L4 Infections in the Immunocompromised

Question 1

Infections in humoral immune deficiency?

Asplenia?

Answer 1

Extracellular pathogens!!

Recurrent RTI with encapsulated bacteria:
Streptococcus pneumoniae
Haemophilus influenzae

Chronic diarrhoea: Giardia lamblia (Protazoa)

Splenectomy, trauma, sickle-cell anaemia (Antibody production is impacted by the absence of a spleen)

Encapsulated bacteria
* Neisseria meningitidis
* Streptococcus pneumoniae
* Haemophilus influenzae

Plasmodium species (Malaria), Babesia species

Question 2

Infections in T lymphocyte deficiency?

Answer 2

Intracellular pathogens!!

Viral
Herpes simplex virus
Cytomegalovirus
HIV

Fungal
Superficial candidiasis
Cryptococcus neoformans
Pneumocystis jiroveci (carinii)

Protozoan
Toxoplasma gondii

Bacterial
Mycobacterium
Listeria

Question 3

How is neutropenia defined?

Answer 3

1. Mild neutropenia: 1000-1500 cells/μl
2. Moderate neutropenia: 500-1000 cells/μl
3. Severe neutropenia: < 500 cells/μl

Question 4

Causes of Neutropenia?

Answer 4

• Cytotoxic chemotherapy or radiotherapy
• Haematological diseases (acute leukaemia)
• Bone marrow transplantation
• Drug reactions (e.g. sulfasalazine, co-trimoxazole,
  penicillins)

Question 5

Pathogens responsible for Infections in Neutropenia?

Most Common Pathogen?

Answer 5

Infectious source identified in only 20-30%

80% arise from patient’s endogenous flora

Gram-positive infections (60%):
S.epidermidis most common pathogen (less virulent)
Also: S.aureus, viridans streptococci, enterococci

*Gram-negative infections (40%):
* Increasing resistance among gram-negative pathogens

Question 6

Most frequent cause of Neutropenic Fever?

Answer 6

Mucositis: may cause seeding of bloodstream by endogenous flora of GIT

Central venous catheter (staphylococci, Gram(-) Bacteria)
Urinary catheter (Gram (-) Bacteria)

Question 7

Most common cause of Fungal Infections in Neutropenia

Other causes?

Answer 7

Invasive yeast infections (Candida Albicans) is the most frequent
* Central line infections
* GI tract/Mucositis
* Fever is often the only symptom
* Blood cultures, b-D-glucan assay
* Hepatosplenic involvement common in disseminated candidiasis

Invasive mold infections
* Environmental spores are inhaled into nose/lung

Aspergillus common fungal pathogen
* Most common manifestation is RESPIRATORY TRACT, also CNS, bones, and skin

Mucorycosis
* rhino-orbital-cerebral, pulmonary, disseminated infections
* Prophylaxis, empiric therapy in high-risk patients

Question 8

Viral Infections in Neutropenia?

Answer 8

Human Herpesviruses

• HSV-1 (HSV-2): Ulcers, stomatitis, encephalitis, pneumonia, hepatitis (Aciclovir Prophylaxis)
• Herpes Zoster (disseminated pattern!)
• EBV, CMV, HHV6

Respiratory viruses

Question 9

Diagnosis/Investigations/Management of Neutropenic sepsis?

Answer 9

Diagnosis
Fever > 38.5°C on one occasion
or
Fever > 38 °C for more than one hour

Fever may be absent (Elderly, steroids)
*Clinical deterioration in the absence of fever

Investigations
– Blood cultures – line and peripheral
– Galactomannan (Aspergillus antigen)
– Sputum, urine, throat, faeces, wounds (Viral specimen!)
– CXR

Empiric treatment: Broadspectrum, aimed at Gram-(-)
– Piptazobactam ± Gentamicin,
– Ceftazidime ± Gentamicin (penicillin allergy)

Persistent Fever (>48 Hours)
>Add Gram-(+) agent (teicoplanin, vancomycin)

> if still pyrexial after 48h add antifungal

Question 10

Prophylaxis in Neutropenia?

Answer 10

> Hand hygiene

> Protective isolation (HEPA filters)

> Line care

> General measures
– No Flowers
– No Uncooked food

> Drugs
– Colony-stimulating factors
– Antiviral
– Antifungal
– (Antibiotic)

Question 11

Difference between Bone Marrow and Solid Organ Transplants?

Answer 11

Bone Marrow
* Profound immunosuppression
* Graft versus host disease occurs frequently
* Previous chemotherapy & antibiotics usual
* Absence of a surgical wound
* Initial period of complete immunosuppression (30 days)

Question 12

Time Frame of Infections in Bone Marrow Transplants?

Answer 12

Days 1-21 (Neutropenia, Pre-engraftment)
* Bacterial
* Systemic fungal
* HSV Infection

Days 30-90 (T Cell & Acute Graft Versus Host Disease)
MORE INTRACEULLAR INFECTIONS
* CMV (Highest risk (D-, R+))
* EBV => PTLD (Posttransplant lymphoproliferative disease)
* Hepatitis B reactivation
*Pneumocystis jiroveci
* Toxoplasma gondii

1-2 years (Chronic Graft Versus Host Disease (CGVHD)
Steroids to reduce response
* Capsulated bacteria
* VZV

Question 13

Solid Origin Transplants with the highest Incidence of Infection?

Answer 13

1. Kidney-Pancreas
2. Lung
3. Liver

Question 14

Time Frame of Post SOT infections?

Answer 14

Early < 1 month: nosocomial – wound, lung, intra-abdominal collection (bacterial, candida)

1-6 months: Opportunistic (CMV, PjP, Aspergillosis, Listeria)

Late > 6 months: community-acquired

Question 15

Immunosuppressive Drugs with Complications?

Answer 15

Steroids
> Dose- and time- dependent
> Pyogenic infections most frequent
> Intracellular pathogens: (PjP, Legionella, TB, Herpes zoster)

Anti-TNF treatment (Infliximab, etanercept):

Indications: IBD, Rheumatoid arthritis, Psoriasis

Associated infections:
* Tuberculosis (screening!)
* HBV reactivation
* Invasive Staph. aureus, Strep. pneumoniae
* Histoplasmosis
* Candida

B cell depleting therapies (Rituximab, alemtuzumab):

Indications: Non-Hodgkin lymphoma, rheumatoid arthritis, vasculitis, multiple sclerosis …….

• Significant increased risk of Hepatitis B reactivation
• Screening, pre-emptive therapy!