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]

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Rev Esp Quimioter 2014:27(2):106-109

First clinical isolate in Europe of clindamycin-resistant group B Streptococcus mediated by the lnu(B) gene                                 
 

 DAVID M ARANA, BEATRIZ ROJO-BEZARES, CARMEN TORRES, JUAN IGNACIO ALÓS               

We characterize the mechanisms implicated in an unusual phenotype of resistance to macrolides-lincosamides (no halos of inhibition around clindamycin and lincomycin discs, and a 15 mm halo around erythromycin disc) in a Streptococcus agalactiae isolate recovered in Spain. The presence of macrolide or lincosamide resistance genes [erm(A),erm(B), erm(C), erm(T), mef(A), mrs(A), lnu(A), lnu(B), lsa(B), lsa(C) and vga(C)] was investigated by PCR and sequencing. The strain showed a resistant phenotype to erythromycin and clindamycin (MIC = 2 mg/L and MIC = 8 mg/L, respectively) and the presence of lnu(B) and mef(A) genes was demonstrated. Clinical microbiology laboratories should be aware of this unusual phenotype due to the association of two mechanisms mediated by lnu(B) and mef(A) genes. This constitute, to our knowledge, the first report of lnu(B) in S. agalactiae in human isolates in Europe.

Rev Esp Quimioter 2014:27(2):106-109 [pdf]

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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.

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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.

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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.

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Rev Esp Quimioter 2014:27(2):110-114

Report of 38 cases of tracheobronchitis in non-immunocompromised patients with dual isolation of Aspergillus in lower respiratory tract samples                                 
 

JOSE BARBERÁN, ELOY SÁNCHEZ-HAYA, DANIEL DEL CASTILLO, FRANCISCO SANZ, BERNARDINO ALCÁZAR, EDUARDO MALMIERCA, ON BEHALF OF THE ASP INVESTIGATOR GROUP               

Introduction. Aspergillus tracheobronchitis is an uncommon manifestation of Aspergillus infection. This study retrospectively analysed patients presenting tracheobronchitis among non-neutropenic/non-transplant adult patients with at least two valuable cultures of respiratory samples yielding Aspergillus spp. in Spanish hospitals.
Methods. Clinical records were retrospectively reviewed. Simple tracheobronchitis was considered when the bronchoscopy report described mucosal inflammation and mucus secretions and invasive tracheobronchitis when ulceration and pseudomembrane formation was reported. Cases were considered “proven” (histopathological confirmation) or “probable” aspergillar tracheobronchitis.
Results. A total of 38 cases of tracheobronchitis (26 simple, 12 invasive) were identified, all considered probable aspergillar tracheobronchitis. Patients were elderly (89.5% patients were ≥65 years), males (76.3%), presented advanced COPD (GOLD III+IV in 81.3%) and heart insufficiency (55.3%), with higher APACHE II score in those with invasive tracheobronchitis (10.17±7.38 vs. 4.32±4.39, p=0.019). Up to 50% patients were taking steroids (accumulated doses >100 mg in 89.5% of them) and 34.2% antibiotics pre-admission. Antifungals were administered to 60.5% patients (57.7% with simple and 66.6% with invasive tracheobronchitis). Voriconazole was the most frequent antifungal (alone or in combination): 69.6% in the 23 treated patients (60.0% simple and 87.5% invasive tracheobronchitis). Mortality was 23.7% (15.4% in simple and 41.7% in invasive tracheobronchitis).
Conclusions. The results of the present studty suggest that aspergillar tacheobronchitis should be considered in the differential diagnosis of non-immunocompromised patients with deteriorating chronic airway limitation.

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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.

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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.

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Rev Esp Quimioter 2014:27(1):1-16

Clinical indications for therapeutic drug monitoring of antifungal agents. In the way for optimizing the treatment of fungal infection                                 
 

EMILIO CENDEJAS-BUENO, MANUEL CUENCA-ESTRELLA, ALICIA GÓMEZ-LÓPEZ               

Therapeutic drug monitoring as a tool in the management of infectious diseases has been introduced in therapy with anti-infective agents for years. Nowadays, it has taken importance in the management of fungal diseases due to the appearance of new antifungal drugs such as new-generation azoles. These azoles have pharmacokinetic characteristics that hinder a proper use to ensure efficacy and minimize toxicity. Monitoring of serum concentrations may help in the better use of these anti-infective agents, as well as in a better management of drug interactions, infectious disease and adverse effects. It has resulted in saving costs of treatment and in avoiding inadequate dosages. This review will attempt to clarify the role of the antifungal agents Therapeutic Drug Monitoring, highlighting the role of azole compounds.

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Rev Esp Quimioter 2014:27(2):115-121

Review of 1.250 episodes of skin and soft tissue infections attended at 49 hospital emergency departments                                 
 

FERRAN LLOPIS, JUAN GONZÁLEZ-CASTILLO, AGUSTÍN JULIÁN-JIMÉNEZ, CARLES FERRÉ, JULIO JAVIER GAMAZO-RÍO, MIKEL MARTÍNEZ Y EL GRUPO DE TRABAJO INFURG-SEMES               

Objetive. To review the prevalence, clinical characteristics, approach and outcome of patients with skin and soft tissue infections (SSTI) evaluated at the Emergency Departments (ED) in Spain.
Methods. A descriptive multicenter cross-sectional analysis in 49 ED of patients with SSTI. Data were collected for age, gender, comorbid conditions, risk factors for multiresistant pathogens, STTI type, sepsis criteria, microbiology, antibiotic treatment, destination and ED mortality.
Results. We documented 1,250 episodes (11% of all infections and 1.6% of all patients seen in ED), mean age 52 years (56% men) and the comorbidities and risk factors for major adverse outcomes were diabetes (15%), heart disease (12%), previous antibiotic therapy (10%) and solid malignancy (5%). 81% of STTI were nonnecrotizing, 3.3% had septic syndrome, in 65% of patients was not practised any microbiological study, and 16% had risk factors for infection for antibiotic-resistant gram-positive bacteria, with adequate empirical antibiotic therapy of 2.5%. 72% of patients were discharged home and 2 died. When comparing STTI discharged home respect those that were admitted, these latter were older patients with more comorbidities and risk factors for multidrug resistance, sepsis and there were more practised cultures (p < 0.05).
Conclusions. The SSTI have a prevalence of 1.6%, representing 11% of visits to the ED for infection. 44% of patients have comorbidity and 16% have risk factors for infection for resistant gram-positive pathogens and they were not made an appropriate antibiotic coverage.

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