Rev Esp Quimioter 2013:26(1):64-69

Treatment of invasive fungal infections in high risk hematological patients. The outcome with liposomal amphotericin B is not negatively affected by prior administration of mold-active azoles
                           

J. DE LA SERNA, I. JARQUE, J.LÓPEZ-JIMÉNEZ,  J.M. FERNÁNDEZ-NAVARRO, V. GÓMEZ, M. JURADO, A. PASCUAL, J. SERRANO, M. ROMERO, C. VALLEJO                         

There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors.

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Rev Esp Quimioter 2013:26(3):214-220

Structural dynamics of Legionella pneumophila and Legionella bozemanii colony/biofilm                                
 

MARÍA LUISA GÓMEZ-LUS, MARÍA TERESA CORCUERA, RAFAEL GÓMEZ-LUS, CLAUDIA SÁNCHEZ-SERRANO,
FERNANDO GÓMEZ-AGUADO, MARÍA JOSÉ ALONSO, JOSÉ PRIETO
             

Objectives. The genus Legionella includes very pleomorphic species responsible for disease outbreaks in humans. The appearance of such has great importance to develop artificial biofilms in aquatic ecosystems. The aim of this work was to study the dynamics of growth and evolution of the internal structure of colonies of representative species of the genus as static biofilm model.
Methods. Isolated colonies of Legionella pneumophila and Legionella bozemanii grown in specific media for three and fifteen days were processed for histological methods and embedded in paraffin and epoxy resin for analysis by light microscopy, electron microscopy and image analysis.
Results. In colonies of both species were observed and defined specific architectural patterns, based on stratification and evolve over time. The strata differ in the amount of extracellular matrix, the morphology and population density and the proportion of dead cells. The internal structure of three days colonies showed large differences between L. pneumophila (two layers) and L. bozemanii (four layers). However, in the fifteen days colonies of both species evolved towards a common unique pattern formed by three layers. In both species the growth was also found within the culture medium, although this phenomenon was more intense in L. bozemanii with unique, central and larger invasions.
Conclusions. Our results demonstrate that Legionella colonies on solid culture media are a good model of static biofilm with a complex structural dynamics characterized by the presence of morphological and functional subpopulations. We bring here an histological approach model, allowing, in further research, detailed studies in evolutionary adaptations in multicellular communities to adverse media and to antimicrobials in Legionella species of clinical interest.

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Rev Esp Quimioter 2013:26(2):81-91

Mathematical modelling of the propagation of infectious diseases: Where we came from, and where we are going                                 
 

MARIA JOSÉ FRESNADILLO-MARTÍNEZ, ENRIQUE GARCÍA-SÁNCHEZ, ENRIQUE GARCÍA-MERINO, ÁNGEL MARTÍN DEL REY, JOSÉ ELÍAS GARCÍA-SÁNCHEZ               

This work deals with the study of the use of mathematical models to simulate the spreading of infectious diseases. There is no doubt about the importance of the use of computational tools that allow the health staff to model and predict the spreading of an infectious disease. Using such tools one can establish and simulate disease control strategies. The development of such technologies is a multidisciplinary issue; in this sense, the mathematical algorithms –that must be computationally implemented- play a central role. The main goal of this work is to highlight among health community the increasing importance of the use of mathematical models for epidemic disease spreading. Consequently, the main features of such models are introduced and their classification is stated taking into account the behavior, the basic population unit or the mathematical objects used. An exhaustive search of related papers through the most important databases (Medline and Web of Science) are performed. The main conclusion obtained from this work is the central role that mathematical models can play in the simulation of epidemic spreading; moreover, some ideas about the future research are stated.

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Rev Esp Quimioter 2013:26(3):221-225

Protection of Enterococcus faecalis in mixed cultures with carbapenemase-producing Escherichia coli and Bacteroides fragilis: effect of the bacterial load                                 
 

DAVID SEVILLANO, LORENZO AGUILAR, LUIS ALOU, MARÍA-JOSÉ GIMÉNEZ, FABIO CAFINI, NATALIA GONZÁLEZ, JOSÉ PRIETO             

Introduction. This study explores effects of pH and inoculum size on imipenem versus tigecycline activity against E. coli, B. fragilis and E. faecalis, both in individual and mixed cultures.
Methods. MIC/MBCs (mg/L) of tigecycline and imipenem were 0.12/≥16 and 4/4 for E. coli, 0.12/0.5 and ≥16/≥16 for B. fragilis, and 0.12/≥16 and 2/≥16 for E. faecalis, respectively. Killing curves in supplemented Brucella broth were performed at pH 7 or 5.8, with two final inocula (≈105 or ≈107 cfu/ml) of each isolate (individual cultures) and with 1:1:1 mixed inocula. Tubes were 48h incubated at 37ºC in anaerobiosis. Final concentrations (estimated concentrations in colon) were 1.50 mg/L for tigecycline and 26.40 mg/L for imipenem, with antibiotic-free curves as controls. Experiments were performed in triplicate.
Results. Imipenem showed inoculum effect against E.coli and B. fragilis, with reductions in initial inocula in experiments with standard inocula contrasting with increases in experiments with high inocula (both individual and mixed cultures). Against E. faecalis no inoculum effect for imipenem was observed in individual cultures, with marked reductions in initial inocula regardless inoculum size. However in mixed experiments the indirect protection of E. faecalis by the two gramnegatives resulted in bacterial regrowth. This protection was inoculum-dependant since it occurred with high but not with standard inocula. Tigecycline reduced initial inocula of the three isolates regardless culture type (individual/mixed) or experimental conditions (pH/inocula size), with lower reductions for the tolerant E. faecalis.
Conclusion. Carbapenemase activity was inoculum-dependant for self-protection and indirect protection of E. faecalis.

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Rev Esp Quimioter 2013:26(2):92-96

Incidence and susceptibility of Campylobacter jejuni in pediatric patients: involvement in bacteremia                                
 

MARÍA JOSÉ GONZÁLEZ-ABAD, MERCEDES ALONSO-SANZ               

Introduction. Invasive disease as a result Campylobacter spp. is rarely reported. Bloodstream infections have been reported in patients with immune deficiency or other serious underlying conditions. We conducted a prospective study to know the incidence of Campylobacter jejuni bacteremia in pediatric patients and its susceptibility to erythromycin and ciprofloxacin.
Methods. The identification of Campylobacter isolates was based on routine culture methods. Antimicrobial susceptibility was performed using a disk diffusion method.
Results. During April 2010-June 2012, at Hospital Niño Jesús of Madrid, Campylobacter spp. was isolated from 171 stool specimens in 154 patients. The median age was 2 years (3 months-21 year). One hundred and one (66%) isolates were identified as C. jejuni. Nine patients with enteritis due C. jejuni (9%) were immunocompromised. Erythromycin resistance was observed in 5% of the isolates. The resistance to ciprofloxacin was 88%. Blood cultures were obtained of 19 patients infected with C. jejuni (19%). Of these, one had C. jejuni bacteremia. During the study period, other episode of C. jejuni bacteremia was detected in one patient different without positive stool culture for C. jejuni (0.34% of all bloodstreams infections). Both patients were immunocompromised.
Conclusions. Campylobacter spp. is an uncommon cause of bloodstream infection in our serie occurring in pediatric patients with immune deficiency as predisposing factor. In our institution, empirical use of fluoroquinolones for Campylobacter infections should not be recommended by the high rate of resistance. Moreover in our study the resistance to erythromycin is low, however is advisable its surveillance.

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Rev Esp Quimioter 2013:26(3):253-260

Control of Chagas disease in pregnant Latin-American women and her children  

 

FRANCISCO J MERINO, ROCÍO MARTÍNEZ-RUIZ, ICIAR OLABARRIETA, PALOMA MERINO, SILVIA GARCÍA-BUJALANCE, TERESA GASTAÑAGA, MARÍA FLORES-CHAVEZ, GRUPO DE ESTUDIO DE LA ENFERMEDAD DE CHAGAS DE LA COMUNIDAD DE MADRID             

Chagas disease is a chronic and systemic infection caused by Trypanosoma cruzi. According to estimates from WHO, 10 million people are affected by this parasite. In the last years, birthrate among the immigrant women from Latin America settled in the Comunidad Autónoma de Madrid has been increasing, and as T. cruzi can be transmitted from mother to child, in fact 11 cases of congenital Chagas disease have been confirmed. Therefore, the aim of this paper is encouraging improvements in the coverage of the anti-T. cruzi antibodies detection in pregnant women from endemic areas. By this strategy, an active search for infected pregnant women and early detection of her infected newborns could be conducted, and then an early specific treatment could be administrated. Thus, there could be an important contribution to the control of Chagas disease in non-endemic area.

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Rev Esp Quimioter 2013:26(2):97-102

Biofilm score: is it a differential element within gram negative bacilli?                                
 

JAVIER GÓMEZ, MARÍA LUISA GÓMEZ-LUS, PEDRO BAS, CARMEN RAMOS, FABIO CAFINI, JUAN RAMÓN MAESTRE, JOSÉ PRIETO             

The aim of the study was to investigate biofilm formation in Gram negative bacteria and to quantify biofilm production applying a new developed technique that made possible to compare results about biofilm formation within the different Gram negative bacteria species. A total of 153 Gram negative strains corresponding to 12 different bacterium species were studied applying a variation of the optic density measurement technique reported by Stepanovic et al. Data obtained with optic density analysis allow to classify microorganisms in strong biofilm developers, moderate biofilm developers, weak biofilm developers and no biofilm developers. The results were expressed in two ways, using in both cases the same statistical method: without standardization, where controls were different depending on the day optic density measurements were performed, and standardized using a correction factor, using the same control for every strain of all our bacterium species in our study, which allows result homogenization. The obtained results in our study after data analysis and standardization show that over the 153 Gram negative strains in our study, 105 of them were no biofilm developers, representing 63.75% of all the studied bacterium genera. We consider that standardization and quantification of biofilm development in Gram negative bacteria can be useful in clinical practice, because biofilm development ability can lead or focus the gold treatment of pathologies produced by these microorganisms.

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Rev Esp Quimioter 2013:26(4):287-297

Immunization practices for workers. Update recommendations

MARÍA CARMEN SÁENZ-GONZÁLEZ, IGNACIO HERNÁNDEZ-GARCÍA             

Introduction. Infectious diseases are a major cause of morbidity and mortality in the workplace. Worker vaccination against a number of infectious diseases is considered the most effective strategy of primary prevention to control them.
Sources. A literature review was performed in Medline and websites of Spanish scientific societies were consulted to detect workers vaccination recommendations. The inclusion criteria was that the recommendation had been made from January 2007 to October 2012.
Development. Seventeen papers were selected and websites of the Ministry of Health, Spanish Society of Chemotherapy, Spanish Society of Preventive Medicine, Public Health and Hygiene, and Vaccinology Spanish Association provided relevant information to our review. Groups of workers at increased risk of acquiring infectious diseases during their professional activity were determined, and vaccination recommendations were established (vaccination against tetanus, diphtheria, pertussis, hepatitis A, hepatitis B, pneumococcus, meningococcus, measles, rubella, mumps, chickenpox, influenza, Haemophilus influenzae b, typhoid, polio, tuberculosis and rabies).
Conclusions. Epidemiological changes in recent years, with the re-emergence of some diseases such as whooping cough, measles or mumps, force the exposed workers (especially the health care workers) to check their immune status.

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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.

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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]

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