Which immune cells do you need? and if they are not there then what type of infections may you get?
- Neutrophils – bacterial & fungal infection
- Monocytes – fungal infection
- Eosinophils – parasitic infections
- T lymphocytes – fungal & viral infection, PJP
- B lymphocytes – bacterial infection
CAUSES OF DEATH AFTER
TRANSPLANTS DONE IN 1996-2000
how do the number of deaths due to infection comapre beteen ALLO and AUTO transplants?
ALLO – allogeneic transplant
Significant number of infections
what are some Supportive measures aimed at reducing risk of sepsis in Haematological malignancy?
•Prophylaxis:
- Antibiotics (ciprofloxacin)
- Anti-fungal (fluconazole or itraconazole)
- Anti-viral (aciclovir)
- PJP (co-trimoxazole)
- Growth factors e.g. G-CSF (important way of speeding neutrophil recovery and reducing duration of neutropenia)
- Stem cell rescue/transplant (If patient has gotten a high dose of chemo we don’t wait for their body to recover, we use stem cells to speed up recovery)
- Protective environment e.g. laminar flow rooms
- Intravenous immunoglobulin replacement
- Vaccination
in this picture showing, what can this lead to?
Neutropenia
Bone marrow - Before you have plenty of cells and fat spaces
Neutropenia is predictable after standard cytotoxic chemotherapy
Neutropenic Risk:
what is the cause of neutropenia?
marrow failure higher risk than immune destruction
Neutropenic Risk:
what is the different degress of neutropenia?
< 0.5 x 109/l - significant risk
< 0.2 x 109/l - high risk
Neutrophil count has to fall significantly before there is a risk of infection
Neutropenic Risk:
what is the duration of neutropenia?
> 7 days - high risk
(AML therapy & stem cell transplantation produces profound neutropenia ~ 14-21 days)
what are some Additional Risk Factors for Infection?
•Disrupted skin / mucosal surfaces
- Hickman line, venflons
- Mucositis affecting GI tract
- GVHD
•Altered flora/antibiotic resistance
- Prophylactic antibiotics
•Lymphopenia
- Disease process e.g. Lymphoma
- Treatment eg Fludarabine, ATG
- Stem cell transplantation, GVHD
•Monocytopenia
- Hairy cell leukaemia
- Chemotherapy
Febrile Neutropenia Bacterial causes:
how common is gram positive or gram negative infections?
- Gram-positive bacteria (60-70%) (Positive often get in through lines)
- Gram-negative bacilli (30-40%)
- These patterns may now relate to antibiotic prophylaxis, emerging infections, use of lines etc
Febrile Neutropenia Bacterial causes:
what are some gram-positive bacteria that may be repsonsible?
•Staphylococci: MSSA,MRSA, coagulase negative
•Streptococci : viridans
- Enterococcus faecalis/faecium
- Corynebacterium spp
- Bacillus spp
Febrile Neutropenia Bacterial causes:
what are some gram-negative bacteria that may be repsonsible?
•Escherichia coli
•Klebsiella spp : ESBL
•Pseudomonas aeruginosa
- Enterobacter spp
- Acinetobacter spp
- Citrobacter spp
- Stenotrophomonas maltophilia
what are some possible sites of infection?
- Respiratory tract (often have signs of pneumonia and hypoxia)
- Gastrointestinal (Typhlitis)
- Dental sepsis
- Mouth ulcers
- Skin sores
- Exit site of central venous catheters
- Perianal (avoid PRs! - When you have patients with low blood counts then don’t do PRs)
Area of cellulitis around hickman line insertion site
Periorbital cellulitis
Disseminated herpes infection associated with secondary cellulitis so combination of a viral and bacterial infection
how does neutropenic sepsis present?
- Fever with no localising signs - Single reading of >38.50C or 380C on two readings one hour apart
- Rigors
- Chest infection/pneumonia
- Skin sepsis - cellulitis
- Urinary tract infection
- Septic shock
Early recognition and treatment of Sepsis is ________________
Life saving
what is the definition of Severe Sepsis/Septic Shock?
Action
Deliver the sepsis six - what is it?
Every hour’s delay in administering antibiotics increases chance of mortality by 8%
- Administer high flow oxygen
- Take blood cultures, other cultures, consider source control
- Give appropriate IV antibiotics within ONE hour (of presentation)
- Measure serum lactate concentration ( can give you an idea of prognosis)
- Start IV fluid resuscitation (maintains blood pressure)
- Assess/measure urine output
what are some Investigations of neutropenic fever
- History and examination
- Blood cultures - Hickman line & peripheral
- CXR
- Throat swab & other clinical sites of infection
- Sputum if productive (if they have productive cough)
- FBC, renal and liver function, coagulation screen
what is the management of neutropenic sepsis?
- Resuscitation – ABC (Resuscitation is the initial goal and getting in the sepsis 6 as soon as possible)
- Broad spectrum I.V. antibiotics - Tazocin and Gentamicin
- If a gram positive organism is identified add vancomycin or teicoplanin
- If no response at 72 hours add I.V. antifungal treatment e.g. Caspofungin - empiric therapy
- CT chest/abdo/pelvis to look for source
- Modify treatment based on culture results
Infection in immunocompromised patients - what may cause a fungal infection and what is it like?
e.g. Candida species, Aspergillus
Life threatening deep seated infection
Lung, liver, sinuses, brain
•Monocytopenia and monocyte dysfunction contributes to risk of fungal infection
Pulmonary aspergillosus
Also can make a microbiological diagnosis
what is the therapy for fungal infections?
- Empirical – echinocandins eg Caspofungin, Anidulafungin
- Aspergillus – Voriconazole, Isavuconazole
- Moulds – Liposomal amphotericin (Ambisome)
(Mould is tough to treat but don’t come across it that often)
Infection in severely lymphopenic patients - what different ways can it occur?
- Stem cell transplant recipients, especially allogeneic
- Recipients of Total Body Irradiation (TBI)
- Graft vs Host Disease
- Nucleoside analogues (fludarabine) or ATG (both very suppressive to T cell making you prone of infection for long periods of time)
- Lymphoid malignancy e.g Lymphoma, CLL, ALL
- Pneumonitis - Pneumocystis Jirovecii (PJP), CMV, RSV
- Viral - Shingles (Varicella Zoster), Mouth ulcers (Herpes simplex), Adenovirus, EBV (PTLD), SARS-CoV2
- Fungal - candida, aspergillus, mucormycosis
- Atypical mycobacteria - Skin lesions, pulmonary and hepatic involvement
what therapies are used for different viral infections?
- PJP – high dose co-trimoxazole
- CMV – ganciclovir, foscarnet
- HSV1, VZV – aciclovir
- Influenza A/B – oseltamivir, zanamivir
- Adenovirus – cidofovir
- RSV – ribavirin
- Immunoglobulin replacement (eg post alloSCT)
Summary:
- Recognise & treat possible infection _____ in post-___________ patients
- Immunity (particularly T cell) can be __________ for a long time due to disease or treatment
- Much lower threshold for ________ and hospitalisation in the immunocompromised
early
chemotherapy
suppressed
antibiotics
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1. Introduction: The scope of clinical haematology40
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3. Red Cells 130
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Red Cells 250
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Haemostasis33
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Blood Transfusion38
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Thrombotic Disorders28
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Bleeding Disorders47
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Haematological Malignancy27
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Myeloid Malignancy34
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Anaemia – in Practice25
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Lymphoproliferative Disorders47
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Haematostasis and Thrombosis in Practice: Clinical Cases Haemostasis and Thrombosis27
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Myeloma and Paraproteins38
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Infection24
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Haematological Malignancy in Practice29
