G. Sanclemente

Early Bacteremia After Solid Organ Transplantation

OBJECTIVE Bloodstream infections (BSI) are a major cause of morbidity and mortality after solid organ transplantation. Our aim was to analyze early BSI after solid organ transplantation. MATERIALS AND METHODS A prospective cohort study included patients undergoing a kidney, simultaneous kidney-pancreas (SPK), or orthotopic liver transplantation (OLT) from 2003-2007. We prospectively collected demographic variables, underlying chronic diseases, transplantation procedures, and posttransplant complications. Recorded cases of BSI were defined as significant according to CDC criteria. Early BSIs were considered to be those appearing within 30 days posttransplantation. RESULTS During the study period, we performed 902 transplantations: 474 renal, 340 liver, and 88 pancreas. Seventy episodes of early BSI were diagnosed in 67 patients (7.4%). The incidences of BSI according to the type of transplantation were: 4.8% in renal, 4.5% in SPK, and 12% in OLT (P < .001). Sixty-three percent of the bacteria isolated were gram-negative, the most frequent being Escherichia coli, of which 18 (54%) were extended-spectrum beta-lactamase-producing (ESBL), and Pseudomonas aeruginosa, of which 18 (31%) were multidrug-resistant. The most frequent gram-positive bacteria were coagulase-negative staphylococci (20%). The urinary tract was a frequent source of BSI (27%), followed by a catheter (18%). Two patients (3%) died, both liver recipients, but neither death was related to the BSI. CONCLUSIONS In our setting, the incidence of early BSI among solid organ transplant recipients was high, especially liver recipients, but with low associated mortality. The most frequent sources of infection were urinary tract and catheter. Gram-negative BSI showed a high rate of multidrug resistance.

Influence of Cytomegalovirus Disease in Outcome of Solid Organ Transplant Patients

INTRODUCTION Despite recent advances in prevention and treatment, cytomegalovirus (CMV) is still a major complication in transplant patients. This study sought to analyze the incidence of CMV disease and its impact on patient and graft survival. METHODS Between June 2003 and December 2009, we included all kidney, liver, heart, and double transplant patients who underwent solid organ transplantation. They had 1-year posttransplant follow-up. RESULTS Among the 1427 patients who received kidney (n = 661), liver (n = 494), heart (n = 89), or double (n = 183) transplants, 103 (7.2%) displayed CMV disease. The incidence by type of transplant was: heart (n = 17, 19%), liver (n = 35, 7%), kidney (n = 41, 6.2%), or double transplant (n = 10, 5.5%; P < .001). In 59% of cases, the infection developed during the first 3 months after transplantation. CMV infections ranged from viral syndrome (n = 47, 45%) to tissue-invasive disease (n = 56, 55%), including 38% with gastrointestinal involvement. Relapsing episodes occurred in 12 patients (11%). Discordant donor/recipient CMV serology was present in 151 patients (donor positive/receptor negative), including 34 (22.5%) who developed primary CMV disease (P < .001). Coinfections mostly bacterial, were diagnosed in 38% of patients. An acute rejection episode was present in 31% of patients with CMV disease compared to 20% without this complication (P = .017). Crude mortality was significantly higher among patients with CMV disease (n = 18 patients [18%] vs 92 patients [7%]; P < .001). CONCLUSION Our data confirmed that CMV disease was associated with worse transplant outcomes, with higher incidences of acute rejection episodes and mortality.

Toxoplasma gondii primary infection in renal transplant recipients. Two case reports and literature review

Toxoplasmosis after solid organ transplantation is a complication associated with high morbidity and mortality. Universal prophylaxis with trimethoprim–sulfamethoxazole (TMP‐SMX) is effective to prevent post‐transplant toxoplasmosis. We report two cases of renal transplant recipients with negative antibodies against Toxoplasma gondii pretransplant who developed toxoplasmosis after TMP‐SMX discontinuation. We have also performed a review of published cases of primary toxoplasmosis after renal transplantation. Of 20 cases reviewed, 11 were male and the mean age was 37.8 years (SD = 13.8). Donor serology for T. gondii was determined in 15 donors, two of them (13%) with negative immunoglobulin (Ig)G and four (27%) with positive IgG and IgM antibodies. Fever was present in 85% of primary toxoplasmosis and hematologic abnormalities were observed in 69% of the cases. Ten patients died (50%). All patients with fatal outcomes had clinical evidence of toxoplasmosis during the early post‐transplant period (first 90 days), while no patient with late toxoplasmosis died (P = 0.003). Primary toxoplasmosis is associated with high mortality rates and TMP‐SMX prophylaxis can delay the onset of symptoms resulting in an improvement of prognosis.

Epidemiology and risk factors for late infection in solid organ transplant recipients

C. Cervera, M. Fernández‐Ruiz, A. Valledor, L. Linares, A. Antón, M. Ángeles Marcos, G. Sanclemente, I. Hoyo, F. Cofán, M.J. Ricart, F. Pérez‐Villa, M. Navasa, T. Pumarola, A. Moreno. Epidemiology and risk factors for late infection in solid organ transplant recipients.
Transpl Infect Dis 2011: 13: 598–607. All rights reserved

Klebsiella pneumoniae infection in solid organ transplant recipients: epidemiology and antibiotic resistance.

BACKGROUND Klebsiella pneumoniae is a well recognized source of nosocomial infection in solid-organ transplant (SOT) recipients. It is also the most common species capable of producing extended-spectrum β-lactamases (ESBL). Its treatment can therefore be a challenge owing to antibiotic resistance. METHODS Prospective study of all transplant recipients from July 2003 to December 2007 at our center. Klebsiellla pneumoniae infectious events were recorded. RESULTS A total of 1,057 patients were enrolled, 509 (48%) renal, 360 (34%) liver, 78 (7%) heart, and 110 (10%) double transplants. We diagnosed 116 episodes of K. pneumoniae infection in 92 patients during the study period, of which 62 were ESBL-producing strains (53%). Thirty-four episodes had bacteremia (29%), 15 of which were caused by ESBL-producing strains. There were no strains of K. pneumoniae producing carbapanemase (KPC). Forty-seven percent of the episodes occurred during the first month after transplantation. The incidence of infection by type of transplant was: renal 11%, liver 7%, cardiac 5%, and double transplant 6% (P=.075). The major sites of infection were urinary tract 72%, surgical wound 5%, intraabdominal 6%, catheter 5%, lung 1%, bloodstream 1%, and others 2%. ESBL-producing K. pneumoniae strains were more common in renal transplant patients (P=.035) and in those who required posttransplant dialysis (P=.022). There were 4 deaths in the first 30 days after the isolation of K. pneumoniae, and 3 of these cases were infections caused by ESBL-producing strains. CONCLUSIONS There was a high incidence of ESBL-producing K. pneumoniae infections in SOT recipients and renal transplant recipients, and those who required dialysis were more likely to develop infection by this strain. No KPC-producing organisms were found in our series. The existence of such a high level of resistance is a well recognized hospital threat, and appropriate policies and interventions should be addressed in high-risk patients.

Impact of Antibiotic Resistance on the Development of Recurrent and Relapsing Symptomatic Urinary Tract Infection in Kidney Recipients

We sought to determine the frequency, risk factors, and clinical impact of recurrent urinary tract infections (UTI) in kidney transplant recipients. Of 867 patients who received a kidney transplant between 2003 and 2010, 174 (20%) presented at least one episode of UTI. Fifty‐five patients presented a recurrent UTI (32%) and 78% of them could be also considered relapsing episodes. Recurrent UTI was caused by extended‐spectrum betalactamase (ESBL)–producing Klebsiella pneumoniae (31%), followed by non‐ESBL producing Escherichia coli (15%), multidrug‐resistant (MDR) Pseudomonas aeruginosa (14%), and ESBL‐producing E. coli (13%). The variables associated with a higher risk of recurrent UTI were a first or second episode of infection by MDR bacteria (OR 12; 95%CI 528), age >60 years (OR 2.2; 95%CI 1.15.1), and reoperation (OR 3; 95%CI 1.37.1). In addition, more relapses were recorded in patients with UTI caused by MDR organisms than in those with susceptible microorganisms. There were no differences in acute rejection, graft function, graft loss or 1 year mortality between groups. In conclusion, recurrent UTI is frequent among kidney recipients and associated with MDR organism. Classic risk factors for UTI (female gender and diabetes) are absent in kidney recipients, thus highlighting the relevance of uropathogens in this population.

Epidemiology of Pneumonia in Kidney Transplantation

BACKGROUND Pneumonia remains an important cause of morbidity among solid organ transplant recipients. METHODS We prospectively evaluated all renal transplant patients at our center from July 2003 to December 2008 who had pneumonia that required hospitalization. We gathered data regarding underlying diseases as well as pretransplant, transplant, and posttransplant characteristics. Pneumonia defined according to the Centers for Disease Control and Prevention criteria was classified depending on its origin as community acquired or nosocomial. In all patients, microbiologic samples of respiratory secretions and blood were collected at the physicians discretion. The indication to perform a fiberoptic bronchoscopy was the presence of multiple, bilateral, or diffuse pulmonary infiltrates or the absence of a clinical or radiologic response after 3 days of antimicrobial therapy. RESULTS Among 610 kidney transplant recipients, we diagnosed 60 episodes of pneumonia in 54 patients (8.8%), of which 23 had a nosocomial origin (38%) and 37 community acquired (62%). Bacterial infection was the most frequent etiology (44%), followed by fungal in 4 (7%) and viral in 2 (3.5%). The most commonly isolated microorganism in nosocomial pneumonia was Pseudomonas aeruginosa (26%, among which 50% was multidrug resistant). In 34% there was no microbiologic isolation. The most common pathogen among community-acquired pneumonias was Strepococcus pneumoniae (11%). In 54% of cases there was no microbiologic confirmation of disease. The overall accuracy of bronchoalveolar lavage was 72%. A total of 21 patients with pneumonia (35%) were admitted to the intensive care unit; of these, 14 had a nosocomial origin (60%) and 9 (15%) died due to the infection (8 [88%] of whom had nosocomial pneumonia; P=.001). CONCLUSIONS Our data confirmed that nosocomial pulmonary infections are associated with considerable morbidity and mortality in renal transplant recipients. The performance of invasive procedures is useful for the diagnosis of pneumonia.

Opportunistic pulmonary infections in solid organ transplant recipients.

BACKGROUND Opportunistic pulmonary infections (OPI) represent common life-threatening complications after solid organ transplantation. Our objective was to describe pulmonary infections caused by opportunistic pathogens in solid-organ transplant patients. METHODS We analyzed all adult solid organ recipients (liver, heart, kidney, and pancreas) between July 2003 and June 2010, reporting all episodes of pulmonary opportunistic infection. RESULTS During the study period, 1656 solid organ transplants were performed and 188 opportunistic infections were diagnosed in 163 patients (incidence 10%). In 40 cases, the site of infection was the lung (21%) with 57.5% occurring between the first and sixth month posttransplantation. The most frequently isolated microorganism was Aspergillus spp (n = 25, 63%), followed by Pneumocystis jirovecii (n = 6 cs, 15%). Twenty-five patients with an opportunistic pulmonary infections died during the follow-up including, 16 related to the infection (40%). The causative organism responsible for the highest mortality was Aspergillus spp (n = 12; 48%). Twenty-one patients with an opportunistic nonrespiratory infection died, five of them related to it (4%). Opportunistic pulmonary infection was associated with an increased mortality rate (P < .001). There was a trend toward a higher mortality among patients who developed OPI during the first 6 months after transplantation. CONCLUSIONS Opportunistic pulmonary infections after solid organ transplantation are not infrequent. The period of risk for developing this infectious complications goes beyond the first 6 months posttransplantation. Mortality due to these infections was high in comparison to that of opportunistic nonrespiratory infections. It is important to keep a high index of suspicion for infectious complications during all posttransplant periods, as this is the first step toward a rapid diagnosis and adequate treatment.

Influence of Mannose-Binding Lectin Gene Polymorphisms on The Invasiveness of Cytomegalovirus Disease After Solid Organ Transplantation

BACKGROUND Mannose-binding lectin (MBL) is a component of the innate immune system that binds the surface of pathogens, activating the complement pathway and acting as opsonin. Certain single-nucleotide polymorphisms of MBL2 are associated with a decrease in the circulating levels of MBL. Our aim was to evaluate the influence of MBL2 polymorphisms in the invasiveness of Cytomegalovirus (CMV) disease after solid organ transplantation. METHODS We include those solid organ transplant recipients who developed CMV disease posttransplant from 2000 to 2006. MBL2 genotyping was performed by sequencing of exon 1 (wild-type allele A and variants B, C, and D) and promoter regions (alleles H and L, X and Y, and P and Q). In the case of liver transplantation, donor MBL2 genotypes were analyzed. Associations were calculated by the chi-square test and binary logistic regression. RESULTS We included 45 transplant recipients with CMV disease (22 renal, 7 simultaneous kidney-pancreas, 11 liver, and 5 heart), of whom 10 (22%) had invasive CMV disease. No differences were found regarding HH (versus HL or LL), YY and YX (versus XX) and QQ (versus QP and PP) haplotypes with invasive CMV disease (P = 1.000 for all 3 comparisons). Patients with an exon 1 wild-type (AA) haplotype had 36% invasive CMV disease in comparison with 9% of patients with A/O or O/O haplotypes (P = .035). Binary logistic regression analysis showed that patients with exon 1 AA haplotype had an independent risk of developing invasive CMV disease (odds ratio, 6.0; 95% confidence interval, 1.1-32.5). CONCLUSIONS Our results suggest that exon 1 wild-type genotypes are associated with a higher risk of invasive CMV disease after solid organ transplantation.

Epidemiology, clinical characteristics, and outcome of invasive aspergillosis in renal transplant patients

Invasive aspergillosis (IA) has been considered an infrequent complication after renal transplantation. We aimed to evaluate the differences in clinical and epidemiologic characteristics of IA between renal and other types of transplantation.