Infections after hematopoietic stem cell transplantation: Difference between revisions

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m (Text replacement - "Varicella zoster" to "Varicella-zoster")
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See also:
 
See also:
  +
* [[Conditioning regimens for HSCT]]
+
*[[Conditioning regimens for HSCT]]
   
 
==Timeline of Infections==
 
==Timeline of Infections==
   
 
{| class="wikitable"
 
{| class="wikitable"
  +
! rowspan="2" |Time
! Time !! Risk factors !! Bacteria !! Viruses !! Fungi !! Parasites
 
  +
! rowspan="2" |Risk factors
  +
! colspan="4" |Organisms
 
|-
 
|-
 
!Bacteria!!Viruses!!Fungi!!Parasites
| '''Pre-engraftment'''<br/>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'''<br/>to day 100
+
|'''Pre-engraftment'''<br />day 0 to 30
| Immunosuppressing meds, acute GVHD, central lines
+
|Neutropenia, mucositis, and central lines
 
|GPCs and GNBs
| GPCs, [[encapsulated bacteria]], [[Listeria]], [[Salmonella]], [[Nocardia]]
 
| [[HSV]], [[CMV]], [[HHV-6]], [[adenovirus]], resp/enteric viruses
+
|[[BK virus]], [[HSV]], and resp/enteric viruses
| [[Aspergillus]], other [[molds]], [[PJP]]
+
|[[Candida]] and [[Aspergillus]]
| [[Strongyloides]], [[Toxoplasma]]
+
|[[Strongyloides]]
 
|-
 
|-
| '''Mid post-engraftment'''<br/>to 1 year
+
|'''Early post-engraftment'''<br />to day 100
| Immunosuppressing meds, chronic GVHD
+
|Immunosuppressing meds, acute GVHD, central lines
| [[Encapsulated bacteria]], [[Listeria]], [[Salmonella]], [[Nocardia]]
+
|GPCs, [[encapsulated bacteria]], [[Listeria]], [[Salmonella]], [[Nocardia]]
| [[VZV]], [[EBV]] (and [[PTLD]]), [[CMV]], respiratory/enteric viruses
+
|[[HSV]], [[CMV]], [[HHV-6]], [[adenovirus]], resp/enteric viruses
| [[Aspergillus]], other [[molds]], [[PJP]]
+
|[[Aspergillus]], other [[molds]], [[PJP]]
 
|[[Strongyloides]], [[Toxoplasma]]
|
 
 
|-
 
|-
| '''Late post-engraftment'''<br/>after 1 year
+
|'''Mid post-engraftment'''<br />to 1 year
| Immunosuppresing meds, chronic GVHD
+
|Immunosuppressing meds, chronic GVHD
| [[Encapsulated bacteria]], [[Listeria]], [[Salmonella]], [[Nocardia]]
+
|[[Encapsulated bacteria]], [[Listeria]], [[Salmonella]], [[Nocardia]]
| [[VZV]], [[CMV]], respiratory/enteric viruses
+
|[[VZV]], [[EBV]] (and [[PTLD]]), [[CMV]], respiratory/enteric viruses
  +
|[[Aspergillus]], other [[molds]], [[PJP]]
 
|
 
|-
  +
|'''Late post-engraftment'''<br />after 1 year
 
|Immunosuppresing meds, chronic GVHD
 
|[[Encapsulated bacteria]], [[Listeria]], [[Salmonella]], [[Nocardia]]
 
|[[VZV]], [[CMV]], respiratory/enteric viruses
 
|
 
|
 
|
 
|
Line 38: Line 43:
 
==Prevention==
 
==Prevention==
 
{| class="wikitable"
 
{| class="wikitable"
! Infection
+
!Infection
! Preventing exposure
+
!Preventing exposure
! Preventing disease
+
!Preventing disease
 
|-
 
|-
! colspan=3 | Bacterial infections
+
! colspan="3" |Bacterial infections
 
|-
 
|-
| Early disease (0-100 days after HCT)
+
|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.
+
|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)
+
|Late disease (100 days after HCT)
|
+
|
| Antibiotic prophylaxis is indicated for alloHSCT recipients with [[chronic GVHD]] to prevent invasive [[pneumococcal]] disease until cGVHD resolves.
+
|Antibiotic prophylaxis is indicated for alloHSCT recipients with [[chronic GVHD]] to prevent invasive [[pneumococcal]] disease until cGVHD resolves.
 
|-
 
|-
| [[CLABSI]]
+
|[[CLABSI]]
| Implement a CLABSI bundle to ensure maximum sterility on insertion.
+
|Implement a CLABSI bundle to ensure maximum sterility on insertion.
| If infection rate is still &gt;1 per 1000 catheter days, can consider prophylactic [[minocycline]] plus [[rifampin]].
+
|If infection rate is still &gt;1 per 1000 catheter days, can consider prophylactic [[minocycline]] plus [[rifampin]].
 
|-
 
|-
| ''[[Streptococcus pneumoniae]]''
+
|''[[Streptococcus pneumoniae]]''
| Routine precautions.
+
|Routine precautions.
| Immunization for all HCT recipients. Antibiotic prophylaxis for [[chronic GVHD]] and for low IgG levels, regardless of vaccination status, usually with [[penicillin]].
+
|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]]
+
|[[Viridans group streptococci]]
|
+
|
| Pre-conditioning dental consults.
+
|Pre-conditioning dental consults.
 
|-
 
|-
| ''[[Haemophilus influenzae]]'' type b
+
|''[[Haemophilus influenzae]]'' type b
| Ensuring up-to-date immunizations of close contacts.
+
|Ensuring up-to-date immunizations of close contacts.
| Immunization of all HCT recipients. Post-exposure prophylaxis if exposed.
+
|Immunization of all HCT recipients. Post-exposure prophylaxis if exposed.
 
|-
 
|-
| ''[[Bordatella pertussis]]''
+
|''[[Bordatella pertussis]]''
| Ensuring up-to-date immunizations of close contacts.
+
|Ensuring up-to-date immunizations of close contacts.
| Immunization of all HCT recipients. Post-exposure prophylaxis if exposed.
+
|Immunization of all HCT recipients. Post-exposure prophylaxis if exposed.
 
|-
 
|-
! colspan=3 | Viral infections
+
! colspan="3" |Viral infections
 
|-
 
|-
| [[Cytomegalovirus]]
+
|[[Cytomegalovirus]]
| Pre-transplant screening of donor and recipient IgG serostatus.
+
|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.
+
|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
+
|[[Epstein-Barr virus]], especially PTLD
| Pre-transplant screening of donor and recipient IgG serostatus, especially in children.
+
|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.
+
|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]]
+
|[[Herpes simplex virus]]
| Pre-transplant screening of donor and recipient IgG serostatus. Counselling of seronegative recipients on protective behaviours.
+
|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.
+
|[[Acyclovir]] for all seropositive recipients of alloHSCT from conditioning until engraftment (about 30 days). Not necessary if receiving prophylaxis for CMV.
 
|-
 
|-
| [[Varicella-zoster virus]]
+
|[[Varicella-zoster virus]]
| Pre-transplant screening of donor and recipient IgG serostatus. Close contacts should have up-to-date vaccinations before visiting.
+
|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.
+
|[[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]]
+
|[[Influenza]]
| Annual immunization of recipient and close contacts.
+
|Annual immunization of recipient and close contacts.
| Consider prophylaxis of recipient and possibly also close contacts during outbreaks.
+
|Consider prophylaxis of recipient and possibly also close contacts during outbreaks.
 
|-
 
|-
| [[Adenovirus]]
+
|[[Adenovirus]]
|
+
|
| Weekly screening PCR for the first 6 months and during severe immunosuppression.
+
|Weekly screening PCR for the first 6 months and during severe immunosuppression.
 
|-
 
|-
| [[Hepatitis B virus]]
+
|[[Hepatitis B virus]]
| Pre-transplant screening of donor and recipient serostatus. Immunization of seronegative recipients.
+
|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.
+
|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]]
+
|[[Hepatitis C virus]]
| Pre-transplant screening of donor and recipient serostatus with viral load if positive or if at elevated risk despite negative serology.
+
|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.
+
|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.
 
|-
 
|-
! colspan=3 | Fungal infections
+
! colspan="3" |Fungal infections
 
|-
 
|-
| Yeasts, especially ''[[Candida]]''
+
|Yeasts, especially ''[[Candida]]''
 
|
 
|
| [[Fluconazole]] or a mold-active azole from conditioning until engraftment, and possibly to day 75.
+
|[[Fluconazole]] or a mold-active azole from conditioning until engraftment, and possibly to day 75.
 
|-
 
|-
| Molds, especially ''[[Aspergillus]]''
+
|Molds, especially ''[[Aspergillus]]''
| Appropriate IPAC practices, including positive-pressure ventilation in recipient rooms.
+
|Appropriate IPAC practices, including positive-pressure ventilation in recipient rooms.
| Unclear role for prophylaxis, though can use [[posaconazole]] during GVHD.
+
|Unclear role for prophylaxis, though can use [[posaconazole]] during GVHD.
 
|-
 
|-
| ''[[Pneumocystis jirovecii]]''
+
|''[[Pneumocystis jirovecii]]''
|
+
|
| [[TMP-SMX]] in recipients of alloHSCT from engraftment until 6 months after transplant.
+
|[[TMP-SMX]] in recipients of alloHSCT from engraftment until 6 months after transplant.
 
|}
 
|}
   
===Antimicrobial prophylaxis===
+
===Antimicrobial Prophylaxis===
 
{| class="wikitable"
 
{| class="wikitable"
  +
! rowspan="2" |Time
! Indication
 
  +
! colspan="3" |Organisms
! Antimicrobial
 
! Timing
 
! GVHD
 
 
|-
 
|-
  +
!Bacteria
| Bacterial infections with neutropenia &gt;7 days
 
  +
!Viruses
| [[levofloxacin]] or other fluoroquinolone
 
  +
!Fungi
| from conditioning to engraftment
 
| no
 
 
|-
 
|-
 
|'''Pre-engraftment'''<br />day 0 to 30
| Invasive [[pneumococcus]]
 
| [[levofloxacin]] or other fluoroquinolone
+
|[[levofloxacin]] or other [[fluoroquinolone]]
 
|[[HSV]]-positive: ([[valacyclovir|val]])[[acyclovir]]
| in chronic GVHD
 
 
[[VZV]]-positive: ([[valacyclovir|val]])[[acyclovir]]
| yes
 
  +
  +
[[CMV]]-positive: [[valganciclovir]] or preemptive therapy (from day 10)
 
|[[fluconazole]] (or [[voriconazole]] or [[posaconazole]])
 
|-
 
|-
  +
|'''Early post-engraftment'''<br />to day 100
| Yeast infections
 
 
|
| [[fluconazole]] (or [[voriconazole]] or [[posaconazole]])
 
  +
|[[VZV]]-positive: ([[valacyclovir|val]])[[acyclovir]]
| from conditioning to engraftment, possibly longer
 
  +
[[CMV]]-positive: [[valganciclovir]] or preemptive therapy
| no
 
  +
|[[fluconazole]] (or [[voriconazole]] or [[posaconazole]]) (to day 75)
 
[[TMP-SMX]] for [[PJP]]
 
|-
 
|-
 
|'''Mid post-engraftment'''<br />to 1 year
| Mold infections
 
| [[posaconazole]]
 
 
|
 
|
  +
|[[VZV]]-positive: ([[valacyclovir|val]])[[acyclovir]]
| yes
 
  +
|[[TMP-SMX]] for [[PJP]] (to 6 months)
 
|-
 
|-
  +
|'''Late post-engraftment'''<br />after 1 year
| [[HSV]]
 
  +
|
| ([[valacyclovir|val]])[[acyclovir]]
 
  +
|
| from conditioning until engraftment
 
| no
+
|
 
|-
 
|-
  +
|'''GVHD'''
| [[VZV]]
 
 
|[[levofloxacin]] or other [[fluoroquinolone]] for [[Streptococcus pneumoniae]]
| ([[valacyclovir|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
 
 
|
 
|
  +
|[[posaconazole]], [[TMP-SMX]] for [[PJP]]
 
|}
 
|}
   
 
==Further Reading==
 
==Further Reading==
  +
* Life-threatening Infection in Transplant Recipients. ''Crit Care Clin''. 2013 Oct;29(4):953-73. doi: [https://doi.org/10.1016/j.ccc.2013.06.012 10.1016/j.ccc.2013.06.012]
 
* Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective. ''Biol Blood Marrow Transplant''. 2009;15:1143-1238. doi: [https://doi.org/10.1016/j.bbmt.2009.06.019 10.1016/j.bbmt.2009.06.019]
+
*Life-threatening Infection in Transplant Recipients. ''Crit Care Clin''. 2013 Oct;29(4):953-73. doi: [https://doi.org/10.1016/j.ccc.2013.06.012 10.1016/j.ccc.2013.06.012]
  +
*Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective. ''Biol Blood Marrow Transplant''. 2009;15:1143-1238. doi: [https://doi.org/10.1016/j.bbmt.2009.06.019 10.1016/j.bbmt.2009.06.019]
   
 
[[Category:Immunocompromised hosts]]
 
[[Category:Immunocompromised hosts]]

Revision as of 10:06, 13 August 2020

See also:

Timeline of Infections

Time Risk factors Organisms
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

Time Organisms
Bacteria Viruses Fungi
Pre-engraftment
day 0 to 30
levofloxacin or other fluoroquinolone HSV-positive: (val)acyclovir

VZV-positive: (val)acyclovir

CMV-positive: valganciclovir or preemptive therapy (from day 10)

fluconazole (or voriconazole or posaconazole)
Early post-engraftment
to day 100
VZV-positive: (val)acyclovir

CMV-positive: valganciclovir or preemptive therapy

fluconazole (or voriconazole or posaconazole) (to day 75)

TMP-SMX for PJP

Mid post-engraftment
to 1 year
VZV-positive: (val)acyclovir TMP-SMX for PJP (to 6 months)
Late post-engraftment
after 1 year
GVHD levofloxacin or other fluoroquinolone for Streptococcus pneumoniae posaconazole, TMP-SMX for PJP

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
  • Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective. Biol Blood Marrow Transplant. 2009;15:1143-1238. doi: 10.1016/j.bbmt.2009.06.019