Delphi-based study and analysis of key risk factors for invasive fungal infection in haematological patients.

OBJECTIVE: Mortality caused by invasive fungal infections due to filamentous fungi (IFI-FF) is high. Predisposing factors to IFI-FF are multiple and should be stratified. The objective of this study was to identify key risk factors for IFI-FF in onco-haematological patients in different clinical settings. METHODS: Prospective national Delphi study. Risk factors for IFI-FF in patients with onco-haematological diseases were identified by a systematic review of the literature. An anonymous survey was sent by e-mail to a panel of experts. A key risk factor was defined when at least 70% of the surveyed participants assigned a "maximal" or "high" risk. RESULTS: In allogenic stem cell transplantation, 18 of the 42 risk factors analyzed were classified as key risk factors, including neutropenia, previous IFI-FF, grade III/IV acute or extensive chronic graft-versus-host disease (GVHD), umbilical cord blood transplantation, HLA mismatching transplantation, graft failure, absence of HEPA filters, absence of laminar air flow, diagnosis of acute myeloid leukaemia, haploidentical transplantation, anti-TNF-α drugs, alemtuzumab, anti-thymocyte globulin, immunosuppressive prophylaxis for GVHD, lymphocytopenia, cytomegalovirus infection, and proximity to construction areas. In acute leukaemia/myelodysplastic syndrome (AL/MDS), 7 of 25 risk factors were defined as key risk factors, including neutropenia, consolidation therapy without response, induction therapy, antifungal prophylaxis with azoles, proximity to construction areas, and absence of HEPA filters. In lymphoma/multiple myeloma (MM), the five key risk factors among 21 analyzed were use of steroids, neutropenia, progressive disease, anti-CD52 therapies, and proximity to construction areas. CONCLUSIONS: The Delphi method was useful for the classification and stratification of risk factors for IFI-FF in patients with onco-haematological diseases. Identifying key risk factors will contribute to a better management of IFI-FF in this group of patients at high or changing risk.

Management of infection and febrile neutropenia in patients with solid cancer.

An expert group from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC, for its acronym in Spanish) and the Spanish Society of Medical Oncology (SEOM, for its acronym in Spanish) have reviewed the main aspects to be considered when evaluating patients with solid cancer and infectious complications contained in this article. Recommendations have, therefore, been put forth regarding the prophylaxis of the most prevalent infections in these patients, the use of vaccines, measures to control infection through vascular catheters, and preventing infection in light of certain surgical maneuvers. The following is a revision of the criteria for febrile neutropenia management and the use of colony-stimulating factors and closes with several guidelines for treating the cancer patient with serious infection. The document concludes with a series of measures to control hospital infection.

Influence of antiviral therapy in the long-term outcome of recurrent hepatitis C virus infection following liver transplantation.

INTRODUCTION: Severity of recurrent hepatitis C virus (HCV) infection in liver transplant recipients (LTR) is variable and the influence of different factors, including the administration of antiviral therapy in the long-term outcome is controversial. METHODS: We analyzed the outcome of a cohort of HCV-infected LTR who were transplanted in our institution. Patients were divided into 2 groups (severe and non-severe HCV disease) depending on the presence of a fibrosis score of F ≥ 2 in the Scheuer index and/or fibrosing cholestasic hepatitis (FCH) in a graft biopsy. Risk factors were studied using logistic regression analysis. Survival of patients was estimated using Kaplan-Meier plots. A total of 146 patients were followed for a mean of 58 months. RESULTS: Fifty-six (34%) patients developed severe HCV disease and showed shorter survival (P < 0.024). Donor age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.02-1.06) and pre-transplant viral load (VL) >10(6) UI/mL (OR: 3.5; 95% CI: 1.42-10.61) were the only factors associated with severe HCV infection. Over-immunosuppression (OR: 2.3; 95% CI: 1.2-4.41) was specifically associated with the development of FCH. Overall, patient survival in recipients who received a full course of anti-HCV therapy was higher than in patients who did not complete antiviral therapy (P = 0.004) or received no treatment (P = 0.007). Patients with non-severe HCV infection have a higher probability of receiving a full course of antiviral therapy (P = 0.033). CONCLUSION: In conclusion, donor age, pre-transplant VL, and over-immunosuppression were associated with the long-term development of severe HCV recurrence in liver grafts. Administration of a full course of antiviral therapy was associated with better survival.

Epidemiology, risk factors and impact on long-term pancreatic function of infection following pancreas-kidney transplantation.

Limited information exists about epidemiology and risk factors of infection following pancreas-kidney transplantation and its impact on long-term pancreatic graft function. A retrospective chart review of episodes of severe infection in consecutive pancreas-kidney transplantations in a single institution was performed to assess the epidemiology, risk factors for infection and their impact on the development of pancreatic graft dysfunction. Ninety-four (81%) of 116 recipients (median follow-up of 1492 days; mean 1594) developed 248 episodes of severe infection. Bacterial infections were present in 208 episodes, with 12% of the isolates resistant to antibiotics used in prophylaxis. There were 40 episodes of fungal infection in 32 patients (28%) (mostly Candida spp), and CMV disease appeared in 20 patients (17%), of which 50% appeared after the third month following surgery. The multivariate analysis identified that surgical re-intervention and the use of steroid pulses were independently associated with the development of any infection. Additionally, pre-transplant evidence of peripheral artery disease, a longer cold ischaemia time and high transfusional requirements were associated with fungal infections. Cytomegalovirus (CMV) mismatch was independently related to CMV disease and female sex, and bladder drainage of the exocrine pancreas was associated with urinary tract infection. At the end of follow-up, 29 patients (25%) had developed severe pancreatic graft dysfunction, and fungal infection was independently associated with it. Our study identifies a subset of pancreas-kidney transplant recipients at a higher risk of developing severe infection. Fungal infection is an independent risk factor for the development of severe pancreatic graft dysfunction.

Preemptive therapy is not adequate for prevention of cytomegalovirus disease in pancreas-kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) remains the most common viral infection after pancreas-kidney transplantation (PKT). Comparative studies about CMV prophylaxis in PKT have not been developed. METHODS: We analyzed CMV disease in a cohort of 84 PKT recipients. All received intravenous ganciclovir during treatment with anti-thymocyte globulin and later one of the following options for pre-transplant CMV-seropositive recipients: (a) no prophylaxis (n=10 patients), (b) preemptive therapy (PT) (n=13), or (c) continuous prophylaxis (CP) for 12 weeks (n=29). Pre-transplant CMV-seronegative recipients received CP (n=21). RESULTS: Eleven patients were excluded because of organ explantation in the first 15 days. Incidence of CMV disease in seropositive recipients was 30% under no prophylaxis, 23% under PT, and 6.9% under CP. Incidence of CMV disease under CP was 33.3% in seronegative recipients. Six of 9 episodes of CMV disease under CP occurred after finishing prophylaxis. Under CP, the incidence of CMV disease was significantly higher in seronegative than in seropositive recipients (P<0.05). CONCLUSION: According to the results of our study, for CMV-seropositive PKT recipients, CP is a better strategy than PT. For CMV-seronegative recipients, 3 months of CP is an inadequate strategy.

Urinary tract infection due to Corynebacterium urealyticum in kidney transplant recipients: an underdiagnosed etiology for obstructive uropathy and graft dysfunction-results of a prospective cohort study.

BACKGROUND: Corynebacterium urealyticum is a cause of urinary tract infection and encrusting cystitis or pyelitis. Information about this infection in renal transplant recipients is based on case reports. We communicate the first prospective epidemiological study for this population. METHODS: We selected a cohort of 163 renal transplant recipients who were screened for urinary tract infection due to C. urealyticum. Long-term incubation and special media were used for culture of C. urealyticum. The cohort was observed for a mean of 26.2 months (standard deviation, 8.7; range, 1-36 months). Risk factors and outcomes were assessed. RESULTS: At baseline, 16 (9.8%) of 163 patients had C. urealyticum bacteriuria (6 were asymptomatic, 9 had acute cystitis, and 1 had encrusting pyelitis). Independent risk factors (assessed by multivariate analysis) for urinary tract C. urealyticum infection were: antibiotic administration during the previous month (odds ratio, 8.04; 95% confidence interval, 1.57-41.06; P = .012), history of nephrostomy (odds ratio, 51.59; 95% confidence interval, 3.62-736.06; P = .004), and skin colonization (odds ratio, 208.35; 95% confidence interval, 21.54-2015.22; P< .001). Presence of urinary tract infection symptoms for >1 month (odds ratio, 27.7; 95% confidence interval, 2.55-300.5; P = .006) and obstructive uropathy (odds ratio 25.9; 95% confidence interval, 4.43-152.31; P < .001) were more frequent during follow-up in patients with C. urealyticum bacteriuria. CONCLUSIONS: When specifically tested for, C. urealyticum bacteriuria is more prevalent than previously thought in renal transplant recipients, and it is closely related to obstructive uropathy. Future studies are necessary to establish the relevance of treating the infection during follow-up after renal transplantation.

[Individualized evaluation of the risk of infections in the oncohematologic patient]. / Evaluación individualizada del riesgo de infecciones en el paciente oncohematológico.

In order to take the best approach to infection in the oncohematologic patient with fever, it is important to know not only how profound the neutropenia is and how long the patient has had it, but also the characteristics of the underlying disease, the immunosuppressive therapy received and the type of hematopoietic stem/progenitor cell transplantation performed. Moreover, is important to consider if these patients have any personal or familial history of infectious diseases. All these aspects let us calculate the net state of immunosuppression and the risk of infection, and provide us with information about the most probable etiology in each case and the best prophylaxis and treatment. In this study we review the more important advances in chemotherapy in recent years that will make it necessary in the future to change our prophylactic guidelines for more effective prevention of infection in the oncohematologic patient.

Accuracy of blood culture for early diagnosis of mediastinitis in febrile patients after cardiac surgery.

Postsurgical mediastinitis (PSM) remains a major cause of morbidity and mortality in patients undergoing cardiac surgery procedures. Although prompt diagnosis is crucial in these patients, neither clinical data nor imaging techniques have shown enough sensitivity or specificity for early diagnosis of PSM. The aim of the present study was to assess the validity of blood cultures as a diagnostic test for the early detection of PSM in patients who become febrile after cardiac surgery procedures. During a 4-year period (1999-2002), patients who developed fever (>37.8 degrees C) in the first 60 days after a cardiac surgery procedure were evaluated. Blood cultures were drawn from these patients. PSM was defined as deep infection involving retrosternal tissue and/or the sternal bone directly observed by the surgeon and confirmed microbiologically. Three criteria for positivity of blood cultures were applied: bacteremia, staphylococcal bacteremia, or Staphylococcus aureus bacteremia. For purposes of the analysis, a positive blood culture in patients with PSM was considered a true-positive test and a negative blood culture a false-negative test. Otherwise, in febrile patients without PSM in the postsurgery period, a positive blood culture was considered a false-positive test and a negative blood culture a true-negative test. Blood cultures were drawn from 266 febrile patients in the postsurgery period. PSM occurred in 38 patients (26 cases due to S. aureus, 8 to Staphylococcus epidermidis, 3 to gram-negative enteric bacteria, and one to Pseudomonas aeruginosa). Within the 60-day postsurgical period, blood culture as a diagnostic test was most accurate in patients with S. aureus bacteremia, providing 68% sensitivity, 98% specificity, a positive predictive value of 87%, and a negative predictive value of 95%. If the analysis was limited to the period during which patients are at maximum risk for PSM (day 7-20), the values in patients with S. aureus bacteremia were as follows: 73% sensitivity, 98% specificity, 90% positive predictive value, and 93% negative predictive value. Blood culture is an accurate test for the early diagnosis of PSM in febrile patients after cardiac surgery, particularly in institutions where S. aureus is prevalent in this context. A negative blood culture practically excludes PSM and, during the period of maximum risk for PSM, the presence of S. aureus bacteremia should compel early surgical management.

[Prospective randomized trial of meropenem versus cefotaxime and metronidazole in the treatment of intraabdominal infections]. / Comparación prospectiva, aleatoria y abierta de meropenem frente a cefotaxima y metronidazol en el tratamiento de las infecciones intraabdominales.

BACKGROUND: The empiric antibiotic treatment of intraabdominal infections is in constant evolution. Monotherapy appears to be a desirable goal because of the simplicity of its administration, lack of toxic effects and wide spectrum. PATIENTS AND METHODS: A multicentre, prospective, randomized, open study was carried out to compare two antibiotic regimens in the treatment of intraabdominal infections in patients undergoing surgery. Ninety-eight consecutive patients were randomly allocated into two groups. One group (GM, n = 51) received meropenem (1 g/8 h) and the other (GCM, n = 47) a combination of cefotaxime (2 g/8 h) plus metronidazol (0.5 g/8 h). Clinical and bacteriological responses were assessed at the end of treatment and at 2-4 weeks. RESULTS: The severity of patients as assessed by the APACHE II score was similar in both groups (GM: 7.2 and GCM: 8.1). Three patients in each group could not be evaluated due to premature interruption of treatment or deviation from the protocol. The mean duration of treatment was 7.4 days in GM and 7.9 days in GCM. A satisfactory clinical response was obtained in 95% of patients in both groups. 31 patients (61%) in GM and 26 patients (55%) in GCM were bacteriologically evaluable. Bacteriological erradication was achieved in 94% of patients in GM and in 92% of patients in GCM. CONCLUSION: Meropenem is a good alternative for single antibiotic therapy in intraabdominal infections of moderate severity.

[Invasive fungal infections in liver transplant recipients: analysis of 21 cases]. / Infección fúngica profunda en receptores de un trasplante de hígado: análisis de 21 casos.

BACKGROUND: Invasive fungal infections (IFI) are one of the most important causes of mortality in liver transplant (LT) recipients. The aim of this study was to describe the characteristics of IFI in the LT program of our institution with an special emphasis in the differences between Candida infections (CI) and that caused by other fungi (NCI). PATIENTS AND METHODS: Retrospective analysis of the hospital charts of 21 patients who underwent a LT from February 1987 to December 1995. The diagnosis of IFI required the histological evidence of tissue invasion or a positive culture in a tissue sample or in an usually sterile fluid. Esophageal candidiasis was not considered as IFI. Antifungal prophylaxis was performed either with nystatin or fluconazole. RESULTS: Twenty-one of 356 patients (6%) developed a total of 23 episodes of IFI. Pathogens were Candida spp. (n = 10), Aspergillus (n = 8), Zygomicetes (n = 4) and Cryptococcus (n = 1). Fifty-seven percent of the episodes of IFI (80% of those caused by Candida and 38% of those produced by other fungi; p < 0.05) developed in the first 3 months after transplantation and only 5 episodes appeared after the sixth month. The diagnosis of IFI was done at autopsy in 6 patients (29%). Overall, NCI (13 episodes) predominated over CI (10 episodes), being the later the cause of the 54% of the episodes in the first 178 recipients but only the 30% in the last 178 patients (p = 0.09). No differences were found in the distribution of the risk factors amongst those patients with CI or NCI. Seventeen of the 21 patients (71%) died and 15 of these deaths (72%) were attributable to fungi; 15 patients who died either did not receive amphotericin (n = 6) or received a cumulative dose lower than 500 mg. Six patients received a cumulative dose of more than 1.5 g (mean, 3.2 g) and four of them were cured. Mortality in the nonfungal infection group was 26% (p < 0.001). CONCLUSIONS: IFI was a rare but severe complication in our LT recipients. The relative frequency of CI was progressively decreasing during the study period, being NCI the predominant infections. Amphotericin therapy was effective only when a high cumulative dose could be administered.

Encrusted pyelitis and cystitis by Corynebacterium urealyticum (CDC group D2): a new and threatening complication following renal transplant.

We evaluated the pathogenic role of Corynebacterium urealyticum in the development of encrusted pyelitis (EP) and encrusted cystitis (EC), and their clinical consequences in renal transplant recipients. During a 4-year period, we studied seven renal transplant recipients with EP and two with EC. The records of 320 other renal transplant patients studied during the same period were used as a control group. C urealyticum (> or = 10(5) CFU/ml) was isolated from 4 patients with EP (urine 3, blood 1) and from 1 patient with EC (urine). Alkaline urines with struvite crystals, microscopic hematuria, and sterile conventional urine cultures were present in all our cases. All the patients with EP developed obstructive uropathy with deterioration of the renal function and pyelonephritis (4 patients) or renal abscesses (3 patients). Chronic urinary discomfort and macroscopic hematuria were present in the 2 patients with EC. Long-term vesical and ureteral catheterization were considered the most important risk factors for the development of EC and EP, respectively. Vancomycin was successfully used in 5 cases, but all the patients required a derivative procedure or a surgical resection of the incrustations to improve. We conclude that EP and EC should be investigated in renal transplant patients who develop pyelonephritis, obstructive uropathy, or chronic urinary symptoms. EP and EC could lead to the loss of their grafts. C urealyticum appears to have a pathogenic role in these entities.

Major bacterial infections following liver transplantation: a prospective study.

The incidence and characteristics of major bacterial infections were studied prospectively in 50 consecutive adult patients who underwent liver transplantation (LT). All patients received the same protocol of immunosuppression, bowel decontamination, antibiotics prophylaxis, and follow-up. Thirty-two patients (64%) had at least one episode of major bacterial infection. One death was directly related to a bacterial infection, accounting for 13% of postoperative mortality. The most critical period for infection was the first 2 months after surgery, when 69% of the infections occurred. The most frequent clinical presentations were bacteremia, pneumonia and abdominal abscesses. Eighty percent of the bacteremias had an identifiable source, the most frequent being intravascular catheters. Gram-positive microorganisms (69%) predominated over gram-negative rods (26%) and anaerobes (5%). The use of selective bowel decontamination (SBD) with norfloxacin may explain this predominance. Major bacterial infections are an important source of morbidity and mortality after LT. Efforts to prevent these infections and to determine their source and specific treatment, will improve the management and the outcome of these patients in the future.

Senior-Loken syndrome (nephronophthisis and pigmentary retinopathy) associated to liver fibrosis: a family study.

We present two sisters with nephronophthisis and pigmentary retinopathy (Senior-Loken syndrome) and associated liver fibrosis. Clinical and histological findings are discussed, as well as the importance of family studies. A comparative analysis with previous published cases is made; we found only three other references with this triad. Our report underlines the need to investigate liver disorders in all patients with nephronophthisis and the existence of liver fibrosis as an element of the hereditary 'nephronophthisis complex.'