives include quinine with doxy or quinine with clinda
61
Q

Treatment of severe falciparum malaria

A
  • IV artesunate first line
  • IV quinine 2nd line (QT prolongation, ECG before, ideally on monitor, monitor BM carefully too)
  • In pregnancy IV artesunate not recommended in frist trimester, might go for quinine and clindamycin
62
Q

Treatment of leishmaniasis

A
  • Visceral leish: ambisome
  • Cutaneous: local infiltration of sodium stibogluconate or systemic
63
Q

Treatment of penicillosis
(septate yeast forms, red colour, SouthEast asia and China)

A
  • Ambisome 2 weeks then intraconazole 10 weeks then maintenance
64
Q

Do ODG in suspected oesophageal candida in the following sitautions:

A
  • No oral lesion
  • Not responding to treatment
  • Alternative condition suspected
65
Q

Most common forms of candida causing infection

A

Candida albicans 62-68%
Candida glabrata 17-21%
Candida dublinessis 6-12%

Glabrata should be treated with alternative to fluconazole unless susceptibility shown
Candida Auris new cause of inherently multi drug resistant

66
Q

First line treatment for oral and oesophageal candida

A

Oral: fluconazole 100-200mg 7-14, chlorhexidine mouthwash and removal of biofilms
- Topical e.g. nystatin has slower clearance of yeast, higher relapse rate and reduced tolerability, might use in pregnancy
Oesophageal: fluconazole 200-400mg 14-21 days depending on severity
- Intraconazole an option but fluconazole better short term response and fewer DDI
- Aim to stop PPIs with fluconazole
- Itraconazole should not be given with enzyme inducers

67
Q

Monitoring with azoles

A
  • Other that fluconazole 100mg OD or less, all require regular LFT monitoring e.g. in the first week then monthly or bimonthly
  • Avoid itraconazole in heart failure
  • If fluconazole not working can try itraconazole/voriconaozle/posiconazonole, if not working or intolerant can try e.g. caspofungin, ambisome etc.
68
Q

Monitoring with azoles

A
  • Other that fluconazole 100mg OD or less, all require regular LFT monitoring e.g. in the first week then monthly or bimonthly
  • Avoid itraconazole in heart failure
  • If fluconazole not working can try itraconazole/voriconaozle/posiconazonole (need TDM with these), if not working or intolerant can try e.g. caspofungin, ambisome etc.
69
Q

Treatment of vulvovaginal candida due to non-albicans candida with reduced fluconazole suscepbibillity e.g. C.glabrata

A

Nystatin pessaries or 5-flucytosine, amphotericin pessaries or topical boric acid

70
Q

Management of latent Tb

A
  • Test with IGRA those from medium (40-150/100,000 person years) and high incidence countries (>151/100,000 person years)
  • Exclude active Tb first
  • Repeat in 4 weeks if indeterminate
  • Don’t test if Hx of Tb
  • Treat with 6 months isoniazid + pyridoxine
  • OR 3 months Rifampicin + isoniazid +pyridoxine
71
Q

Tb treatment if on a PI

A

Replace rifampicin with rifabutin

72
Q

When to start ART in active Tb

A
  • If CD4<50 start as soon as possible within 2 weeks
  • if CD4>200 benefit of early ART less clear, could wait until induction (2 months) over
  • Don’t start early if TBM
  • SAPIT + CAMELIA: early ART (within 2 weeks or so) where CD4< 50- less death
  • In SAPIT, deferral of ART to 4 weeks post ART in those with higher CD4 reduced risk of IRIS without increasing AIDS or death
73
Q

What ART with Tb treatment?

A
  • Truvada + EFV is first line in those taking rifampicin
  • RAL 800mg BD or DTG 50mg BD can be used, continue BD for 2 weeks after stopping rifampicin
  • Aim to avoid kivexa as ABC hypersensitivity may confuse the picture
  • Rilpivirine should not be given with rifamycins
  • Do not use cobi with rifamycins as no data, if ritonavir boosted PI use rifabutin
  • Do not use doravirine with rifampicin, can do 100mg BD doravirine with rifabutin continuing 2 weeks after stop rifabutin
  • Don’t use fixed combinations with TAF or BIC, or dual therapy or injectables until further data
74
Q

IGRA Vs tuberculin skin test

A
  • Both less likely to be positive in presence of advanced immunosuppresion, but IGRA less affected
  • IGRA not affected by prior BCG vaccination but tuberculin skin test is
  • IGRA do not require follow up visit to read the result like tuberculin skin test
  • Both may be negative early in the window perio
75
Q

What mutation do Xpert MTB/RIF look for fo rapid identification or rifampicin resistance?

A

rpoB

76
Q

Sensitivity and specificity or Xpert MTB/RIF

A
  • In smear positive Tb 98-99% sensitive and specific
  • However in smear negative Tb more like 67% sensitive
    (Newer Xpert MTB/RIF Ultra has improved sensitivity but lower specificity)
    (WGS requires a culture isolate, Xpert don’t)
77
Q

Diagnosis of Tb meningitis

A
  • CSF usually lymphocytic, low glucose, high protein, can be accelular in advanced disease
  • Gold standard is Mt by culture, but limited sensitivity
  • Staining for AFB has low sensitivity, so use large volumes, Xpert MTB/RIF Ultra better however negative still doesn’t exclude
  • ADA can be useful but not standardised so not recommended
    Do MRI
78
Q

Diagnosis of pleural Tb

A
  • Pleural fluid PCR has low sensitivity for diagnosis of pleural Tb, same with culture
  • Even if not obvious cough or parenchymal disease do induced sputum or BAL for culture
  • Medical thoracoscopy may be useful
  • ADA may be useful, if lymphocyte predominant exudative effusion with raised ADA -> high probability of Tb
79
Q

Tb mimics on histopathology

A

Histoplasmosis (always do fungal stain), sarcoidosis, nocardiosis, leishmaniasis, tumour, vasculitis, brucellosis, meliondosis

80
Q

What should you consider if smear positive for AFB with negative molecular tests for TB, whilst awaiting cultures?

A

Consider covering for MAC too by using rifabutin instead of rifampicin and adding cali or azithromycin to regimen until cultures available

81
Q

Tb treatment interruptions

A
  • During intensive phase if <14 days just complete, but if >14 days start again
  • During continuation phase varies, but if received less than 80% doses and lapse >3 months restart from beginning with intensive
82
Q

Investigations and monitoring in Tb treatment

A
  • At start of treatment do HIV VL, CD4, ALT/AST, Bili, ALP, creatinine, platelets, hep B and C, Snellen and Ishihara plates
  • Liver check at 2 weeks then 2-4 weekly
83
Q

Definition of treatment failure in Tb

A
  • Smear or culture positive at 5 months
  • Usually an adherence issue
84
Q

What to give for isolated isoniazid resistance?

A

Rifampicin, ethambutol, pyrazinamide and levofloxacin (moxiflox and rifampicin DDI)

85
Q

Definition of MDR and XDR

A

MDR is at least isoniazid and rifampicin resistance (1.5% in UK), if also fluoroquinolone and injectables (e.g. amikacin) resistant then XDR
(get specialist input, an all oral regimen might be constructed with bedaquilline, don’t give if QT interval>500ms

86
Q

Example of fluoroquinolone

A

Moxiflox
Levoflox
Ciproflox
(Tendon pain)

87
Q

Rifamycins and steroid

A
  • Increase steroid dose 50% with rifampicin
  • Increase steroid dose 33% with rifabutin
88
Q

Rifampicin and methadone

A
  • Rifampicin will reduce levels of methadone and could cause symptomatic withdrawal, equally when rifampicin stopped could get methadone side effects
  • No issue with rifabutin
89
Q

Definition of DILI

A
  • AST/ALT X3 upper limit of normal if symptomatic
  • AST/ALT X5 upper limit of normal if asymptomatic
90
Q

What to do if DILI

A
  • Consider stopping all potentially liver toxic drugs: rifampicin, isoniazid, pyrazinamide, septrin, some ART
  • Aim to continue Tb treatment with liver friendly regimen such as ethambutol, streptomycin, amikacin, levoflox (not moxiflox)
  • Monitor LFTs regularly
  • Once ALT/AST drops to <2x upper limit normal can re-introduce a first line regimen with a reintroduction regimen
  • If initial reaction was life threatening, use different drugs
91
Q

If have pre-existing liver disease, which Tb drug to stop first if DILI?

A

Pyrazinamide
If don’t already have liver disease ?isoniazid

92
Q

Most likely cause of rash with Tb treatment?

A
  • Ethambutol
  • If no mucosal involvement, treat symptomatically, if widespread of worsening stop all drugs and use reintroduction regimen