Rev Esp Quimioter 2015:28(Suppl. 1):8-11

Laboratory detection of carbapenemase-producing Enterobacteriaceae     

                        
EMILIA CERCENADO              

Detection of carbapenemase-producing Enterobacteriaceae in the laboratory requires an exhaustive analysis of the antibiogram and susceptibility to all beta-lactams, the implementation with phenotypic methods of screening as well as confirmatory procedures including the detection of the carbapenem hydrolysis, the inhibition of the enzyme activity with several specific inhibitor compounds and by molecular methods.

Rev Esp Quimioter 2015:28(Suppl. 1):8-11 [pdf]

/por

Rev Esp Quimioter 2015:28(5):256-262

Bacteraemia due to extended-spectrum beta-lactamases (ESBL) and other beta-lactamases (ampC and carbapenemase) producing Enterobacteriaceae: association with health-care and cancer)     

                        
MIRIAM GARCÍA-GÓMEZ, LAURA GUÍO, JOSÉ LUIS HERNÁNDEZ, BEGOÑA VILAR, JOSÉ IGNACIO PIJOÁN, JOSÉ MIGUEL MONTEJO              

Introduction. Bloodstream infections due to multire-sistant Enterobacteriaceae are a major matter of concern nowadays. The present study evaluated the impact of these infections in our area.
Methods. Prospective observational study of a cohort of patients with bacteraemia due to extended-spectrum beta-lactamases (ESBL) and other beta-lactamases producing organisms among hospitalized patients in Cruces Hospital for 2 years. We conducted a descriptive analysis, a subgroup analysis (cancer vs. non-cancer patients) and a mortality analysis.
Results. During the study period, 3409 episodes of bacteraemia were diagnosed, of which 124 (3.6%) were ESBL and other beta-lactamases producing Enterobacteriaceae. 40.3% of the cases were nosocomial, 15.3% community acquired and 44.4% were health-care associated. 44.4% of the cohort had cancer as underlying disease. The most commonly isolated organism was E. coli (83% of cases), regardless of the source of infection. 58.1% of patients received inadequate empirical therapy. 7 day-mortality was 10.5% and 30 day-mortality was 21.8%. None of the analyzed variables showed association with 7 and 14 day-mortality, but the presence of solid cancer (p= 0.032) and advanced HIV infection (p = 0.027), were significantly associated with higher 30 day-mortality.
Conclusions. More than half of bacteraemia episodes affected outpatients and most of them were health-care associated episodes. Even though more than half of the patients received inadequate empirical treatment, this was not related to higher mortality. We only found an association between 30 day-mortality and the presence of underlying solid malignancy or advanced HIV infection.

Rev Esp Quimioter 2015:28(5):256-262 [pdf]

/por

Rev Esp Quimioter 2015:28(3):125-131

The late media emergency of smallpox vaccine, news coverage of Spanish press (1999-2004)                                 
 


PEDRO JAVIER MARTÍNEZ-MARTINEZ,  JOSÉ TUELLS, GEMA COLMENAR-JARILLO              

 

Introduction. Discussions on the need for smallpox virus preservation in 1999 focused attention on an eradicated disease 20 years ago. Smallpox was replaced as a potential candidate to be used as a bioterrorist weapon because of the international alarm scenario produced after the 11/9 events in USA. The reactivation of a vaccine which remained forgotten was the direct consequence. The initial target groups were the security forces of America. Spain was also among the countries that were interested in acquiring the smallpox vaccine. The aim of this study is to analyze the considerable media coverage of smallpox obtained in our country.
Methods. Systematic review of published news in the four largest national daily newspapers (ABC, El Mundo, El País and La Vanguardia) for the period 1999-2004 of the Dow Jones Factiva document database. “Smallpox” were used as a key word. From the obtained data, a qualitative and quantitative analysis was done.
Results. 416 reviews were analyzed; the newspaper El Mundo was the most interested in these news (158 citations, 37.98%). Most of the news were published in 2003 (152, 36.5%) The year with more news about smallpox (2003) coincides with the purchase of vaccines in Spain. The type of messages in the news was highly changeable over this six-year period. Those related to “politics and diplomacy”, “epidemiological risk”, “bioterrorism” and “vaccine” were predominant.
Conclusions. The alarm raised around the smallpox vaccination was a media phenomenon due to political strategy issues rather than a real public health problem.

Rev Esp Quimioter 2015:28(3):125-131 [pdf]

/por

Rev Esp Quimioter 2015:28(Suppl. 1):12-15

Therapeutic options for carbapenemase-producing Enterobacteriaceae    

                        
PATRICIA SALGADO, FERNANDO GILSANZ, EMILIO MASEDA              

Carbapenemase-producing Enterobacteriaceae (CPE) has spread worldwide becoming a threat to public health. However, no randomized clinical trials about the efficacy of optimizing antibiotic treatment have been published. Experimental studies have been designed to find combinations of antibiotics with synergistic activity. Their main aim has been increasing the speed of bacterial destruction and decreasing resistance. The latest guidelines recommend combination therapy. The carbapenems has been chosen as the basis of such therapy. We face limited therapeutic options. Polymyxins, fosfomycin and gentamicin have reemerged in this context, becoming the basis of multiple combination regimens, with beneficial effects both in vitro and in murine models of infection.

Rev Esp Quimioter 2015:28(Suppl. 1):12-15 [pdf]

/por

Rev Esp Quimioter 2015:28(5):263-266

Evaluation of antibiotic resistance of Escherichia coli in urinary tract infections in Primary Care Barbastro Sector (Huesca)     

                        
ANA BETRÁN, ANA Mª CORTÉS, CONCEPCIÓN LÓPEZ              

Objectives. Evaluate the resistance of community-uropathogen, Escherichia coli to several antibiotics in our health sector and deduce empirical treatment options.
Methods. E. coli strains isolated from urine cultures of patients from Primary Care Barbastro Sector, between January 2011 and December 2013, were studied. The resistances rates for nine common antibiotics were determined, and differences in sensitivity were analyzed, comparing confidence intervals for proportions by the method of Wilson.
Results. E. coli was the most frequently isolated bacteria (61.08% of positive urine cultures sent from Primary Care). Overall, there has been an increase in resistance of E. coli isolates in all antimicrobials studied. Still, resistance has remained below 4% compared to fosfomycin and nitrofurantoin and below 10% in cephalosporins second and third generation. Resistance to amoxicillin-clavulanate has increased progressively reaching 21.5% in 2013; only this antibiotic has presented a statistically significant increase. The maximum levels of resistance (over 30%) were found in the antibiotics administered orally and often indicated in uncomplicated urinary tract infections: trimethoprim-sulfamethoxazole, ciprofloxacin and ampicillin.
Conclusions. Update knowledge susceptibility patterns of microorganisms most commonly isolated in urine samples in each health area allows to choose the most suitable and effective treatments trough empirical knowledge.

Rev Esp Quimioter 2015:28(5):263-266 [pdf]

/por

Rev Esp Quimioter 2015:28(3):132-138

A practice-based observational study on the use of micafungin in Surgical Critical Care Units                                 
 


EMILIO MASEDA, CARLOS A. GARCÍA-BERNEDO, ISABEL FRÍAS, JOSÉ-ALEJANDRO NAVARRO, JESÚS RICO, REYES IRANZO, JUAN-JOSÉ GRANIZO, MARÍA-JOSÉ VILLAGRÁN, ENRIC SAMSÓ, FERNANDO GILSANZ ON BEHALF OF THE MYCREA STUDY GROUP              

 

Introduction. Echinocandins are first-line therapy in critically ill patients with invasive Candida infection (ICI). This study describes our experience with micafungin at Surgical Critical Care Units (SCCUs).
Methods. A multicenter, observational, retrospective study was performed (12 SCCUs) by reviewing all adult patients receiving 100 mg/24h micafungin for ≥72h during ad-mission (April 2011-July 2013). Patients were divided by ICI category (possible, probable + proven), 24h-SOFA (<7, ≥7) and outcome.
Results. 72 patients were included (29 possible, 13 probable, 30 proven ICI). Forty patients (55.6%) presented SOFA ≥7. Up to 78.0% patients were admitted after urgent surgery (64.3% with SOFA <7 vs. 90.3% with SOFA ≥7, p=0.016), and 84.7% presented septic shock. In 66.7% the site of infection was intraabdominal. Forty-nine isolates were recovered (51.0% C. albicans). Treatment was empirical (59.7%), microbiologically directed (19.4%), rescue therapy (15.3%), or anticipated therapy and prophylaxis (2.8% each). Empirical treatment was more frequent (p<0.001) in possible versus probable + proven ICI (86.2% vs. 41.9%). Treatment (median) was longer (p=0.002) in probable + proven versus possible ICI (13.0 vs. 8.0 days). Favorable response was 86.1%, without differences by group. Age, blood Candida isolation, rescue therapy, final MELD value and %MELD variation were significantly higher in patients with non-favorable response. In the multivariate analysis (R2=0.246, p<0.001) non-favorable response was associated with positive %MELD variations (OR=15.445, 95%CI= 2.529-94.308, p=0.003) and blood Candida isolation (OR=11.409, 95%CI=1.843-70.634, p=0.009).
Conclusion. High favorable response was obtained, with blood Candida isolation associated with non-favorable response, in this series with high percentage of patients with intraabdominal ICI, septic shock and microbiological criteria for ICI.

Rev Esp Quimioter 2015:28(3):132-138 [pdf]

/por

Rev Esp Quimioter 2015:28(Suppl. 1):16-18

Usefulness of PK/PD parameters of antimicrobials in the treatment of complex and extremely-resistant infections     

                        
JUAN PABLO HORCAJADA              

Complex or difficult to treat infections should benefit from antimicrobial PK/PD data in each specific situation. In the case of multidrug resistant gram negative infections the optimized use of colistin needs the using of PK/PD indexes. Likewise, in infections of inaccessible sources, PK/PD concepts play a key role in choosing the best antimicrobial and dosage. An example would be the potential role of linezolid in CNS infections. Among fungal infections, symptomatic candiduria by fluconazole-resistant strains are a therapeutic challenge. In this context micafungin could be a good alternative, again based on PK/PD concepts.

Rev Esp Quimioter 2015:28(Suppl. 1):16-18 [pdf]

/por

Rev Esp Quimioter 2015:28(6):275-281

Liposomal formulations of amphotericin B: differences according to the scientific evidence     

                        
JOSÉ RAMÓN AZANZA, BELÉN SÁDABA, JOANA REIS              

This article presents an overview of the characteristics of liposomes as drug carriers, particularly in relation to liposomal formulations of amphotericin B. General features regarding structure, liposome-cell interactions, stability, encapsulation of active substances and elimination of liposomes are described. Up to the present time extensive efforts to produce similar or bioequivalent products of amphotericin B formulations, in particular in the case of liposomal amphotericin B, have been unsuccessful in spite of having a very similar composition and even an apparently identical manufacturing process. Guidelines for the development of generic liposomal formulations developed by the FDA and EMA are also summarized. Based on the available evidence of the composition of liposomes, any differences in the manufacturing process even if the same lipid composition is used may result in different final products. Therefore, it seems unreasonable to infer that all amphotericin B liposomal formulations are equal in efficacy and safety.

Rev Esp Quimioter 2015;28(6):275-281 [pdf]

/por

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]

/por

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.

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

/por