Long-term treatment with nebulized colistin in oncological patients with recurrent respiratory infections.

OBJECTIVES: To assess the efficacy of long-term treatment with nebulized colistin in reducing the number of respiratory infections, emergency consultations and hospitalizations in oncological patients. METHODS: A retrospective, observational, single-centre study including patients with solid or haematologic malignancies, or pulmonary GVHD after HSTC who received treatment with nebulized colistin for at least six-months to prevent recurrent respiratory infections (July 2010 to June 2017). RESULTS: Twelve patients were included (median age: 54.4, range: 23-85), 7 with solid malignancies and 5 with haematologic malignancies (2 with pulmonary GVHD). Pseudomonas aeruginosa was the most frequent microorganism in sputum cultures (11/12 patients), all strains were susceptible to colistin. There was a statistically significant reduction (p=0.01) in respiratory infections in the six-month period after starting colistin (median: 1, range: 0-4) compared to the six-month period before (median: 4, range: 1-8). There was also a reduction in emergency consultations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) and hospitalizations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) due to respiratory infections. No colistin-resistant strains were identified. CONCLUSIONS: Long-term treatment with nebulized colistin may be useful to reduce the number of exacerbations in oncological patients with recurrent respiratory infections.

Taking a look on fungi in cystic fibrosis: More questions than answers.

Cystic fibrosis (CF) is one of the most frequent recessive inherited diseases in western countries. Advances in medical care have led to a substantial increase in the life expectancy of CF patients. Survival beyond adolescence has permitted to see fungi not only as late colonizers, but also as potential pathogens responsible of allergic reactions and chronic infections related to lung function deterioration. The role of fungi, nevertheless, has been overlooked until recently. As a result, a number of questions on their epidemiology, clinical significance, or diagnosis, among others, remain unanswered. Besides more in depth studies about the extent of the deleterious effect of fungi on the CF host, new technologies may provide the key to understand its pathogenic role, its interaction with other microbial components of the respiratory microbiota, and should pave the way to define subsets of patients at risk who would benefit from specific therapy. This review is intended to provide a quick overview on what we know about the presence of fungi in the CF airway and its repercussion in the host, and to point out some of the many knowledge gaps needed to understand and advance in the management of fungi in the airway of CF subjects.

Molecular Diagnosis of Pneumocystis jirovecii Pneumonia by Use of Oral Wash Samples in Immunocompromised Patients: Usefulness and Importance of the DNA Target.

Pneumocystis jirovecii pneumonia (PJP) is an important cause of pneumonia in the HIV-negative immunocompromised population, for whom the fungal load is low, the differential diagnosis is difficult, and a bronchoalveolar lavage (BAL) sample is often not readily available. Molecular techniques have improved the microbiological diagnosis in this scenario. The usefulness of two real-time PCR techniques targeting nuclear single-copy and mitochondrial multicopy genes, respectively, applied to oral wash specimens (OW) for PJP diagnosis was assessed, and its accuracy was compared to a BAL fluid-based diagnosis. Immunocompromised patients having PJP in the differential diagnosis of an acute respiratory episode, and from whom OW and BAL or lung biopsy specimens were obtained ≤48 h apart, were retrospectively included. PCRs targeting the dihydropteroate synthase gene (DHPS) and the mitochondrial small-subunit (mtSSU) rRNA gene were performed in paired OW-BAL specimens. Thirty-six patients were included (88.6% HIV negative). Fifteen patients (41.7%) were classified as PJP, and a further 8 were considered P. jirovecii colonized. Quantification of DHPS and mtSSU in BAL fluid showed an accuracy of 96.9% and 93.0%, respectively, for PJP diagnosis, whereas a qualitative approach performed better when applied to OW (accuracy, 91.7%) irrespective of the PCR target studied (kappa = 1). Qualitative molecular diagnosis applied to OW showed an excellent performance for PJP diagnosis regardless of the target studied, being easier to interpret than the quantitative approach needed for BAL fluid.

Cutaneous infections by dematiaceous opportunistic fungi: Diagnosis and management in 11 solid organ transplant recipients.

BACKGROUND: The incidence of cutaneous infections by dematiaceous fungi is rising in our environment due to the high number of solid organ transplant recipients (SOTR). OBJECTIVE: To review our experience in the management of cutaneous phaeohyphomycoses in a Spanish reference centre for dermatological care of SOTR. METHODS: Retrospective clinical, histopathological and microbiological review of all SOTR diagnosed of a phaeohyphomycosis in a 7-year period. RESULTS: Eleven SOTR were identified (8 lung and 3 kidney). The lesions were solitary in six patients and multiple in five, affecting mostly the lower extremities. Early lesions showed epidermal hyperplasia and a diffuse dermal suppurative granulomatous infiltrate that was progressively substituted by fibrosis when the lesions were treated. Septated fungal structures with refractile walls were identified. DNA sequencing confirmed the presence of Alternaria spp (8 cases), Cladosporium cladosporioides, Microsphaeropsis arundinis and Exophiala oligosperma. Three patients with single lesions were treated with surgery, while the other 8 required long-term antifungal therapy, including itraconazole, voriconazole and/or terbinafine, combined with surgery and reduction in tacrolimus doses. CONCLUSION: A clinical, histopathological and microbiological correlation is essential to corroborate this diagnosis. Solitary lesions are easily treated with surgery, but larger or multiple lesions may require long medical treatments combined with surgery and modification of immunosuppressive medication. The list of dematiaceous fungi implicated in cutaneous infections is expanding, in line with the availability of more sophisticated identification methods and the increasing number of immunosuppressed patients.

Candida guilliermondii Complex Is Characterized by High Antifungal Resistance but Low Mortality in 22 Cases of Candidemia.

The objectives of our study were to describe the characteristics of patients with Candida guilliermondii candidemia and to perform an in-depth microbiological characterization of isolates and compare them with those of patients with C. albicans candidemia. We described the risk factors and outcomes of 22 patients with candidemia caused by the C. guilliermondii complex. Incident isolates were identified using molecular techniques, and susceptibility to fluconazole, anidulafungin, and micafungin was studied. Biofilm formation was measured using the crystal violet assay (biomass production) and the XTT reduction assay (metabolic activity), and virulence was studied using the Galleria mellonella model. Biofilm formation was compared with that observed for C. albicans The main conditions predisposing to infection were malignancy (68%), immunosuppressive therapy (59%), and neutropenia (18%). Clinical presentation of candidemia was less severe in patients infected by the C. guilliermondii complex than in patients infected by C. albicans, and 30-day mortality was lower in C. guilliermondii patients (13.6% versus 33.9%, respectively; P = 0.049). Isolates were identified as C. guilliermondiisensu stricto (n = 17) and Candida fermentati (n = 5). The isolates produced biofilms with low metabolic activity and moderate biomass. The G. mellonella model showed that C. guilliermondii was less virulent than C. albicans (mean of 6 days versus 1 day of survival, respectively; P < 0.001). Patients with candidemia caused by the C. guilliermondii complex had severe and debilitating underlying conditions. Overall, the isolates showed diminished susceptibility to fluconazole and echinocandins, although poor biofilm formation and the low virulence were associated with a favorable outcome.

Fixed-altitude stair-climbing test replacing the conventional symptom-limited test. A pilot study.

INTRODUCTION: The objective of this study was to investigate whether a patient's maximum capacity is comparable in 2 different stair-climbing tests, allowing the simplest to be used in clinical practice. METHOD: Prospective, observational study of repeated measures on 33 consecutive patients scheduled for lung resection. Stair-climbing tests were: the standard test (climb to 27 m) and the alternative fixed-altitude test (climb to 12 m). In both cases, heart rate and oxygen saturation were monitored before and after the test. The power output of stair-climbing for each test (Watt1 for the standard and Watt2 for the fixed-altitude test) was calculated using the following equation: Power (watt)=weight (kg)*9.8*height (m)/time (sec). Concordance between tests was evaluated using a regression model and the residuals were plotted against Watt1. Finally, power output values were analyzed using a Bland-Altman plot. RESULTS: Twenty-one male and 12 female patients (mean age 63.2±11.2) completed both tests. Only 12 patients finished the standard test, while all finished the fixed-altitude test. Mean power output values were Watt1: 184.1±65 and Watt2: 214.5±75.1. The coefficient of determination (R(2)) in the linear regression was 0.67. No fixed bias was detected after plotting the residuals. The Bland-Altman plot showed that 32 out of 33 values were within 2 standard deviations of the differences between methods. CONCLUSIONS: The results of this study show a reasonable level of concordance between both stair-climbing tests. The standard test can be replaced by the fixed-altitude test up to 12 m.