Rev Esp Quimioter 2013:26(3):203-213

Study of a cohort of patients with Enterococcus spp. Bacteraemia. Risk factors associated to high-level resistance to aminoglycosides                                
 

ELISA GARCÍA-VÁZQUEZ, HELENA ALBENDÍN, ALICIA HERNÁNDEZ-TORRES, MANUEL CANTERAS, GENOVEVA YAGÜE, JOAQUÍN RUIZ, JOAQUÍN GÓMEZ
             

Objectives. To analyze a cohort of patients with Enterococcus sp. bacteraemia.
Patients and methods. Retrospective and observational study of a cohort of non-pediatric in-patients with Enterococcus spp. bacteraemia (June 2007-September 2009). Data collection from clinical records was done according to a standard protocol. We analyzed epidemiological, clinical and microbiological data. Treatment with glycopeptides in non allergic patients or in case of betalactam susceptibility (ampicillin) was considered “optimizable”.
Results. Three were 106 cases of bacteraemia (2.2/1000 admitted patients; 84% E. faecalis); 83% had an underlying condition; 88% nosocomial or health related cases. Urinary infection was present in 20% and primary bacteraemia in 47%. High level resistance to gentamicin (HLRG) was present in 60%; there was no vancomycin or linezolid resistance. Most frequent empiric treatments were penicillin-betalactamase inhibitor (25%) and glycopeptides (22%). Most frequent definitive treatment was glycopeptides (34%), being “optimized” 21% and 44% of empiric and definitive treatments, respectively. Mortality was 23% (related, 14%). In the multivariate analysis, risk factors associated with HLRG were nosocomial acquired infection (OR 6.083; 95CI% 1.428-25.915) and no-abdominal origin (OR 6.006; 95CI%1.398-25.805). In multivariate analysis, independent risk factors for mortality were: Pitt > 3 (OR 14.405; 95CI%2.236-92.808) and active empiric treatment (OR 8.849; 95CI% 1.101-71.429).). Incidence in previous cohort was similar but HLRG rate has increased.
Conclusions. Risk factors associated with HLRG were nosocomial acquired infection and no-abdominal origin. Risk factors for mortality were initial clinical severity and having received active empiric treatment. HLRG rate has increased.

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Rev Esp Quimioter 2014:27(1):28-35

Antibiotic prescribing and changes in antimicrobial resistances in the health area of Segovia (Spain) during the period between 2007 and 2011                                
 

SONIA MIGUÉLEZ-FERREIRO, ELENA MORENO-SÁNCHEZ, MARÍA GUTIÉRREZ-DE ANTONIO, SUSANA HERNANDO-REAL               

Introduction. We analyzed the antibiotic prescribing and resistances of respiratory and urinary pathogens more common in the Health Area of Segovia in the period 2007-2011. The aim of the study was to investigate variability, time trends of antibiotic prescribing and correlation with changes in the antimicrobial resistance patterns.
Material and methods. Retrospective cross-sectional study. Antibiotic consumption was expressed in defined daily doses (DDD) per 1000 inhabitants per day (DHD). The antimicrobial resistance was expressed in percentages. Trend analysis was performed testing Spearman and Pearson correlation coefficients.
Results. The average antibiotic prescribing was 14.17 DHD, the coefficient and low ratio was 38.93% and 17.94. Penicillins was the most prescribed group (73%). Rural localization, lack of training MIR, distance to hospital and percentage of patients >65 years; showed significant association with increased antibiotic prescribing. Resistance of E. coli to cotrimoxazole and resistance of H. influenzae to amoxicillin decreased both by 8%. Resistance of S. pyogenes to erythromycin decreased by 5%. Resistances of S. pneumoniae to penicillin and E.coli to cephalosporins were both increased by 12%. Correlation between antibiotic prescription and resistances did not show singnificative results.
Conclusions. Prescribing of antibiotics decreased by 3.2% during the period. The use of broad-spectrum antibiotics was increased. Geographic wide variation in antibiotic prescribing was detected, also between physicians. There were not obtained conclusive data from the correlation between antibiotic prescribing and antimicrobial resistance.

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Rev Esp Quimioter 2014:27(3):159-169

Pharmaceutical intervention in duration of antimicrobial treatment at hospital ambit                                 
 

MARÍA MORANTE, CARMEN MATOSES-CHIRIVELLA, FRANCISCO JOSÉ RODRÍGUEZ-LUCENA, JOSÉ MANUEL DEL MORAL, MONTSERRAT RUIZ-GARCÍA, ANDRÉS NAVARRO-RUIZ               

Objective. To estimate the acceptance of the pharmaceutical intervention in controlling duration of antimicrobial therapy
and to evaluate their impact on optimizing the treatment.
Methods. Prospective observational study for two years in a General University Hospital. For the patients record, we followed non critical adult patients with antibiotic treatment. When the duration of antimicrobial treatment not complied with established criteria for each antibiotic and pathology, there was a communication with the physician, at which is recommended to assess the need for continue treatment. The acceptance of pharmaceutical intervention was collected and afterwards we analyzed the impact of this work by antimicrobial consumption and incidence of Clostridium difficile.
Results. In 122 patients the pharmacist made a pharmaceutical intervention due to prolonged antibiotic treatment. The most prevalent antibiotics were β-lactams, specifically meropenem. The intravenous administration was more frequent. In 77 cases it was decided to recommend the suspension of treatment, we conducted an orally prospective intervention at 70.15 % and the rest of interventions were written. Acceptance was 65.95 % and 65.00%, respectively. During the study period, the DDD of the antimicrobials decreased by 8.89% and expenditure on antimicrobials one 40.12%. The incidence of C. difficile was stable.
Conclusions. In a hospital, a pharmaceutical counselling program on the duration of antimicrobial therapy is well accepted by the prescriber physician, but it must be improved. The route of information does not affect the degree of acceptance. These actions could involve a reduction of antimicrobial consumption.

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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 2014:27(1):36-42

Use of Digital Health Records and “WebMovil” corporate service in the communication management of critical results of Microbiology, in the context of a primary health care area                                
 

ANTONIO FRANCISCO GUZMÁN-GONZÁLEZ, FEDERICO NAVAJAS-LUQUE, JOSÉ DE LA TORRE-FERNÁNDEZ               

Introduction. The objective was to describe and evaluate a new communication protocol of reporting critical results applied to Microbiology in a health area of Andalusia.
Material and methods. The size and type of the critical values of Microbiology are analyzed for primary care patients. A new computerized reporting system was analyzed, in real time, through Diraya Digital Health Records, which integrates the analytical test module (MPA). The protocol is complemented, in collaboration with the Information Technology (IT), with the Junta de Andalucía short message service (SMS) “WebMovil”.
Results. The total number of notices of critical results by the new protocol in 2012 was 817. The number of critical values for primary care was 570, of which 90 were for Microbiology. The most frequent notice was by isolation in the stool culture (n = 51; 56.67%). The prevalence of the critical values of Microbiology in primary care was 0.45/100. The average time of notifications was 13 minutes. The success rate of notifications was 97.7% and 0% obtained in the number of withdrawals. In 99.93% of cases the contact with the patient was stated and in 98.55% the medical intervention was also confirmed.
Conclusions. Communication by a computerized system linked to the SMS technology showed a reduction in the time of notification, and produced additional benefits, such as eliminating the risk of error when there is no repetition of information from the recipient received by the laboratory. Furthermore, the use of SMS messages ensures that doctors on duty always receive information immediately.

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Rev Esp Quimioter 2014:27(3):170-179

Reduction in diabetic amputations over 15 years in a defined Spain population. Benefits of a critical pathway approach and multidisciplinary team work                                 
 

DIEGO DE ALCALÁ MARTÍNEZ-GÓMEZ, M. ANGELES MORENO-CARRILLO, ALVARO CAMPILLO-SOTO, ANDRÉS CARRILLO-GARCÍA, JOSÉ LUÍS AGUAYO-ALBASINI               

Objective. To assess changes in diabetic lower-extremity amputations (LEA) rates in a defined population over a 15-year period, following a multidisciplinary approach including a critical pathway in an inpatient setting with standardized preoperative and postoperative care, as well as in an outpatient setting through the establishment of a diabetic foot clinic.
Methods. This is a study of the incidence and types of LEAs performed in patients with diabetic foot disease complicated admitted to Morales Meseguer Hospital (Murcia, Spain), a large district general hospital, before (1998-2000) and after (2001-2012) of the introduction of better organized diabetes foot care. Hospital and clinic characteristics to the success of the programme are described. All cases of LEA in diabetic patients (1998-2012) within the area were identified by ICD-9-Clinical modification (CM) diagnostic codes. A chi square test was used to compare the frequency and level of amputations.
Results. Over all inpatients with diabetes admitted with foot infections and gangrene, there was a significant decrease in the proportion of total major amputations (47%) and elective major amputations (66%) (p<0.001). The incidence of total major amputations rates per 100.000 of the general population fell with statistical significance (p=0.009). The biggest improvement in LEA incidence was seen in the reduction of major elective amputation with fell 60%, from 7.6 to 3.1 per 100,000 (p<0.001).
Conclusions. Significant reductions in total and major amputations rates occurred over the 15-year period following improvements in foot care services included multidisciplinary teamwork (critical pathway and diabetic foot clinic).

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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 2014:27(1):43-45

Evaluation of galactomannan antigen and Aspergillus real time PCR for diagnosis of invasive aspergillosis                                
 

MERCEDES CHANZÁ, Mª TERESA FRAILE, CONCEPCIÓN GIMENO, Mª DOLORES OCETE               

Introduction. The aim of the study was to compare the galactomannan antigen (GA) and  molecular biology(PCRrt) tests with the culture in the diagnosis of invasive aspergillosis (IA). 
Material and methods. Four hundred and seventy two samples were analyzed: 388 respiratory and 84 serum samples from 271 patients. Culture and GA were evaluated in the respiratory samples and GA in the serum samples. PCR was used when discrepancies were observed among culture and GA tests.
Results. The detection of GA in serum was positive in 22 (of 84), 21 had the test positive respiratory sample. Of the 62 sera with negative GA, 45 were also negative respiratory specimens. The culture was positive in 37 of which were positive for GA. Comparing culture with AG, it showed PPV=23%, NPV=100%, S=100% and E=52%. The PCR showed respect to culture: PPV=69%, NPV=89%, S=64% and E=82%. In sera were found in 60% discrepancies between PCRrt and GA.
Conclusions. We consider useful the GA detection in serum combined with culture and GA in respiratory samples, for diagnosis of AI. PCR requires further studies for standardization and set breakpoints.

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