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Rev Esp Quimioter 2018; 31(1): 1-12

Antibiotic diffusion to central nervous system

JOSÉ MARÍA CABRERA-MAQUEDA, LUNA FUENTES RUMÍ, GABRIEL VALERO LÓPEZ, ANA ESTHER BAIDEZ GUERRERO, ESTEFANÍA GARCÍA MOLINA, JOSÉ DÍAZ PÉREZ, ELISA GARCÍA-VÁZQUEZ

Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly controlled within CNS, where vasculature exhibits a blood-brain barrier (BBB).The entry of drugs, including antibiotics, into the cerebro-spinal fluid (CSF) is governed by molecular size, lipophilicity, plasma protein binding and their affinity to transport systems at the BBB. The ratio of the AUCCSF (Area under the curve in CSF)/AUCS (Area under the curve in serum) is the most accurate parameter to characterize drug penetration into the CSF. Linezolid, some fluoroquinolones and metronidazole get high CSF concentrations and are useful for treating susceptible pathogens. Some highly active antibiotic compounds with low BBB permeability can be directly administered into the ventricles together with concomitant intravenous therapy. The ideal antibiotic to treat CNS infections should be that with a small moderately lipophilic molecule, low plasma protein binding and low affinity to efflux pumps at BBB. Knowledge of the pharmacokinetics and pharmacodynamics of antibiotics at the BBB will assist to optimize antibiotic treatment in CNS infections. This article reviews the physicochemical properties of the main groups of antibiotics to assess which compounds are most promising for the treatment of CNS infections and how to use them in the daily clinical practice.

Rev Esp Quimioter 2017; 31(1): 1-12 [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(1): 35-42

Interferon-free treatments in patients with hepatitis C genotype 3 infection in a tertiary hospital

JUAN CARLOS DEL RIO-VALENCIA, ROCÍO ASENSI-DIEZ, RAQUEL MADERA-PAJIN, LUCÍA YUNQUERA-ROMERO, ISABEL MUÑOZ-CASTILLO

Introduction. Hepatitis C virus genotype 3 represents a unique entity within HCV treatment and multiple studies have documented that HCV genotype 3 infection is associated with more rapid disease progression than other genotypes, resulting in increased risk of cirrhosis, hepatocellular carcinoma, and all-cause mortality. In the current study, we further evaluated the real-world effectiveness of 12 weeks of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) and sofosbuvir + daclatasvir (SOF + DCV) for treatment-naive or treatment-experienced patients infected with HCV genotype 3, with or without cirrhosis.
Material and methods. Retrospective and observational study carried out in a third level hospital. Study period: April 2015 to January 2016. Inclusion criteria: Patients with HCV genotype-3 infection treated either with LDV/SOF ± RBV or with SOF + DCV during study period treated for 12 weeks. The patients that were treated during 24 weeks were excluded and those treated with peg-interferon. The main endpoint measured was the sustained virologic response (SVR) at 12 weeks (SVR12) and the secondary endpoint was SVR at 24 weeks (SVR24).
Results. During the study period, 603 patients were treated in our hospital: 71 with genotype 3. We included 46 patients who were treated with LDV/SOF ± RBV or SOF + DCV for 12 weeks. A 43.75% (7/16) of all patients treated with LDV/SOF achieved SVR12, 90% (9/10) of the patients treated with LDV/SOF+RBV achieved SVR12 and 95% (19/20) of the patients treated with SOF+DCV achieved SVR12. There was statistically significant difference (p=0.001) between LDV/SOF respect to SOF+DCV and between LDV/SOF with regard to LDV/SOF +RBV (p=0.018) used to treat HCV genotype 3 infection.
Conclusions.  In conclusion, in our cohort of patients, the combination of SOF + DCV followed by LDV/SOF + RBV 12 weeks were the most effective in patients with HCV genotype 3 and with cirrhosis (SVR12 90% and 80%, respectively) and in those without cirrhosis (SVR12 100% in both combinations). All patients who achieved SVR12 also achieved SVR24, regardless of the regimen received.

Rev Esp Quimioter 2017; 31(1): 35-42 [Full-text PDF]

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Rev Esp Quimioter 2018; 31(1): 13-20

URISCAM project: Multicenter evaluation of the UF-Series cytometer in the urinary tract infections screening

MARÍA DEL MONTE JARABO, MARÍA ÁNGELES ASENCIO, RAFAEL CARRANZA, ÓSCAR HERRÁEZ, MARÍA HUERTAS, ÁNGEL ARIAS-ARIAS, OLGA REDONDO, MARÍA ÁNGELES GALÁN, MARÍA SOLEDAD ILLESCAS, PILAR ZAMARRÓN, SONIA SOLÍS, SILVIA JIMÉNEZ-ALVAREZ

Introduction. Urine culture, the gold standard to confirm the presence of urinary tract infection (UTI), is the most requested assay in the microbiology department. Our objective was to determine the diagnostic yield of the UF-Series cytometer as a screening method for UTI.
Material and methods. All the urine samples sent to the six Microbiology Laboratories participating in a period of 5 working days were analyzed. We collected demographic variables, apart from those variables related to urine samples: source and sample type (midstream, catheterized or nephrostomy urines), collection with/without boric acid, cytometer parameters (leukocyturia, bacteriuria, bacteria morphology and epithelial cells) and urine culture results. ROC curves were plotted to determine predictive capacity of the cytometer.
Results. A sample of 2,468 patients with average age of 53 years were processed (ratio women:men 2:1). Urine culture detected 23% of positive urine samples. The predictor variables of UTI were: morphology of bacilli, bacteriuria ≥21 bacteria/µL, age ≥65 years, samples collected in the emergency service and hospitalization and preserving conditions. With 21 bacteria/µL as a cut-off point, we obtained a sensitivity of 93.3% and 94.5% negative predictive value, then reducing the samples to be cultured by 28.9% with 1.6% false negatives.
Conclusions. We consider that the UF-Series is a valid and accurate tool for the detection of UTI. Therefore, it could be used as screening method in the clinical practice prior to the urine culture, reducing culture requirement by approximately 30%, with a low false negative rate.

Rev Esp Quimioter 2017; 31(1): 13-20 [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(1): 27-34

Analysis on the ambulatory usage of antibiotics at general hospitals in Asturias (2006-2015)

MARÍA LUISA SÁNCHEZ-NÚÑEZ, MANUEL JAVIER VALLINA-VICTORERO, MARÍA ROSARIO BACHILLER-LUQUE, JOSÉ MARÍA PINILLA SÁNCHEZ, JOSÉ MARÍA EIROS

Introduction. The Organization for Economic Co-operation and Development (OECD) emphasize, in its report on health policies from 2017 that, Spain is one of the countries with largest consumption of antibiotics, 21.6 DHD (defined daily dose per 1000 inhibitants per day) in 2014 greater than the average 20.5 DHD in their countries, ranking according to the European Center for Disease Prevention and Control (ECDC) in the 11th place out of 30 European countries in 2016. The outpatient prescription of specialized care is analyzed less frequently, due to the greater contribution in consumption and expenditure of primary care.
Material and methods. A descriptive, observational, and retrospective study of the consumption and expenditure of the J01 group derived from outpatient prescription (outpatient and urgent care) of public hospitals in Asturias, in a period of ten years (2006-2015). Consumption data were obtained using the database of prescription billing of the Health Service of the Principality of Asturias, demographic data were provided by the National Institute of Statistics. Consumption was expressed in DHD and antibiotics expenditure in: expenditure per capita and expenditure in euros per defined daily dose.
Results. The average global ambulatory consumption for the period was 23.4 DHD, corresponding 11.5% (2.7 DHD) to the ambulatory specialty care prescription. In terms of expenditure, it accounted for 13.6% of overall outpatient spending on antibiotics.
Conclusions. Outlay and consumption had opposite tendencies, the expenditure control measures did not have or had little impact on consumption, therefore, independent and spe-cific rationalization measures are required in this area.

Rev Esp Quimioter 2017; 31(1): 27-34 [Texto completo PDF]

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Rev Esp Quimioter 2018; 31(1): 43-52

Economic and Health impact of influenza vaccination with adjuvant MF59 in population over 64 years in Spain

ALBERTO PÉREZ-RUBIO, JOSÉ MARÍA EIROS

Introduction. Influenza is an important health problem due to the mortality it can cause directly or indirectly as well as the complications and the economic and social costs it produces. Influenza epidemics are being addressed through vaccination campaigns aimed at preventing cases and complications, and the vaccine is officially recommended, as in the case of Spain, for certain risk groups, such as older people, chronic diseases and institutionalized population. The adjuvanted influenza vaccine with MF59, indicated for population over 65 years, has been shown to be more immunogenic than conventional influenza vaccines. The objective of this study is to assess the impact on the national and regional budget of the seasonal vaccination campaigns carried out in Spain using the MF59 adjuvanted vaccine compared to a conventional vaccine in a population older than 65 years.
Material and methods. We analyzed the budgetary impact of the use of the MF59-adjuvanted vaccine in the national territory and by Autonomous Communities through a modeling of two alternatives, conventional vaccination versus adjuvant vaccination with MF59 in a population older than 65 years. The cases of avoided influenza, avoided complications and avoided costs, as well as the economic impact of the vaccination program have been calculated.
Results. With the available information, the budgetary impact of using the influenza vaccine with MF59 in all the over 65 years, amounts to 6,967,288.10 €, avoiding for the national set a cost of 89.5 million Euros, which represents a potential savings of 82 million Euros and a cost-benefit ratio of 12.83.
Conclusion. The use of the influenza vaccine with the MF59 adjuvant to all those over 65 years would mean an increase in the efficiency of the vaccination programs currently proposed in all the Autonomous Communities and in the Spanish state.

Rev Esp Quimioter 2017; 31(1): 43-52 [Texto completo PDF]

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Rev Esp Quimioter 2017; 30(6):407-412

Cefditoren: a reality for the treatment of community infections

BEATRIZ SÁNCHEZ ARTOLA, JOSÉ BARBERÁN

Cefditoren, a third-generation cephalosporin, is the oral β-lactam more active against the main community-acquired respiratory tract pathogens (including resistance phenotypes such as penicillin-resistant Streptococcus pneumoniae and ampicillin-resistant Haemophilus influenzae), similar to cefotaxime. Data obtained from clinical trials and later evidence on efficacy and safety, support that cefditoren is an suitable option for the treatment of mild-to moderate community respiratory and urinary tract infections, particularly in regions where non-susceptible phenotipes to common oral antibiotics are prevalent.

Rev Esp Quimioter 2017; 30(6):407-412 [Texto completo PDF]

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Rev Esp Quimioter 2017; 30(6): 468-471

Infection by the Epstein-Barr virus between the years 2006-2015 in the health area of Santiago de Compostela. Relationship with age and sex

ROCÍO TRASTOY PENA, JOSÉ JAVIER COSTA ALCALDE, JAVIER RODRÍGUEZ CALVIÑO, DANIEL NAVARRO DE LA CRUZ, GEMA BARBEITO CASTIÑEIRAS, ANTONIO AGUILERA GUIRAO

Introduction. In Spain, the age and sex to which the primary infection by EBV is produced is poorly studied. The objective of this work is to know its relation with the presence of the primary infection by EBV between the years 2006 and 2015 in our health area.
Patients and methods. From the Santiago de Compostela health area between 2006 and 2015, 578 patients with serological patterns of EBV primoinfection were selected. This patients presented serological results of IgM-VCA positive, IgG-VCA positive and EBNA negative.
Results. We found 260/578 (45%) adolescents (11- 19 years). In the number of cases by age the maximum was observed, at 2 and 16 years. Between 14-19 years, 62% (79/127) of women between 14-16 years of age, median age 15.8 years (IQ: 14.8-16.4) compared to 48% (49/102) of men, median age 16 years (IQ: 15.7-16.6) (p = 0.032, p = 0.02, respectively).
Conclusions. As in our study, in the developed countries the majority of primary infections by EBV occur in adolescence and a bimodal distribution is observed in relation to age. During adolescence women acquire before men the first infection by EBV.

Rev Esp Quimioter 2017; 30(6): 468-471 [Texto completo PDF]

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Rev Esp Quimioter 2017; 30(6): 464-467

Performance of the KAtex test in screening and diagnosis for visceral leishmaniasis in a reference hospital

CONCEPCIÓN FERNÁNDEZ-ROLDÁN, JAVIER RODRÍGUEZ-GRANGÉR, ROSARIO JAVIER MARTÍNEZ, MIGUEL ÁNGEL LÓPEZ-RUZ, JOSÉ MARÍA NAVARRO-MARÍ, JOSÉ GUTIÉRREZ-FERNÁNDEZ

Introduction. Performing of diagnostic test simple using samples not invasive in the diagnosis of visceral leishmaniasis (VL) may be very beneficial, being necessary comparing to traditional methods.  The objective of this study was to know the reliability of test KAtex in the urine of patients with suspicion of VL.
Material and methods. Retrospectively were reviewed the medical histories of patients with suspected of VL to which are performed the test between 2009 and 2015. For its analysis were selected the patients to which is them had made study of the parasite in bone marrow.
Results. A total of 110 patients were studied, and bone marrow biopsy for research of Leishmania was performed in 44 (40%). In these patients the sensitivity of the test was 50%, the specificity of 96.7%, positive predictive value of 87.5% and negative predictive value of 80.5%.
Conclusions. KAtex antigenuria sensitivity is too low recommending it as a unique method in the detection of VL in our medium.

Rev Esp Quimioter 2017; 30(6): 464-467 [Texto completo PDF]

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Rev Esp Quimioter 2017; 30(6): 458-463

Epidemiology of the carbapenemase-producing Enterobacteriaceae spread in a community acute hospital and a non-acute rehabilitation hospital in Madrid

MARCOS LÓPEZ-DOSIL, CORNELIA BISCHOFBERGE, DAVID SÁEZ, LUISA GARCÍA-PICAZO

Introduction. In Spain, the overall prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is increasing. We describe the epidemiological, clinical and microbiological characteristics features of patients with colonization or infection due to CRE in two hospitals in the north-west of Madrid during two years. One hospital was a community acute hospital and the second one was a non-acute rehabilitation hospital
Material and methods. A total of 197 CPE isolates were detected during 2013-2014.  Microbiological, epidemiological and clinical data were collected, since the first isolate was found in March 2013.
Results. A 33.5% of patients with CRE had symptomatic infection and the remaining 66.5% were colonizations. Klebsiella pneumoniae (87.8%) was the most prevalent species and OXA-48 the most frequent carbapenemase (91.9%). We found intra-interhospital spread and some differences in the epidemiology of CRE depending on the hospital, such as more genetic variability in the non-acute rehabilitation hospital.
Conclusions. Studying the CRE transmission we founded an increased incidence in a short period of time and a rapid dissemination of strains between both hospitals. This highlights the need to standardize screening measures for potential carriers and infection control programs in our hospitals.

Rev Esp Quimioter 2017; 30(6): 458-463 [Texto completo PDF]

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Rev Esp Quimioter 2017; 30(6): 443-449

Simulation of an outbreak of Acinetobacter baumannii in hospitals

ÁNGEL MARTÍN-DEL REY, MARÍA GARCÍA-MORO, ENRIQUE GARCÍA-SÁNCHEZ, ENRIQUE GARCÍA-MERINO, JOSÉ ELÍAS GARCÍA-SÁNCHEZ

Introduction. Acinetobacter baumannii infections have increased over time becoming a significant issue. Consequently, those applications that allow to predict the evolution of an outbreak and the relevance of the different control methods, are very important. The design of mathematical models plays a central role in this topic.
Material and methods. Development of a deterministic mathematical model based on ordinary differential equations whose variables and parameters are defined upon the basis of knowledge of the epidemiology and characteristics of A. baumannii. This model is analyzed from a qualitative point of view and, also, its computational implementation is derived.
Results. Several simulations were obtained developed from different initial conditions. The qualitative analysis of these simulations provides formal evidence of most effective control measures.
Conclusions. The implementation of the computational model is an extremely useful tool in terms of managing A. baumannii outbreaks. There is mathematical proof of the fact that the observance of efficient hygiene and screening rules reduces the number of infected patients.

Rev Esp Quimioter 2017; 30(6): 443-449 [Texto completo PDF]