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Timing, Etiology, and Location of First Infection in First Year After Heart Transplantation
Timing, Etiology, and Location of First Infection in First Year After Heart Transplantation I.J. Sánchez-Lázaro, L. Almenar, M. Blanes, L. Martínez-Dolz, M. Portolés, E. Roselló, M. Rivera, and A. Salvador ABSTRACT Background. Infections are the leading cause of death in the first year after heart transplantation (HTx) after the postoperative period. Objective. To describe the timing, etiology, and location of the first infection occurring in the first year after HTx. Patients and Methods. The study included 604 HTx procedures performed at our center from November 1987 to September 2009. Infections were classified as those requiring hospital admission or that prolonged hospital stay. Infection was established on the basis of clinical findings and supplementary test results. Etiologic diagnosis was established at microbiological culture. Infections were categorized as bacterial, viral, fungal, protozoal, or of unknown origin, and were grouped according to microorganism family. Time to occurrence of infection is given as mean (interquartile range). Locations considered were systemic, pulmonary, genitourinary, cutaneous, oropharyngeal, mediastinal, sternal, gastrointestinal, and other. Results. Mean (SD) patient age was 51 (12) years, and 83.8% of patients were men. Almost half of all patients (42.9%) experienced some type of infection in the first year after HTx. The most frequently occurring infections were bacterial (49.6%) and viral (38.7%), with fewer fungal (6.3%), protozoal (1.2%), and of unknown origin (4.3%). Staphylococci were the most commonly isolated organisms (10.5%) in bacterial infections, cytomegalovirus (21.1%) in viral infections, and Candida (2.3%) and Aspergillus (2.3%) in fungal infections. Early-onset infections (n ⫽ 2; 1–7 days) were caused by Candida spp, and late-onset infections (n ⫽ 110; 14 –182 days) by a mixed group of bacteria. The sternum was the site of early-onset infections (n ⫽ 9; 6 –14 days), and the genitourinary tract was the site of late-onset infections (n ⫽ 110; 28 –180 days). Conclusions. Nearly half of HTx recipients experience a significant infection during the first year posttransplantation. Early-onset infections occur in critical care units, are caused by nosocomial organisms, and involve the sternum or mediastinum, whereas late- onset infections have a more varied etiology and preferentially affect the skin and genitourinary tract. NFECTIONS are the leading cause of death in the first year after heart transplantation (HTx) after the postoperative period. Among factors that influence infection are immunosuppression, surgical procedure, critical care unit stay, and donor transmission. The objective of this study was to describe the timing, etiology, and location of the first infection occurring in the first year after HTx.
I
MATERIALS AND METHODS The present study included 604 HTx procedures performed at our center from November 1987 to September 2009. For the purposes
of the study, infections were classified as those occurring in the first year after HTx and requiring hospital admission or that prolonged
From the Heart Failure and Transplantation Unit, Cardiology Department, Hospital Universitario La Fe. Valencia, Spain (I.J.SL., L.A., L.M-D., A.S.); Infectious Department, Hospital Universitario La Fe, Valencia, Spain (M.B.); Research Center, Hospital Universitario La Fe, Valencia, Spain (M.P., E.R., M.R.). Address reprint requests to Ignacio J. Sánchez-Lázaro, La Fe University Hospital, Avda Ausias March 2, esc 2, pta 15, Rocafort, 46111 Valencia, Spain. E-mail: [email protected]
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2010.07.052
Transplantation Proceedings, 42, 3017–3019 (2010)
3017
3018 hospital stay. Timing of infections was based on the median (interquartile range) time of onset. Infection was established on the basis of clinical findings and supplementary test results. Etiologic diagnosis was established at microbiological culture, when possible. Infections were categorized as bacterial, viral, fungal, protozoal, or of unknown origin. Each category was then classified by microorganism family. Locations considered were systemic, pulmonary, genitourinary, cutaneous, oropharyngeal, mediastinal, sternal, gastrointestinal and other. Statistical analysis was performed using commercially available software (SPSS version 12.0, SPSS, Inc, Chicago, Illinois).
RESULTS
Mean (SD) patient age was 51 (12) years, 83.8% were men, and 25.2% underwent urgent transplantation. Almost half of all the patients (42.9%) experienced some type of infection in the first year after HTx. The most frequently recurring infections were bacterial (49.6%) and viral (38.7%), with fewer fungal (6.3%), protozoal (1.2%), and of unknown origin (4.3%). Staphylococci (10.5%) and Pseudomonas (6.6% of total) were the most commonly isolated agents in bacterial infections; cytomegalovirus (21.1%) and herpesvirus (14.5% of total) were the predominant organisms isolated in viral infections; and Candida spp (2.3%) and Aspergillus (2.3% of total) were the most common causative organisms in fungal infections. Early-onset infections were caused by organisms from the Candida (n ⫽ 2; 1–7 days) and Staphylococcus (n ⫽ 8; 4 –19 days) groups, and late-onset infections were caused a mixed group of bacteria (n ⫽ 110; 14 –182 days). By location, early-onset infections were in the sternum (n ⫽ 9; 6 –14 days) and mediastinum (n ⫽ 15; 10 –22 days), and late-onset infections were cutaneous (n ⫽ 36; 22–174 days) and genitourinary (n ⫽ 110; 28 –180 days).
Fig 1. Chronology of infections after heart transplantation. Values are given as median (interquartile range) days. CMV, cytomegalovirus; HSV, herpes simplex virus.
SÁNCHEZ-LÁZARO, ALMENAR, BLANES ET AL
DISCUSSION
Heart transplantation is the treatment of choice in patients with advanced heart failure without significant associated comorbid conditions. Despite this, HTx is associated with a series of potentially serious and often frequent comorbidities including acute graft failure, occurrence of tumors, and propensity for infections. Infections are the leading cause of death in the first year after HTx, surpassed only by acute graft failure.1 Among factors that influence post-HTx infections are the surgical procedure, critical care unit stay, hospital stay, donor transmission, and, in particular, the immunosuppression treatment, which is indispensable for maintaining graft function.2 Almost half of all patients who underwent HTx experienced a significant infection during the first year after HTx, and more than 75% of these infections occurred within the first 3 months. This period coincides with that of the surgical procedure, maximum instrumentation, critical care unit stay, and maximum immunosuppression including induction. Pathogens involved in infections occurring in the first 3 months post-HTx are primarily nosocomial (Acinetobacter, Aspergillus, and Pseudomonas) except for the viral infections. The site of infection in the first 3 months was also typical of nosocomial infections, and were associated with the surgical procedure and instrumentation (sternum, mediastinum, and systemic sepsis). These results are in accord with those of other studies, in both HTx and other solid-organ transplantation. The difference insofar as other organ transplantation procedures is involvement of the sternum and mediastinum.3 At 3 months after HTx, an important change occurs in infections. In this phase, the patient is usually being treated
FIRST INFECTION IN YEAR 1 POSTTRANSPLANTATION
on an outpatient basis, and immunosuppression therapy is being progressively decreased. This causes the etiology of infections to be more varied and occasionally unknown. Similarly, the site of infections varies, and resembles that in the general population. This study has some limitations. Only the first infection was assessed, and the variables that may have influenced infections were not considered. In conclusion, almost half of patients who undergo HTx experience a significant infection during the first year posttransplantation. Early-onset infections occur in critical care units by nosocomial organisms, and involve the sternum or mediastinum. Late-onset infections have
3019
a more varied etiology, and preferentially affect the skin and genitourinary tract. (Fig 1). REFERENCES 1. Almenar Bonet L; Spanish Heart Transplantation Registry. 20th official report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984 –2008). Rev Esp Cardiol 62:1286, 2009 2. Garrido RS, Augado JM, Díaz-Pedroche C, et al: A review of critical periods for opportunistic infection in the new transplantation era. Transplantation 82:1457, 2006 3. Aguado Garcia JM, Fortín Abete J, Gavaldá Santapau J, Pahissa Berga A y de la Torre Cisneros: Infecciones en pacientes trasplantados. 3rd ed. Barcelona, Spain: Elsevier; 2009
I
MATERIALS AND METHODS The present study included 604 HTx procedures performed at our center from November 1987 to September 2009. For the purposes
of the study, infections were classified as those occurring in the first year after HTx and requiring hospital admission or that prolonged
From the Heart Failure and Transplantation Unit, Cardiology Department, Hospital Universitario La Fe. Valencia, Spain (I.J.SL., L.A., L.M-D., A.S.); Infectious Department, Hospital Universitario La Fe, Valencia, Spain (M.B.); Research Center, Hospital Universitario La Fe, Valencia, Spain (M.P., E.R., M.R.). Address reprint requests to Ignacio J. Sánchez-Lázaro, La Fe University Hospital, Avda Ausias March 2, esc 2, pta 15, Rocafort, 46111 Valencia, Spain. E-mail: [email protected]
© 2010 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2010.07.052
Transplantation Proceedings, 42, 3017–3019 (2010)
3017
3018 hospital stay. Timing of infections was based on the median (interquartile range) time of onset. Infection was established on the basis of clinical findings and supplementary test results. Etiologic diagnosis was established at microbiological culture, when possible. Infections were categorized as bacterial, viral, fungal, protozoal, or of unknown origin. Each category was then classified by microorganism family. Locations considered were systemic, pulmonary, genitourinary, cutaneous, oropharyngeal, mediastinal, sternal, gastrointestinal and other. Statistical analysis was performed using commercially available software (SPSS version 12.0, SPSS, Inc, Chicago, Illinois).
RESULTS
Mean (SD) patient age was 51 (12) years, 83.8% were men, and 25.2% underwent urgent transplantation. Almost half of all the patients (42.9%) experienced some type of infection in the first year after HTx. The most frequently recurring infections were bacterial (49.6%) and viral (38.7%), with fewer fungal (6.3%), protozoal (1.2%), and of unknown origin (4.3%). Staphylococci (10.5%) and Pseudomonas (6.6% of total) were the most commonly isolated agents in bacterial infections; cytomegalovirus (21.1%) and herpesvirus (14.5% of total) were the predominant organisms isolated in viral infections; and Candida spp (2.3%) and Aspergillus (2.3% of total) were the most common causative organisms in fungal infections. Early-onset infections were caused by organisms from the Candida (n ⫽ 2; 1–7 days) and Staphylococcus (n ⫽ 8; 4 –19 days) groups, and late-onset infections were caused a mixed group of bacteria (n ⫽ 110; 14 –182 days). By location, early-onset infections were in the sternum (n ⫽ 9; 6 –14 days) and mediastinum (n ⫽ 15; 10 –22 days), and late-onset infections were cutaneous (n ⫽ 36; 22–174 days) and genitourinary (n ⫽ 110; 28 –180 days).
Fig 1. Chronology of infections after heart transplantation. Values are given as median (interquartile range) days. CMV, cytomegalovirus; HSV, herpes simplex virus.
SÁNCHEZ-LÁZARO, ALMENAR, BLANES ET AL
DISCUSSION
Heart transplantation is the treatment of choice in patients with advanced heart failure without significant associated comorbid conditions. Despite this, HTx is associated with a series of potentially serious and often frequent comorbidities including acute graft failure, occurrence of tumors, and propensity for infections. Infections are the leading cause of death in the first year after HTx, surpassed only by acute graft failure.1 Among factors that influence post-HTx infections are the surgical procedure, critical care unit stay, hospital stay, donor transmission, and, in particular, the immunosuppression treatment, which is indispensable for maintaining graft function.2 Almost half of all patients who underwent HTx experienced a significant infection during the first year after HTx, and more than 75% of these infections occurred within the first 3 months. This period coincides with that of the surgical procedure, maximum instrumentation, critical care unit stay, and maximum immunosuppression including induction. Pathogens involved in infections occurring in the first 3 months post-HTx are primarily nosocomial (Acinetobacter, Aspergillus, and Pseudomonas) except for the viral infections. The site of infection in the first 3 months was also typical of nosocomial infections, and were associated with the surgical procedure and instrumentation (sternum, mediastinum, and systemic sepsis). These results are in accord with those of other studies, in both HTx and other solid-organ transplantation. The difference insofar as other organ transplantation procedures is involvement of the sternum and mediastinum.3 At 3 months after HTx, an important change occurs in infections. In this phase, the patient is usually being treated
FIRST INFECTION IN YEAR 1 POSTTRANSPLANTATION
on an outpatient basis, and immunosuppression therapy is being progressively decreased. This causes the etiology of infections to be more varied and occasionally unknown. Similarly, the site of infections varies, and resembles that in the general population. This study has some limitations. Only the first infection was assessed, and the variables that may have influenced infections were not considered. In conclusion, almost half of patients who undergo HTx experience a significant infection during the first year posttransplantation. Early-onset infections occur in critical care units by nosocomial organisms, and involve the sternum or mediastinum. Late-onset infections have
3019
a more varied etiology, and preferentially affect the skin and genitourinary tract. (Fig 1). REFERENCES 1. Almenar Bonet L; Spanish Heart Transplantation Registry. 20th official report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984 –2008). Rev Esp Cardiol 62:1286, 2009 2. Garrido RS, Augado JM, Díaz-Pedroche C, et al: A review of critical periods for opportunistic infection in the new transplantation era. Transplantation 82:1457, 2006 3. Aguado Garcia JM, Fortín Abete J, Gavaldá Santapau J, Pahissa Berga A y de la Torre Cisneros: Infecciones en pacientes trasplantados. 3rd ed. Barcelona, Spain: Elsevier; 2009