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.

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Rev Esp Quimioter 2015:28(Suppl. 1):19-24

Inhaled medication and inhalation devices for lung disease     

                        
AMPARO SOLÉ, ROSA Mª GIRÓN              

Nebulized antibiotic therapy is an attractive therapeutic option given the high concentration obtained from the drug at the site of infection, minimizing the adverse effects and possible drug interactions. Inhalation of drugs as treatment of cystic fibrosis (CF) related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. Other limited areas of experience in this field are lung transplant recipients, immunosuppressed patients, bronchiectasis and ventilated patients. In this review document we analyse the current status of the inhaled medications, their modes of administration and indications and their results as well as side effects. Specifically we address antibiotics, and additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Several factors contribute to a highly variable pulmonary drug deposition as the devices, the physical properties of the administered antimicrobial agent, the type of respiratory disease and the inhalation technique. Despite many clinicians have obtained a valuable experience from the aerosolized administration of antimicrobials and persuaded of their efficacy and safety. However, RCTs out of CF are needed to answer important clinical questions, such as what is the appropriate dose, the optimal delivery device, the optimal way of drug administration, as well as the exact therapeutic role and pharmacokinetic profile of aerosolized drug.

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Rev Esp Quimioter 2015:28(6):282-288

Potential antimicrobial drug interactions in clinical practice: consequences of polypharmacy and multidrug resistance     

                        
CRISTINA MARTÍNEZ-MÚGICA              

Background. Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the antiinfective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure.
Methods. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked.
Results. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin.
Conclusions. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.

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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(Suppl. 1):25-29

Cloxacillin-susceptible Staphylococcus aureus with high MIC to glycopeptides. Ever we use cloxacillin?     

                        
ALEJANDRA MORALES, ANTONIO LALUEZA, RAFAEL SAN JUAN, JOSÉ MARÍA AGUADO              

Staphylococcus aureus infections are yet an important cause of morbidity and mortality despite of numerous effective anti-staphylococcal antibiotics available. There has been an increasing incidence of methicillin-resistant strains which might have led to a wider use of vancomycin. This seems to ride alongside a covert progressive increase of S. aureus vancomycin minimum inhibitory concentration. In this way, the emergence of vancomycin-intermediate S. aureus (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant S. aureus. Ultimately, various debate issues have arisen regarding the emergence of S. aureus strains with decreased vancomycin susceptibility, within the range still considered sensitive. These strains have shown a different clinical behaviour regardless of vancomycin use, both in methicillin resistant and sensitive S. aureus. The emergence of increasing vancomycin-resistance in S. aureus isolates, has stirred up the basis of therapeutic approach in staphylococcal infections. There is yet much to explore to better define the impact of higher vancomycin minimum inhibitory concentration in staphylococcal infections.

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Rev Esp Quimioter 2015:28(6):289-294

Surveillance of resistance of Staphylococcus aureus to antibiotics in Galicia: 2007-2012     

                        
MERCEDES TREVIÑO, ISABEL LOSADA, MARÍA ÁNGELES PALLARÉS, FRANCISCO JOSÉ VASALLO, AMPARO COIRA, BEGOÑA FERNÁNDEZ-PÉREZ, ISABEL PAZ, FERNANDA PEÑA, PATRICIA ALEJANDRA ROMERO, LUCÍA MARTÍNEZ-LAMAS, GAEL NAVEIRA, XURXO HERVADA              

Introduction. Since 2007 the Galician Surveillance Program on Antimicrobial Resistance has been collected data of Staphylococcus aureus susceptibility patterns. The data from 2007 to 2012 have been analyzed and are reported.
Methods. A total of 4,577 different isolates of S. aureus from cerebrospinal fluid and blood cultures were included. The Institutions involved provided the information about the susceptibility patterns, the assay methods used and the interpretative guidelines followed, and demographic data of patients.
Results. The rate of methicillin-resistance S. aureus (MRSA) was 22% in 2007-2010 and 26% in 2011-2012, although in some areas the percentage reached 57% (2007- 2010) or 66% (2011-2012). The higher rates of resistance were found in patients older than 75 years. Gentamycin resistance was less than 9% and for quinolones were about 25%. A strong association between methicillin and quinolone-resistance were observed (91%). The resistance against linezolid and glycopeptides were exceptional.
Conclusions. The percentage of MRSA has evolved slightly along the period of this study reaching no significant differences between Galicia and the global data in Spain in 2012. Nevertheless, there are significant differences among the geographic areas studied. Most MRSA isolates were recovered from hospitalized patients, but an increase in the number of MRSA among outpatients was observed, while old patients from nur-sing homes are included in the outpatient group, so the MRSA rate in this group could be overestimated.

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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):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(Suppl. 1):30-33

Duration of antimicrobial therapy     

                        
JUAN PASQUAU, MAYRA MATESANZ              

The management of infectious diseases is always complex, not only because of its high incidence and mortality, but the difficulty of designing effective treatments that minimize the development of bacterial resistance in the clinical setting. One of the most important options is the reduction of exposure to antibiotic treatment, optimizing by desescalation and shortening the duration of therapy.

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Rev Esp Quimioter 2015:28(6):295-301

Analysis of the concordance of antibiotic treatment for patients with severe sepsis in emergencies     

                        
MARÍA ANTONIA PÉREZ-MORENO, BEATRIZ CALDERÓN-HERNANZ, BERNARDINO COMAS-DÍAZ, JORDI TARRADAS-TORRAS, MARCIO BORGES-SA              

Objectives. Antibiotic treatment is vital in patients with severe sepsis/septic shock. The objectives were to assess the degree of concordance between antibiotic prescribed in emergencies and post requirements; to relate it to health outcomes (mortality) and to analyze the reasons for disagreement.
Material and methods. Retrospective descriptive study of antibiotic treatment prescribed in emergencies and the subsequent treatment in patients with criteria of severe sepsis/septic shock in 2013. We collected patient demographic characteristics, infectious focus, antibiotic prescribed from emergencies and subsequent changes. It was considered concordant if there were no changes, if there were changes, but the initial antibiotic was right and suspensions for end of treatment. Mortality and evolution were analyzed.
Results. Six hundred patients were included. A 60% experienced changes respect to the antibiotic treatment initiated in emergencies (87.6% justified), with a degree of overall antibiotic concordance of 47.5% The mortality rate at end-point was 9.83%, with no statistically significant relationship with the degree of concordance (OR=0.864 (0.503-1.484)/χ2=0.28; p=0.597). Reasons for change of antibiotic:  clinical outcome (17.96%), change of spectrum (35.03%), de-escalation (41.32%), sequential therapy (8.68%). An 11% required ICU admission. Clinical outcomes: resolution of the disease (79.2%), readmission after 30 days (7.7%) and transfer to health centers (4.5%). The median hospital stay was 7 days.
Conclusions. The degree of concordance antibiotic was quite high, and the mortality rate was lower than that described in the literature, without relating to the discordance. The presence of concordance was associated with fewer readmissions and ICU admissions. The main reasons for disagreement were inadequate spectrum selection and change after microbiological crops.

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