Unusual forms of subacute invasive pulmonary aspergillosis in patients with solid tumors.

OBJECTIVES: Aspergillus spp. can cause acute invasive disease in severely immunocompromised patients. Nonetheless, there are few reports of solid tumors complicated with subacute invasive pulmonary aspergillosis (subacute IPA). METHODS: Retrospective observational cohort study, performed in patients with primary lung cancer or secondary lung metastasis complicated with subacute IPA in three referral hospitals. RESULTS: From 2008 to 2011, 14 episodes of subacute IPA were diagnosed, including 11 (78.6%) probable and 3 proven (21.4%). Nine patients (64.3%) had primary lung cancer. Thirteen patients (92.9%) had more than one local or systemic predisposing factor for subacute IPA. No patient had previous fungal colonization. Aspergillus spp. was isolated in 6 specimens of bronchoalveolar lavage, 6 sputum, 2 biopsies, and 1 percutaneous lung puncture. At the time Aspergillus spp. was isolated, the most common radiologic findings on chest computed tomography (CT) were cavitary masses, and development or expansion of cavitation in existing masses or nodules (10/14, 71.4%). On CT follow-up, most patients (8/12, 66.7%) had new cavity formation or expansion of one or more existing cavities. All patients were treated with azoles and two underwent surgery. Ten (71.4%) patients died after Aspergillus spp. was detected (median time 73 days, IQR 33-243): 2 (20%) deaths were subacute IPA-attributable and 6 (60%) were related. CONCLUSIONS: Primary lung cancer and secondary lung metastasis seem to be triggering factors for Aspergillus spp. implantation, and predispose to subacute IPA. Once localized in the damaged lung, the mold can grow and cause or expand cavities. In lung cancer patients, Aspergillus spp. detection is associated with a very poor prognosis.

Liver lipocalin 2 expression in severely obese women with non alcoholic fatty liver disease.

BACKGROUND: Lipocalin 2 (LCN2) has been related to obesity, insulin resistance and metabolic disturbance. However, its relation with non alcoholic fatty liver disease (NAFLD) has hardly been studied. METHODS: We examined LCN2 circulating levels and its protein and gene expression in liver from women with severe obesity and NAFLD. We analyzed the liver histology of 59 white severely obese women (BMI ≥40 Kg/m²): 15 subjects presented normal liver histology or non-significant liver disease (NL), 18 simple steatosis (SS) and 26 non alcoholic steatohepatitis (NASH). We determined the anthropometric and metabolic features of the women. LCN2 levels were determined by an ELISA and liver mRNA expression by real time RT-PCR. We also studied LCN2 expression in HepG2 liver cells under various inflammatory stimuli. RESULTS: Liver LCN2 protein and gene expression were higher in NAFLD than in obese with NL. Liver LCN2 gene expression correlated with SS (r=0.351, p=0.016), and its protein expression correlated with NASH (r=0.705, p=0.003). LCN2 expression was detected in HepG2 cells after the administration of TNFα, IL6, resistin or adiponectin. LCN2 expression was induced by TNFα, IL6 and resistin. CONCLUSIONS: Liver LCN2 is related to NAFLD in severely obese women. Up-regulation of LCN2 expression is detected in HepG2 cells after exposure to TNFα, IL6 and resistin. These results suggest that LCN2 expression is induced under liver harmful conditions.

Impact of valganciclovir on Epstein-Barr Virus polymerase chain reaction in pediatric liver transplantation: preliminary report.

UNLABELLED: Preemptive therapy with ganciclovir has been recommended in the pediatric liver transplant strategy to avoid the development of posttransplant lymphoproliferative disorder (PTLD) from an high Epstein-Barr virus (EBV) is detected. We sought viral load to analyze the response to preemptive therapy with valganciclovir (VGC) in children with liver transplantations and an high quantitative EBV-PCR. METHODS: From June 2005 to December 2007, we tested 979 EBV-PCR among 80 pediatric liver transplant recipients, from those 21/80 PCR were tested from the date of transplantation and 59/80 belonged to the historical cohort (7/59 had a prior history of PTLD). Patients were divided into 2 groups depending upon whether they did (n = 22) or did not (n = 19) receive VGC treatment. The response to VGC was considered complete, if the PCR was negative at 30 and 60 days of treatment; and partial, when the PCR decreased at least 50%. Ganciclovir blood levels tested in 109 cases instances and correlated with the EBV-PCR. RESULTS: A total of 369 (33%) positive PCR were detected in 36/80 patients (mean, 75,000 copies; range = 5000-4,200,000). Among the 22 episodes treated for 30 days, 34% showed complete responses, 41%, partial, and 23%, no response. Among the non-treated group the rates were 6%, 25%, and 68%, respectively (P = .01). However, no differences were observed among those episodes treated for 60 days. At the administered doses, hardly any patient reached the recommended ganciclovir therapeutic level at 2 hours (6 micro/mL). However, the mean PCR was lower when the ganciclovir levels were greater than 4 mg/L when compared with lower levels (P = .03). CONCLUSION: After 30 days of treatment there was a response to VGC in the EBV viral load. There was high interpatient variability of ganciclovir serum concentrations, suggesting the need for pharmacokinetic monitoring to optimize treatment. There was a relationship between the concentration of ganciclovir and the EBV viral load.

Bloodstream infections among transplant recipients: results of a nationwide surveillance in Spain.

Bloodstream infections (BSIs) are a major cause of morbidity and mortality in transplant recipients. The aim of this study is to describe the incidence, microbiology and outcomes of BSIs in transplant recipients in Spain. The Spanish Network for Research on Infection in Transplantation (RESITRA) is formed by 16 centers with transplant program in Spain. The incidence and characteristics of BSIs in transplant patients were obtained prospectively from the cohort. We included 3926 transplant recipients (2935 solid organ and 991 hematopoietic stem cell transplants). Overall, 730 episodes of BSIs were recorded with an incidence rate ranging from 3 episodes per 10 000 transplant days in kidney recipients to 44 episodes per 10 000 transplant days in allogeneic hematopoietic stem cell transplantation (HSCT). The most frequent sources were intravascular catheters and the most frequent microorganisms isolated were coagulase-negative staphylococci. Crude mortality of BSIs was 7.8%, being highest in liver recipients (16%). Multidrug resistant nonfermentative gram-negative BSIs had significantly worse prognosis than those caused by their susceptible counterparts (p = 0.015), but no differences were found between resistant and susceptible gram-negative enteric bacilli, S. aureus or Candida spp. BSIs are still a major concern in transplant recipients. The increasing isolations of multiresistant microorganisms represent a challenge for the next years.

Management of catheter-related Staphylococcus aureus bacteremia: when may sonographic study be unnecessary?

This study reviews the outcome of patients with uncomplicated catheter-related Staphylococcus aureus bacteremia diagnosed in our hospital from January 1997 to December 1999 and treated with short-course antibiotic therapy. Our aim was to assess the effectiveness of this regimen for minimizing complications (relapses, endocarditis and metastatic foci). A total of 213 episodes of bacteremia were registered and 167 (78.4%) were nosocomial. Among these, 87 (52.1%) were catheter-related Staphylococcus aureus bacteremia and 20 were primary nosocomial bacteremia. Endocarditis was diagnosed during the acute episode in 7/107 of these patients (2 by persistent fever after catheter removal and 5 by metastatic foci; 3 of them also had cardiac risk factors) and confirmed with transesophageal echocardiography. Among the 84/87 catheter-related Staphylococcus aureus bacteremia and 16/20 primary nosocomial bacteremia patients who did not develop endocarditis, 31 patients died during the acute episode (16 due to sepsis despite initiation of antibiotic treatment and 15 due to the underlying disease) and five had osteoarticular foci. The remaining 64 episodes were considered to be uncomplicated bacteremia (no cardiac risk factors, persistent fever, metastatic foci, or clinical signs of endocarditis) and were treated with 10-14 days of high-dose antistaphylococcal antibiotics. Echocardiography was not mandatory in these patients. Of the 64 uncomplicated episodes, 62 were followed for at least 3 months and none relapsed or developed endocarditis. Even though some of the patients might have had subclinical endocarditis, short-course therapy with high doses of antistaphylococcal antibiotics was effective for treating uncomplicated catheter-related Staphylococcus aureus bacteremia. Transesophageal echocardiography may not be necessary in these cases.

[Strains of ganciclovir-resistant cytomegalovirus]. / Cepas de citomegalovirus resistentes a ganciclovir.

BACKGROUND: In countries where the resistance of cytomegalovirus to ganciclovir has been studied, strains resistant to therapeutic doses of this drug have been isolated. When a change in treatment has been impossible the patient has shown bad clinical evolution. The aim of this study was to investigate the presence of these strains in our medium, observe whether the resistances appear in patients previously treated with ganciclovir and determine its implication in the evolution of cytomegalovirus infection. PATIENTS AND METHODS: One hundred twenty-three stains of cytomegalovirus, isolated during the period 1990-1998, corresponding to the following 94 patients were studied: 17 breast feeding children of healthy parents who were negative controls (sensitive strains), 43 organ transplant recipients, 29 AIDS patients, 2 with other immunodeficiencies and 3 children with intrauterine infection. Seventeen patients were studied due to the insidious course of the infection despite treatment. The remaining were random. The technique used was that of growth inhibition of the strains seeded on different gradients of ganciclovir: 0, 1, 5, 10 and 20 microM. The inoculate consisted in a cellular suspension evaluated according to the degree of viral growth. The strains presenting an inhibitory doses 50% (ID 50%) greater than 10 microM were considered as resistant. RESULTS: Eighty-two strains presented an ID 50% lower than 5 microM, 24 from 5 to 10 microM and in the 17 remaining strains, corresponding to 12 patients, the ID 50% was greater than 10 microM. The evolution of these latter 12 patients with strains considered to be resistant to ganciclovir was of death in 8. All were immunodepressed and with a history of having previously received ganciclovir. Another currently has a chronic evolution and the three remaining patients, who presented better immunity, became cured. All patients has a chronic evolution and the three remaining patients, who presented better immunity, became cured. All patients had undergone previous treatment with ganciclovir except two: one patient with Wegener disease treated with acyclovir 15 days before, and the other was an infant of an HIV positive mother who had received the drug. CONCLUSIONS: The presence of cytomegalovirus strains resistant to ganciclovir was confirmed in our patients. The previous use of ganciclovir and, in one case of acyclovir, appears to be implicated in the appearance of resistance. The evolution of the immunodepressed patients with infection by resistant strains was mortal except when their immunity was improved.

Listeria monocytogenes-associated acute hepatitis in a liver transplant recipient.

We report a case of Listeria monocytogenes bacteriemia with liver involvement mimicking acute viral hepatitis in a liver transplant recipient. The patient presented with fever, jaundice and alanine aminotransferase levels ten times the upper limit of normal. Liver biopsy showed signs of acute hepatitis and occasional granulomas. Both blood and liver biopsy cultures were positive for Listeria monocytogenes. The patient received a 3 week course of ampicillin and gentamicin with clinical and biochemical recovery. Liver involvement during Listeria infections is unusual, and most cases occur in patients with underlying hepatic disease and impaired cell-mediated immunity. To our knowledge only one such case has previously been reported in a liver transplant patient. Furthermore, in the present case we isolated the causal agent from the liver biopsy specimen.

Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA.

BACKGROUND: Tuberculosis is unusual in transplant recipients. The incidence, clinical manifestations, and optimal treatment of this disease in this population has not been adequately defined. The present study was undertaken to assess the incidence, clinical features, and response to therapy of Mycobacterium tuberculosis infection in solid-organ transplant recipients. METHODS: We evaluated retrospectively the incidence, clinical characteristics, diagnostic procedures, antituberculous treatment, clinical course, and factors influencing mortality in 51 solid-organ transplant recipients who developed tuberculosis after transplantation. We also reviewed the world literature on tuberculosis in solid-organ transplantation. RESULTS: The overall incidence of tuberculosis was 0.8%. The localization was pulmonary in 63% of the cases, disseminated in 25%, and extrapulmonary in 12%. Tuberculosis developed from 15 days to 13 years after surgery (mean, 23 months). In one third of the cases, diagnosis was not suspected initially, and in three cases, diagnosis was made at necropsy. Fever was the most frequent symptom, followed by constitutional symptoms, cough, respiratory insufficiency, and pleuritic pain. Fifteen patients (33%) developed hepatotoxicity during treatment; hepatotoxicity was severe in seven cases. Hepatotoxicity was higher in patients receiving four or more antituberculous drugs (50%) than in patients receiving three drugs (21%; P=0.03). Serum levels of cyclosporine decreased in the 26 patients under the simultaneous use of rifampin. Nine of them (35%) developed acute rejection, and five (56%) died, in comparison with 3 of 17 patients (18%) who did not develop rejection after the use of cyclosporine and rifampin (P=0.03). Although microbiological response was favorable in 94% of the 35 patients who completed 6 or more months of treatment, 16 other patients (31%) died before diagnosis or in the course of treatment. None of the patients treated for more than 9 months died as a consequence of tuberculosis, whereas the mortality rate was 33% among those treated for 6 to 9 months (P=0.03). Use of antilymphocyte antibodies or high doses of steroids for acute rejection before tuberculosis was associated with a higher mortality rate. CONCLUSIONS: M tuberculosis causes serious and potentially life-threatening disease in solid-organ transplant recipients. Treatment with at least three drugs during 9 months or more, avoiding the use of rifampin, appears to be appropriate.

Rhodococcus equi pneumonia in patients infected with the human immunodeficiency virus. Report of 2 cases and review of the literature.

Rhodococcus equi is a cause of lung infection in immunosuppressed hosts. Since the start of the HIV epidemic, 76 cases of R. equi lung infection (MEDLINE 1985-96) affecting this population have been described. We report 2 additional cases and review the clinical data, radiological findings, treatment and outcome of these 78 patients. The mean age of these patients was 33 y; 69 were male. 71 met the criteria for AIDS (CDC 1993). Fever and cough were the presenting complaints in the majority of patients (84.3%). A single cavitary lung lesion in the upper lobes was the most common radiological finding (57.7%), although multiple cavitations, alveolar infiltrates and pleural effusion were also found. Treatment usually was based on synergistic antibiotic combinations for a long period of time determined on an individual basis. Surgery was performed only in 11 patients. Death attributable directly to R. equi infection is low (15.4%), however only half of the patients (53.8%) were completely cured. We conclude that R. equi infection should be strongly considered in any HIV patient who presents with cavitary lesions in the lung, especially if mycobacteria are not identified. Treatment must be based on synergistic antibiotic combinations, and surgery relegated to cases of chronic single cavitary lesions not responding to antibiotics.

Bacteremia due to Campylobacter species: clinical findings and antimicrobial susceptibility patterns.

From 1979 to 1996, 58 patients (mean age, 39.4 years) were treated for bacteremia due to Campylobacter species at the Hospitals Vall d'Hebron in Barcelona, Spain. Bacteremia was considered to be hospital acquired in 30% of these patients. Almost all the patients (93%) had underlying conditions; liver cirrhosis was the most frequent (34% of patients), and neoplasia, immunosuppressive therapy, and human immunodeficiency virus disease were also common. Of the 58 Campylobacter strains isolated, 81% were C. jejuni, 10% were Campylobacter species, 7% were C. fetus, and one (2%) was C. coli. Resistance rates were: cephalothin, 82%; co-trimoxazole, 79%; quinolones, 54%; ampicillin, 20%; amoxicillin/clavulanate, 4%; erythromycin, 7%; gentamicin, 0; and tetracyclines, 0. Even though the majority of patients were immunocompromised, mortality was low (10.5%), and only one patient relapsed. Because of the high level of resistance to the quinolones in Campylobacter species, these drugs should not be used as empirical treatment, at least in Spain. Although the macrolides remain the antibiotics of choice, amoxicillin/clavulanate may be an effective alternative therapy.