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

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]

Rev Esp Quimioter 2013:26(2):103-107

Reasons for the introduction of darunavir in the antirretroviral treatment in HIV-infected patients                                
 

ENRIC PEDROL, JUAN CARLOS LÓPEZ-BERNALDO DE QUIRÓS, SHEILA RUIZ, HENAR HEVIA, FRANCISCO LEDESMA             

Introduction. In 2009 a deep change in ARV treatment took place in Spain with the introduction of new ARV drugs.The principal objective of the study was to determine the clinical situation of the patients in which DRV/r was introduced in the ARV therapy.
Methods. Observational, cross sectional and multicentre study in which 91 reference hospitals participated. Patient’s enrolment was carried out between 2008 and 2009. Data were collected retrospectively considering standard clinical practice.
Results. 719 medical records were reviewed. Patients had a different clinical situation compared to nowadays with predominance of multiresistant virus which leaded to virologic failure. The principal reason for introducing DRV/r in the ARV regimen was the virologic failure (54.2%).
Conclusions. Considering this situation, DRV/r became a therapeutic option which represented a change in the ARV paradigm in that period.

Rev Esp Quimioter 2013:26(2):103-107 [pdf]

Rev Esp Quimioter 2013:26(4):298-311

Prevention and control of nosocomial and health-care facilities associated infections caused by species of Candida and other yeasts

JAVIER PEMÁN, RAFAEL ZARAGOZA, MIGUEL SALAVERT             

Knowledge of the epidemiology of invasive fungal diseases caused by yeasts (Candida spp., especially) in health care settings allows the establishment of the levels necessary for its prevention. A first step is to identify groups of patients at high risk of nosocomial invasive fungal infections, establish accurate risk factors, observing the periods of greatest risk, and analyze the epidemiological profile in genera and species as well as the patterns of antifungal resistance. Secondly, mechanisms to avoid persistent exposure to potential fungal pathogens must be programed, protecting areas and recommending measures such as the control of the quality of the air and water, inside and outside the hospital, and other products or substances able to cause outbreaks. Finally, apart from the correct implementation of these measures, in selected patients at very high risk, the use of antifungal prophylaxis should be considered following the guidelines published.

Rev Esp Quimioter 2013:26(4):298-311 [pdf]

Rev Esp Quimioter 2014:27(1):56-62

C. albicans, C. parapsilosis and C. tropicalis invasive infections in the PICU: clinical features, prognosis and mortality                                
 

IOLANDA JORDAN, LLUÏSA HERNANDEZ, MÓNICA BALAGUER, JOSÉ-DOMINGO LÓPEZ-CASTILLA, LIDIA CASANUEVA, CRISTINA SHUFFELMAN, MARÍA-ANGELES GARCÍA-TERESA, JUAN-CARLOS DE CARLOS, PALOMA ANGUITA, LORENZO AGUILAR, ON BEHALF OF THE ERICAP STUDY GROUP               

Candida albicans remains the most common agent associated with invasive Candida infection (ICI), but with increasing
number of non-albicans species. An epidemiological, observational study exploring host criteria, clinical characteristics and mortality of ICI was performed in 24 pediatric intensive care units (PICU) in Spain. Patients were analyzed in global and distributed by infecting species (for groups with ≥15 patients). A total of 125 ICI were included: 47 by C. albicans, 37 by C. parapsilosis, 19 by C. tropicalis, 4 C. glabrata, and 18 others. Up to 66% of ICI by C. albicans and 75.7% by C. parapsilosis occurred in children ≤24 months, while the percentage of children >60 months was higher in ICI by C. tropicalis. Bloodstream infection was most common among C. tropicalis (78.9%) or C. parapsilosis (83.8%) ICI, but urinary infections were almost as common as bloodstream infections among C. albicans ICI (31.9% and 38.3%, respectively). Fever refractory to antimicrobials was the most frequent host criterion (46.4% patients), but with equal frequency than prolonged neutropenia in C. tropicalis ICI. Thrombopenia was more frequent (p<0.05) in C. parapsilosis (60.7%) or C. tropicalis (66.7%) ICI than in C. albicans ICI (26.5%). Uremia was more frequent (p<0.05) in C. albicans (78.3%) or C. tropicalis (73.3%) than in C. parapsilosis ICI (40.7%). Multiple organ failure and heart insufficiency was higher in C. tropicalis ICI. Short duration (≤7 days) of PICU stay was more frequent in C. albicans ICI. Mortality rates were: 8.5% (C. albicans ICI), 13.5% (C. parapsilosis ICI) and 23.3% (C. tropicalis ICI). ICI by different Candida species showed different clinical profiles and mortality, making essential identification at species level.

Rev Esp Quimioter 2014:27(1):56-62 [pdf]

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

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]

Rev Esp Quimioter 2013:26(1):1-5

Use of peripheral catheters: too much to learn                                 
 

J. A. CAPDEVILA               

Frequently incident complications due to the use of peripheral catheters are considered not relevant. However, recently multiple observational studies have demonstrated its role causing nosocomial bacteraemia. Guidelines about prevention of catheter-related infection are focused in central lines instead of peripheral ones. This approach causes an important lack of knowledge about the best manner to manipulate peripheral lines.
Risk factors related to the development of a peripheral phlebitis, its clinical relevance and doubts related to prevention are presented and discussed in this article. The main objective is to alert about the importance of peripheral catheters in the prevention of nosocomial infection.

Rev Esp Quimioter 2013:26(1):1-5 [pdf]

Rev Esp Quimioter 2013:26(2):108-111

Serological markers of Spanish and immigrant pregnant women in the south of Madrid during the period 2007-2010                                
 

FÁTIMA LÓPEZ-FABAL, JOSÉ LUÍS GÓMEZ-GARCÉS             

Objective. The prevalence and evolution of the markers including in the serologic profile of pregnant woman was studied in our hospital during a period of 4 years.
Material and methods. A retrospective study of the prevalence of antibodies against Treponema pallidum, human immunodeficiency virus (HIV), Toxoplasma gondii, rubeola virus and hepatitis B virus (HBV), was performed in our hospital among Spanish and immigrant pregnant women, from January 2007 to December 2010.
Results. A total of 8,012 pregnant were studied, 2,752 (34.2%) of them were foreign. The non-treponemal tests (RPR) were positive in 40 (0.49%) women, being the prevalence slightly superior in foreigners than in natives (0.8 as opposed to 0.3%). The IgG anti-T. gondii global prevalence was 23,35% (1,874 patients). In Spanish pregnant this prevalence was 18%, and 33.8% in the immigrant women. Almost the total of Spanish pregnant (99.5%) displayed IgG antibodies against rubeola virus whereas in the foreigners this rate was 61.6%. The presence of HBsAg for HBV was tested in 86.6% of pregnant women (6,939/8,012), being positive the 0.75% (59 patients), with a prevalence in foreigners greater than in Spanish (1.65 as opposed to 0.4%). Antibodies anti-HVI were detected in 22 patients (0.22%), being the prevalence 0.15% among the Spanish and 0.51% among the foreigners.

Rev Esp Quimioter 2013:26(2):108-111 [pdf]

Rev Esp Quimioter 2013:26(4):312-331

Bugs, hosts and ICU environment: Countering pan-resistance in nosocomial microbiota and treating bacterial infections in the critical care setting 

EMILIO MASEDA, JOSÉ MENSA, JUAN-CARLOS VALÍA, JOSE-IGNACIO GOMEZ-HERRERAS, FERNANDO RAMASCO, ENRIC SAMSO, MIGUEL-ANGEL CHIVELI, JORGE PEREIRA, RAFAEL GONZÁLEZ, GERARDO AGUILAR, GONZALO TAMAYO, NAZARIO OJEDA, JESÚS RICO, MARÍA JOSÉ GIMENEZ, LORENZO AGUILAR             

ICUs are areas where resistance problems are the largest, and they constitutes a major problem for the intensivist’s clinical practice. Main resistance phenotypes among nosocomial microbiota are: i) vancomycin-resistance/heteroresistance and tolerance in grampositives (MRSA, enterococci) and ii) efflux pumps/enzymatic resistance mechanisms (ESBLs, AmpC, metallobetalactamases) in gramnegatives. These phenotypes are found at different rates in pathogens causing respiratory (nosocomial pneumonia/ventilator-associated pneumonia), bloodstream (primary bacteremia/catheter-associated bacteremia), urinary, intraabdominal and surgical wound infections and endocarditis in the ICU. New antibiotics are available to overcome non-susceptibility in grampositives; however, accumulation of resistance traits in gramnegatives has lead to multidrug resistance, a worrisome problem nowadays. This article reviews by microorganism/infection risk factors for multidrug resistance, suggesting adequate empirical treatments. Drugs, patient and environmental factors all play a role in the decision to prescribe/recommend antibiotic regimens in the specific ICU patient, implying that intensivists should be familiar with available drugs, environmental epidemiology and patient factors.

Rev Esp Quimioter 2013:26(4):312-331 [pdf]

Rev Esp Quimioter 2014:27(1):69-86

Guidelines for the management of community-acquired pneumonia in the elderly patient                                 
 

JUAN GONZÁLEZ-CASTILLO, FRANCISCO JAVIER MARTÍN-SÁNCHEZ, PEDRO LLINARES, ROSARIO MENÉNDEZ, ABEL MUJAL, ENRIQUE NAVAS, JOSÉ BARBERÁN               

The incidence of community-acquired pneumonia (CAP) increases with age and is associated with an elevated morbimortality due to the physiological changes associated with aging and a greater presence of chronic disease. Taking into account the importance of this disease from an epidemiological and prognostic point of view, and the enormous heterogeneity described in the clinical management of the elderly, we believe a specific consensus document regarding this patient profile is necessary. The purpose of the present work was to perform a review of the evidence related to the risk factors for the etiology, the clinical presentation, the management and the treatment of CAP in elderly patients with the aim of elaborating a series of specific recommendations based on critical analysis of the literature. This document is the fruit of the collaboration of different specialists representing the Spanish Society of Emergency Medicine and Emergency Care (SEMES), the Spanish Society of Geriatrics (SEG), the Spanish Society of Chemotherapy (SEQ), the Spanish Society of Internal Medicine (SEMI), the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) and the Spanish Society of Home Hospitalization (SEHAD).

Rev Esp Quimioter 2014:27(1):69-86 [pdf]

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

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]