M.J. Ricart

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.

The influence of innate immunity gene receptors polymorphisms in renal transplant infections.

Background. Genetically defined deficiencies in key components of the innate immune system have been associated with a greater risk of infection. The aim of this study was to assess the influence of genetic variability of innate immune receptors (mannose-binding lectin [MBL], mannose-associated serine-protease-2 [MASP-2], and Toll-like receptors [TLR4]) in the risk of infections after a kidney transplantation. Methods. All patients undergoing a kidney or kidney–pancreas transplantation during a 3-year period were included. Functionally relevant mutations in MBL2, MASP2, and TLR4 genes were determined by DNA sequencing. The incidence of major bacterial infections, asymptomatic cytomegalovirus (CMV) infection, and CMV disease were compared among groups. Results. There were no differences regarding major transplant characteristics among groups. Older age, requirements for posttransplant hemodialysis, and pretransplant diabetes, but not gene polymorphisms, were associated with a greater number of bacterial infections. In univariate analysis, low-MBL genotypes were associated with CMV disease in pretransplant CMV seropositive patients (P=0.015), whereas the TLR4 mutation was associated with higher risk of CMV primary infection (P=0.024). TLR4 mutation was an independent factor associated with CMV disease (odds ratio 5.84, 95% confidence interval 1.35−25.20, P=0.018). Conclusion. Polymorphisms of innate immunity receptors, especially TLR4 mutation, were associated with higher risk of CMV disease, while susceptibility to other infectious disorders was not observed.

Renal transplantation in HIV-infected patients: 2010 update

The prognosis of human immunodeficiency virus (HIV) infection has improved in recent years with the introduction of antiretroviral treatment. While the frequency of AIDS-defining events has decreased as a cause of death, mortality from non-AIDS-related events including end-stage renal diseases has increased. The etiology of chronic kidney disease is multifactorial: immune-mediated glomerulonephritis, HIV-associated nephropathy, thrombotic microangiopathies, and so on. HIV infection is no longer a contraindication to transplantation and is becoming standard therapy in most developed countries. The HIV criteria used to select patients for renal transplantation are similar in Europe and North America. Current criteria state that prior opportunistic infections are not a strict exclusion criterion, but patients must have a CD4+ count above 200 cells/mm(3) and a HIV-1 RNA viral load suppressible with treatment. In recent years, more than 200 renal transplants have been performed in HIV-infected patients worldwide, and mid-term patient and graft survival rates have been similar to that of HIV-negative patients. The main issues in post-transplant period are pharmacokinetic interactions between antiretrovirals and immunosuppressants, a high rate of acute rejection, the management of hepatitis C virus coinfection, and the high cardiovascular risk after transplantation. More studies are needed to determine the most appropriate antiretroviral and immunosuppressive regimens and the long-term outcome of HIV infection and kidney graft.

Risk Factors for Infection with Extended‐Spectrum and AmpC β‐Lactamase‐Producing Gram‐Negative Rods in Renal Transplantation

Increasing prevalence of infections caused by multi‐resistant gram‐negative enteric bacilli due to synthesis of extended‐spectrum β‐lactamase (ESBL) or to desrepressed chromosomic AmpC β‐lactamase (AmpC) is a major concern in the hospitalized patient population. Renal transplant recipients are especially susceptible to these infections. A cohort observational study in a 3‐year period was performed. ESBL‐production was determined by phenotypic analysis based on the CLSI recommendations. A multi‐variate logistic regression analysis was performed to identify independent variables associated with multi‐resistant gram‐negative bacilli infection. The study included 417 patients (61 double kidney‐pancreas recipients). The incidence of ESBL‐producing and desrepressed chromosomic AmpC β‐lactamase resistance was 11.8% (49 patients). The most frequent bacteria isolated was E. coli (35/60 isolations), followed by Klebsiella spp (12/60 isolations). Double kidney‐pancreas transplantation (OR 3.5, CI95% 1.6–7.8), previous use of antibiotics (OR 2.1,CI95% 1.1–4.1), posttransplant dialysis requirement (OR 3.1, CI95% 1.5–6.4) and posttransplant urinary obstruction (OR 5.8, CI95% 2.2–14.9) were independent variables associated with these multi‐resistant gram‐negative enteric bacilli infections. The incidence of ESBL‐producing and desrepressed AmpC β‐lactamase gram‐negative enteric bacilli infection in our population was high. These infections are associated with significant morbidity after renal transplantation.

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.

Immunohistochemically proven cytomegalovirus end-organ disease in solid organ transplant patients: clinical features and usefulness of conventional diagnostic tests.

Abstract: We studied the main clinical features, outcome, and laboratory parameters in a group of solid organ transplant (SOT) patients with immunohistochemically proven cytomegalovirus (CMV) disease. Confirmed CMV cases were obtained through databases. Demographics, clinical data, transplantation type, immunosuppressive regimens, donor and recipient CMV serostatus, therapy, outcome and laboratory results, pp65 antigenemia, and qualitative polymerase chain reaction (PCR) for CMV were analyzed. From 1995 to 2004, 31 cases with complete medical records were identified. Disease appeared between 24 and 2538 days after transplantation but most cases presented in the first 100 days. Gastrointestinal CMV disease was the most frequent form (71%), while thrombocytopenia was present in 50% of cases, and leukopenia was less common (35.5%). CMV pp65 antigenemia was positive in 58% of patients, but its sensitivity increased to 71% if performed during the first 6 months. A qualitative CMV PCR technique gave similar results during this period (71.4%). Most patients were treated with intravenous ganciclovir (n=25; 80.6%). In 4 cases (19.4%), use of foscarnet alone or a sequential regimen with ganciclovir–foscarnet was deemed necessary. Surgical procedures were necessary in 5 patients (16%). The death rate reached 13%. CMV end‐organ disease can be a life‐threatening infection in SOT patients. Gastrointestinal disease was the most frequent end‐organ disease. CMV antigen detection is best suited for the early period after transplantation.

Recurrence of immunological markers for type 1 (insulin-dependent) diabetes mellitus in immunosuppressed patients after pancreas transplantation.

BACKGROUND Type 1 (insulin dependent) diabetes mellitus (IDDM) is an autoimmune disease in which autoantibodies against islet cells develop concomitantly with or even preceding diagnosis. Because the recurrence of diabetes can be the cause of graft failure in patients with pancreas transplantation, we studied the possible recurrence of IDDM immunomarkers after transplantation. METHODS The following determinations were performed every 1-2 years after transplantation in 50 immunosuppressed IDDM patients with simultaneous kidney and pancreas transplantation (bladder drainage of exocrine secretion): islet cell antibodies (ICA) by direct immunofluorescence, antibodies against glutamic acid decarboxylase (GADab) by radiobinding assay, and the oral glucose tolerance test. The mean follow-up was 4.1+/-6.3 (range 1 to 9 years). RESULTS GADab were detected in 11 patients after transplantation, 10 of whom had been positive beforehand. ICA reappearance after transplantation was detected in seven patients (14%). The presence of ICA was related to GADab positivity (P=0.001) and HLA DR3 patients (P=0.04), but not with pancreatitis and rejection episodes, immunosuppression induction therapy, or donor HLA haplotype. During follow-up, an abnormal oral glucose tolerance test was more frequent in ICA-positive patients (P=0.02), with no differences in metabolic control or insulin secretion. CONCLUSION We conclude that GADab persist and ICA reappear despite immunosuppressive therapy in patients with functioning pancreas transplants. The relevance and the risk that this implies for IDDM development should be determined.

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.

Tuberculosis in Solid Organ Transplant Recipients at a Tertiary Hospital in the Last 20 Years in Barcelona, Spain

OBJECTIVE Mycobacterium tuberculosis (TB) is a serious opportunistic infection in solid organ transplant recipients. The TB incidence is 20 to 74 times greater than that among the general population. Our aim was to determine the incidence as well as the clinical, radiological, and microbiological features and outcomes of TB in these patients. MATERIALS AND METHODS We reviewed the clinical records of subjects with posttransplant TB from January 1988 to December 2007. A definite TB case was defined by a positive culture; probable TB by a positive smear or histological finding; and disseminated TB when 2 organs were involved. We noted an early diagnosis as ones in the first year posttransplantation. Outcomes were classified following the WHO recommendation and mortality related defined by death during treatment. RESULTS Among 4634 recipients (2757 kidney, 1334 liver, 361 double kidney-pancreas, and 182 heart), 21 (0.45%) developed posttransplant TB: namely, 0.47%, 0.22%, 1.1%, and 0.54%, respectively. In 2 cases M. tuberculosis did not grow upon culture; the diagnosis was established by positive acid-fast bacilli on a sputum smear or by histological findings on biopsy. The mean posttransplantation time to TB diagnosis was 21 months (48% early TB). Two patients had a previous history of TB. Fever was the most common symptom (71%). Pulmonary tuberculosis represented 47.6% of cases; extrapulmonary, 28.6%; and disseminated, 23.8%. Among the cases of pulmonary TB, 60% had unilateral infiltrates and 10% cavitations on X ray. Eighteen patients completed treatment. Five patients displayed adverse events, 3 of which were liver toxicity. Four patients died, with 3 deaths related to TB. CONCLUSIONS The incidence of TB in this cohort was higher than that among the general population (450 cases/100,000 recipients). TB was associated with adverse effects of treatment and significant mortality.

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.