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