EDITORIAL 10.1111/1469-0691.

12658

A special issue on infections in solid organ transplant recipients

a1, J. M. Aguado2, O. Manuel3, P. Grossi4, H. H. Hirsch5 on behalf of the ESCMID Study Group of Infection in
J. Gavald
Compromised Hosts (ESGICH)
1) Infectious Diseases Department, Hospital Vall d’Hebron, Vall d’Hebron Research Institute VHIR, Barcelona, 2) Hospital Universitario 12 de Octubre, Madrid,
Spain, 3) Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Lausanne, Switzerland, 4) Infectious Diseases
Section, Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy and 5) Transplantation & Clinical Virology, Department
Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland
E-mail: joan.gavalda@vhir.org
Article published online: 8 May 2014
Clin Microbiol Infect 2014; 20 (Suppl. 7): 1–3

Nowadays transplantation is a consolidated therapeutic option [7]. Oncogenesis should also be considered an MDIM effect
for many kidney, heart, liver and lung disease patients in the of these viruses. This is well illustrated when we analyse the
terminal stage. During the last two decades, the survival of relationship between Epstein Barr Virus and PTLD or
solid organ transplant (SOT) recipients has increased. Castleman’s disease, HV8 and Kaposi’s sarcoma, HBV and
Advances in the optimal tissue typing of organ donors, in the hepatocellular carcinoma, BK virus and ureteric smooth
pretransplant risk assessment of donor and recipient, in muscle proliferation, and papillomavirus with squamous,
surgical skills and in immunosuppressive treatment, have all anogenital and skin cancers [4,8].
contributed to this improvement. Despite the advances in  As mentioned above, despite the advances in prevention and
prevention and treatment, infection in SOT recipients is a treatment, infection is still one of the main causes of
moving target, and this pathology is still one of the main causes morbidity and mortality in SOT recipients. It is the most
of morbidity and mortality [1–3]. To achieve control of a frequent cause of death in the first year post-transplant,
complex subject such as infection in SOT recipients, the basically in the first 3 months [1–3,9]. In liver transplant
participation and collaboration of different disciplines or recipients, infection is the leading cause of death over the
specialties is essential. This mutual collaboration between first 1–3 years, with the majority occurring in the first 3–
specialists provides the basis for a new medical subspecialty 6 months [1]. Infection is also the main cause of death in
called Transplant Infectious Diseases (TID). We would like to kidney transplantation in the immediate post-transplant
make some considerations of the key points that should period. According to the registry of the International
support this new specialty. Society for Heart and Lung Transplantation (ISHLT) (www.
 It is better to prevent than to treat an infection in SOT ishlt.org/registries/) [2], the major identified causes of death
recipients, not only because the infection carries a high risk in the first 30 days were non-CMV infections (42%) and graft
of morbidity and mortality, but also because the indirect failure (18%). After the first year, the most common causes
consequences of infection or ‘microbially determined of death were CLAD (26%) and non-CMV infections (21%).
immune modulation’ (MDIM), following the new Fishman’s  Another important aspect is the economic impact that
concept [4] that mediates allograft injury, increase the risk infections have on the cost of a transplant procedure.
and severity of a wide variety of opportunistic pathogens and Suffering an infection directly implies a longer hospital stay,
favour the development of certain forms of malignancy. The which means higher expenses for diagnosis, treatment and
MDIM is best described for CMV and includes proliferative monitoring. In parallel, infection is associated with an
graft injury and chronic graft rejection (chronic lung allograft increased loss of transplanted organs and with the develop-
dysfunction (CLAD) and accelerated atherogenesis in ment of neoplasms. It is worth noting that infections lead to
hearts), enhanced viral replication of other herpes viruses a notable decline in potential quality and years of life. Thus,
and HCV, and increased susceptibility to PTLD and other for example, CMV infection has a negative impact on the
opportunistic infections (Aspergillus spp., bacteria and PCP) quality of healthcare achieved after kidney transplantation
[4]. Similar effects have been observed for other viruses and increases healthcare expenditure. It has been shown
(EBV, HHV-6, HHV-7 and HCV) [5]. Moreover, in lung that an additional cost of US $14 400 was needed for the
transplantation, different studies have shown a relationship in-hospital care of a renal transplant patient with CMV
between CLAD and previous infections due to respiratory infection and disease (2008 value) [10]. SOT patients with
viruses [5], Aspergillus spp. [6] and Pseudomonas aeruginosa invasive fungal infection had a 4-fold increase in mortality, an

ª2014 The Authors

Clinical Microbiology and Infection ª2014 European Society of Clinical Microbiology and Infectious Diseases
2 Clinical Microbiology and Infection, Volume 20 Supplement 7, September 2014 CMI

TABLE 1. Summary and index of authors of the supplement: ‘Recommendations for the Prevention and Management of
Infections in Solid Organ Transplantation. A European Perspective’
1. Editorial
J. Gavalda, J.M. Aguado, O. Manuel, P. Grossi and H.H. Hirsch on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH)
2. From the Classic Concepts to Modern Practice
J Fishman
3. Recommendations for Screening of Donor and Recipient Prior to Solid Organ Transplantation and to Minimize Transmission of Donor-Derived Infections
O. Len, C. Garzoni, C. Lumbreras, I. Molina, Y. Meije, A. Pahissa and P. Grossi; on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH)
4. Cytomegalovirus Infection in Solid Organ Transplant Recipients
C. Lumbreras, O. Manuel, O. Len, I.J.M. ten Berge, D. Sgarabotto and H.H. Hirsch; on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH)
5. Invasive Fungal Infections in Solid Organ Transplant Recipients
J. Gavalda, Y. Meije, J. Fort
un, E. Roilides, F. Saliba, O. Lortholary, P. Muñoz, P. Grossi and M. Cuenca-Estrella; on behalf of the ESCMID Study Group of Infection in
Compromised Hosts (ESGICH)
6. Multidrug-resistant Bacteria in Solid Organ Transplant Recipients.
C. Cevera, C. van Delden, J. Gavalda, T. Welte, M. Akova and J. Carratala; on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH)
7. European Perspective on Human Polyomavirus Infection, Replication and Disease in Solid Organ Transplantation
H.H. Hirsch, N. Babel, P. Comoli, V. Friman, F. Ginevri, A. Jardine, I. Lautenschlager, C. Legendre, K. Midtvedt, P. Mu~noz, P. Randhawa, C.H. Rinaldo and A. Wieszek;
on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH)
8. Mycobacterial Infections in Solid Organ Transplant Recipients
Y. Meije, C. Piersimoni, J. Torre-Cisneros, A.G. Dilektasli and J.M. Aguado; on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH)
9. Influenza and Other Respiratory Viral Infections in Solid Organ Transplant Recipients
O. Manuel, F. L opez-Medrano, L. Kaiser, T. Welte, J. Carratala, E. Cordero and H.H. Hirsch; on behalf of the ESCMID Study Group of Infection in Compromised Hosts
(ESGICH)
10. Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder in Solid Organ Transplant Recipients
R. San-Juan, P. Comoli, S. Caillard, B. Moulin, H.H. Hirsch and P. Meylan; on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH)
11. Infections in Solid Organ Transplant HIV-Infected Patients
J.M. Miro, F. Ag€uero, J.-C. Duclos-Vallee, N.J. Mueller, P. Grossi and A. Moreno; on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH)

TABLE 2. Infectious Diseases Society of America–United the best therapeutic strategy. Special attention has been paid
States Public Health Service grading system for ranking to donor-related issues and considerations about infection in
recommendations in clinical guidelines HIV transplant recipients have also been discussed in the last
chapter (Table 1).
Category, grade Definition
The recommendations included in this supplement of
Strength of recommendation Clinical Microbiology and Infection (CMI) have been developed
A Good evidence to support a recommendation for use
B Moderate evidence to support a recommendation for use to provide a practical clinical resource for understanding and
C Poor evidence to support a recommendation
D Moderate evidence to support a recommendation managing infectious diseases in SOT. The ESCMID Study
against use.
E Good evidence to support a recommendation against use Group for Infections in Compromised Hosts (ESGICH)
Quality of evidence
I Evidence from >1 properly randomized, controlled trial commissioned the editors to elaborate on these recommen-
II Evidence from >1 well-designed clinical trial, without
randomization; from cohort or case-controlled analytic
dations. The editors selected the topics and the authors
studies (preferably from >1 centre); from multiple based on their expertise in the different topics of TID
time-series; or from dramatic results from uncontrolled
experiments medicine. The summary and the index of authors were sent
III Evidence from opinions of respected authorities,
based on clinical experience, descriptive studies to the Clinical Microbiology and Infection editorial office for
or reports of expert committees
approval and after that the editors sent an official letter to
the authors of each section inviting them to participate in the
supplement. Authors were required to adhere to a specific
additional 23.5 in-patient hospital days and $62 697 (95% CI format for chapter development. Authors were challenged to
$30 377–95 107) excess costs compared with patients produce focused, specific and clinically useful chapters. Their
without an IFI (2007 value) [11]. recommendations are based on the best evidence that is
currently available in TID along with their invaluable clinical
The main idea when creating these recommendations was experience. Given the varying degrees of evidence in TID, the
to focus on the European perspective because the epidemi- editors considered it important that all recommendations be
ology and management of prevention and treatment of TID graded according to the level of evidence to improve the
may be different in Europe compared with other regions in the reader’s experience and comprehension of the recommen-
world. The expert panel in TID has tried to be a representative dations. The gradation of recommendations has been based
sample of most European countries. The aim of this supple- on the ‘Infectious Diseases Society of America–United States
ment was to represent the most frequent and problematic Public Health Service Grading System for ranking recom-
types of infection syndrome in SOT. Each chapter includes the mendations in clinical guidelines’. The strength of the
most relevant hot topics, the situations where prophylaxis is recommendations’ gradation and the quality of the evidence
required and types of recipients who require prophylaxis, the are shown in Table 2 and have been used for each chapter.
selection of the best diagnosis and monitoring techniques and Each section of the supplement followed the Author Guide-

ª2014 The Authors

Clinical Microbiology and Infection ª2014 European Society of Clinical Microbiology and Infectious Diseases, CMI, 20 (Suppl. 7), 1–3
CMI Editorial 3

lines for CMI, and then every manuscript had a peer review 2. Christie JD, Edwards LB, Kucheryavaya AY et al. The Registry of the
International Society for Heart and Lung Transplantation: twenty-sev-
process that was managed by the Editor-in-Chief or Associate
enth official adult lung and heart-lung transplant report–2010. J Heart
Editors, who were responsible for assessing priority and for Lung Transplant 2010; 29: 1104–1118.
selection of reviewers. Of note, neither CMI nor the ESGICH 3. Kahwaji J, Bunnapradist S, Hsu JW, Idroos ML, Dudek R. Cause of
dictated the contents of the recommendations. death with graft function among renal transplant recipients in an
integrated healthcare system. Transplantation 2011; 91: 225–230.
The editors would like to say thank you for the enormous 4. Fishman JA. Transplant infectious diseases: from the classic concepts to
effort and dedication of all authors and reviewers involved in modern practice. Clin Microbiol Infect 2014; 20(Suppl. 7): 4–9.
this supplement. Their excellent work, knowledge and exper- 5. Vu DL, Bridevaux PO, Aubert JD, Soccal PM, Kaiser L. Respiratory
tise have been critical for the creation and development of viruses in lung transplant recipients: a critical review and pooled
analysis of clinical studies. Am J Transplant 2011; 11: 1071–1078.
these recommendations. We also want to thank the European
6. Charlson ES, Diamond JM, Bittinger K et al. Lung-enriched organisms
Society of Clinical Microbiology and Infectious Disease (ESC- and aberrant bacterial and fungal respiratory microbiota after lung
MID) and the ESCMID Study Group for Infections in Com- transplant. Am J Respir Crit Care Med 2012; 186: 536–545.
7. Botha P, Archer L, Anderson RL et al. Pseudomonas aeruginosa
promised Hosts – ESGICH for their support, as well as the
colonization of the allograft after lung transplantation and the risk of
Clinical Microbiology and Infection journal and the Editor-in Chief bronchiolitis obliterans syndrome. Transplantation 2008; 85: 771–774.
for unconditional support and editorial assistance. 8. Fishman JA, Issa NC. Infection in organ transplantation: risk factors and
evolving patterns of infection. Infect Dis Clin North Am 2010; 24: 273–
The Editors 283.
9. Watt KD, Pedersen RA, Kremers WK, Heimbach JK, Charlton MR.
Evolution of causes and risk factors for mortality post-liver transplant:
Transparency Declaration results of the NIDDK long-term follow-up study. Am J Transplant 2010;
10: 1420–1427.
10. Luan FL, Kommareddi M, Ojo AO. Universal prophylaxis is cost
The authors have no conflicts of interest with respect to this effective in cytomegalovirus serology-positive kidney transplant
article, or as the editors of this supplement. patients. Transplantation 2011; 91: 237–244.
11. Menzin J, Meyers JL, Friedman M et al. The economic costs to United
States hospitals of invasive fungal infections in transplant patients. Am J
Infect Control 2011; 39: e15–e20.
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ª2014 The Authors

Clinical Microbiology and Infection ª2014 European Society of Clinical Microbiology and Infectious Diseases, CMI, 20 (Suppl. 7), 1–3