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 ) •...
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
• 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
• 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
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
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
• 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
• 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
• 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
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
• 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
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
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
Broth Microdilution Method
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
Non-Tuberculous Mycobacteria (NTM) - Not Far Behind in Resistance
JAPI 2015
CIDSCON 2012,
Chennai
• 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
•
• Inj Cefepime, Clofazimine,
& Clarithromycin (Till Aug 2018)
• Tac level monitored