EDITORIAL
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
for many kidney, heart, liver and lung disease patients in the
terminal stage. During the last two decades, the survival of
solid organ transplant (SOT) recipients has increased.
Advances in the optimal tissue typing of organ donors, in the
pretransplant risk assessment of donor and recipient, in
surgical skills and in immunosuppressive treatment, have all
contributed to this improvement. Despite the advances in
prevention and treatment, infection in SOT recipients is a
moving target, and this pathology is still one of the main causes
of morbidity and mortality [1–3]. To achieve control of a
complex subject such as infection in SOT recipients, the
participation and collaboration of different disciplines or
specialties is essential. This mutual collaboration between
specialists provides the basis for a new medical subspecialty
called Transplant Infectious Diseases (TID). We would like to
make some considerations of the key points that should
support this new specialty.
 It is better to prevent than to treat an infection in SOT
recipients, not only because the infection carries a high risk
of morbidity and mortality, but also because the indirect
consequences of infection or ‘microbially determined
immune modulation’ (MDIM), following the new Fishman’s
concept [4] that mediates allograft injury, increase the risk
and severity of a wide variety of opportunistic pathogens and
favour the development of certain forms of malignancy. The
MDIM is best described for CMV and includes proliferative
graft injury and chronic graft rejection (chronic lung allograft
dysfunction (CLAD) and accelerated atherogenesis in
hearts), enhanced viral replication of other herpes viruses
and HCV, and increased susceptibility to PTLD and other
opportunistic infections (Aspergillus spp., bacteria and PCP)
[4]. Similar effects have been observed for other viruses
(EBV, HHV-6, HHV-7 and HCV) [5]. Moreover, in lung
transplantation, different studies have shown a relationship
between CLAD and previous infections due to respiratory
viruses [5], Aspergillus spp. [6] and Pseudomonas aeruginosa
Clinical Microbiology and Infection ª2014 European Society of Clinical Microbiology and Infectious Diseases
10.1111/1469-0691.
[7]. Oncogenesis should also be considered an MDIM effect
of these viruses. This is well illustrated when we analyse the
relationship between Epstein Barr Virus and PTLD or
Castleman’s disease, HV8 and Kaposi’s sarcoma, HBV and
hepatocellular carcinoma, BK virus and ureteric smooth
muscle proliferation, and papillomavirus with squamous,
anogenital and skin cancers [4,8].
 As mentioned above, despite the advances in prevention and
treatment, infection is still one of the main causes of
morbidity and mortality in SOT recipients. It is the most
frequent cause of death in the first year post-transplant,
basically in the first 3 months [1–3,9]. In liver transplant
recipients, infection is the leading cause of death over the
first 1–3 years, with the majority occurring in the first 3–
6 months [1]. Infection is also the main cause of death in
kidney transplantation in the immediate post-transplant
period. According to the registry of the International
Society for Heart and Lung Transplantation (ISHLT) (www.
ishlt.org/registries/) [2], the major identified causes of death
in the first 30 days were non-CMV infections (42%) and graft
failure (18%). After the first year, the most common causes
of death were CLAD (26%) and non-CMV infections (21%).
 Another important aspect is the economic impact that
infections have on the cost of a transplant procedure.
Suffering an infection directly implies a longer hospital stay,
which means higher expenses for diagnosis, treatment and
monitoring. In parallel, infection is associated with an
increased loss of transplanted organs and with the develop-
ment of neoplasms. It is worth noting that infections lead to
a notable decline in potential quality and years of life. Thus,
for example, CMV infection has a negative impact on the
quality of healthcare achieved after kidney transplantation
and increases healthcare expenditure. It has been shown
that an additional cost of US $14 400 was needed for the
in-hospital care of a renal transplant patient with CMV
infection and disease (2008 value) [10]. SOT patients with
invasive fungal infection had a 4-fold increase in mortality, an
ª2014 The Authors
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
States Public Health Service grading system for ranking
recommendations in clinical guidelines
Category, grade Definition
Strength of recommendation
A Good evidence to support a recommendation for use
B Moderate evidence to support a recommendation for use
C Poor evidence to support a recommendation
D Moderate evidence to support a recommendation
against use.
E Good evidence to support a recommendation against use
Quality of evidence
I Evidence from >1 properly randomized, controlled trial
II Evidence from >1 well-designed clinical trial, without
randomization; from cohort or case-controlled analytic
studies (preferably from >1 centre); from multiple
time-series; or from dramatic results from uncontrolled
experiments
III Evidence from opinions of respected authorities,
based on clinical experience, descriptive studies
or reports of expert committees
additional 23.5 in-patient hospital days and $62 697 (95% CI
$30 377–95 107) excess costs compared with patients
without an IFI (2007 value) [11].
The main idea when creating these recommendations was
to focus on the European perspective because the epidemi-
ology and management of prevention and treatment of TID
may be different in Europe compared with other regions in the
world. The expert panel in TID has tried to be a representative
sample of most European countries. The aim of this supple-
ment was to represent the most frequent and problematic
types of infection syndrome in SOT. Each chapter includes the
most relevant hot topics, the situations where prophylaxis is
required and types of recipients who require prophylaxis, the
selection of the best diagnosis and monitoring techniques and
the best therapeutic strategy. Special attention has been paid
to donor-related issues and considerations about infection in
HIV transplant recipients have also been discussed in the last
chapter (Table 1).
The recommendations included in this supplement of
Clinical Microbiology and Infection (CMI) have been developed
to provide a practical clinical resource for understanding and
managing infectious diseases in SOT. The ESCMID Study
Group for Infections in Compromised Hosts (ESGICH)
commissioned the editors to elaborate on these recommen-
dations. The editors selected the topics and the authors
based on their expertise in the different topics of TID
medicine. The summary and the index of authors were sent
to the Clinical Microbiology and Infection editorial office for
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
format for chapter development. Authors were challenged to
produce focused, specific and clinically useful chapters. Their
recommendations are based on the best evidence that is
currently available in TID along with their invaluable clinical
experience. Given the varying degrees of evidence in TID, the
editors considered it important that all recommendations be
graded according to the level of evidence to improve the
reader’s experience and comprehension of the recommen-
dations. The gradation of recommendations has been based
on the ‘Infectious Diseases Society of America–United States
Public Health Service Grading System for ranking recom-
mendations in clinical guidelines’. The strength of the
recommendations’ gradation and the quality of the evidence
are shown in Table 2 and have been used for each chapter.
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
lines for CMI, and then every manuscript had a peer review
process that was managed by the Editor-in-Chief or Associate
Editors, who were responsible for assessing priority and for
selection of reviewers. Of note, neither CMI nor the ESGICH
dictated the contents of the recommendations.
The editors would like to say thank you for the enormous
effort and dedication of all authors and reviewers involved in
this supplement. Their excellent work, knowledge and exper-
tise have been critical for the creation and development of
these recommendations. We also want to thank the European
Society of Clinical Microbiology and Infectious Disease (ESC-
MID) and the ESCMID Study Group for Infections in Com-
promised Hosts – ESGICH for their support, as well as the
Clinical Microbiology and Infection journal and the Editor-in Chief
for unconditional support and editorial assistance.
The Editors
Transparency Declaration
10. Luan FL, Kommareddi M, Ojo AO. Universal prophylaxis is cost
The authors have no conflicts of interest with respect to this
article, or as the editors of this supplement.
11. Menzin J, Meyers JL, Friedman M et al. The economic costs to United
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ª2014 The Authors