Wine yeast selection in the Iberian Peninsula: Saccharomyces and non-Saccharomyces as drivers of innovation in Spanish and Portuguese wine industries.

Yeast selection for the wine industry in Spain started in 1950 for the understanding of the microbial ecology, and for the selection of optimal strains to improve the performance of alcoholic fermentation and the overall wine quality. This process has been strongly developed over the last 30 years, firstly on Saccharomyces cerevisiae, and, lately, with intense activity on non-Saccharomyces. Several thousand yeast strains have been isolated, identified and tested to select those with better performance and/or specific technological properties. The present review proposes a global survey of this massive ex-situ preservation of eukaryotic microorganisms, a reservoir of biotechnological solutions for the wine sector, overviewing relevant screenings that led to the selection of strains from 12 genera and 22 species of oenological significance. In the first part, the attention goes to the selection programmes related to relevant wine-producing areas (i.e. Douro, Extremadura, Galicia, La Mancha and Uclés, Ribera del Duero, Rioja, Sherry area, and Valencia). In the second part, the focus shifted on specific non-Saccharomyces genera/species selected from different Spanish and Portuguese regions, exploited to enhance particular attributes of the wines. A fil rouge of the dissertation is the design of tailored biotechnological solutions for wines typical of given geographic areas.

Mecanismos de resistencia en bacterias gramnegativas / Resistance mechanisms in Gram-negative bacteria

Los Enterobacterales resistentes a carbapenémicos o productores de betalactamasas de espectro extendido (BLEE) y los no fermentadores resistentes a carbapenémicos presentan resistencia a muchos de los antimicrobianos comúnmente empleados en la práctica clínica, y han sido reconocidos por la Organización Mundial de la Salud como una prioridad crítica para el desarrollo de nuevos antimicrobianos. En esta revisión se abordarán los principales mecanismos de resistencia de los Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii y Stenotrophomonas maltophilia a betalactámicos, quinolonas, aminoglucósidos y polimixinas. Se presentará información actualizada sobre la importancia en la resistencia de mecanismos de modificación de antimicrobianos (incluyendo betalactamasas de claseC de espectro extendido, carbapenemasas y enzimas modificadoras de aminoglucósidos), alteraciones de la permeabilidad por trastornos en la expresión de porinas o del lipopolisacárido, producción de bombas de expulsión activa, alteraciones de la diana o protección de la misma y expresión de sistemas de doble componente (AU)

Enterobacterales resistant to carbapenems or producing extended-spectrum β-lactamases (ESBL) and non-fermenters resistant to carbapenems present resistance to many of the antimicrobials commonly used in clinical practice, and have been recognized by the World Health Organization as a critical priority for the development of new antimicrobials. In this review, the main mechanisms of resistance of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia to β-lactams, quinolones, aminoglycosides and polymyxins will be addressed. Updated information will be presented on the importance in resistance of antimicrobial modification mechanisms (including classC or extended-spectrum β-lactamases, carbapenemases and aminoglycoside-modifying enzymes), permeability alterations due to porin or lipopolysaccharide expression disorders, production of active efflux pumps, target alterations or protection, and expression of two-component systems (AU)

Resistance mechanisms in Gram-negative bacteria.

Enterobacterales resistant to carbapenems or producing extended-spectrum ß-lactamases (ESBL) and non-fermenters resistant to carbapenems present resistance to many of the antimicrobials commonly used in clinical practice, and have been recognized by the World Health Organization as a critical priority for the development of new antimicrobials. In this review, the main mechanisms of resistance of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia to ß-lactams, quinolones, aminoglycosides and polymyxins will be addressed. Updated information will be presented on the importance in resistance of antimicrobial modification mechanisms (including class C or extended-spectrum ß-lactamases, carbapenemases and aminoglycoside-modifying enzymes), permeability alterations due to porin or lipopolysaccharide expression disorders, production of active efflux pumps, target alterations or protection, and expression of two-component systems.

In vitro study of synergy of ampicillin with ceftriaxone against Listeria monocytogenes.

OBJECTIVE: To evaluate if the in vitro activity of ampicillin increases when combined with ceftriaxone. METHODS: The activity of ampicillin and ceftriaxone was evaluated against six Listeria monocytogenes invasive clinical isolates. Ampicillin and ceftriaxone MICs were determined by the broth microdilution method. Synergy was evaluated by checkerboard and time-kill curves methods. RESULTS: All six L. monocytogenes strains were susceptible to ampicillin (MICs 0.25-0.5 mg/L). A bacteriostatic synergy was demonstrated by the FIC index of 0.5 and a 2.5 log10 CFU reduction on the six strains studied for MIC ampicillin plus 16 mg/L ceftriaxone concentrations. CONCLUSIONS: The association of ceftriaxone with ampicillin increases the in vitro activity of ampicillin, and therefore could be a valuable option in the treatment of invasive infection by L. monocytogenes.

Application of BioFire FilmArray Blood Culture Identification panel for rapid identification of the causative agents of ventilator-associated pneumonia.

OBJECTIVE: To evaluate the ability of the BioFire FilmArray Blood Culture Identification (BCID) panel to rapidly detect pathogens producing late-onset ventilator-associated pneumonia (VAP), a severe infection often produced by Gram-negative bacteria. These microorganisms are frequently multidrug resistant and typically require broad-spectrum empiric treatment. METHODS: In the context of an international multicentre clinical trial (MagicBullet), respiratory samples were collected at the time of suspicion of VAP from 165 patients in 32 participating hospitals in Spain, Greece and Italy. Microorganisms were identified using the BCID panel and compared with results obtained by conventional microbiologic techniques. RESULTS: Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae were the most commonly identified species, representing 54.7% (70/128) of microorganisms. The BCID panel showed high global specificity (98.1%; 95% confidence interval, 96-100) and negative predictive values (96.6%) and a global sensitivity and positive predictive value of 78.6% (95% confidence interval, 70-88) and 87.3%, respectively, for these microorganisms. Importantly, the BCID panel provided results in only 1 hour directly from respiratory samples with minimal sample processing times. CONCLUSIONS: The BCID panel may have clinical utility in rapidly ruling out microorganisms causing VAP, specifically multidrug-resistant Gram-negative species. This could facilitate the optimization of empiric treatment.

Endocarditis caused by anaerobic bacteria.

BACKGROUND: Infective endocarditis (IE) caused by anaerobic bacteria is a rare and poorly characterized disease. Most data reported in the literature are from case reports [1-3]. Therefore, we assessed the situation of anaerobic IE (AIE) in Spain using the database of the Spanish Collaboration on Endocarditis (GAMES). METHODS: We performed a prospective study from 2008 to 2016 in 26 Spanish centers. We included 2491 consecutive cases of definite IE (Duke criteria). RESULTS: Anaerobic bacteria caused 22 cases (0.9%) of definite IE. Median age was 66 years (IQR, 56-73), and 19 (86.4%) patients were men. Most patients (14 [63.6%]) had prosthetic valve IE and all episodes were left-sided: aortic valves, 12 (54.5%); and mitral valves, 8 (36.4%). The most common pathogens were Propionibacterium acnes (14 [63.6%]), Lactobacillus spp (3 [13.63%]), and Clostridium spp. (2 [9.0%]), and the infection was mainly odontogenic. Fifteen of the 22 patients (68.2%) underwent cardiac surgery. Mortality was 18.2% during admission and 5.5% after 1 year of follow-up. When patients with AIE were compared with the rest of the cohort, we found that although those with AIE had a similar age and Charlson comorbidity index, they were more likely to have community-acquired IE (86.4% vs. 60.9%, p = 0.01), have undergone cardiac surgery (68.2% vs 48.7% p = 0.06), and have had lower mortality rates during admission (18.2% vs. 27.3%). CONCLUSION: IE due to anaerobic bacteria is an uncommon disease that affects mainly prosthetic valves and frequently requires surgery. Otherwise, there are no major differences between AIE and IE caused by other microorganisms.

Characterization of polymeric pigments and pyranoanthocyanins formed in microfermentations of non-Saccharomyces yeasts.

AIMS: To assess the influence of non-Saccharomyces yeasts on the pyranoanthocyanins and polymeric pigments formation after the addition of (+)-catechin and procyanidin B2 to fresh red grape must. METHODS AND RESULTS: The fermentation of red grape musts was done with non-Saccharomyces yeasts either alone or in sequential fermentations with the Saccharomyces cerevisiae species. The characterization of both pyranoanthocyanin and polymeric pigments has been carried out with liquid chromatography coupled to mass spectroscopy (HPLC-DAD-ESI/MS). Red wines were also characterized by infrared spectroscopy (FTIR), gas chromatography (GC-FID) and spectrophotometry (UV-Vis). It has been observed that fermentation with the species Schizosaccharomyces pombe led to higher concentrations of pigments of all types: anthocyanins, polymeric pigments and pyranoanthocyanins, particularly vitisin A. CONCLUSIONS: The use of non-Saccharomyces yeasts improve the formation of stable pigments in red wines thanks to the differences in the microbial metabolism from among the yeasts studied. SIGNIFICANCE AND IMPACT OF THE STUDY: Colour stability as one of the main organoleptic properties in red wines, may be improved by the controlled use of selected non-Saccharomyces yeasts during red must fermentation.

Use of Schizosaccharomyces strains for wine fermentation-Effect on the wine composition and food safety.

Schizosaccharomyces was initially considered as a spoilage yeast because of the production of undesirable metabolites such as acetic acid, hydrogen sulfide, or acetaldehyde, but it currently seems to be of great value in enology.o ced Nevertheless, Schizosaccharomyces can reduce all of the malic acid in must, leading to malolactic fermentation. Malolactic fermentation is a highly complicated process in enology and leads to a higher concentration of biogenic amines, so the use of Schizosaccharomyces pombe can be an excellent tool for assuring wine safety. Schizosaccharomyces also has much more potential than only reducing the malic acid content, such as increasing the level of pyruvic acid and thus the vinylphenolic pyranoanthocyanin content. Until now, few commercial strains have been available and little research on the selection of appropriate yeast strains with such potential has been conducted. In this study, selected and wild Sc. pombe strains were used along with a Saccharomyces cerevisiae strain to ferment red grape must. The results showed significant differences in several parameters including non-volatile and volatile compounds, anthocyanins, biogenic amines and sensory parameters.

Factors associated with severity in invasive community-acquired Staphylococcus aureus infections in children: a prospective European multicentre study.

Staphylococcus aureus is the main pathogen responsible for bone and joint infections worldwide and is also capable of causing pneumonia and other invasive severe diseases. Panton-Valentine leukocidin (PVL) and methicillin-resistant S. aureus (MRSA) have been studied as factors related with severity in these infections. The aims of this study were to describe invasive community-acquired S. aureus (CA-SA) infections and to analyse factors related to severity of disease. Paediatric patients (aged 0-16 years) who had a CA-SA invasive infection were prospectively recruited from 13 centres in 7 European countries. Demographic, clinical and microbiological data were collected. Severe infection was defined as invasive infection leading to death or admission to intensive care due to haemodynamic instability or respiratory failure. A total of 152 children (88 boys) were included. The median age was 7.2 years (interquartile range, 1.3-11.9). Twenty-six (17%) of the 152 patients had a severe infection, including 3 deaths (2%). Prevalence of PVL-positive CA-SA infections was 18.6%, and 7.8% of the isolates were MRSA. The multivariate analysis identified pneumonia (adjusted odds ratio (aOR) 13.39 (95% confidence interval (CI) 4.11-43.56); p 0.008), leukopenia at admission (<3000/mm(3)) (aOR 18.3 (95% CI 1.3-259.9); p 0.03) and PVL-positive infections (aOR 4.69 (95% CI 1.39-15.81); p 0.01) as the only factors independently associated with severe outcome. There were no differences in MRSA prevalence between severe and nonsevere cases (aOR 4.30 (95% CI 0.68- 28.95); p 0.13). Our results show that in European children, PVL is associated with more severe infections, regardless of methicillin resistance.

Selection of appropriate Schizosaccharomyces strains for winemaking.

This paper describes the selection of Schizosaccharomyces yeasts with adequate oenological suitability and high capacity for the degradation of malic acid. Despite the almost non-existent number of commercial strains, the use of this yeast genus has recently been recommended by the International Organisation of Vine and Wine (OIV, in French). Thus, in the present study, a large number of Schizosaccharomyces strains were isolated using a selective differential medium. Initially, classic parameters of oenological interest for the use of fermentative strains of Saccharomyces cerevisiae (the most frequently used type of yeast) were assessed. Only five strains of moderate acetic acid production lower than 0.4 g/L were obtained at the end of fermentation. Other, more specific features of this yeast genus' physiology were also studied, including urease activity and the production of pyruvic acid and glycerol. Finally, oenological suitability was determined by comparing selected strains with other Schizosaccharomyces reference and S cerevisiae control strains. Schizosaccharomyces strains produced 80% less urea content, four times higher pyruvic acid levels and 1 g higher glycerol contents than the Saccharomyces reference strains. The results confirmed that it is possible to perform selective processes on microorganisms from the genus Schizosaccharomyces using methodology developed in this work to obtain strains of industrial interest.

Catheter-related Mycobacterium fortuitum bloodstream infection: rapid identification using MALDI-TOF mass spectrometry.

We present the case of a 6-year-old boy diagnosed with stage III mediastinal Non Hodgkin Lymphoblastic T cell Lymphoma who suffered from catheter-related bloodstream infection (CRBI) due to Mycobacterium fortuitum whilst receiving chemotherapy. Isolation of this rare pathogen was done directly from blood culture and identification was made rapidly within 48 h using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectro-metry as well as specific polymerase chain reaction (PCR)-reverse hybridization method. This allowed prompt directed antibiotic therapy apart from central venous catheter removal and resulted in an excellent clinical response. This case highlights the potential benefit of using MALDI-TOF mass spectrometry, a fast, cost-effective and precise methodology, in the diagnosis and subsequent management of invasive bacterial infection.

Global impact of an educational antimicrobial stewardship programme on prescribing practice in a tertiary hospital centre.

The misuse of antibiotics has been related to increased morbidity, mortality and bacterial resistance. The development of antimicrobial stewardship programmes (ASPs) has been encouraged by scientific societies as an essential measure. An educational, institutionally supported ASP was developed in our tertiary-care centre. Local guidelines on the management of infectious syndromes were created. Antimicrobial prescriptions were chosen arbitrarily weekly and counselling interviews by expert clinicians were carried out, using a paedagogic, non-restrictive methodology. Satisfaction with the interview was assessed using anonymous questionnaires. The appropriateness of antimicrobial prescriptions as well as consumption was assessed prospectively throughout the year. Feedback regarding the correct use of treatments was communicated to each participating department periodically. The improvement in antimicrobial prescription was included among the annual objectives linked to economic incentives in every department. A total of 1206 counselling interviews were carried out during the first year. Fifty-three per cent of antimicrobial prescriptions (176/332) were inappropriate when the programme started. The rate of inappropriate prescriptions continuously declined to 26.4% (107/405) in the fourth trimester (p <0.001; RR = 0.38; 95% CI, 0.23-0.43). Antimicrobial consumption decreased from 1150 defined daily doses (DDDs) per 1000 occupied bed-days in the first trimester to 852 DDDs in the fourth, reflecting a reduction in antimicrobial expenditures of 42%. A total of 352 satisfaction questionnaires were received and 98% described the advice as positive. In conclusion, the implementation of an education-based ASP achieved a significant improvement in all antimicrobial prescriptions in the centre and a reduction in antimicrobial consumption, even when no restrictive measures were implemented. The programme was highly accepted by all prescribers.

Chryseobacterium indologenes central nervous system infection in infancy: an emergent pathogen?

The isolation of Chryseobacterium indologenes as a causative micro-organism in human diseases is rare. Risk factors for infections caused by this pathogen include very young and very old age, indwelling devices, immune suppression and recent use of broad-spectrum antibiotics. Most cases suffer from bacteraemia or nosocomial pneumonia, whilst infection of the central nervous system (CNS) is extremely rare. We present a term-born infant diagnosed prenatally with holoprosencephaly and obstructive hydrocephalus, requiring post-natal ventriculoperitoneal shunt insertion. At 6 weeks of age, he suffered from Escherichia coli meningitis, showing satisfactory clinical response with antimicrobial therapy. Aged 11 months, he suffered from hyper-drainage syndrome, resulting in the removal of the shunt system. He represented 11 days post-operatively, with low-grade fever, irritability and cerebrospinal fluid (CSF) leakage. C. indologenes from CSF was isolated and antimicrobial therapy with ceftazidime and trimethoprim-sulfamethoxazole for 3 weeks resulted in good clinical response. This is the first documented community-acquired CNS infection due to C. indologenes in an infant without concomitant indwelling device or previous antibiotic pressure.

Effect of Saccharomyces strains on the quality of red wines aged on lees.

Ageing on lees involves ageing the wine in contact with yeast cells after fermentation. If combined with the addition of oak chips, it can soften the wood flavour and increase the aromatic complexity of wine. The aim of the present work is to optimise both ageing techniques through selection of an adequate Saccharomyces cerevisiae strain. The study lasted 6 months and content of polysaccharides, anthocyanins, proanthocyanidins, volatile compounds, colour parameters and sensory analysis, were periodically evaluated. Among the strains tested, G37 showed the highest release of polysaccharides (24.4±5.5 mg l(-1)). Vanillin, syringaldehyde and furfuryl alcohol increased with ageing time in 7VA2 treatment. The wine aged with CTPL14 strain presented fewer monomeric and oligomeric proanthocyanidins (12.4±0.6 and 83.4±8.3 mg l(-1), respectively), and showed the lowest astringency and bitterness sensations. Results show an improvement in the sensory profile of the red wine aged with a combination of these two techniques.

Predictive factors for early mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: A high proportion of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia die within a few days of the onset of infection. However, predictive factors for early mortality (EM) have barely been examined. The aim of this study was to determine the predictive factors for EM in patients with MRSA bacteraemia. METHODS: All episodes of MRSA bacteraemia were prospectively followed in 21 Spanish hospitals from June 2008 to December 2009. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed in a central laboratory. Mortality was defined as death from any cause occurring in the 30 days after the onset of MRSA bacteraemia. EM was defined as patients who died within the first 2 days, and late mortality (LM) for patients who died after this period. Multivariate analyses were performed by using logistic regression models. RESULTS: A total of 579 episodes were recorded. Mortality was observed in 179 patients (31%): it was early in 49 (8.5%) patients and late in 130 (22.5%). Independent risk factors for EM were [OR (95% CI)] initial Pitt score >3 [3.99 (1.72-3.24)], previous rapid fatal disease [3.67 (1.32-10.24)], source of infection lower respiratory tract or unknown [3.76 (1.31-10.83) and 2.83 (1.11-7.21)], non-nosocomial acquisition [2.59 (1.16-5.77)] and inappropriate initial antibiotic therapy [3.59 (1.63-7.89)]. When predictive factors for EM and LM were compared, inappropriate initial antibiotic therapy was the only distinctive predictor of EM, while endocarditis and lower respiratory tract sources both predicted LM. CONCLUSIONS: In our large cohort of patients several factors were related to EM, but the only distinctive predictor of EM was inappropriate initial antibiotic therapy.

Reduction of 4-ethylphenol production in red wines using HCDC+ yeasts and cinnamyl esterases.

Hydroxycinnamate decarboxylase (HCDC) activity has been evaluated in several commercial yeast strains. The combined effect of using cinnamyl esterases (CE) and HCDC+ Saccharomyces cerevisiae strains has been studied in the formation of vinylphenolic pyranoanthocyanins (VPAs) during fermentation, analysing the kind and concentration of pigments formed according to the yeast strain used. Wines fermented with yeasts HCDC+ were contaminated with Dekkera bruxellensis and afterwards analysed to evaluate the formation of ethylphenols (EPs). The musts treated with CE and later fermented with HCDC+ yeast strains showed lower contents of 4-ethylphenol than those fermented with HCDC- strains. This reduction in the EP content is due to the transformation of hydroxycinnamic acids in stable VPAs pigments. The associated use of CEs and HCDC+ Saccharomyces strains is a natural strategy to reduce the formation of EPs in wines contaminated by Dekkera/Brettanomyces.

Mortality and hospital stay related to coagulase-negative Staphylococci bacteremia in non-critical patients.

OBJECTIVES: To describe the morbidity and mortality related to coagulase-negative Staphylococci (CNS) bacteremia in non-critical patients. METHODS: Prospective, matched case-control study nested in a cohort. Patients with CNS bacteremia and no other isolate in blood cultures during their admission were defined as cases. Each case was matched by age, sex and area of hospitalization to one control. A 30-day follow-up was performed. Mortality and hospital stay were defined as endpoints. RESULTS: 105 cases and 105 controls were included. All cases carried intravascular catheters at the time of inclusion. Cases presented higher mortality compared to controls (14.3% vs. 4.8%), although this association was not independent in a multivariate analysis (p = 0.11). CNS bacteremia was independently associated with longer hospital stay (mean 12 vs. 8.5 days, p = 0.008). Moreover, when patients with CNS bacteremia were specifically analyzed, the persistence of fever (p = 0.005) and inappropriate empirical treatment (p = 0.04) were independently related to mortality. CONCLUSION: We did not observe increased mortality attributable to CNS bacteremia, although it was associated with longer hospitalizations. Early appropriate empirical antibiotic therapy pending blood culture results might improve the outcome of patients with CNS bacteremia. Close follow-up is recommended if fever persists beyond 72 h.

Formation of pyranoanthocyanins by Schizosaccharomyces pombe during the fermentation of red must.

Schizosaccharomyces pombe is a non-Saccharomyces yeast strain that can ferment grape musts with high sugar contents - but it also has other metabolic and physiological properties that render it of great interest to wine biotechnologists. This work compares the production of pyranoanthocyanins by S. pombe, Saccharomyces cerevisiae and Saccharomyces uvarum during fermentation. Total pyranoanthocyanins ranged from 11.9 to 19.4 mg/l depending on the strain of S. pombe used. On average, S. pombe produced more pyruvic acid than did either Saccharomyces species; as a consequence it also formed more vitisin A-type pigments. S. pombe 938 produced the largest quantity of vitisin A (11.03±0.82 mg/l). The formation of large amounts of pyranoanthocyanins intensifies the post-fermentation colour of wines somewhat, a phenomenon that helps them maintain their colour over ageing as the natural grape anthocyanins become degraded. Some of the S. pombe strains showed hydroxycinnamate decarboxylase activity, which favours the formation of vinylphenolic pyranoanthocyanins. Fermentation with S. pombe therefore provides an interesting way of increasing the overall pyranoanthocyanin content of red wines, and of stabilising their colour during ageing.

Clinical and molecular epidemiology of meticillin-resistant Staphylococcus aureus causing bacteraemia in Southern Spain.

BACKGROUND: Some molecular features of meticillin-resistant Staphylococcus aureus (MRSA) isolates causing invasive infections have been shown to have clinical implications. There is a need to monitor the situation using a combination of molecular and clinical data because, although MRSA clones tend to predominate over wide geographical areas, clonal shifts may take place. AIM: To study the epidemiological features and perform molecular characterization of a retrospective cohort of 98 cases of nosocomial and healthcare-associated MRSA bacteraemia in 10 hospitals in Andalusia, Spain. METHODS: Relatedness of isolates was investigated using pulsed-field gel electrophoresis (PFGE), S. aureus protein A (spa) typing and clonal complex (CC) assignment. Staphylococcal chromosomal cassette mec (SCCmec) type and accessory gene regulator (agr) group were studied by polymerase chain reaction. agr function was assessed. RESULTS: Most isolates were CC5, SCCmec type IV and agr group II. The most common spa type was t067. Six major clusters were identified by PFGE. Six small clusters of epidemiologically related cases sharing isolates from the same PFGE subtype were identified. Five percent of isolates had a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL on broth microdilution, although 44% had an MIC >1 µg/mL on E-test. Variables independently associated with MIC >1 mg/L on E-test were surgery during present admission and Charlson index ≥2. CONCLUSION: A specific CC that has been predominant in Spain over the last decade caused most of the cases in this study. PFGE was more discriminatory than spa typing in showing clusters of epidemiologically related cases. Some patient features were associated with vancomycin MIC >1 mg/L on E-test.

Efficacy of daptomycin versus vancomycin in an experimental model of foreign-body and systemic infection caused by biofilm producers and methicillin-resistant Staphylococcus epidermidis.

Staphylococcus epidermidis is a frequent cause of device-associated infections. In this study, we compared the efficacy of daptomycin versus vancomycin against biofilm-producing methicillin-resistant S. epidermidis (MRSE) strains in a murine model of foreign-body and systemic infection. Two bacteremic biofilm-producing MRSE strains were used (SE284 and SE385). The MIC of daptomycin was 1 mg/liter for both strains, and the MICs of vancomycin were 4 and 2 mg/liter for SE284 and for SE385, respectively. The in vitro bactericidal activities of daptomycin and vancomycin were evaluated by using time-kill curves. The model of foreign-body and systemic infection of neutropenic female C57BL/6 mice was used to ascertain in vivo efficacy. Animals were randomly allocated into three groups (n = 15): without treatment (controls) or treated with daptomycin at 50 mg/kg/day or vancomycin at 440 mg/kg/day. In vitro, daptomycin showed concentration-dependent bactericidal activity, while vancomycin presented time-dependent activity. In the experimental in vivo model, daptomycin and vancomycin decreased liver and catheter bacterial concentrations (P < 0.05) and increased the survival and the number of sterile blood cultures (P < 0.05) using both strains. Daptomycin produced a reduction in the bacterial liver concentration higher than 2.5 log(10) CFU/g compared to vancomycin using both strains, with this difference being significant (P < 0.05) for infection with SE385. For the catheter bacterial concentrations, daptomycin reduced the concentration of SE284 3.0 log(10) CFU/ml more than did vancomycin (P < 0.05). Daptomycin is more effective than vancomycin for the treatment of experimental foreign-body and systemic infections by biofilm-producing methicillin-resistant S. epidermidis.