EPICO 2.0 PROJECT. Development of educational therapeutic recommendations using the DELPHI technique on invasive candidiasis in critically ill adult patients in special situations                                 
 

RAFAEL ZARAGOZA, RICARD FERRER, EMILIO MASEDA, PEDRO LLINARES, ALEJANDRO RODRIGUEZ ON BEHALF OF THE EPICO PROJECT GROUP               

Introduction. Although there has been an improved management of Invasive Candidiasis in the last decade, still controversial issues remain, especially in different therapeutic critical care scenarios.
Objectives. We sought to identify the core clinical knowledge and to achieve high agreement recommendations required to care for critically ill adult patients with Invasive Candidiasis for antifungal treatment in special situations and different scenarios.
Methods. Second Prospective Spanish survey reaching consensus by the Delphi technique, conducted anonymously by electronic e-mail in the first phase to 23 national multidisciplinary experts in invasive fungal infections from five national scientific societies including Intensivists, Anesthesiologists, Microbiologists, Pharmacologists and Infectious disease specialists, answering 30 questions prepared by a coordination group after a strict review of literature in the last five years. The educational objectives spanned four categories, including peritoneal candidiasis, immunocompromised patients, special situations and organ failures. The agreement among panellists in each item should be higher than 75% to be selected. In a second phase, after extracting recommendations from the selected items, a meeting was heldwith more than 60 specialists in a second round invited to validate the preselectedrecommendations.
Measurements and Main Results. In the first phase, 15 recommendations were preselected (peritoneal candidiasis (3), immunocompromised patients (6), special situations (3) and organ failures (3)). After the second round the following 13 were validated: Peritoneal candidiasis (3): Source control and early adequate antifungal treatment is mandatory; empirical antifungal treatment is recommended in secondary nosocomial peritonitis with Candida spp colonization risk factors and in tertiary peritonitis. Immunocompromised patients (5): Consider hepatotoxicity and interactions before starting antifungal treatment with azoles in transplanted patients; treat candidemia in neutropenic adult patients with antifungal drugs at least 14 days after the first negative blood culture and until normalization of neutrophil count is achieved. Caspofungin, if needed, is the echinocandin with most scientific evidence to treat candidemia in neutropenic adult patients; Caspofungin is also the first choice drug to treat febrile candidemia; in neutropenic patients with candidemia remove catheter. Special situations (2): In moderate hepatocelular failure, patients with invasive candidiasis use echinocandins (preferably low doses of anidulafungin and caspofungin) and try to avoid azoles; in case of possible interactions review all of the drugs involved and preferably use Anidulafungin. Organ failures (3): Echinocandins are the safest antifungal drugs; reconsider the use of azoles in patients under renal replacement therapy; all of the echinocandins are accepted for the treatment of patients under continuous renal replacement therapy and do not require dosage adjustment.
Conclusions. Treatment of Invasive Candidiasis in ICU patients requires a broad range of knowledge and skills as summarized in our recommendations. These recommendations may help to optimize the therapeutic management of these patients in special situations and different scenarios and improve
their outcome based on the DELPHI methodology.

Rev Esp Quimioter 2014:27(3):196-212 [pdf]

Characterization of gene expression associated with both the AcrAB/TolC system and the membrane permeability, in Salmonella spp isolates with and without gyrA mutation                                 
 

ANTONIO GALIANA, LAURA SÁNCHEZ-GUILLÉN, JUAN CARLOS RODRÍGUEZ, ROSA CREMADES, MIGUEL SANTIBAÑEZ, RAFAELA FERRARI, MONTSERRAT RUIZ-GARCÍA, PILAR LÓPEZ, GLORIA ROYO               

Introduction. The marA, soxS, ramA, acrB and ompF genes have been studied in order to characterize mechanisms of AcrAB-TolC active efflux pumps and membrane permeabilityalterations that reduce fluoroquinolones susceptibility in Salmonella spp.
Methods. Mutations in marA, soxS, ramA, acrB and ompF genes were detected, as well as their expression levels in presence and absence of ciprofloxacin, calculating the level of change between them by qPCR. Data were analysed by using SPSS 19.0.
Results. No mutations in these genes were found, but both AcrAB-TolC regulatory genes and structural acrB gene expression were affected by ciprofloxacin in both mutant strains and wild type bacterial strains (WT). The activation of the marA gene in presence of drug was higher in WT strains (level of change 0.823) than in mutants strains (level of change 0.158; p=0.049). In gyrA mutants, a reduction in ompF gene expression in presence of ciprofloxacin was found (level of change -0.949 p=0.017).
Conclusion. The reduction of fluoroquinolones susceptibility in Salmonella spp is a complex process, in which several different bacterial mechanisms are involved. This study has found a high difference in the degree of participation among studied mechanisms, between bacterial strains with and without gyrA mutation. Whereas WT strains activated efflux pumps especially through marA gene, mutants supressed ompF gene expression related to porins.

Rev Esp Quimioter 2014:27(4):239-243 [pdf]

Prospective follow-up of results of tuberculosis treatment                                 
 

MARTA MORENO-GÓMEZ, MONTSERRAT ALONSO-SARDÓN, HELENA IGLESIAS-DE-SENA, LUCIANA LUCENA ARANHA DE MACÈDO               

Objective. The aim of the study was to analyze tuberculosis treatment outcomes in a health area of the National Health System.
Material and Methods. Analytical cohort study of tuberculosis’ cases treated in the hospital care of the health area of Salamanca (Spain) 6 months. The clinical record constituted the basic source of data, whose information was complemented by a clinical interview to the patient. The microbiological records were additionally used for classifying the therapeutic outcomes in satisfactory outcome (SO), potentially unsatisfactory outcome (PUO) and death. A total of 146 patients met the inclusion criteria; 108 patients were interviewed. Their average age was 49 years. Out of them, 29.6% (32/108) showed some social risk factor (SRF).
Results. The SO level was 55.6% (IC 95%: 55.6±9); the variables associated with the SO were young elderly patients, living in family and patterns of 6 months. The PUO proportion stood at 40.7% (IC 95%: 40.7±9); the variables which increased the PUO probability were adulthood, residing in other provinces, living alone, comorbidity, human immunodeficiency virus (HIV), alcoholism and social maladjustment. The variables included in the final model for PUO in logistic regression were adult, comorbidity and SFR, while the institutional conditions associated the mortality.
Conclusions. The SO rates can be improved. The PUO level is conditioned by high loss rates, 31.5% (95% CI: 31.5 ± 9), so measures should be established for reduction and improve the effectiveness of the overall treatment.

Rev Esp Quimioter 2014:27(4):244-251 [pdf]