Rev Esp Quimioter 2013:26(2):131-150

EPICO PROJECT. Development of educational recommendations using the DELPHI technique on invasive candidiasis in non- neutropenic critically ill adult patients                                
 

THE EPICO PROJECT GROUP
     
        

Introduction. Although there has been an improved management of Invasive Candidiasis in the last decade, controversial issues still remain, especially in the diagnostic and therapeutic approaches.
Objectives. We sought to identify the core clinical knowledge and to achieve high level agreement recommendations required to care for critically ill adult patients with Invasive Candidiasis.
Methods. Prospective Spanish survey reaching consensus by the Delphi technique, anonymously conducted by electronic e-mail in a first term to 25 national multidisciplinary experts in invasive fungal infections from five national scientific societies, including Intensivists, Anesthesiologists, Microbiologists, Pharmacologists and Infectious Disease Specialists, responding to 47 questions prepared by a coordination group after a strict review of the literature in the last five years. The educational objectives spanned five categories, including epidemiology, diagnostic tools, prediction rules, and treatment and de-escalation approaches. The level of agreement achieved among the panel experts in each item should exceed 75% to be selected. In a second term, after extracting recommendations from the selected items, a face to face meeting was performed where more than 80 specialists in a second round were invited to validate the preselected recommendations.
Measurements and Main Results. In the first term, 20 recommendations were preselected (Epidemiology 4, Scores 3, Diagnostic tools 4, Treatment 6 and De-escalation approaches 3). After the second round, the following 12 were validated: Epidemiology: Think about Candidiasis in your ICU and do not forget that non-albicans species also exist. Diagnostic tools: Blood cultures should be performed under suspicion every 2-3 days and, if positive, every 3 days until obtaining the first negative result. Obtain sterile fluid and tissue, if possible (direct examination of the sample is important). Use nonculture based methods of microbiological tools, whenever possible. Determination of antifungal susceptibility is mandatory. Scores: As screening tool, use the Candida Score and determine multicolonization in high risk patients. Treatment: Start early. Choose Echinocandins. Withdraw the catheter. Fundoscopy is needed. De-escalation: Only applied when knowing susceptibility determinations and after 3 days of clinical stability. The higher rate of agreement was achieved in the optimization of microbiological tools and the withdrawal of the catheter, whereas the lower rate corresponded to de-escalation therapy and the use of scores.
Conclusions. The management of invasive candidiasis in ICU patients requires the application of a broad range of knowledge and skills that our summarized in our recommendations. These recommendations may help to identify the potential patients, standardize their global management and improve their outcomes, based on the DELPHI methodology.

Rev Esp Quimioter 2013:26(2):131-150 [pdf]

Rev Esp Quimioter 2013:26(4):360-368

Effectiveness of liposomal amphotericin B in patients admitted to the ICU on renal replacement therapy 

FRANCISCO ÁLVAREZ-LERMA, MONTSERRAT RODRIGUEZ, MARI CRUZ SORIANO, MERCEDES CATALÁN, ANA MARÍA LLORENTE, NIEVES VIDART, MARÍA GARITACELAYA, ENRIQUE MARAVI, ELISABETH FERNÁNDEZ REY, FRANCISCO ALVARADO, MARTA LÓPEZ-SÁNCHEZ, BERNABÉ ALVAREZ-SÁNCHEZ, DAVID GRANADO, ELISABETH QUINTANA AND THE STUDY GROUP OF LIPOSOMAL AMPHOTERICIN B IN THE ICU             

Introduction. This study was designed to compare the effectiveness of liposomal amphotericin B (L-AmB) in ICU patients with and without renal replacement therapy (RRT).
Methods. Observational, retrospective, comparative and multicenter study conducted in critically ill patients treated with L-AmB for 3 or more days, divided into two cohorts depending on the use of RRT before or within the first 48 hours after starting L-AmB. Clinical and microbiological response at the end of treatment was evaluated.
Results. A total of 158 patients met the inclusion criteria, 36 (22.8%) of which required RRT during the ICU stay. Patients with RRT as compared with those without RRT showed a higher APACHE II score on admission (21.4 vs 18.4, P = 0.041), greater systemic response against infection (P = 0.047) and higher need of supportive techniques (P = 0.002). In both groups, main reasons for the use of L-AmB were broad spectrum and hemodynamic instability. A higher daily dose of L-AmB was used in the RRT group (4.30 vs 3.84 mg/kg, P = 0.030) without differences in the total cumulative dose or treatment duration. There were no differences in the clinical response (61.1% vs 56.6%, P = 0.953) or microbiological eradication rate (74.1% vs 64.6%, P = 0.382). In patients with proven invasive fungal infection, satisfactory clinical response was obtained in 74.1% and microbiological eradication 85.7%.
Conclusions. Although the study sample is small, this study shows that L-AmB is effective in critically ill patients admitted to the ICU requiring RRT.

Rev Esp Quimioter 2013:26(4):360-368 [pdf]

Rev Esp Quimioter 2013:26(1):39-42

Relevance of the detection of Streptococcus pneumoniae antigen in human urine in the diagnosis of lower respiratory tract infections                                  
 

A. SORLÓZANO, S. CEDEÑO, J. GUTIÉRREZ-FERNÁNDEZ, P. POLO, J. M. NAVARRO                   

Background and objective. Techniques membrane antigen immunochromatographic detecting in urine the pneumococcal polysaccharide C, have developed significantly, increasing requests for antigenuria to clinical microbiology laboratories. We evaluated the impact of the application of this test in the diagnosis of infections of lower respiratory tract.
Patients and method. Six hundred and sixteen determinations were performed by antigenuria BinaxNOW® S. pneumoniae in as many patients over 14 years admitted to the Hospital Universitario Virgen de las Nieves (Granada) between November 2010 and March 2011.
Results. In 91.1% of patients who were determined antigenuria the presence of respiratory symptoms justified the request. Only 8.4% of 616 antigenurias performed were positive. S. pneumoniae was isolated from the respiratory sample culture in 8 of these 52 patients. In 29.8% of patients the diagnosis of lower respiratory tract infection was based on clinical, radiological and/or analytical, as antigenurias were negative and did not involve any other additional microbiological test.
Conclusions. We believe that this technique should be used in a complementary manner, and never to the detriment of other microbiological tests, especially in hospitalized patients.

Rev Esp Quimioter 2013:26(1):39-42 [pdf]

Rev Esp Quimioter 2013:26(2):151-158

Direct hemoperfusion with polymyxin B-immobilized cartridge in severe sepsis due to intestinal perforation: hemodynamic findings and clinical considerations in anticoagulation therapy                               
 

JAVIER MAYNAR, FERNANDO MARTÍNEZ-SAGASTI, MANUEL HERRERA-GUTIÉRREZ, FRANCISCO MARTÍ, FRANCISCO JAVIER CANDEL, JAVIER BELDA, SERGIO CASTAÑO, JOSÉ ÁNGEL SANCHEZ-IZQUIERDO
     
        

Background. High levels of endotoxin have been reported as a risk factor for mortality in critical patients. Toraymyxin® is a column designed to remove circulating blood endotoxin by direct hemoperfusion widely used in Japan.
Objectives. To evaluate the effect of direct hemoperfusion with Toraymyxin® (DHP-PMX) as an adjuvant treatment in patients with severe sepsis due to intestinal perforation in terms of hemodynamic function and coagulation abnormalities.
Methods. Prospective cohort study with a historical control group. Cohort 1: prospective cohort undergoing two sessions of DHP-PMX (n=14). Cohort 2: retrospective historical cohort (n=7). The anticoagulation regime was used according to the protocol of each centre and to the special conditions of each patient.
Results. Mean norepinephrine dose was significantly reduced (0.9 ± 0.5 μg/kg/min pre-first DHP-PMX vs 0.3 ± 0.4 μg/kg/min post-second DHP-PMX treatment, p<0.05). Central venous pressure (CVP) and stroke volume variation (SVV) remained without significant changes during the study, as well as cardiac index (CI) in patients with initial CI≥2.5 L/min/m2. CI significantly increased in patients with initial CI<2.5 L/min/m2 (2.1±0.4 pre-first DHP-PMX vs 3.4 ± 0.4 pre-second DHP-PMX session, p=0.01). Mean platelet count pre-first and post-second DHP-PMX decreased significantly (213.9×103 ± 138.5×103 platelets/mm3 vs 91.0×103 ± 53.5×103 platelets/mm3, p=0.03), without significant changes during each DHP-PMX treatment. Patients did not experience bleeding nor complications derived from DHP-PMX treatments. Survival rates at 28 and 56 days did not differ significantly between cohort 1 and 2 (21.4% vs 42.9%; 42.9% vs 57.1%; respectively).
Conclusions. Performing two sessions of DHP-PMX treatment in a cohort of patients with abdominal sepsis is a feasible adjuvant therapeutic approach, safe in terms of coagulation abnormalities, can be done with different anticoagulation protocols, improves hemodynamic status and may impact on survival.

Rev Esp Quimioter 2013:26(2):151-158 [pdf]

Rev Esp Quimioter 2013:26(4):378-386

Treatment of invasive fungal infections in high-risk haematological patients: What have we learnt in the past 10 years? 

CARLOS VALLEJO, LOURDES VÁZQUEZ, JOSÉ RAFAEL CABRERA MARTÍN, ENRIC CARRERAS, JULIO GARCÍA RODRÍGUEZ, ISABEL RUIZ CAMPS, JESÚS FORTÚN, JOSEP MENSA, JOSÉ BARBERÁN             

Invasive fungal infection (IFI) caused by filamentous fungi remains a very severe infectious complication in patients with onco-haematological diseases. Last advances in the diagnostic and therapeutic fields, today we know that their contributions are limited. Something similar can be said of clinical trials especially in relation to some changes in the characteristics of the host. The development of promising diagnostic techniques and the relative expansion in the number of antifungal agents has been associated with diversification of therapeutic strategies (prophylaxis with extended-spectrum azoles and preemptive antifungal treatment). However, the low sensitivity of AGA testing in some circumstances, and the potential delay in starting treatment due to logistic reasons, has been reflected by a greater mortality in certain type of patients and a significant increase in the days of treatment. All these circumstances has once again focus attention to the empirical approach as a central strategy in high-risk patients. The objective of this article is to review the clinical experience in the treatment of IFI in onco-haematological patients according to data published in the literature in the last decade and to present a set of recommendations.

Rev Esp Quimioter 2013:26(4):378-386 [pdf]

Rev Esp Quimioter 2013:26(1):43-46

Aumento significativo de la resistencia a fosfomicina en cepas de Escherichia coli productoras de ß-lactamasas de espectro extendido (BLEE) aisladas de urocultivos (2005-2009-2011)                                   
 

C. RODRÍGUEZ-AVIAL, I. RODRÍGUEZ-AVIAL, E. HERNÁNDEZ, J. J. PICAZO                    

Introducción. Escherichia coli es el principal uropatógeno. La aparición de cepas productoras de β-lactamasas de espectro extendido (BLEE), que con frecuencia presentan multirresistencia, deja pocas opciones terapéuticas, y es necesario realizar un seguimiento de su sensibilidad a lo largo del tiempo. En el presente trabajo se presentan los porcentajes de aislados urinarios de E.coli productores de BLEE durante 2005, 2009 y 2011 y se comparan los resultados de la determinación de su sensibilidad a antibióticos de diferentes grupos, fosfomicina entre ellos.
Métodos. Se analizaron 5.053, 6.324 y 6.644 aislados urinarios de E. coli en 2005, 2009 y 2011 respectivamente. Se excluyeron duplicados. La sensibilidad se determinó por microdilución con el sistema Wider (Soria Melguizo S.A.) y se seleccionó el fenotipo que indicaba producción de BLEE (CLSI 2009).
Resultados. El 3,9% de las cepas (198) resultó productor de BLEE en 2005, el 7,3% (463) en 2009 y el 8,7% (584) en 2011. Se detectó resistencia a carbapenemicos en 2009, aunque continúan con un 95% de sensibilidad. Entre los no-β-lactámicos, colistina fue el más activo, seguido de nitrofurantoina. Ciprofloxacino y sulfametoxazol-trimetoprim presentaron un 80% y 60% de resistencia, respectivamente. Se observó una tendencia al aumento de la resistencia en fosfomicina, desde 0% a 9,3 llegando al 14,4% en 2011.
Conclusiones. Se observó una creciente prevalencia de cepas de E. coli productoras de BLEE aisladas de urocultivos, alcanzando el 8,7% en 2011. Los carbapenemicos siguen siendo los antibióticos más activos frente a este tipo de cepas. El aumento de resistencia a fosfomicina fue significativo.

Rev Esp Quimioter 2013:26(1):43-46 [pdf]

Rev Esp Quimioter 2013:26(2):173-188

Epidemiology, diagnosis and treatment of fungal respiratory infections in the critically ill patient                                
 

JOSÉ GARNACHO-MONTERO, PEDRO OLAECHEA, FRANCISCO ALVAREZ-LERMA, LUIS ALVAREZ-ROCHA,  JOSÉ BLANQUER, BEATRIZ GALVÁN, ALEJANDRO RODRIGUEZ, RAFAEL ZARAGOZA, JOSÉ-MARÍA AGUADO, JOSÉ MENSA, AMPARO SOLÉ, JOSÉ BARBERÁN
     
        

Objective. To elaborate practical recommendations based on scientific evidence, when available, or on expert opinions for the diagnosis, treatment and prevention of fungal respiratory infections in the critically ill patient, including solid organ transplant recipients.
Methods. Twelve experts from two scientific societies (The Spanish Society for Chemotherapy and The Spanish Society of Intensive Care and Coronary Units) reviewed in a meeting held in March 2012 epidemiological issues and risk factors as basis for a document about prevention, diagnosis and treatment of respiratory fungal infections caused by Candida spp., Aspergillus spp or Zygomycetes.
Results. Despite the frequent isolation of Candida spp. from respiratory tract samples, antifungal treatment is not recommended since pneumonia by this fungal species is exceptional in non-neutropenic patients. In the case of Aspergillus spp., approximately 50% isolates from the ICU represent colonization, and the remaining 50% cases are linked to invasive pulmonary aspergillosis (IPA), an infection of high mortality. Main risk factors for invasive disease in the ICU are previous treatment with steroids and chronic obstructive pulmonary disease (COPD). Collection of BAL sample is recommended for culture and galactomannan determination. Voriconazole and liposomal amphotericin B have the indication as primary therapy while caspofungin has the indication as salvage therapy. Although there is no solid data supporting scientific evidence, the group of experts recommends combination therapy in the critically ill patient with sepsis or severe respiratory failure. Zygomycetes cause respiratory infection mainly in neutropenic patients, and liposomal amphotericin B is the elective therapy.
Conclusions. Presence of fungi in respiratory samples from critically ill patients drives to different diagnostic and clinical management approaches. IPA is the most frequent infection and with high mortality.

Rev Esp Quimioter 2013:26(2):173-188 [pdf]

Rev Esp Quimioter 2013:26(1):47-50

Detection and genotyping of human respiratory viruses in clinical specimens from children with acute respiratory tract infections 
                                 
 

E. CULEBRAS, C. BETRIU, E. VÁZQUEZ-CID, E. LÓPEZ-VARELA, S. RUEDA, J. J. PICAZO                     

Respiratory virus infections are a major health concern and represent the primary cause of testing consultation and hospitalization for young children. The application of nucleic acid amplification technology, particularly multiplex PCR coupled with fluidic or fixed microarrays, provides an important new approach for the detection of multiple respiratory viruses in a single test. The aim of this study was to analyze respiratory samples from children with acute respiratory tract infection (ARTI) using a commercial array-based method (CLART® PneumoVir Genomica, Coslada, Spain). These tests were used to identify viruses in 281 nasopharyngeal samples obtained from children affected by ARTI. Samples were obtained form October 2008 to April 2009. Viruses were identified in 80% of the studied ARTI providing useful information on clinical features and epidemiology of specific agents affecting children in cold months. Multiple viral infections were found in 33.45% of the specimens.

Rev Esp Quimioter 2013:26(1):47-50 [pdf]

Rev Esp Quimioter 2013:26(3):193-197

Identification of fungal clinical isolates by matrix-assisted laser desorption
ionization-time-of-flight mass spectrometry                                

 

LAURA FERREIRA, FERNANDO SÁNCHEZ-JUANES, SILVIA VEGA, MAGDALENA GONZÁLEZ, Mª INMACULADA GARCÍA, SILVIA RODRÍGUEZ, JOSÉ MANUEL GONZÁLEZ-BUITRAGO, JUAN LUIS MUÑOZ-BELLIDO
     
        

Background. Recently, bacterial identification by MALDI-TOF MS has acquired a high relevance in terms of speed and reliability. Conventional mycological identification has some disadvantages: it is frequently slow, reliability is sometimes low, and an extensive experience is required. The risk population for fungal infections, and therefore their clinical significance has progressively increased in recent years.
Methods. 153 yeast and mould clinical isolates were analyzed by MALDI-TOF MS and conventional identification. When both methods were discrepant to the genus or species level, ITS-2 sequencing was performed.
Results. The correlation in yeasts identification between conventional identification methods and MALDI-TOF MS was extremely high (99.2% to the species level and 100% to the genus level). The only discrepancy was checked by ITS-2 sequencing and confirmed the MALDI-TOF identification. The correlation in moulds identification was more heterogeneous. 68.7% of the isolates showed correlation at least to the genus level and 40.6% to the species level. Therefore, the correlation between conventional identification and MALDI-TOF MS in fungal identification was, in whole, 87% to the species level, and 93.5% to the genus level.
Conclusions. Identification of fungi by MALDI-TOF MS is reliable and shows potential advantages over conventional identification methods.

Rev Esp Quimioter 2013:26(3):193-197 [pdf]

Rev Esp Quimioter 2013:26(1):51-55

Candida sp endocarditis. Experience in a third level hospital and review of the literature 
                                 
 

A.HERNÁNDEZ-TORRES, E. GARCÍA-VÁZQUEZ, A. LASO-ORTIZ, J. A. HERRERO-MARTÍNEZ, J. GÓMEZ-GÓMEZ                      

Despite the relative high frequency of Candida bloodstream infection, Candida endocarditis is a rare entity. We report five cases of Candida endocarditis admitted to our hospital in the period between 2005 and 2011. Two cases were caused by C. albicans, two cases were caused by C. parapsilosis and in the last one, we didn´t identify the species of Candida. All but one had clear risk factors for candidemia. Treatment consisted of amphotericin B with / without flucytosine in four patients, and they all underwent surgery for valve replacement and / or removal of intravascular devices. Overall mortality was 60% (40% of mortality was directly related to endocarditis). All patients who survived were given suppressive therapy with fluconazole for a minimum of two years. After stopping fluconazole there was a case of recurrence.

Rev Esp Quimioter 2013:26(1):51-55 [pdf]