Feasibility and outcomes after dose reduction of immunochemotherapy in young adults with Burkitt lymphoma and leukemia: results of the BURKIMAB14 trial.

High dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473).

[Fungal sinus infection by Schizophyllum commune: Report of two clinical cases]. / Infección fúngica sinusal por Schizophyllum commune: a propósito de dos casos clínicos.

BACKGROUND: Schizophyllum commune is a basidiomycete fungus which is widely distributed in nature. Its role as responsible for disease in humans is not well known, partly due to its difficult identification. The incorporation of mass spectrometry techniques (MALDI-TOF) and molecular biology to the laboratories has allowed the description of a greater number of cases. CASE REPORT: In this paper, we present two cases in which S. commune was identified as the causative agent of disease: in the first case an immunocompetent patient suffered from chronic rhinosinusitis, and in the second one a sphenoid sinus infection was diagnosed in an immunocompromised patient. In both cases, S. commune was isolated. Its identification was possible by means of MALDI-TOF and this was confirmed in both patients by amplification and sequencing of the ITS region. CONCLUSIONS: In conclusion, S. commune should be considered a potential causative agent of fungal disease. Currently, MALDI-TOF and sequencing techniques are necessary for its identification.

[Chryseobacterium spp., a new opportunistic pathogen associated with cystic fibrosis?]. / Chryseobacterium spp., ¿nuevo patógeno oportunista asociado a fibrosis quística?

INTRODUCTION: There is an increase in the isolation of non-fermenting gramnegative bacilli in patients with cystic fibrosis (CF). The present study evaluates the frequency of isolates of Chryseobacterium spp., analyzing its characteristics, resistance patterns and clinical outcome of patients. METHODS: It has been collected all respiratory isolates of Chryseobacterium spp. of patients attended in the CF unit of Hospital de la Princesa for three years (march 2009-march 2012). For phenotypic and genotypic identification and sensitivity study conventional methodology was used. For the assessment of the patients lung function was considered the forced expiratory volume in one second (FEV1) and the results were analyzed with SPSS. RESULTS: There was an increase in the incidence of Chryseobacterium spp. with 17 isolates from 9 patients. Three patients had chronic colonization by this microorganism and one showed significant impairment of lung function. Seven patients showed also colonization with Staphylococcus aureus and 4 of them with Pseudomonas aeruginosa. CONCLUSION: Chryseobacterium spp. should be considered as a new emerging opportunistic pathogen in patients with CF. It is essential the clinical and microbiological monitoring of this group of patients for detection of Chryseobacterium spp. colonization and to prevent the chronic infection. In these circumstances it must assess its possible eradication, though its clinical impact is unknown. Cotrimoxazole being the best treatment option.

Burkholderia cepacia complex infection in an Adult Cystic Fibrosis unit in Madrid.

INTRODUCTION: Burkholderia cepacia complex have emerged as significant pathogens in cystic fibrosis (CF) patients due to the risk of cepacia syndrome and the innate multi-resistance of the microorganisms to antibiotics. The aim of this study was to describe the antimicrobial susceptibility profiles, the genotypes and subtypes of BCC, and the clinical evolution of CF patients with BCC. METHODS: The lung function and Brasfield and Shwachman score were assessed in 12 patients. BCC were identified and susceptibility was studied by MicroScan (Siemens). Species and genospecies of BCC were confirmed by molecular methods in a Reference Centre (Majadahonda). RESULTS: BCC were identified in 12 of 70 patients (17.1%) over a ten year period. The mean age to colonization by BCC was 24.4 years (SD: 7.71). B. cenocepacia was isolated in 4 patients (33.3%), B. contaminans was isolated in 3 patients (25%), both B. vietnamiensis and B. stabilis were isolated in 2 patients (16.7%), and B. cepacia, B. multivorans and B. late were isolated in one patient (8.3%). Among the B. cenocepacia, subtype IIIa was identified in two strains, and subtype IIIb was identified in the other two strains. There was susceptibility to meropenem in 90% of BCC, 80% to cotrimoxazole, 60% to minocycline, 50% to ceftazidime, and 40% to levofloxacin. CONCLUSIONS: B. cenocepacia was the most prevalent species among the BCC isolated in CF adult patients, and subtypes IIIa and IIIb were identified in the 50% of the strains. Meropenem and cotrimoxazole showed the best activity.

Breakthrough pulmonary Aspergillus fumigatus infection with multiple triazole resistance in a Spanish patient with chronic myeloid leukemia.

BACKGROUND: An allogeneic hematopoietic cell transplantation (allo-HCT) patient presented with chronic pulmonary aspergillosis associated to pulmonary graft versus host disease (GVHD) and was treated for a long time with several antifungal agents that were administered as prophylaxis, combination therapies, and maintenance treatment. The patient suffered from a breakthrough invasive pulmonary aspergillosis due to Aspergillus fumigatus after long-term antifungal therapy. MATERIAL AND METHODS: Several isolates were analyzed. First isolates were susceptible in vitro to all azole agents. However, after prolonged treatment with itraconazole and voriconazole a multiple azole resistant A. fumigatus isolate was cultured from bronchoalveolar lavage (BAL) when the patient was suffering from an invasive infection, and cavitary lesions were observed. RESULTS: Analysis of the resistant mechanisms operating in the last strain led us to report the first isolation in Spain of an azole resistant A. fumigatus strain harboring the L98H mutation in combination with the tandem repeat (TR) alteration in CYP51A gene (TR-L98H). Long-term azole therapy may increase the risk of resistance selecting strains exhibiting reduced susceptibility to these compounds. However, since the isolates were genetically different the suggestion that could be made is that the resistance was not induced during the prolonged azole therapy but the patient might simply have acquired this resistant isolate from the environment, selected by the therapy. CONCLUSIONS: These findings suggest that in all long-term treatments with antifungal agents, especially with azoles, repeated sampling and regular susceptibility testing of strains isolated is necessary as resistant isolates could be selected.

[Methicillin-resistant Staphylococcus aureus in patients with cystic fibrosis]. / Staphylococcus aureus resistente a meticilina en pacientes adultos con fibrosis quística.

OBJECTIVE: To determine the prevalence of chronic colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis, describe antibiotic sensitivity of the strains, and compare the patients' clinical characteristics with those of patients infected with methicillin-sensitive S. aureus (MSSA). PATIENTS AND METHODS: Patients with chronic S. aureus colonization were selected from a total of 50 patients with cystic fibrosis. Sputum samples were cultured according to standard microbiological procedures. Patients were considered to have chronic bronchial colonization if the same microorganism was isolated in 3 consecutive sputum samples, separated by an interval of at least 1 month. The following variables were compared between patients with MSSA (17) and MRSA (8): sex, body mass index, presence of pancreatic insufficiency, bacterial colonization, pulmonary function, Brasfield radiological score, Shwachman clinical score, and number of respiratory exacerbations in the previous year. RESULTS: The prevalence of infection by MRSA was 16%. All the MRSA strains were sensitive to vancomycin, teicoplanin, and linezolid. Patients with MRSA were older and had a larger number of respiratory exacerbations than patients with MSSA. CONCLUSIONS: There is a high percentage of colonization by MRSA in adult cystic fibrosis patients. Although the pathogenic role of this microorganism remains unclear, patients with MRSA had more frequent exacerbations and poorer lung function. Thus, infection control is important and patients should be adequately monitored.