Infections in Immunocompromised & HIV Challenging Cases …...Case • DVS 61 M DM (MM00318824 ) •...
Transcript of Infections in Immunocompromised & HIV Challenging Cases …...Case • DVS 61 M DM (MM00318824 ) •...
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Infections in Immunocompromised & HIV –
Challenging Cases
Dr Neha Gupta
MD (Gen Medicine), FNB Infectious Diseases
ID Fellowship (Hinduja Hospital )
ID Observership (CMC Vellore & Wayne State, USA)
Infectious Diseases Specialist, MEDANTA-The Medicity
& Fortis Memorial Research Institute , Gurugram
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• Infections in Immunocomprimised coexists as an uneasy
relationship
• Differs considerably in approach, investigations & management
• Empiric treatment has its limitations
• Appropriate investigations may be better than toxic & ineffective
therapy
• History, examination, appropriate tests & interpretation
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• S 28 YGirl
• 2017- SLE with DM & HTN – Hepatitis with LV EF-30%, Cr -4 mg %
• Azathoprine, Prednisolone 25 mg OD
• Dec 2019: OT/PT - 3805/3407 – Biopsy could not be performed
• Dec 2018: IV GCV - 1186/1063
• June 2019- ID Reference
• c/ severe myalgia
• Fever lethargy
• c/o loose motions
• CBC – TLC 21,500
• Plt – 185
• Hb – 7 gm %
• SGOT – 1678/ 1764
• Albumin 2.5, Globulin 2.2
• Creat – 3.2
Case
8 Dec
2018
29th
Jan
2019
March
2019
May
2019
June
2019
June
2019
CMV
DNAe
mia
98,000
Copies
/ml
ND 29,000 66,000 71,
415
GCV/
VGCV
dose
IV
GCV
75 mg
thrice/
week
VGCV
450
mg
twice
/wk
IV
GCV
62.5
mg
OD
IV
GCV
62.5
mg
OD
VGCV
450 twice
/week
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Which of the following is false?
1.Persistent CMV DNAemia at 2 weeks is not predictive of
emerging drug resistance
2.Genotypic assays for viral DR mutations is reliable with CMV
copy of atleast 1000 IU/mL
3.UL97 (90%) & UL54 mutations cause most GCV resistance
4.Full –high dose GCV is recommended if severe disease is
present in suspected resistant cases
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Which of the following is false?
1. Persistent CMV DNAemia at 2 weeks is not predictive of
emerging drug resistance
2. Antiviral resistance is suspected with 6 or more weeks of
cumulative GCV exposure & treatment failure
3. UL97 (90%) & UL54 mutations cause most GCV resistance
4. Full –high dose GCV is recommended if severe disease is
present in suspected resistant cases
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• Resistance to antiviral agents has been increasingly recognized as an
important problem in antiviral therapy
• CMV VL IU has better standardization than in house assays of
copies/ml (1 copy ~ 0.9 IU) - (WHO 2010)
• vGCV & IV GCV similar outcomes in SOTRs for non-severe CMV syndrome &
tissue –invasive CMV disease –VICTOR Study
• Induction with IV GCV in preferred - GI disease, severe disease & accurate
dose modification
• Induction till for a minimum of 2 weeks, until clinical resolution of disease &
eradication of CMV DNAemia below a specific threshold (LLOQ < 200 IU/mL)
on 1 or 2 consecutive weekly samples (strong, moderate)
Camille Kotton et al. CMV Consensus Guidelines 2018
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• The viral load declined with a median half-life of ~11 days after an initial lag of
6 days & the median time to viral load below 200 copies/mL was 21 days;
longer with starting viral loads of more than 50000 copies/mL. Thus,
persistent viral loads in the first 2 weeks of treatment are not predictive of
emerging drug resistance
Ref: Asberg et al. Am J Transplant. 2007;7:2106-2113
• Antiviral Resistance Suspected
- 6 or more weeks of cumulative GCV exposure & treatment failure (No clinical
response or improvement pVL) after > 2 weeks of ongoing full dose GCV or
VGCV
- Risk factors for drug resistance include
Prolonged antiviral drug exposure (median, 5 months) & ongoing active
viral replication due to factors such as the lack of prior CMV immunity (D+/R-
), high levels of immunosuppressive therapy, or inadequate antiviral drug
delivery
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• Genotypic assays for viral DR mutations is reliable with CMV copy of
atleast 1000 IU/mL with atleast 20-30% resistant population
Resistance Cross Resistance
UL 97 ( 450 -650) GCV
UL 54 (300-1000) GCV CDV &/or Fos
7 canonical mutations confer for 80% resistance
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Case
• DVS 61 M DM (MM00318824 )
• 2012: LDRT on Tac 2.5 mg BD, Pred 75 mg
once OD, Azathioprine 50 mg 1-0-0 &
Insulin. Creat – 1.5 mg%
• Nov 2017- developed small abscess (not so
painful) followed by ulcer
• 30th Nov 2017: Plastic Surgery -Carbuncle &
first debridement
• G stain, Aerobic culture – Negative
• TB Culture & Fungal cultures – not sent
Amox Clav & Linezolid
• Recurrence- 13 March 2018 - Second
debridement - G stain, Aerobic culture –
Negative, TB cultures not sent
• ID reference for non-healing ulcer Courtesy: Dr Sanjay Mahendru, Plastic Surgeon, Medanta
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• CT sinogram- sinus at the left anterior
abdominal wall
• Sinus excision done (Plastic Surgery)
– chronic granulomatous inflammation
• Tissue – AFB Positive
• Gene X Pert MTB/RIF – negative
(Courtesy – Dr Smita Sarma)
• History – Using same insulin syringe
for 15-20 days
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What is the best treatment option for this patient?
1. Clarithromycin + rifampicin + Ethambutol
2. Amikacin + Clarithromycin + Clofazimine
3. Moxifloxacin + TMP/SMX + Imipenem
4. Linezolid + Clarithromycin + Clofazimine
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What is the best treatment option for this patient?
1. Clarithromycin + rifampicin + Ethambutol ( MAC/ DI)
2 Amikacin (Nephrotoxicity) + Clarithromycin + Clofazimine
3. Moxifloxacin + TMP/SMX + Imipenem (R)
4. Linezolid + Clarithromycin + Clofazimine
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Broth Microdilution Method
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The treatment of NTM ( RGM) infections will be based
on the likely site of infection, susceptibility, toxicity
(Amikacin in a renal transplant recipient; Linezolid ),
drug interactions (clarithro-linezolid; clarithromycin-
tacrolimus), immune status, IV or oral option,
costs of therapy
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Non-Tuberculous Mycobacteria (NTM) - Not Far Behind in Resistance
JAPI 2015
CIDSCON 2012,
Chennai
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• Atleast 3 drugs with sensitivity to which NTM is
susceptible should be used
• Amikacin is potentially combined with linezolid &
clarithromycin. Alternatives like clofazimine if intolerance
( For example- Amikacin in a renal transplant recipient
may not be a good choice ) or resistance ( in our patient
– Linezolid was resistant )
• Treatment duration – depending upon the site of
infection - 2 months
• Inj Amikacin (After Nephrology clearance)+ clarithromycin +
clofazimine & then, later Amikacin d/c as creat increased
to 1.8 – Cefipime added
•
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• Inj Cefepime, Clofazimine,
& Clarithromycin (Till Aug 2018)
• Tac level monitored