Infections after hematopoietic stem cell transplantation

Timeline of Infections

Time	Risk factors	Bacteria	Viruses	Fungi	Parasites
Pre-engraftment day 0 to 30	Neutropenia, mucositis, and central lines	GPCs and GNBs	BK virus, HSV, and resp/enteric viruses	Candida and Aspergillus	Strongyloides
Early post-engraftment to day 100	Immunosuppressing meds, acute GVHD, central lines	GPCs, encapsulated bacteria, Listeria, Salmonella, Nocardia	HSV, CMV, HHV-6, adenovirus, resp/enteric viruses	Aspergillus, other molds, PJP	Strongyloides, Toxoplasma
Mid post-engraftment to 1 year	Immunosuppressing meds, chronic GVHD	Encapsulated bacteria, Listeria, Salmonella, Nocardia	VZV, EBV (and PTLD), CMV, respiratory/enteric viruses	Aspergillus, other molds, PJP
Late post-engraftment after 1 year	Immunosuppresing meds, chronic GVHD	Encapsulated bacteria, Listeria, Salmonella, Nocardia	VZV, CMV, respiratory/enteric viruses

Prevention

Infection	Preventing exposure	Preventing disease
Bacterial infections
Early disease (0-100 days after HCT)		Use levofloxacin or other respiratory fluoroquinolone in adult patients with anticipated neutropenia of 7 or more days until recovery of neutropenia. GM-CSF or G-CSF may decrease risk of infection, but unclear if it decreases mortality.
Late disease (100 days after HCT)		Antibiotic prophylaxis is indicated for alloHSCT recipients with chronic GVHD to prevent invasive pneumococcal disease until cGVHD resolves.
CLABSI	Implement a CLABSI bundle to ensure maximum sterility on insertion.	If infection rate is still >1 per 1000 catheter days, can consider prophylactic minocycline plus rifampin.
Streptococcus pneumoniae	Routine precautions.	Immunization for all HCT recipients. Antibiotic prophylaxis for chronic GVHD and for low IgG levels, regardless of vaccination status, usually with penicillin.
Viridans group streptococci		Pre-conditioning dental consults.
Haemophilus influenzae type b	Ensuring up-to-date immunizations of close contacts.	Immunization of all HCT recipients. Post-exposure prophylaxis if exposed.
Bordatella pertussis	Ensuring up-to-date immunizations of close contacts.	Immunization of all HCT recipients. Post-exposure prophylaxis if exposed.
Viral infections
Cytomegalovirus	Pre-transplant screening of donor and recipient IgG serostatus.	All R+ or D+ recipients should have either prophylaxis or close monitoring with preemptive treatment until at least day 100. Monitoring should start on day 10 and continue weekly until at least day 100.
Epstein-Barr virus, especially PTLD	Pre-transplant screening of donor and recipient IgG serostatus, especially in children.	Monitor high-risk recipients (T-cell depletion, ant-T-cell antibodies, umbilical cord transplants, and haplo-identical transplants), with reduction in immunosuppression if rising viral load.
Herpes simplex virus	Pre-transplant screening of donor and recipient IgG serostatus. Counselling of seronegative recipients on protective behaviours.	Acyclovir for all seropositive recipients of alloHSCT from conditioning until engraftment (about 30 days). Not necessary if receiving prophylaxis for CMV.
Varicella zoster virus	Pre-transplant screening of donor and recipient IgG serostatus. Close contacts should have up-to-date vaccinations before visiting.	Acyclovir or valacyclovir for all seropositive recipients of alloHSCT from conditioning until 1 year and during chronic GVHD. Post-exposure prophylaxis with VariZIG for seronegative recipients.
Influenza	Annual immunization of recipient and close contacts.	Consider prophylaxis of recipient and possibly also close contacts during outbreaks.
Adenovirus		Weekly screening PCR for the first 6 months and during severe immunosuppression.
Hepatitis B virus	Pre-transplant screening of donor and recipient serostatus. Immunization of seronegative recipients.	Monitoring ALT during prolonged corticosteroid use with HBV DNA viral load if ALT is elevated, and pre-emptive antiviral therapy if the viral load is positive. Consider prophylaxis for anti-HBc-positive recipients from conditioning to 6 months after transplant. Monitor anti-HBs titres every 3 months, with viral load if it is decreasing. Re-immunize if titres become negative. Treatment of choice is lamivudine 100 mg/day.
Hepatitis C virus	Pre-transplant screening of donor and recipient serostatus with viral load if positive or if at elevated risk despite negative serology.	For those with HCV, consider liver biopsy if iron overloaded, alcohol abuse, HCV for longer than 10 years, or clinical evidence of chronic liver disease. Consider treatment after 2 years post-transplant if without GVHD and no immunosuppressing medications for at least 6 months.
Fungal infections
Yeasts, especially Candida		Fluconazole or a mold-active azole from conditioning until engraftment, and possibly to day 75.
Molds, especially Aspergillus	Appropriate IPAC practices, including positive-pressure ventilation in recipient rooms.	Unclear role for prophylaxis, though can use posaconazole during GVHD.
Pneumocystis jirovecii		TMP-SMX in recipients of alloHSCT from engraftment until 6 months after transplant.

Antimicrobial prophylaxis

Indication	Antimicrobial	Timing	GVHD
Bacterial infections with neutropenia >7 days	levofloxacin or other fluoroquinolone	from conditioning to engraftment	in chronic GVHD, but only to prevent invasive pneumococcus
Yeast infections	fluconazole (or voriconazole or posaconazole)	from conditioning to engraftment, possibly longer	no
Mold infections	posaconazole		yes
HSV	(val)acyclovir	from conditioning until engraftment	no
VZV	(val)acyclovir	from conditioning until 1 year	yes
CMV	preemptive therapy or valganciclovir	from day 10 to early postengraftment (day 100)	no
Pneumocystis	TMP-SMX	from engraftment to 6 months

Further Reading

• Life-threatening Infection in Transplant Recipients. Crit Care Clin. 2013 Oct;29(4):953-73. doi: 10.1016/j.ccc.2013.06.012