Rev Esp Quimioter 2015:28(1):10-20

Prevention of an outbreak of Acinetobacter baumannii in intensive care units: study of the efficacy of different mathematical methods                                 
 


MARÍA JOSÉ FRESNADILLO-MARTÍNEZ, ENRIQUE GARCÍA-MERINO, ENRIQUE GARCÍA-SÁNCHEZ, ÁNGEL MARTÍN-DEL REY, ÁNGEL RODRÍGUEZ-ENCINAS, GERARDO RODRÍGUEZ-SÁNCHEZ, JOSÉ ELÍAS GARCÍA-SÁNCHEZ              

Introduction. Although in past decades, Acinetobacter baumanni infections have been sporadically identified in hospitals, nowadays the nosocomial infections due to this pathogen have notably increased. Its importance is due to its multidrug-resistance, morbidity and mortatility in healthcare settings. Consequently, it is important to predict the evolution of these outbreaks in order to stablish the most efficient control measures. There are several experimental studies shown that the compliance with hand and environmental hygiene and the efficient management of the healthcare work help to control the evolution of these outbreaks. The goal of this work is to formally proof these experimental results by means of the analysis of the results provided by the model.
Methods. A stochastic mathematical model based on cellular automata was developed. The variables and parameters involved in it have been identified from the knowledge of the epidemiology and main characteristics of Acinetobacter infections.
Results. The model provides several simulations from different initial conditions. The analysis of these results proofs in a formal way that the compliance with hand and environmental hygiene and an efficient plannification of the work of healtcare workers yield a decrease in the colonized patients. Moreover, this is the unique model proposed studying the dynamics of an outbreak of A. baumanni.
Conclusions. The computational implementation of the model provides us an efficient tool in the management of outbreaks due to A. baumanni. The analysis of the simulations obtained allows us to obtain a formal proof of the behaviour of the measures for control and prevention.

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Rev Esp Quimioter 2015:28(3):139-144

Role of double strand DNA break repair for quino-lone sensitivity in Escherichia coli: therapeutic implications                                 
 


ROCÍO GONZÁLEZ-SOLTERO, ANA GARCÍA-CAÑAS, ROSA B. MOHEDANO, BELÉN MENDOZA-CHAMIZO, EMILIA BOTELLO              

 

Introduction. Quinolones are one of the types of antibiotics with higher resistance rates in the last years. At molecular level, quinolones block  type II topoisomerases producing double strand breaks (DSBs). These DSBs could play a double role, as inductors of the  quinolone bactericidal effects but also as mediators of the resistance and tolerance mechanisms.
Material and methods. In this work we have studied the molecular pathways responsible for DSBs repair in the quinolone susceptibility: the stalled replication fork reversal (recombination-dependent) (RFR), the SOS response induction, the translesional DNA synthesis (TLS) and the nucleotide excision repair mechanisms (NER). For this reason, at the European University in Madrid, we analysed the minimal inhibitory concentration (MIC) to three different quinolones in Escherichia coli mutant strains coming from different type culture collections.
Results. recA, recBC, priA and lexA mutants showed a significant reduction on the MIC values for all quinolones tested. No significant changes were observed on mutant strains for TLS and NER.
Discussion. These data indicate that in the presence of quinolones, RFR mechanisms and the SOS response could be involved in the quinolone susceptibility.

Rev Esp Quimioter 2015:28(3):139-144 [pdf]

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Rev Esp Quimioter 2015:28(3):145-153

Profiles and clinical management of hepatitis C patients in Spain: disHCovery study                                 
 


MARÍA BUTI, ALEJANDRO FRANCO, ISABEL CARMONA, JUAN JOSÉ SÁNCHEZ-RUANO, ANDREU SANSÓ, MARINA BERENGUER, LUISA GARCÍA-BUEY, MANUEL HERNÁNDEZ-GUERRA, ROSA MARÍA MORILLAS, FRANCISCO LEDESMA, RAFAEL ESTEBAN, AND THE DISHCOVERY STUDY GROUP              

 

Introduction. To assess the clinical profile and management of patients with hepatitis C (HCV) infection in an observational study in Spanish hospitals.
Methods. The study included an initial cross-sectional phase (study phase I), in which investigators at 48 hospitals from 14 Spanish regions collected data from approximately 20 consecutive patients each (a total of 1,000 patients) to assess the general features of HCV-infected patients of any genotype. During the second phase (study phase II), data from 878 patients that were infected exclusively with genotype 1 HCV were assessed retrospectively. Eight pre-defined clinical profiles were established, in order to assess clinical and previous treatments characteristics.
Results. Among the HCV-infected individuals that were analysed during the first part, HCV genotype 1 was found to be predominant (with a prevalence of 76.6%), prevailing the subtype 1b (69.8%), with other significant groups infected by genotype 3 (12.3%) and 4 (7.4%). In the second part of the study, 44% of the HCV genotype 1-infected patients were at a F3/F4 fibrosis stage. 15.9% had never been treated, and previously unsuccessfully treated patients that were no longer receiving anti-HCV treatment accounted for 50.8% of cases. Individuals with a sustained virologic response (SVR) to pre-vious dual therapies (based on Interferon and Ribavirin) were only 14.5% and patients under treatment during the study accounted for the remaining 18.8%. A total of 713 patients (81.2%) in the second phase were not receiving any type of therapy over the period analysed, mainly due to the anticipation of new anti-HCV drugs (41.8%), SVR achievement (17.8%) and unresponsiveness to therapies available at the time of the study (9.5%).
Conclusions. HCV genotype 1, predominately 1b, is the most prevalent type in Spain. Advanced fibrosis or cirrhosis is frequent in this group, mainly patients not yet cured.

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Rev Esp Quimioter 2015:28(3):154-156

Nebulized medication is not associated with nosocomial infections. A pilot study                                 
 


DAVID VINUESA, VIOLETA RAMOS, ALEJANDRO PEÑA, MARÍA RUIZ-RUIGÓMEZ, JON BADIOLA, LEOPOLDO MUÑOZ-MEDINA, JOSÉ HERNÁNDEZ-QUERO, JORGE PARRA-RUIZ              

 

Introduction. Nebulized devices are commonly used in the treatment of respiratory infection, and other respiratory diseases. It has been reported nosocomial infections in cystic fibrosis patients as a result of the use of contaminated devices. However, little is known about nosocomial infections secondary to aerosolized therapy in COPD patients admitted for acute exacerbation.
Methods. Thirty consecutive patients (13 males) were included. All of them received aerosolized medication.  Each patient used their own facemask and nebulizer cup, which were stored in the room after its use. Samples from nebulizer cups were obtained on days 0, 4 and 7. In addition, sputum samples were obtained on day 0 (prior to any nebulization) and on day 7, and cultivated in enriched media.
Results. Only nine nebulizer cups had positive microbiological cultures. Coagulase negative staphylococci (CoNS) were isolated in all cases. Sputum samples could be obtained in 27 patients. None grew CoNS after 7 days of aerosolized therapy. Gram-negative non-fermenting bacilli were isolated in three patients without concomitant grown in nebulizer cups.
Conclusions. We did not find any nosocomial infection related to aerosolize medications in COPD patients admitted for acute exacerbation.

 

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Rev Esp Quimioter 2015:28(3):157-159

New methodological advances: algorithm proposal for management of Clostridium difficile infection                                 
 


MARÍA JOSÉ GONZÁLEZ-ABAD,  MERCEDES ALONSO-SANZ              

 


Introduction. Clostridium difficile infection (CDI) is considered the most common cause of health care-associated diarrhea and also is an etiologic agent of community diarrhea. The aim of this study was to assess the potential benefit of a test that detects glutamate dehydrogenase (GDH) antigen and C. difficile toxin A/B, simultaneously, followed by detection of C. difficile toxin B (tcdB) gene by PCR as confirmatory assay on discrepant samples, and to propose an algorithm more efficient.
Material and Methods. From June 2012 to January 2013 at Hospital Infantil Universitario Niño Jesús, Madrid, the stool samples were studied for the simultaneous detection of GDH and toxin A/B, and also for detection of toxin A/B alone. When results between GDH and toxin A/B were discordant, a single sample for patient was selected for detection of C. difficile toxin B (tcdB) gene.
Results. A total of 116 samples (52 patients) were tested. Four were positive and 75 negative for toxigenic C. difficile (Toxin A/B, alone or combined with GDH). C. difficile was detected in the remaining 37 samples but not toxin A/B, regardless of the method used, except one. Twenty of the 37 specimens were further tested for C. difficile toxin B (tcdB) gene and 7 were positive.
Discussion. The simultaneous detection of GDH and toxin A/B combined with PCR recovered undiagnosed cases of CDI. In accordance with our data, we propose a two-step algorithm: detection of GDH and PCR (in samples GDH positive). This algorithm could provide a superior cost-benefit ratio in our population.

 

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Rev Esp Quimioter 2015:28(4):169-182

Clinical usefulness of triazole derivatives in the management of fungal infections                                 
 

ALFONSO JAVIER CARRILLO-MUÑOZ, GUSTAVO GIUSIANO, ALICIA ARECHAVALA, CRISTINA TUR-TUR, ELENA ERASO, NEREA JAUREGIZAR, GUILLERMO QUINDÓS, RICARDO NEGRONI              

Current therapy for mycoses is limited to the use of a relative reduced number of antifungal drugs. Although amphotericin B still remains considered as the “gold standard” for treatment, acute and chronic toxicity, such as impairment of renal function, limits its use and enhances the investigation and clinical use other chemical families of antifungal drugs. One of these chemical class of active drugs are azole derivatives, discovered in 70s and introduced in clinical practice in 80s. Being the most prolific antifungal class, investigation about more molecules, with a safer and better pharmacological profile, active against a wide spectrum of fungi, with a wide range of administration routes gives us some azole representatives.

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Rev Esp Quimioter 2015:28(4):183-192

Variability in antibiotic consumption within a regional health service, according to health area and model of healthcare coverage: national health system vs. civil servants’ mutual insurance society                                 
 

DIEGO PABLO SÁNCHEZ-MARTÍNEZ, JOSÉ JESÚS GUILLÉN-PÉREZ, FERNANDO IGNACIO SÁNCHEZ-MARTÍNEZ, ALBERTO MANUEL TORRES-CANTERO              

Introduction. The aim of this study is to describe antibiotic consumption in the Region of Murcia in 2011, within the Spanish and European context, as well as to analyze the differences within the Region, both between health areas, and between users of the regional health service and those protected by the civil servants’ mutual insurance society (MUFACE).
Methods. Retrospective observational study of prescriptions dispensed by the pharmacies in the Region of Murcia during 2011. Consumption rates were expressed as defined daily doses (DDD) per 1,000 inhabitants/day and standardized consumption ratios (SCR).
Results. Overall antibiotics consumption rate in the Region of Murcia in 2011 was 30.05 DDD/1000/ day (DID), which is much above the average rate for Spain (20.9 DID) and for the European Union (21.57 DID). Health areas within the Region with the highest and lowest consumption rate are, respectively, Vega Alta (SCR: 124.44; CI95% 124.26 to 124.61) and Cartagena (SCR:84.16; CI95% 84.10 to 84.22). Civil servants covered by the mutual society have higher consumption rates than users of the regional health service (SCR: 105.01; CI95% 104.86 to 105.17).
Conclusions. There is a high level of antibiotic prescription in the Region of Murcia Region in relative terms. A great variability in antibiotics consumption was observed between the different health areas, which might be related to the higher rate of the frequency of visits. The highest amount of variability in antibiotics prescription was found in cephalosporins and macrolides.

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Rev Esp Quimioter 2015:28(4):193-199

Safety of influenza vaccines in risk groups: analysis of adverse events following immunization reported in Valencian Community from 2005 to 2011                                 
 

ANA MARÍA ALGUACIL-RAMOS, TERESA Mª GARRIGUES-PELUFO, JULIO MUELAS-TIRADO, ANTONIO PORTERO-ALONSO, JORDI PEREZ-PANADÉS, JAIME FONS-MARTÍNEZ              

Objective. To evaluate reports of adverse events following influenza immunization by sex, risk and age groups in Valencian Community from 2005 to 2011.
Methods. A pharmacoepidemiological descriptive cross-sectional observational study based on the reports of adverse events following immunization (AEFI) against influenza, registered through the Vaccination Information System (SIV) of Valencian Community from 1 January 2005 until 31 December 2011 was done.
Results. During the study period 5,107,790 doses of vaccine against influenza were reported, with an AEFI incidence of 1.94 per 100,000 (95% CI 1.59 to 2.36), and 228,094 doses of vaccine for influenza A (H1N1) pdm09 (96.45 per 100,000, 95%CI 84.52-110.06). The 70.71% (70) and 64.55% (142), respectively, of AEFI were in women. The healthcare workers group had a higher reporting rate for seasonal influenza (25.35 per 100,000; 95%CI: 17.65-36.40) and for influenza A(H1N1) pdm09 (864.13 per 100,000; 95%CI 714.38-1044.93) during the study period.
Conclusions. Vaccines against influenza administered during the study had a high safety profile in both populations with disease risk and other susceptible target groups of vaccination. Adverse reactions reported during the study mostly coincide with those described in the summary of product characteristics of vaccines.

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Rev Esp Quimioter 2015:28(4):200-206

Maraviroc modifies gut microbiota composition in a mouse model of obesity: a plausible therapeutic option to prevent metabolic disorders in HIV-infected patients                                 
 

PATRICIA PÉREZ-MATUTE, LAURA PÉREZ-MARTÍNEZ, JAVIER AGUILERA-LIZARRAGA, JOSÉ R. BLANCO, JOSE A. OTEO              

Introduction. The proportion of HIV-infected patients with overweight/obesity has increased in recent years. These patients have an increased metabolic/cardiovascular risk compared with non-obese patients. Modulation of gut microbiota composition arises as a promising tool to prevent the develop-ment of obesity and associated disorders. The aim of this study was to investigate the impacts of maraviroc (MVC), a CCR5 antagonist approved for clinical use in HIV-infected patients, on gut microbiota composition in a mouse model of obesity.
Methods. Thirty two male C57BL/6 mice were assigned to:a) Control (chow diet), b) MVC (chow diet plus 300 mg/L MVC), c) High-fat diet (HFD) or d) HFD/MVC (HFD plus 300 mg/L MVC) groups. Body weight and food intake was recorded every 2-3 days. Mice were euthanized after 16 weeks of treatment and cecal contents were removed to analyse by real-time PCR four bacterial orders from the most dominant phyla in gut.
Results. Mice fed with a HFD showed a significant increase in Enterobacteriales (p<0.001 vs. control). MVC treatment induced a significant decrease in control (p<0.05) and HFD fed mice (p<0.001). Interestingly, this order was positively associated with body weight gain, insulin resistance and fatty liver. HFD induced a significant decrease in Bacteroidales and Clostridiales levels (p<0.05 and p<0.01, respectively). MVC decreased the presence of Bacteroidales (p<0.05 vs. control) while an increase was observed in HFD/MVC mice (p=0.01 vs. HFD). No direct effects of MVC were observed on Clostridiales and Lactobacillales.
Conclusions. MVC may constitute a new therapeutic option to prevent obesity and related disorders in HIV-infected patients.

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Rev Esp Quimioter 2015:28(4):207-209

Characterization of daptomycin non-susceptible Enterococcus faecium producing urinary tract infection in a renal transplant recipient      

                          

ANTONIO SORLÓZANO, DIANA PANESSO, JOSÉ MARÍA NAVARRO-MARÍ, CESAR A ARIAS, JOSÉ GUTIÉRREZ-FERNÁNDEZ              

Objectives. Characterization of a urine isolate of daptomycin non-susceptible Enterococcus faecium recovered from a patient with kidney transplantation and no history of daptomycin exposure.
Methods. After isolation in a urine sample, identification of E. faecium was confirmed by amplification of the E. faecium-specific gene encoding D-alanyl-D-alanine ligase (ddl) and daptomycin susceptibility testing was performed by E-test on cation-adjusted Mueller-Hinton agar. In order to determine the genetic bases of daptomycin resistance, the open reading frames of five genes previously associated with daptomycin resistance in enterococci were sequenced.
Results. Substitutions in the response regulator LiaR (S19F) and cardiolipin synthase (R218Q) were identified.
Conclusions. To the best of our knowledge, this is the first characterization of emerging daptomycin resistance in E. faecium in a Spanish hospital in the absence of daptomycin exposure and in a renal transplant recipient.

Rev Esp Quimioter 2015:28(4):207-209 [pdf]

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