Biomedical subjects

Carlos Lumbreras

Publications and source records attributed to Carlos Lumbreras.

15 recordsLinked to original sources

PubMed2006

A review of critical periods for opportunistic infection in the new transplantation era.

BACKGROUND: The risk of opportunistic infection (OI) is considered to be maximum during the first six months after solid organ transplantation. The aim of this study was to know the incidence and risk factors for OI in the late period (>6 months) compared with the early period (<6 months) after solid organ transplantation. METHODS: We used the online database of the Spanish Network of Infection in Transplantation (RESITRA), which prospectively analyzed 2,702 solid organ transplantation recipients from August 2003 to February 2005. Univariate and multivariate analyses were performed to calculate the risk factors associated with the development of late OI. RESULTS: A total of 131 patients (6%) developed 176 infectious episodes in the late period. Although the incidence of infection and cytomegalovirus disease (0.4 per 1000 transplant days and 0.05 per 1000 transplant days, respectively) was lower than in the early period (3.5 per 1000 transplant days and 0.8 per 1000 transplant days; P<0.0001), the incidence of other OIs was similar in both periods (0.05 per 1000 transplant days versus 0.03 per 1000 transplant-days, P=0.5). Patients with the higher risk for developing late OI were those receiving early cytomegalovirus prophylaxis, patients who developed two or more episodes of acute rejection during the early period, patients with recurrent bacterial infection during the early period, patients with renal failure requiring dialysis, and patients with chronic graft malfunction. CONCLUSIONS: Our data suggest that in some high-risk patients, the critical period of risk for OI must be expanded beyond the first six months after transplant.

Adult↗

PubMed2006

Valganciclovir preemptive therapy for the prevention of cytomegalovirus disease in high-risk seropositive solid-organ transplant recipients.

BACKGROUND: The role of valganciclovir in the prevention of cytomegalovirus (CMV) disease in high-risk seropositive transplant patients is not known. METHODS: We prospectively followed 301 seropositive solid organ transplant recipients to assess the efficacy and safety of valganciclovir (VGCV) in the prevention of CMV disease in high-risk patients. Asymptomatic patients with an antigenemia test >or=25 positive cells/2x10(5) polymorphonuclear cells received valganciclovir 900 mg twice a day as preemptive therapy until resolution of antigenemia (minimum 14 days). Additionally, patients treated with antilymphocytic drugs for more than 6 days received prophylaxis with VGCV 900 mg once a day during 90 days. Mean follow-up was 14 months (range 6-20 months). RESULTS: Thirty-eight patients received VGCV; 24 as preemptive therapy and 14 due to the use of antilymphocytic drugs. No patient developed CMV disease during the follow-up. Viral load (antigenemia) decreased a mean of 78% from baseline after 7 days of VGCV therapy (P=0.024) and 98% at day 14 (P=0.029). Two patients showed a relapse of the antigenemia test >or=25 positive cells and were successfully treated with a repeated course of VGCV. Leukopenia (<2500/mm3) developed in 3/24 (12.5%) recipients in the preemptive therapy group and required to discontinuing the drug in one of them. CONCLUSIONS: VGCV is safe and highly efficacious in the prevention of CMV disease in high-risk seropositive organ transplant recipients.

Adolescent↗

PubMed2006

Interferon gamma quantification in cerebrospinal fluid compared with PCR for the diagnosis of tuberculous meningitis.

PURPOSE: To assess the utility of interferon gamma (INF-gamma) levels in cerebrospinal fluid (CSF), for the diagnosis of tuberculous meningitis (TBM), and compare these results with aPCR technique. METHODS: We studied CSF samples from patients with proven or probable TBM and a control group, composed by patients with other causes of meningitis and without meningitis. INFgamma levels were measured by radioimmunoassay. A PCR technique was performed using IS6110 primers. RESULTS: Of the 127 patients studied, 20 (15.6%) had TBM, 59 (46%) had meningitis of another aetiology and 49 (38.4%) had were HIV and non-HIV patients with normal CSF. The area below the ROC curve for interferon gamma levels in the diagnosis of TBM was 0.94. A cut-off of 6.4 IU/mL yielded a sensitivity of 70% and a specificity of 94%. False positive results were observed in 7 of the 59 patients (11.8%) with non-TB meningitis, (patients with herpetic meningoencephalitis and meningitis due to intracellular microorganisms). INF-gamma sensitivity was higher than PCR (70% vs. 65%). Both tests performed together showed higher sensitivity (80%) and specificity (92.6%). CONCLUSION: CSF INF-gamma levels (> 6.4 IU/mL) are very valuable in TBM diagnosis. PCR and INF-gamma could be simultaneously used to increase the diagnostic yield.

Adolescent↗

PubMed2006

Blood and urine samples as useful sources for the direct detection of tuberculosis by polymerase chain reaction.

The aim of the study was to assess the utility of the polymerase chain reaction (PCR) assay in blood and urine for the diagnosis of tuberculosis (TB). We prospectively evaluated the usefulness of PCR performed in blood and urine samples from patients with proved or probable TB compared with a control group of patients. The PCR technique was performed using IS6110 primers. We included in the study 57 patients (43 with definite TB and 14 with probable TB) and 26 controls. Blood and urine samples were drawn at the time of microbiologic diagnosis and 3, 6, 9, and 12 months later. Cultures were positive in the early period (<1 month after treatment) in 11 of 57 patients (19%) with probable or definite TB, in comparison with 42% of patients (24/57) who yielded a positive PCR (P = 0.02). Urine samples increased the sensitivity of PCR determination in blood samples by 10%. The PCR in blood and/or urine was positive in 41% of patients with pulmonary TB, in 36% of patients with extrapulmonary TB, and in 50% of patients with disseminated TB. Mycobacterium tuberculosis was still detectable by PCR in 5 of 13 patients with cured TB after 1 or more months of antituberculous treatment. The PCR detection of M. tuberculosis in blood and urine samples is useful for the diagnosis of different clinical forms of TB, mostly in those patients in which sample extraction is difficult or requires aggressive techniques. The sensitivity of this technique could be improved studying more than 1 sample in each patient, even after initiating an antituberculous treatment.

Antitubercular Agents↗

PubMed2006

Clinical and histological efficacy of pegylated interferon and ribavirin therapy of recurrent hepatitis C after liver transplantation.

Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG-IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT). We prospectively included 47 liver transplant patients with: 1) a positive test for hepatitis C virus (HCV)-ribonucleic acid (RNA) in serum; 2) alanine aminotransferase (ALT) >45 UI/mL; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months. Patients received PEG-IFN (1.5 microg/kg/week) and ribavirin (800-1,000 mg/day) for 12 months. Follow-up was based on biochemical (ALT), virological (RNA-HCV), and histological (liver biopsy) examinations. Follow-up lasted a minimum of 6 months after the end of antiviral therapy. Sustained virological response (SVR) was achieved in 23% of the patients. A total of 33 (70%) patients had normalized ALT levels at the end of therapy. Inflammatory portal and lobular score declined significantly in patients with SVR (P < 0.05) but not in nonresponder patients. Fibrosis did not change significantly in either group. SVR was significantly associated with low gamma-glutamyltransferase GGT (P = 0.04) and HCV-RNA levels (P = 0.03), a virological response at 12 weeks (P = 0.002) and patient's compliance (P = 0.04). Ten (21%) patients were withdrawn prematurely due to adverse effects. In conclusion, Therapy with PEG-IFN and ribavirin achieved SVR and a significant histological improvement in 23% of liver transplant recipients with chronic hepatitis C. Toxicity is an important drawback of this therapy.

Adult↗

PubMed2006

[Nosocomial outbreak of influenza in high-risk hematological patients. Efficacy of control measures and the use of zanamivir].

INTRODUCTION: This study describes a nosocomial outbreak of influenza in high-risk-hematological patients, and the usefulness of epidemiological measures and zanamivir administration for its control. METHODS: Fifteen patients who had been in contact with a patient with influenza A were included in the study. Viral culture of nasopharyngeal exudate was performed and the epidemiological data, risk factors and clinical outcome were evaluated. The efficacy of early therapy and preventive use of zanamivir was also assessed. RESULTS: Seven out of 15 patients (46.6%) developed symptoms and in 5 of these 7 cases (71.4%), influenza A virus was isolated. Eight patients did not develop symptoms and viral culture was sterile. All symptomatic patients were isolated, and treatment with inhaled zanamivir (10 mg/12 h, 5 days) was initiated as soon as possible; only one patient developed respiratory failure; the remaining cases had self-limited upper respiratory tract symptoms. There was no associated mortality. Zanamivir prophylaxis was used in three non-symptomatic patients considered to be at high risk. Tolerance to zanamivir was excellent. No new cases were observed after initiation of the preventive measures and use of zanamivir. CONCLUSION: The attack rate in a nosocomial influenza outbreak can be very high in immunocompromised patients. Prompt initiation of preventive measures, early treatment and prophylaxis with zanamivir may help to limit the extension of these outbreaks.

Antiviral Agents↗

PubMed2005

Advanced donor age increases the risk of severe recurrent hepatitis C after liver transplantation.

The association between donor age and the severity of recurrent hepatitis C and, whether there is any donor age above which severity of recurrence increases significantly, were analyzed. A total of 131 liver grafts of hepatitis C virus (HCV)-infected recipients were selected for the study. Distribution of donor age was compared between grafts with and without severe recurrence. The risk of developing severe recurrence as well as the hepatitis-free, severe hepatitis-free and HCV-related graft survival was compared between different donor age groups. Mean donor age was higher for grafts with severe recurrence (P = 0.007). The risk of developing severe recurrence within 2 years post-transplant increased with donors aged > or =50 years (RR = 1.34) and donors aged > or =70 years (RR = 1.61). Five-year severe hepatitis-free survival rates decreased progressively when donor age was over 50 years (P < 0.001). The study shows 50 and 70 years as the donor age cut-off points above which the evolution of HCV-infected recipients worsens.

Adolescent↗

PubMed2005

[Impact of a non-compulsory antibiotic control program (PACTA): cost reductions and decreases in some nosocomial infections].

BACKGROUND: Antibiotics account for 30% of hospital pharmacy expenses. More than 50% of the prescriptions are considered inappropriate; hence, programs devoted to optimizing the prescription of antibiotics should be developed. We present the results of a non-compulsory program for the assessment and control of antibiotic treatment in the University Hospital 12 de Octubre in Madrid. METHODS: The program was applied in the hospitalization units of six medical and surgical departments. Treatments in all patients were checked daily and recommendations were made in writing, according to previously established criteria. The program was used for 12 months and the results were compared with those of the previous 12 months. RESULTS: 1,280 treatments were reviewed and 524 recommendations were made (80% of them were accepted). There was a 13.82% reduction in the number of defined daily doses of antibiotics/100 inpatient-days. Antibiotic expenditure decreased by 65,352 euros (5,446 euros/month), implying a reduction of 1.21 euros/hospitalization-bed/day. There were no statistically significant differences in length of hospital stay or mortality between the two periods. A reduction in the incidence of Clostridium difficile diarrhea (p < 0.0001) and Candida spp. isolations (p < 0.05) was observed. CONCLUSIONS: Following application of a non-compulsory control program, antibiotic prescription improved and expenditure decreased, with no change in length of hospital stay or mortality. There was a reduction in the incidence of some nosocomial infections. Acceptation of the program by the physicians of the departments implicated was favorable.

Anti-Bacterial Agents↗

PubMed2004

[Efficacy preemptive therapy with ganciclovir for the prevention of cytomegalovirus disease in liver transplant recipients].

BACKGROUND AND OBJECTIVE: In liver transplant recipients the most frequent infection is that produced by cytomegalovirus (CMV). One of the methods to reduce the incidence of that infection is the CMV pp65 antigenemia-guided preemptive therapy with intravenous ganciclovir. PATIENTS AND METHOD: Liver transplant recipients were tested for CMV antigenemia at days 14, 28, 45, 60, 90 and 180 postransplantation and when clinically indicated. Patients showing > 50/200.000 leukocytes received ganciclovir 5 mg/kg/12 h for 14 days. Risk factors for active CMV disease where studied. RESULTS: 182 CMV seropositive patients where included in the study. 16 patients with > 50/200.000 leukocytes received ganciclovir as preemptive therapy. CMV disease appeared in 9/182 patients (4.9%): 2/16 who received PT and 7/166 among those who did not receive preemptive therapy. The only factor associated with increased incidence of CMV disease was to have missing samples for CMV antigenemia during the follow up (p < 0.0042; OR = 8,17; 95% CI, 1.94-34.36). CONCLUSIONS: Ganciclovir antigenemia-guided preemptive therapy is associated with a low incidence of CMV disease. Bad adherence to the protocol of antigenemia samples increases the risk for CMV disease.

Adult↗

PubMed2004

The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome.

Cardiovascular infections due to Salmonella enterica are infrequently reported, so their clinical features, prognosis, and optimal treatment are not completely known. Mortality associated with aortitis and endocarditis caused by nontyphoidal Salmonella remains exceedingly high. In this review of cases of cardiovascular infections due to Salmonella enterica studied in 2 hospitals in Madrid, we tried to assess the clinical manifestations and the procedures leading to diagnosis in addition to treatment and outcome. To complete the spectrum of infections related to cardiovascular surgery, cases of postoperative mediastinitis, pericarditis, and infections associated with cardiac devices were also included.Twenty-three patients were reviewed: 11 had mycotic aneurysms; 7 had endocarditis; 2 had device-related infections; and 3 had pericarditis, mediastinitis, and infection of an arteriovenous fistula, respectively. The risk of endovascular infection in patients older than 60 years with bacteremia due to nontyphoidal Salmonella was 23%. Most patients with aortitis had risk factors for atherosclerosis, and 6 had preexisting atherosclerotic aortic aneurysms. All except 1 patient with endocarditis had underlying cardiac disorders. Acquired immunodeficiency disease (AIDS) was a major risk factor for salmonella bacteremia in 1 patient with aortitis and 1 with endocarditis. Fever, unremitting sepsis, "breakthrough" and relapsing bacteremia were the most common clinical findings. In addition, abdominal or thoracic pain and cardiac failure and pericarditis were common features in patients with aortitis and endocarditis respectively. Computed tomography (CT) scan, arteriography, and echocardiography were the main diagnostic tools. Mortality associated with mycotic aneurysms and endocarditis due to S. enterica was 45% and 28%, respectively. Thoracic aneurysms, rupture, and shock at the time of diagnosis were associated with increased mortality in patients with aortitis. In situ bypass grafting was successfully performed in most cases. After surgery, antimicrobial therapy was continued for 4-9 weeks. No relapses were observed after a mean follow-up of 64 months. Antimicrobial therapy alone or combined with valve replacement or excision of a ventricular aneurysm was successful treatment for most patients with salmonella endocarditis. Combined medical and surgical treatment was required for patients with mediastinitis and pericarditis, and patients with device-related infections needed removal of the complete device. Diagnosis of aortitis due to nontyphoidal Salmonella should be established as early as possible to reduce mortality. Patients older than 60 years who have positive blood cultures for Salmonella along with fever and back, abdominal, or chest pain should have an extensive workup for infective aortitis. Immediate bactericidal antimicrobial therapy should be started and a CT scan should be performed on an emergency basis. If a mycotic aneurysm is found, surgical resection should follow as soon as possible. Resection of the aneurysm with in situ bypass grafting is the procedure of choice. Postoperative antimicrobial therapy for 6-8 weeks seems enough to avoid relapses. Optimal treatment of patients with endocarditis occurring on ventricular aneurysms must include resection of the aneurysmal sac. Salmonella endocarditis can be successfully treated with antimicrobials alone. Valve replacement should be reserved for patients with cardiac failure or persisting sepsis, and for those who relapse after discontinuation of antimicrobial therapy.

Acquired Immunodeficiency Syndrome↗

PubMed2003

[Invasive aspergillosis: clinical manifestations and treatment].

During the last decade the incidence of invasive aspergillosis has substantially grown due to the increasing use of powerful immunosupressive drugs in more patients. Unfortunately, the associated mortality with this infection is still very high and has not decreased in recent years. Pulmonary aspergillosis is by far the most frequent clinical picture of this infection, followed by sinus, tracheo-bronchial and central nervous system disease. The degree of immunosupression is the main factor influencing the evolution and dissemination of aspergillosis. Conventional amphotericin B has been the first-line therapy of invasive aspergillosis for the last 30 years, and most authors have long considered amphotericin B related toxicity as one of the main causes for the poor results obtained in the outcome of patients who developed this infection. Fortunately, in the last few years new safer and more effective drugs have been developed for the treatment of this entity. However, if we are really trying to substantially decrease invasive aspergillosis associated-mortality we should use these drugs earlier in the development of the infection, using new more sensitive diagnostic tests and/or a riskbase strategy which could identify patients at the highest risk to develop this infection.

Amphotericin B↗

PubMed2002

Successful treatment of mucor infection after liver or pancreas-kidney transplantation.

BACKGROUND: Mucormycosis is a rare and opportunistic infection usually associated with hematologic diseases, diabetes mellitus, renal failure, solid tumors, and organ transplantation. METHODS: We present five cases of mucor infection after transplantation (three after a series of 750 orthotopic liver transplantation and two after a series of 13 simultaneous pancreas-kidney transplantation in patients with type 1 diabetes) subjected to medical and surgical treatment and analyze the factors related to the development of this infection. RESULTS: The clinical forms were two cutaneous (laparotomy wound or prior surgical drain site), two rhino-maxillary, and one pulmonary. As risk factors for mucormycosis all patients had pre- or posttransplantation diabetes, and showed at least one episode of acute rejection that required aggressive immunosuppression (2-7 g of methylprednisolone; also three patients were treated with antithymocyte globulin [ATG] monoclonal antibody [orthoclone and/or OKT3]). We also found renal failure, acidosis, malnutrition, and Candida and cytomegalovirus infections as factors related to mucor infection. Diagnosis of fungal infection was confirmed by exudate or fluid culture in three cases and by biopsy in two. All patients were treated with liposomal amphotericin B (from 3.5 to 5.6 g of total dose) and resection until the surgical margins were free of infection. All patients survived after this severe infection. CONCLUSIONS: With an early diagnosis of mucormycosis by clinical findings, culture, or tissue biopsy, and aggressive treatment consisting of administration of liposomal amphotericin B and surgical resection of all infected tissue, excellent results are achieved.

Adult↗

PubMedDate not supplied

[Systemic antifungal agents].

Invasive fungal infection is the infectious complication with highest associated mortality. Until the 90's amphotericin B was the only drug available to treat these infections. Its spectrum of antifungal activity is excellent, but its use is associated with toxicity in many cases. The development of amphotericin B lipid formulations has resulted in a significant decrease in most of the side effects associated with this drug. Triazoles are safe and effective for treating most invasive fungal infections. Fluconazole is an excellent drug for the prevention and treatment of Candida and Cryptococcus infections, itraconazole has good activity against Candida and Aspergillus, and voriconazole has shown to be better than amphotericin B for invasive aspergillosis. Caspofungin belongs to a new group of antifungal agents, the echinocandins, which are very safe and present excellent activity against Candida and Aspergillus.

Administration, Oral↗

PubMedDate not supplied

[GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain (March, 2005)].

Solid organ transplant may be the only therapeutic alternative in some HIV-infected patients. Experience in North America and Europe during the last five years shows that survival at three years after an organ transplant is similar to that observed in HIV-negative patients. The criteria agreed upon to select HIV patients for transplant are: no opportunistic infections (except tuberculosis, oesophageal candidiasis or P. jiroveci -previously carinii- pneumonia), CD4 lymphocyte count above 200 cells/.L (100 cells/.L in the case of liver transplant) and an HIV viral load which is undetectable or suppressible with antiretroviral therapy. Another criterion is a two-year abstinence from heroin and cocaine, although the patient may be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretorivirals and immunosuppressors, rejection and the management of relapse of HCV infection, which is one of the main causes of post-liver transplant mortality. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. The English version of the manuscript is available at http://www.gesidaseimc.com.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Consensus document from GESITRA-SEIMC on the prevention and treatment of cytomegalovirus infection in transplanted patients].

Cytomegalovirus (CMV) infection remains an important complication of transplantation. The last decade has been characterized by improvements to management that has reduced its morbidity and mortality. The advance has been particularly important in the diagnosis and prevention. Several techniques have been developed that allow the increasingly rapid and sensitive diagnosis. The different preventive strategies include use of appropriate blood products, immune globulin, and antiviral agents either as prophylaxis or pre-emptive therapy. The development of effective oral drugs as valganciclovir also represents a new advance. It is necessary to summarize these advances to facilitate the development of local policies reflecting recent changes. The Group of Study of Infections in Transplantation (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has therefore produced actual recommendations in the management of CMV infection after transplantation.

Antiviral Agents↗