Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival

Sumeet S. Teotia, Randall C. Walker, Johannes M. Schirmer, Henry D. Tazelaar, Marian G. Michaels, Jack M. Risdahl, Guerard W. Byrne, John S. Logan, Christopher G A McGregor

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: We analyzed bacterial and fungal infectious complications in a cohort of 16 consecutive experiments with the longest surviving cardiac xenografts to date. Methods: Transgenic, porcine-to-baboon, heterotopic (abdomen) cardiac xenotransplantation was performed in 16 consecutive experiments, using rapamycin, tacrolimus, corticosteroids, anti-CD20 monoclonal antibody, and an alpha-Gal-PEG polymer, as immunosuppression. Prophylactic anti-microbials included i.v. trimethoprim/sulfamethoxazole, oral ganciclovir/valganciclovir, and oral itraconazole. An episode of bacterial infection was denned as a positive blood and/or wound culture with: leukocytosis, fever > 101.5°F, and/or clinical deterioration. Results: Mean graft survival was 71 ± 29 days; the longest was 113 days. There were 23 episodes of bacterial infection; 14 resolved with treatment. The mean time to the first episode of infection was 44 ± 21 days (n = 12). Eight of 16 deaths were due to infection: two bacterial-only, two cytomegalovirus (CMV) only, four both bacterial and CMV, and none fungal. The frequency of infection was 1, 2.8, and 1.8 episodes/100 survival days, respectively, for animals whose grafts survived for 30 to 59, 60 to 89, and > 90 days. CMV infection (reviewed in detail in a separate communications) was due to baboon CMV, and was associated with low serum levels of ganciclovir. Conclusion: In a cardiac xenograft model that achieved prolonged (> 3 months) survival, bacteremia was common, but usually reversible, and fungal infection was prevented with prophylaxis. The level of immunosuppression required to achieve clinically meaningful xenograft survival is associated with a level of bacterial and fungal infectious complications that is manageable and similar to the early clinical experiences in human transplantation. Further research will determine if the viral infectious complications observed in these experiments can be reduced by optimizing blood levels of anti-viral prophylaxis and monitoring viral polymerase chain reaction levels.

Original languageEnglish (US)
Pages (from-to)127-133
Number of pages7
JournalXenotransplantation
Volume12
Issue number2
DOIs
StatePublished - Mar 2005

Fingerprint

Heterologous Transplantation
Mycoses
Cytomegalovirus
Bacterial Infections
Heterografts
Ganciclovir
Papio
Immunosuppression
Itraconazole
Survival
Leukocytosis
Sulfamethoxazole Drug Combination Trimethoprim
Cytomegalovirus Infections
Tacrolimus
Graft Survival
Sirolimus
Bacteremia
Infection
Abdomen
Adrenal Cortex Hormones

Keywords

  • Bacterial infections
  • Cardiac transplantation
  • Cytomegalovirus
  • Epstein-Barr virus
  • Fungal infections
  • Porcine
  • Porcine-endogenous retrovirus infection
  • Primate
  • Xenotransplantation

ASJC Scopus subject areas

  • Immunology

Cite this

Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival. / Teotia, Sumeet S.; Walker, Randall C.; Schirmer, Johannes M.; Tazelaar, Henry D.; Michaels, Marian G.; Risdahl, Jack M.; Byrne, Guerard W.; Logan, John S.; McGregor, Christopher G A.

In: Xenotransplantation, Vol. 12, No. 2, 03.2005, p. 127-133.

Research output: Contribution to journalArticle

Teotia, SS, Walker, RC, Schirmer, JM, Tazelaar, HD, Michaels, MG, Risdahl, JM, Byrne, GW, Logan, JS & McGregor, CGA 2005, 'Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival', Xenotransplantation, vol. 12, no. 2, pp. 127-133. https://doi.org/10.1111/j.1399-3089.2005.00205.x
Teotia, Sumeet S. ; Walker, Randall C. ; Schirmer, Johannes M. ; Tazelaar, Henry D. ; Michaels, Marian G. ; Risdahl, Jack M. ; Byrne, Guerard W. ; Logan, John S. ; McGregor, Christopher G A. / Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival. In: Xenotransplantation. 2005 ; Vol. 12, No. 2. pp. 127-133.
@article{93b84c87192f4a44a5eee0b35ef392ae,
title = "Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival",
abstract = "Background: We analyzed bacterial and fungal infectious complications in a cohort of 16 consecutive experiments with the longest surviving cardiac xenografts to date. Methods: Transgenic, porcine-to-baboon, heterotopic (abdomen) cardiac xenotransplantation was performed in 16 consecutive experiments, using rapamycin, tacrolimus, corticosteroids, anti-CD20 monoclonal antibody, and an alpha-Gal-PEG polymer, as immunosuppression. Prophylactic anti-microbials included i.v. trimethoprim/sulfamethoxazole, oral ganciclovir/valganciclovir, and oral itraconazole. An episode of bacterial infection was denned as a positive blood and/or wound culture with: leukocytosis, fever > 101.5°F, and/or clinical deterioration. Results: Mean graft survival was 71 ± 29 days; the longest was 113 days. There were 23 episodes of bacterial infection; 14 resolved with treatment. The mean time to the first episode of infection was 44 ± 21 days (n = 12). Eight of 16 deaths were due to infection: two bacterial-only, two cytomegalovirus (CMV) only, four both bacterial and CMV, and none fungal. The frequency of infection was 1, 2.8, and 1.8 episodes/100 survival days, respectively, for animals whose grafts survived for 30 to 59, 60 to 89, and > 90 days. CMV infection (reviewed in detail in a separate communications) was due to baboon CMV, and was associated with low serum levels of ganciclovir. Conclusion: In a cardiac xenograft model that achieved prolonged (> 3 months) survival, bacteremia was common, but usually reversible, and fungal infection was prevented with prophylaxis. The level of immunosuppression required to achieve clinically meaningful xenograft survival is associated with a level of bacterial and fungal infectious complications that is manageable and similar to the early clinical experiences in human transplantation. Further research will determine if the viral infectious complications observed in these experiments can be reduced by optimizing blood levels of anti-viral prophylaxis and monitoring viral polymerase chain reaction levels.",
keywords = "Bacterial infections, Cardiac transplantation, Cytomegalovirus, Epstein-Barr virus, Fungal infections, Porcine, Porcine-endogenous retrovirus infection, Primate, Xenotransplantation",
author = "Teotia, {Sumeet S.} and Walker, {Randall C.} and Schirmer, {Johannes M.} and Tazelaar, {Henry D.} and Michaels, {Marian G.} and Risdahl, {Jack M.} and Byrne, {Guerard W.} and Logan, {John S.} and McGregor, {Christopher G A}",
year = "2005",
month = "3",
doi = "10.1111/j.1399-3089.2005.00205.x",
language = "English (US)",
volume = "12",
pages = "127--133",
journal = "Xenotransplantation",
issn = "0908-665X",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival

AU - Teotia, Sumeet S.

AU - Walker, Randall C.

AU - Schirmer, Johannes M.

AU - Tazelaar, Henry D.

AU - Michaels, Marian G.

AU - Risdahl, Jack M.

AU - Byrne, Guerard W.

AU - Logan, John S.

AU - McGregor, Christopher G A

PY - 2005/3

Y1 - 2005/3

N2 - Background: We analyzed bacterial and fungal infectious complications in a cohort of 16 consecutive experiments with the longest surviving cardiac xenografts to date. Methods: Transgenic, porcine-to-baboon, heterotopic (abdomen) cardiac xenotransplantation was performed in 16 consecutive experiments, using rapamycin, tacrolimus, corticosteroids, anti-CD20 monoclonal antibody, and an alpha-Gal-PEG polymer, as immunosuppression. Prophylactic anti-microbials included i.v. trimethoprim/sulfamethoxazole, oral ganciclovir/valganciclovir, and oral itraconazole. An episode of bacterial infection was denned as a positive blood and/or wound culture with: leukocytosis, fever > 101.5°F, and/or clinical deterioration. Results: Mean graft survival was 71 ± 29 days; the longest was 113 days. There were 23 episodes of bacterial infection; 14 resolved with treatment. The mean time to the first episode of infection was 44 ± 21 days (n = 12). Eight of 16 deaths were due to infection: two bacterial-only, two cytomegalovirus (CMV) only, four both bacterial and CMV, and none fungal. The frequency of infection was 1, 2.8, and 1.8 episodes/100 survival days, respectively, for animals whose grafts survived for 30 to 59, 60 to 89, and > 90 days. CMV infection (reviewed in detail in a separate communications) was due to baboon CMV, and was associated with low serum levels of ganciclovir. Conclusion: In a cardiac xenograft model that achieved prolonged (> 3 months) survival, bacteremia was common, but usually reversible, and fungal infection was prevented with prophylaxis. The level of immunosuppression required to achieve clinically meaningful xenograft survival is associated with a level of bacterial and fungal infectious complications that is manageable and similar to the early clinical experiences in human transplantation. Further research will determine if the viral infectious complications observed in these experiments can be reduced by optimizing blood levels of anti-viral prophylaxis and monitoring viral polymerase chain reaction levels.

AB - Background: We analyzed bacterial and fungal infectious complications in a cohort of 16 consecutive experiments with the longest surviving cardiac xenografts to date. Methods: Transgenic, porcine-to-baboon, heterotopic (abdomen) cardiac xenotransplantation was performed in 16 consecutive experiments, using rapamycin, tacrolimus, corticosteroids, anti-CD20 monoclonal antibody, and an alpha-Gal-PEG polymer, as immunosuppression. Prophylactic anti-microbials included i.v. trimethoprim/sulfamethoxazole, oral ganciclovir/valganciclovir, and oral itraconazole. An episode of bacterial infection was denned as a positive blood and/or wound culture with: leukocytosis, fever > 101.5°F, and/or clinical deterioration. Results: Mean graft survival was 71 ± 29 days; the longest was 113 days. There were 23 episodes of bacterial infection; 14 resolved with treatment. The mean time to the first episode of infection was 44 ± 21 days (n = 12). Eight of 16 deaths were due to infection: two bacterial-only, two cytomegalovirus (CMV) only, four both bacterial and CMV, and none fungal. The frequency of infection was 1, 2.8, and 1.8 episodes/100 survival days, respectively, for animals whose grafts survived for 30 to 59, 60 to 89, and > 90 days. CMV infection (reviewed in detail in a separate communications) was due to baboon CMV, and was associated with low serum levels of ganciclovir. Conclusion: In a cardiac xenograft model that achieved prolonged (> 3 months) survival, bacteremia was common, but usually reversible, and fungal infection was prevented with prophylaxis. The level of immunosuppression required to achieve clinically meaningful xenograft survival is associated with a level of bacterial and fungal infectious complications that is manageable and similar to the early clinical experiences in human transplantation. Further research will determine if the viral infectious complications observed in these experiments can be reduced by optimizing blood levels of anti-viral prophylaxis and monitoring viral polymerase chain reaction levels.

KW - Bacterial infections

KW - Cardiac transplantation

KW - Cytomegalovirus

KW - Epstein-Barr virus

KW - Fungal infections

KW - Porcine

KW - Porcine-endogenous retrovirus infection

KW - Primate

KW - Xenotransplantation

UR - http://www.scopus.com/inward/record.url?scp=14644406764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14644406764&partnerID=8YFLogxK

U2 - 10.1111/j.1399-3089.2005.00205.x

DO - 10.1111/j.1399-3089.2005.00205.x

M3 - Article

VL - 12

SP - 127

EP - 133

JO - Xenotransplantation

JF - Xenotransplantation

SN - 0908-665X

IS - 2

ER -