infections in patients w/ haematological malignancy Flashcards
cause of death after stem cell transplants
supportive measures aimed at reducing risk of sepsis in haematological malignancy
prophylaxis growth factors e.g. G-CSF stem cell rescue/transplant protective environment e.g. laminar flow rooms IV immunoglobulin replacement vaccination
prophylaxis to reduce risk of sepsis in haematological malignancy
abx - ciprofloxacin
anti-fungal - fluconazole, itraconazole
anti-viral - aciclovir
PJP - co-trimoxazole
who is at highest risk of neutropenic infection
cause of neutropenia (marrow failure > immune destruction)
degree of neutropenia
- <0.5x10^9/L - significant risk
- <0.2x10^9/L - highest risk
duration of neutropenia
- >7days - high risk
(AML therapy and stem cell transplantation produces profound neutropenia ~14-21 days)
why do marrow failure pts have higher risk of neutropenic infection than immune destruction pts
bone marrow failure = failure of production
- only neutrophils left are old and dying and less functional
immune destruction - bone marrow is still able to respond to infection and produce more neutrophils which are able to fight the infection
additional risk factors for infection
disrupted skin/mucosal surfaces
altered flora/abx resistance
lymphopenia
monocytopenia
disrupted skin/mucosal surfaces examples
hickman line, venflons
mucositis affecting GI tract
GVHD
altered flora and antibiotic resistance - how can it occur
prophylactic abx can save lives in severe neutropenia but also have -ve side effects
lymphopenia as an additional risk factor for infection - what causes it
common in lymphoma
result of treatment e.g. fludarabine, ATG
stem cell transplantation, GVHD
what causes monocytopenia
hairy cell leukaemia
chemotherapy
bacterial causes of febrile neutropenia
gram +ve - 60-70%
gram -ve bacilli - 30-40%
patterns may now relate to abx prophylaxis, emerging infections, use of lines etc
what types of gram +ve bacteria infections are seen
staphylococci: MSSA, MRSA, coagulase -ve
streptococci: viridans
enterococcus faecalis/faecium
corynebacterium spp
bacillus spp
what types of gram -ve bacterial infections are seen
escherichia coli
Klebsiella spp: ESBL
psuedomonas aeruginosa
enterobacter spp
acinetobacter spp
citrobacter spp
stenotrophomonas maltophilia
possible sites of infection
resp tract GI - typhlitis dental sepsis mouth ulcers skin sores exit site of central venous catheters perianal (avoid PRs)
presentation of neutropenic sepsis
fever w/ no localising signs - single reading of >38.5 or 38 on two readings 1hr apart
rigors chest infection/pneumonia skin sepsis - cellulitis UTI septic shock
what is crucial in sepsis
early recognition and treatment
consider it in any one who has recently had chemotherapy (even up to 6 weeks after last dose)
what is severe sepsis/septic shock
signs of systemic inflammation (SIRS) AND presumed organ infection and organ dysfunction
what is the sepsis 6
GIVE:
- high flow oxygen
- appropriate IV abx within 1hr
- IV fluid resus
TAKE:
- blood cultures, other cultures, consider source control
- serum lactate concentration
- UO
why is important to administer abx early in sepsis
every hr delay increases chance of mortality by 8%
investigation of a neutropenic fever
hx and examination
blood cultures - hickman line and peripheral
CXR
throat swab and other clinical sites of infection
sputum if productive
FBC, renal function, LFTs, coagulation screen
management of neutropenic sepsis
resus - ABC and sepsis 6
broad spectrum IV abx
- tazocin and gentamicin
- if gram +ve identified: add vancomycin or
if no response at 72hrs: add IV antifungal treatment
- capsofungin (empiric therapy)
CT chest/abdo/pelvis to look for source
modify treatment based on culture results
fungal infection in immunocompromised patients
candida spp e.g. aspergillus
life threatening, deep seated infection
lung, liver, sinuses, brain
what contributes to the risk of fungal infection
monocytopenia and monocyte dysfunction
where is fungal infection most commonly seen
in pts who’ve either had transplant or treatment for acute leukaemia
therapy of fungal infections
empirical - echinocandins e.g. capsofungin, anidulafungin
aspergillus - voriconazole, isavuconazole (can both be given IV/oral)
moulds - liposomal amphotericin (ambisome)
infections in severely lymphopenic patients - when does it happen
stem cell transplant recipients, esp allogenic
recipients of total body irradiation
GVHD
use of nucleoside analogues (fludarabine) or ATG
lymphoid malignancy e.g. lymphoma, CLL, ALL
types of infections seen in severely lymphopenic patients
pneumonitis
viral
fungal
atypical mycobacteria
pneumonitis infections seen in severely lymphopenic patients
- pneumocystis jirovecii (PJP)
- CMV - can also cause GI infection
- RSV
viral infections seen in severely lymphopenic patients
- shingels (VZV)
- mouth ulcers (HSV)
- adenovirus
- EBV (PTLD)
- SARS-CoV2
what is PTLD
post-transplantive lymphoproliferative disorders
driven entirely through activation of EBV
happens in pts who are immunocompromised after transplants (bone marrow/stem cell)
fungal infections seen in severely lymphopenic patients
candida
aspergillus
murormycosis
atypical mycobacteria infections seen in severely lymphopenic patients
skin lesions
pulmonary and hepatic involvement
therapy for viral infections - PJP
high dose trimoxazole
IV initially then switch to oral if patients can tolerate it
therapy for viral infections - CMV
ganciclovir, foscarnet
both IV
oral preparation: valganciclovir (mostly for post-allogenic transplant pts where you are monitoring for CMV reactivation)
therapy for viral infections - HSV1, VZV
aciclovir
treat promptly to reduce risk of postherpetic neuralgia
therapy for viral infections - influenza A/B
oseltamivir
zanamivir
therapy for viral infections - adenovirus
cidofovir
IV
therapy for viral infections - RSV
ribavirin
therapy for viral infections - not anti-viral
immunoglobulin replacement e.g. post alloSCT