[Show abstract][Hide abstract] ABSTRACT: The new cobas® Cdiff and cobas® MRSA/SA tests were compared with conventional methods for the rapid detection of toxigenic Clostridium difficile and methicillin-resistant Staphylococcus aureus. The concordance between cobas Cdiff Test and GDH/toxin gene screening was 96.44% and between cobas MRSA/SA Test and chromogenic culture, 83.33%.
[Show abstract][Hide abstract] ABSTRACT: Background:
Most available information on carbapenemase-producing Enterobacteriaceae (CPE) is usually associated with specific types of infection or patient or with descriptions of outbreaks. The aim of this study was to comprehensively analyse the clinical epidemiology, clinical features and outcomes of colonisation and infections due to CPE in Spain.
A multicentre prospective cohort study was carried out in 34 Spanish hospitals from February to May 2013. All new patients testing positive for CPE in clinical samples were included. Logistic regression was used to identify predictors of mortality.
Overall, 245 cases were included. The most frequent organism was Klebsiella pneumoniae (74%) and the carbapenemases belonged to the OXA-48 (74%), metallo-β-lactamase (MBL) (24%) and KPC (2%) groups. Acquisition was nosocomial in 145 cases (60%) and health care-associated (HCA) in 91 (37%); 42% of the latter were nursing home residents, in whom OXA-48-producing K. pneumoniae ST405 predominated. MBLs and OXA-48 predominated in ICU and medical patients, respectively. Overall, 67% of patients had infections. The most frequent infections identified in this study were urinary tract (43%) and skin structure (21%) infections, and 10% of infections were bacteraemic. Crude mortality was 20%. Inappropriate antibiotic therapy was independently associated with an increased risk of death (OR=3.30; 95% CI: 1.34-8.11).
We found some differences in the epidemiology of CPE depending on the type of carbapenemase produced. Although a low proportion of CPE infections were bacteraemic, active antibiotic therapy was a protective factor for reducing mortality.
The Journal of infection 11/2015; DOI:10.1016/j.jinf.2015.10.008 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acinetobacter baumannii
, a worldwide emerging nosocomial pathogen, acquires antimicrobial resistances in response to DNA-damaging agents, which increase the expression of multiple error-prone DNA polymerase components. Here we show that the aminocoumarine novobiocin, which inhibits the DNA damage response in gram-positive bacteria, also inhibits the expression of error-prone DNA polymerases in this gram-negative multidrug-resistant pathogen and, consequently, its potential acquisition of antimicrobial resistance through DNA damage-induced mutagenesis.
Antimicrobial Agents and Chemotherapy 10/2015; DOI:10.1128/AAC.01810-15 · 4.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives The objective of this study was to analyse whether there is an association between reduced susceptibility to biocides in Acinetobacter baumannii and (i) antimicrobial resistance (co-resistance), (ii) prevalent (epidemic) clones, (iii) changes in the fitness or (iv) expression of genes related to efflux pumps and porins.
Methods Susceptibility to biocides and antimicrobials was determined in 49 clonally unrelated isolates of A. baumannii. Biological cost, in terms of mean generation time, was determined by spectrophotometry. Quantitative real-time RT–PCR was used to determine the relative expression of genes encoding several efflux pumps and porins.
Results Reduced susceptibility to chlorhexidine digluconate, benzalkonium chloride and Irgasan® was associated with resistance to aminoglycosides, tetracycline and ciprofloxacin (P < 0.05). The MICs of carbapenems, aminoglycosides, doxycycline and ciprofloxacin for isolate Ab70 (epidemic clone) exposed to these biocides increased by ≥2 dilutions. Reduced susceptibility to Orsan® was more frequent among prevalent clones than non-prevalent clones (P < 0.05). Mean generation times for Ab70 before and after exposure to benzalkonium chloride were 57.8 and 78.1 min, respectively (P = 0.02). Relative expression of abeS and adeB was increased in Ab46 and Ab70 after exposure to chlorhexidine digluconate, but was decreased for ompA and carO after exposure to Irgasan®.
Conclusions Reduced susceptibility to biocides is associated with co-resistance to carbapenems, aminoglycosides, tetracycline and ciprofloxacin. Reduced susceptibility to Orsan® may be a marker of prevalent clones. Acquisition of reduced susceptibility to benzalkonium chloride has a biological cost. Exposure to biocides affects the relative expression of genes related to some efflux pump genes (increased expression) or porins (reduced expression).
Journal of Antimicrobial Chemotherapy 09/2015; · 5.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the draft genome sequence of Acinetobacter baumannii strain MAR002, a biofilm-hyperproducing clinical strain isolated during the study CP/09/0033 (GEIH/REIPI-Ab2010, Spain). The genome of A. baumannii MAR002 has an approximate length of 3,717,929 bp and 3,300 protein-coding sequences, with a C+G content of 39.09%.
[Show abstract][Hide abstract] ABSTRACT: Background: Acinetobacter baumannii is a major health problem. The most common infection caused by A. baumanniiis hospital acquired pneumonia, and the associated mortality rate is approximately 50 %. Neither in vivo nor ex vivo expression profiling has been performed at the proteomic or transcriptomic level for pneumonia caused by A. baumannii.
In this study, we characterized the proteome of A. baumannii under conditions that simulate those found in the airways, to gain some insight into how A. baumannii adapts to the host and to improve knowledge about the pathogenesis and virulence of this bacterium. A clinical strain of A. baumannii was grown under different conditions: in the presence of bronchoalveolar lavage fluid from infected rats, of RAW 264.7 cells to simulate conditions in the respiratory tract and in control conditions. We used iTRAQ labelling and LC-MALDI-TOF/TOF to investigate how A. baumannii responds on exposure to macrophages/BALF.
Results: 179 proteins showed differential expression. In both models, proteins involved in the following proceses were over-expressed: (i) pathogenesis and virulence (OmpA, YjjK); (ii) cell wall/membrane/envelope biogenesis (MurC); (iii) energy production and conversion (acetyl-CoA hydrolase); and (iv) translation (50S ribosomal protein L9). Proteins involved in the following were under-expressed: (i) lipid metabolism (short-chain dehydrogenase); (ii) amibo acid metabolism and transport (aspartate aminotransferase); (iii) unknown function (DNA-binding protein); and (iv) inorganic ion transport and metabolism (hydroperoxidase). Conclusions: We observed alterations in cell wall synthesis and identified 2 upregulated virulence-associated proteins with >15 peptides/protein in both ex vivo models (OmpA and YjjK), suggesting that these proteins are fundamental for pathogenesis and virulence in the airways. This study is the first comprehensive overview of the ex vivo proteome of A. baumannii and is an important step towards identification of diagnostic biomarkers. Novel drug targets and potential vaccine candidates in the fight against pneumonia caused by A. baumannii.
[Show abstract][Hide abstract] ABSTRACT: The spread of multidrug-resistant Enterobacteriaceae related to the production of
extended-spectrum β-lactamases and carbapenemases is a serious public health
problem worldwide. Microbiological diagnosis and therapy of these infections are
challenging and controversial. Clinically relevant questions were selected and
the literature was reviewed for each of them. The information from the selected
articles was extracted and recommendations were provided and graded according to
the strength of the recommendations and quality of the evidence. The document was
opened to comments from the members from the Spanish Society of Infectious
Diseases and Clinical Microbiology, which were considered for inclusion in the
final version. Evidence-based recommendations are provided for the use of
microbiological techniques for the detection of extended-spectrum β-lactamases
and carbapenemases in Enterobacteriaceae, and for antibiotic therapy for
invasive/severe infections caused by these organisms. The absence of randomised
controlled trials is noteworthy; thus, recommendations are mainly based on
observational studies (that have important methodological limitations),
pharmacokinetic and pharmacodynamics models, and data from animal studies.
Additionally, areas for future research were identified.
[Show abstract][Hide abstract] ABSTRACT: The effect of antimicrobials on SOS-mediated mutagenesis induction depends on the bacterial species and the antimicrobial
group. In this work, we studied the effect of different families of antimicrobial agents used in clinical therapy against
Acinetobacter baumannii in the induction of mutagenesis in this multiresistant Gram-negative pathogen. The data showed that ciprofloxacin and tetracycline
induce SOS-mediated mutagenesis, whereas colistin and meropenem, which are extensively used in clinical therapy, do not.
[Show abstract][Hide abstract] ABSTRACT: Detection of carbapenemase-producing Enterobacteriaceae (CPE) is an important task at microbiology laboratories in hospitals. As the prevalence of CPE is increasing worldwide, the implementation of phenotypically based screening as well as confirmatory procedures to detect CPE are important for microbiologists. In addition to detection of carbapenem hydrolysis, the inhibition of activity against a carbapenem in the presence of several inhibitor compounds specific to class A, B, or class C beta-lactamases is a useful method to confirm the presence of carbapenemases in bacterial isolates. There is also a proteomic approach that compares the MALDI-TOF spectrum generated by the intact carbapenem (non-hydrolyzed) with that obtained after hydrolysis of the beta-lactam ring by beta-lactamase to reveal the presence of carbapenemases in bacterial isolates. Proteomic methods will probably be more frequently implemented in laboratories in the near future. Finally, molecular methods to directly or indirectly detect the presence of a carbapenemase genes are increasingly being used in microbiology laboratories. One of the main advantages of these methods is their speed, and also that they can be used directly with the clinical sample without the need for an isolated bacterial colony. Multiplex PCR, real-time PCR, DNA microarrays and pyrosequencing are some examples of molecular-based tests. Their main disadvantage is their cost, although prices are going down as the range of services increases. Surveillance of carriers is also an important task for infection control purposes. In this case, commercially available chromogenic medium supplemented with low carbapenem concentrations has shown an excellent ability to detect CPE. Moreover, molecular methods to detect specific carbapenemase genes directly from rectal swabs, stools, or other colonization sources have had excellent results.
[Show abstract][Hide abstract] ABSTRACT: Antivirulence therapy inhibits bacterial virulence factors,
thus preventing the development of infection without
affecting bacterial growth. The development of new
antibiotics is complicated by the increasing incidence
of antibiotic resistance in pathogenic bacteria. Antivirulence
therapy is a promising alternative to traditional antibiotic
therapy for the treatment of infectious disease,
either alone or in combination with antibiotic treatment.
In this review, we consider patents concerning inhibition
of several bacterial virulence factors: adhesion/colonization,
secretion systems, cellular signalling systems and
antimicrobial resistance mechanisms. Finally, we emphasize
the importance of analyzing new targets and/or
molecules in this field and of considering possible resistance
[Show abstract][Hide abstract] ABSTRACT: The US Centers for Disease Control and Prevention (CDC) recently add the advice of one-time testing of HCV infection in persons born during 1945-1965. Moreover, the US Preventive Services Task Force (USPSTF) newly recommended one-time HIV testing for persons aged 15-65. Herein, we evaluate the potential impact of these recommendations in a reference medical area of Spain.
All assays results entries for HCV and HIV serological markers ordered at a reference lab from primary care and specialized physicians between 2008 and 2012 were recorded in a medical area which covers 501,526 citizens in Northern Spain. The year of birth were also documented.
A total of 108,159 anti-HCV-Ab results were generated during the study period. The global rate of anti-HCV-Ab+ was 7.7% (95% CI: 7.6%-7.9%), being more prevalent in men than women (8.6% vs. 4.5%). By year of birth, the highest prevalence was found in persons born between 1955 and 1970. HCV genotype 1 was the most prevalent (59.7%) followed by genotype 3 (22.7%). Regard HIV infection, among 65,279 anti-HIV results generated the prevalence of anti-HIV+ was 1.1% (95% CI: 1.0%-1.2%), being more frequent in men (2% vs 0.5%). The years of birth with highest rates of HIV infection exactly match with those for HCV infection.
The highest rates of HCV and HIV infections are found between 1960 and 1965. Different historical and social circumstances such as the huge intravenous drug use epidemic in the eighties in Spain, might explain it. Therefore, each country needs to determine its own HCV and HIV seroprevalences by year of birth to establish the proper recommendations for the screening of both infections.
PLoS ONE 12/2014; 9(12):e113062. DOI:10.1371/journal.pone.0113062 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Treatment of multidrug-resistant Acinetobacter baumannii (MDRAB) infection presents a challenge because of the scarcity of available options. Even though combination therapy (CT)
is frequently used in clinical practice, data are needed to support its use instead of monotherapy (MT).