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Smibert OC, Vogrin S, Sinclair M, Majumdar A, Nasra M, Pandey D, Jahanabadi H, Trubiano JA, Markey KA, Slavin MA, Testro A, Kwong JC. Antibiotic Exposure and Risk of Allograft Rejection and Survival After Liver Transplant: An Observational Cohort Study From a Tertiary Referral Centre. Transpl Infect Dis 2025:e70026. [PMID: 40153422 DOI: 10.1111/tid.70026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Revised: 03/07/2025] [Accepted: 03/12/2025] [Indexed: 03/30/2025]
Abstract
INTRODUCTION Our goal is to understand whether there is an association between Abx exposure-and the inferred downstream damage to the intestinal microbiome-and the key patient outcomes of overall survival and rejection following liver transplant. METHODS We conducted a retrospective cohort study of 462 liver transplant recipients treated at a multistate liver transplant (LTx) service during a 7-year period. The association between antibiotic exposure and outcome was tested across models that addressed antibiotic spectrum, duration, and timing relative to transplant. Cox proportional hazard regression was used to evaluate the relationship between antibiotics with survival and rejection. RESULTS The observed 1-year survival in this cohort was 95% (95% CI: 93%, 97%), and 20.8% of patients (96/462) experienced rejection at 1 year. In multivariable analyses, exposure to anaerobe-targeting antibiotics for longer than 14 days pretransplant (p = 0.055) or posttransplant (p = 0.040) was significantly associated with reduced 1-year survival. In multivariable analyses, exposure to any anaerobe-targeting Abx posttransplant was significantly associated with an increased risk of rejection (p = 0.001). CONCLUSIONS Exposure to anaerobic spectrum antibiotics either before or after LTx was associated with poor outcomes during the first year posttransplant and provides an impetus to further characterize the relationship between antibiotic use, microbiota disruption, and cellular immunity in liver transplantation.
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Affiliation(s)
- Olivia C Smibert
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Department of Infectious Diseases and Immunology, Austin Health, Melbourne, Victoria, Australia
- Department of Infectious Diseases, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Sara Vogrin
- Department of Medicine, St Vincent's Hospital, Victoria Parade, University of Melbourne, Fitzroy, Australia
| | - Marie Sinclair
- Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- School of Medicine, Dentistry and Health Sciences, the University of Melbourne, Melbourne, Victoria, Australia
| | - Avik Majumdar
- Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- School of Medicine, Dentistry and Health Sciences, the University of Melbourne, Melbourne, Victoria, Australia
| | - Mohamed Nasra
- Department of Infectious Diseases and Immunology, Austin Health, Melbourne, Victoria, Australia
| | - Dinesh Pandey
- Data Analytics Research and Evaluation (DARE) Centre, The University of Melbourne and Austin Hospital, Melbourne, Victoria, Australia
- Clinical Analytics and Reporting, Performance Reporting and Decision Support, Austin Health, Melbourne, Victoria, Australia
| | - Hossein Jahanabadi
- Data Analytics Research and Evaluation (DARE) Centre, The University of Melbourne and Austin Hospital, Melbourne, Victoria, Australia
- Clinical Analytics and Reporting, Performance Reporting and Decision Support, Austin Health, Melbourne, Victoria, Australia
| | - Jason A Trubiano
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Department of Infectious Diseases and Immunology, Austin Health, Melbourne, Victoria, Australia
- Department of Infectious Diseases, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Kate A Markey
- Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center (FHCC), Seattle, Washington, USA
- Department of Medicine, University of Washington, Seattle, Washington, USA
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Weill Cornell Medical College, New York, New York, USA
| | - Monica A Slavin
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
- Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Department of Infectious Diseases, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
| | - Adam Testro
- Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- School of Medicine, Dentistry and Health Sciences, the University of Melbourne, Melbourne, Victoria, Australia
| | - Jason C Kwong
- Department of Infectious Diseases and Immunology, Austin Health, Melbourne, Victoria, Australia
- Department of Microbiology & Immunology, The Peter Doherty Institute for Infection and Immunity, the University of Melbourne, Melbourne, Victoria, Australia
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Zuccaro V, Giordani P, Binda F, Asperges E, Farina E, Viganò M, Gervasi E, Pagani E, Fagiuoli S, Bruno R. Antibiotic Stewardship Based on Colonization with Multi-Drug-Resistant Bacteria in Liver Transplantation: A Narrative Review. Microorganisms 2024; 12:2493. [PMID: 39770696 PMCID: PMC11728255 DOI: 10.3390/microorganisms12122493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/30/2024] [Accepted: 12/02/2024] [Indexed: 01/16/2025] Open
Abstract
In solid organs post-transplant, bacterial infections can complicate the course of recovery with devastating consequences, such as graft loss and death. We provide an expert review on early post-liver transplant bacterial infections, with a focus on infections with multi-drug-resistant organism (MDRO) etiologies. Best practice recommendations are derived from a combination of available evidence and expert consensus. The main challenge in managing antibiotic therapy arises in patients with severe clinical conditions but negative MDRO screening results, as well as in those with positive MDRO screening results but uncomplicated infections. With the aim of shedding light on these "gray areas", we propose an algorithm where the patient is stratified as being at low risk or high risk of developing an MDRO infection.
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Affiliation(s)
- Valentina Zuccaro
- Department of Diagnostic, Paediatric, Clinical and Surgical Science, University of Pavia, 27100 Pavia, Italy
- Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (P.G.); (E.A.); (E.P.)
| | - Paola Giordani
- Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (P.G.); (E.A.); (E.P.)
| | - Francesca Binda
- Infectious Diseases Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy; (F.B.); (E.G.)
| | - Erika Asperges
- Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (P.G.); (E.A.); (E.P.)
| | - Elisa Farina
- Gastroenterology, Hepatology and Liver Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy; (E.F.); (M.V.); (S.F.)
| | - Mauro Viganò
- Gastroenterology, Hepatology and Liver Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy; (E.F.); (M.V.); (S.F.)
| | - Elena Gervasi
- Infectious Diseases Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy; (F.B.); (E.G.)
| | - Elisabetta Pagani
- Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (P.G.); (E.A.); (E.P.)
| | - Stefano Fagiuoli
- Gastroenterology, Hepatology and Liver Transplantation Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy; (E.F.); (M.V.); (S.F.)
- Gastroenterology, Department of Medicine & Surgery, University Milan Bicocca, 20126 Milan, Italy
| | - Raffaele Bruno
- Department of Diagnostic, Paediatric, Clinical and Surgical Science, University of Pavia, 27100 Pavia, Italy
- Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (P.G.); (E.A.); (E.P.)
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Laquian L, Efron PA. Antibiotic Use in the Surgical Intensive Care Unit. Adv Surg 2024; 58:203-221. [PMID: 39089778 DOI: 10.1016/j.yasu.2024.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
Judicious use of antibiotics in the critically ill starts with the evaluation for suspected infection, including close consideration of the patient's history. If infection is present or strongly suspected, empiric antibiotics should be promptly initiated and selected based on the source of infection, patient factors, and local resistance patterns. If the surgeon decides source control is indicated, they must determine the optimal approach and timing. As soon as culture and sensitivity data are available, de-escalation to narrower spectrum agents is essential to decrease the risks of antibiotic toxicity and resistance. Importantly, surgeons should participate in antibiotic stewardship in their patients.
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Affiliation(s)
- Liza Laquian
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA
| | - Philip A Efron
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
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Khalid K, Poh CL. The Promising Potential of Reverse Vaccinology-Based Next-Generation Vaccine Development over Conventional Vaccines against Antibiotic-Resistant Bacteria. Vaccines (Basel) 2023; 11:1264. [PMID: 37515079 PMCID: PMC10385262 DOI: 10.3390/vaccines11071264] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/14/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
The clinical use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria, leading to the current antibiotic resistance crisis. To address this issue, next-generation vaccines are being developed to prevent antimicrobial resistance caused by MDR bacteria. Traditional vaccine platforms, such as inactivated vaccines (IVs) and live attenuated vaccines (LAVs), were effective in preventing bacterial infections. However, they have shown reduced efficacy against emerging antibiotic-resistant bacteria, including MDR M. tuberculosis. Additionally, the large-scale production of LAVs and IVs requires the growth of live pathogenic microorganisms. A more promising approach for the accelerated development of vaccines against antibiotic-resistant bacteria involves the use of in silico immunoinformatics techniques and reverse vaccinology. The bioinformatics approach can identify highly conserved antigenic targets capable of providing broader protection against emerging drug-resistant bacteria. Multi-epitope vaccines, such as recombinant protein-, DNA-, or mRNA-based vaccines, which incorporate several antigenic targets, offer the potential for accelerated development timelines. This review evaluates the potential of next-generation vaccine development based on the reverse vaccinology approach and highlights the development of safe and immunogenic vaccines through relevant examples from successful preclinical and clinical studies.
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Affiliation(s)
- Kanwal Khalid
- Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Subang Jaya 47500, Malaysia
| | - Chit Laa Poh
- Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Subang Jaya 47500, Malaysia
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Keller MR, Dörr T. Bacterial metabolism and susceptibility to cell wall-active antibiotics. Adv Microb Physiol 2023; 83:181-219. [PMID: 37507159 PMCID: PMC11024984 DOI: 10.1016/bs.ampbs.2023.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/30/2023]
Abstract
Bacterial infections are increasingly resistant to antimicrobial therapy. Intense research focus has thus been placed on identifying the mechanisms that bacteria use to resist killing or growth inhibition by antibiotics and the ways in which bacteria share these traits with one another. This work has led to the advancement of new drugs, combination therapy regimens, and a deeper appreciation for the adaptability seen in microorganisms. However, while the primary mechanisms of action of most antibiotics are well understood, the more subtle contributions of bacterial metabolic state to repairing or preventing damage caused by antimicrobials (thereby promoting survival) are still understudied. Here, we review a modern viewpoint on a classical system: examining bacterial metabolism's connection to antibiotic susceptibility. We dive into the relationship between metabolism and antibiotic efficacy through the lens of growth rate, energy state, resource allocation, and the infection environment, focusing on cell wall-active antibiotics.
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Affiliation(s)
- Megan Renee Keller
- Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, United States
| | - Tobias Dörr
- Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, United States; Department of Microbiology, Cornell University, Ithaca, NY, United States; Cornell Institute of Host-Microbe Interactions and Disease, Cornell University, Ithaca, NY, United States.
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Elalouf A. Infections after organ transplantation and immune response. Transpl Immunol 2023; 77:101798. [PMID: 36731780 DOI: 10.1016/j.trim.2023.101798] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 01/08/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023]
Abstract
Organ transplantation has provided another chance of survival for end-stage organ failure patients. Yet, transplant rejection is still a main challenging factor. Immunosuppressive drugs have been used to avoid rejection and suppress the immune response against allografts. Thus, immunosuppressants increase the risk of infection in immunocompromised organ transplant recipients. The infection risk reflects the relationship between the nature and severity of immunosuppression and infectious diseases. Furthermore, immunosuppressants show an immunological impact on the genetics of innate and adaptive immune responses. This effect usually reactivates the post-transplant infection in the donor and recipient tissues since T-cell activation has a substantial role in allograft rejection. Meanwhile, different infections have been found to activate the T-cells into CD4+ helper T-cell subset and CD8+ cytotoxic T-lymphocyte that affect the infection and the allograft. Therefore, the best management and preventive strategies of immunosuppression, antimicrobial prophylaxis, and intensive medical care are required for successful organ transplantation. This review addresses the activation of immune responses against different infections in immunocompromised individuals after organ transplantation.
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Affiliation(s)
- Amir Elalouf
- Bar-Ilan University, Department of Management, Ramat Gan 5290002, Israel.
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Goenaga-Mafud LC, Gamez YM, Campos CP, Vollet-Filho JD, Inada NM, Kurachi C, Bagnato VS. ERRATUM: Kidney decontamination during perfusion for transplantation procedure: In vitro and ex vivo viability analysis. JOURNAL OF BIOPHOTONICS 2023; 16:e202200363. [PMID: 36529999 DOI: 10.1002/jbio.202200363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 12/15/2022] [Indexed: 06/17/2023]
Abstract
Organ transplantations have an increasing medical relevance. It is becoming a regular procedure with an increase in individuals waiting for organs. The increase in the number of discarded organs is mostly due to the donor's bacterial and/or viral infection. In this article, we are demonstrating the feasibility of reduction of the bacterial load in the kidney model by using Ultraviolet-C (UV-C) as a germicidal agent in circulating liquids. Using Staphylococcus aureus as a bacteria model, we were able to demonstrate that in less than 30 min of liquid circulation and associated to irradiation, the bacterial load of the perfusate Custodiol® HTK, histidine-tryptophan-ketoglutarate (solution with 5 log CFU ml-1 ), was fully eliminated. A modeling approach was created to verify the possibility of bacterial load decrease, when an organ (here, a renal experimental model) is present in the circuit, releasing a varied rate of microorganisms over time, while the solution is irradiated. Finally, we use an ex vivo model with a swine kidney, circulating in the preservation solution with a Lifeport® Kidney Transporter machine, to demonstrate that we can contaminate the organ and then promote the elimination of the microbiological load. The results show the feasibility of the technique.
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Affiliation(s)
| | | | - Carolina P Campos
- São Carlos Institute of Physics, University of São Paulo, Sao Paulo, Brazil
| | | | | | - Cristina Kurachi
- São Carlos Institute of Physics, University of São Paulo, Sao Paulo, Brazil
| | - Vanderlei Salvador Bagnato
- São Carlos Institute of Physics, University of São Paulo, Sao Paulo, Brazil
- Hagler Institute for Advanced Studies, Texas A&M University, College Station, Texas, USA
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Cruz KCP, Enekegho LO, Stuart DT. Bioengineered Probiotics: Synthetic Biology Can Provide Live Cell Therapeutics for the Treatment of Foodborne Diseases. Front Bioeng Biotechnol 2022; 10:890479. [PMID: 35656199 PMCID: PMC9152101 DOI: 10.3389/fbioe.2022.890479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 04/29/2022] [Indexed: 11/15/2022] Open
Abstract
The rising prevalence of antibiotic resistant microbial pathogens presents an ominous health and economic challenge to modern society. The discovery and large-scale development of antibiotic drugs in previous decades was transformational, providing cheap, effective treatment for what would previously have been a lethal infection. As microbial strains resistant to many or even all antibiotic drug treatments have evolved, there is an urgent need for new drugs or antimicrobial treatments to control these pathogens. The ability to sequence and mine the genomes of an increasing number of microbial strains from previously unexplored environments has the potential to identify new natural product antibiotic biosynthesis pathways. This coupled with the power of synthetic biology to generate new production chassis, biosensors and “weaponized” live cell therapeutics may provide new means to combat the rapidly evolving threat of drug resistant microbial pathogens. This review focuses on the application of synthetic biology to construct probiotic strains that have been endowed with functionalities allowing them to identify, compete with and in some cases kill microbial pathogens as well as stimulate host immunity. Weaponized probiotics may have the greatest potential for use against pathogens that infect the gastrointestinal tract: Vibrio cholerae, Staphylococcus aureus, Clostridium perfringens and Clostridioides difficile. The potential benefits of engineered probiotics are highlighted along with the challenges that must still be met before these intriguing and exciting new therapeutic tools can be widely deployed.
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9
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Goenaga-Mafud LC, Gamez YM, Campos CP, Vollet-Filho JD, Inada NM, Kurachi C, Bagnato VS. Kidney decontamination during perfusion for transplantation procedure: In vitro and ex vivo viability analysis. JOURNAL OF BIOPHOTONICS 2022; 15:e202100319. [PMID: 35048532 DOI: 10.1002/jbio.202100319] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/27/2021] [Accepted: 01/18/2022] [Indexed: 06/14/2023]
Abstract
Organ transplantations have an increasing medical relevance. It is becoming a regular procedure with an increase in individuals waiting for organs. The increase in the number of discarded organs is mostly due to the donor bacterial and/or viral infection. In this article, we are demonstrating the feasibility of reduction of the bacterial load in kidney model by using ultraviolet-C as a germicidal agent in circulating liquids. Using Staphylococcus aureus as a bacteria model, we were able to demonstrate that in less than 30 min of liquid circulation and associated to irradiation, the bacterial load of the perfusate Custodiol HTK, histidine-tryptophan-ketoglutarate (solution with 5 log CFU mL-1 ), was fully eliminated. A modeling approach was created to verify the possibility of bacterial load decrease, when an organ (here, a renal experimental model) is present in the circuit, releasing a varied rate of microorganisms over time, while the solution is irradiated. Finally, we use an ex vivo model with swine kidney, circulating in the preservation solution with a Lifeport Kidney Transporter machine, to demonstrate that we can contaminate the organ and then promote the elimination of the microbiological load. The results show the feasibility of the technique.
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Affiliation(s)
| | | | - Carolina P Campos
- São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil
| | | | | | - Cristina Kurachi
- São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil
| | - Vanderlei Salvador Bagnato
- São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil
- Hagler Institute for Advanced Studies, Texas A&M University, College Station, Texas, USA
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Møller DL, Sørensen SS, Wareham NE, Rezahosseini O, Knudsen AD, Knudsen JD, Rasmussen A, Nielsen SD. Bacterial and fungal bloodstream infections in pediatric liver and kidney transplant recipients. BMC Infect Dis 2021; 21:541. [PMID: 34103013 PMCID: PMC8188646 DOI: 10.1186/s12879-021-06224-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 05/19/2021] [Indexed: 12/11/2022] Open
Abstract
Background Bacterial and fungal bloodstream infections (BSI) are common after pediatric liver and kidney transplantations and associated with morbidity and mortality. However, knowledge about incidence rates, pathogen composition, and resistance patterns is limited. We aimed to describe the pattern of bacterial and fungal BSI in a cohort of pediatric liver and kidney transplant recipients. Methods A prospective study of 85 pediatric liver and kidney transplant recipients transplanted from 2010 to 2017 with a total of 390 person-years of follow-up. Clinical characteristics and BSI were retrieved from national registries assuring nationwide follow-up for at least 1 year. BSI incidence rates and pathogen composition were investigated and stratified by the time post-transplantation and type of transplanted organ. Results A total of 29 BSI were observed within the first 5 years post-transplantation with 16 different pathogens. The overall incidence rate of first BSI was 1.91 per 100 recipients per month (95% CI, 1.1–3.1) in the first year post-transplantation. The most common pathogens were Enterococcus faecium, Candida albicans, Escherichia coli, and Klebsiella pneumoniae. The pathogen composition depended on the transplanted organ with a higher proportion of BSI with Enterobacterales in kidney transplant recipients than in liver transplant recipients (67% vs. 20%, p = 0.03), while multiple pathogens were detected in the liver transplant recipients. Conclusions BSI were common in pediatric liver and kidney transplant recipients and the pathogen composition differed between liver and kidney transplant recipients. Guidelines for empiric antibiotic therapy should consider the type of transplanted organ as well as the local resistance patterns. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06224-2.
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Affiliation(s)
- Dina Leth Møller
- Viro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Blegdamsvej 9B, DK-2100, Copenhagen Ø, Denmark
| | - Søren Schwartz Sørensen
- Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Neval Ete Wareham
- Centre of Excellence for Health, Immunity, and Infections, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Omid Rezahosseini
- Viro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Blegdamsvej 9B, DK-2100, Copenhagen Ø, Denmark
| | - Andreas Dehlbæk Knudsen
- Viro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Blegdamsvej 9B, DK-2100, Copenhagen Ø, Denmark.,Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Jenny Dahl Knudsen
- Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Susanne Dam Nielsen
- Viro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Blegdamsvej 9B, DK-2100, Copenhagen Ø, Denmark. .,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
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