Development of an Anti-Acinetobacter baumannii Biofilm Phage Cocktail: Genomic Adaptation to the Host.

The need for alternatives to antibiotic therapy due to the emergence of multidrug resistant bacteria (MDR), such as the nosocomial pathogen Acinetobacter baumannii, has led to the recovery of phage therapy. In addition, phages can be combined in cocktails to increase the host range. In this study, the evolutionary mechanism of adaptation was utilized in order to develop a phage adapted to A. baumannii, named phage Ab105-2phiΔCI404ad, from a mutant lytic phage, Ab105-2phiΔCI, previously developed by our group. The whole genome sequence of phage Ab105-2phiΔCI404ad was determined, showing that four genomic rearrangements events occurred in the tail morphogenesis module affecting the ORFs encoding the host receptor binding sites. As a consequence of the genomic rearrangements, 10 ORFs were lost and four new ORFs were obtained, all encoding tail proteins; two inverted regions were also derived from these events. The adaptation process increased the host range of the adapted phage by almost 3-fold. In addition, a depolymerase-expressing phenotype, indicated by formation of a halo, which was not observed in the ancestral phage, was obtained in 81% of the infected strains. A phage cocktail was formed by combining this phage with the A. baumannii phage vB_AbaP_B3, known to express a depolymerase. Both the individual phages and the phage cocktail showed strong antimicrobial activity against 5 clinical strains and 1 reference strain of A. baumannii tested. However, in all cases resistance to the bacterial strains was also observed. The antibiofilm activity of the individual phages and the cocktail was assayed. The phage cocktail displayed strong antibiofilm activity.

Tranexamic acid in cardiac surgery: Are low doses enough?

OBJECTIVES: Tranexamic acid is used to prevent hyperfibrinolysis and reduce postoperative bleeding and blood transfusions in on-pump cardiac surgery. We evaluate the efficacy of low or high dose tranexamic acid in a prospective cohort study conducted in Valencia. MATERIALS AND METHODS: A total of 427 patients were recruited between January 2019 and January 2020, 207 in the Hospital General Universitario (low dose [LD]) and 220 in the Hospital Universitario y Politécnico La Fe (high dose [HD] and intermediate dose [ID]). We recorded the presence of hyperfibrinolysis on rotational thromboelastometry, intra- and postoperative administration of blood products, chest tube output within the first 12 h, and incidence of convulsions. Univariate and multivariate comparisons were performed. Univariate analysis of all categories was performed after propensity score matching between LD and HD and between LD and ID. RESULTS: There were no statistically significant differences in: appearance of hyperfibrinolysis, administration of blood products, postoperative chest tube output within the first 12 h, or occurrence of convulsions. Group LD received less fibrinogen than group HD (P = .014) and ID (P = .040) but more fresh frozen plasma than group ID (P = .0002). CONCLUSIONS: Administration of low-dose tranexamic acid is as effective as higher doses in hyperfibrinolysis prophylaxis and the prevention of postoperative bleeding in cardiac surgery.

Tranexamic acid in cardiac surgery: Are low doses enough? / Ácido tranexámico en cirugía cardíaca: ¿las dosis bajas son suficientes?

OBJECTIVES: Tranexamic acid is used to prevent hyperfibrinolysis and reduce postoperative bleeding and blood transfusions in on-pump cardiac surgery. We evaluate the efficacy of low or high dose tranexamic acid in a prospective cohort study conducted in Valencia. MATERIALS AND METHODS: A total of 427 patients were recruited between January 2019 and January 2020, 207 in the Hospital General Universitario (low dose [LD]) and 220 in the Hospital Universitario y Politécnico La Fe (high dose [HD] and intermediate dose [ID]). We recorded the presence of hyperfibrinolysis on rotational thromboelastometry, intra- and postoperative administration of blood products, chest tube output within the first 12h, and incidence of convulsions. Univariate and multivariate comparisons were performed. Univariate analysis of all categories was performed after propensity score matching between LD and HD and between LD and ID. RESULTS: There were no statistically significant differences in: appearance of hyperfibrinolysis, administration of blood products, postoperative chest tube output within the first 12h, or occurrence of convulsions. Group LD received less fibrinogen than group HD (P=.014) and ID (P=.040) but more fresh frozen plasma than group ID (P=.0002). CONCLUSIONS: Administration of low-dose tranexamic acid is as effective as higher doses in hyperfibrinolysis prophylaxis and the prevention of postoperative bleeding in cardiac surgery.

Efficacy of dual carbapenem treatment in a murine sepsis model of infection due to carbapenemase-producing Acinetobacter baumannii.

OBJECTIVES: To evaluate the in vivo efficacy of a dual carbapenem combination containing imipenem plus meropenem against carbapenem-resistant Acinetobacter baumannii producing carbapenemases OXA-23 or OXA-58. METHODS: An experimental model of peritonitis using C57BL/6J female mice was developed and the minimum lethal doses were calculated for infections due to OXA-23 or OXA-58 producers of A. baumannii clinical isolates. The efficacies of the carbapenems in monotherapy and in combination were tested. RESULTS: Meropenem was better than imipenem in mice infected with either of the carbapenem-resistant A. baumannii (CRAb) strains. The combination of meropenem plus imipenem significantly improved the clearance of CRAbs from spleen compared with non-treated groups. The carbapenem-containing combination was better than imipenem for treating mice infected with both carbapenemase producers. In blood, the carbapenem combination significantly decreased the bacterial load of the OXA-23 producers compared with imipenem or meropenem used in monotherapy. CONCLUSIONS: These results suggest that dual carbapenem combination could be an option for the treatment of infections due to carbapenemase-producing A. baumannii such as OXA-23 and OXA-58 producers.

Measuring the sustainability of a natural system by using multi-criteria distance function methods: Some critical issues.

There is an important body of literature using multi-criteria distance function methods for the aggregation of a battery of sustainability indicators in order to obtain a composite index. This index is considered to be a proxy of the sustainability goodness of a natural system. Although this approach has been profusely used in the literature, it is not exempt from difficulties and potential pitfalls. Thus, in this paper, a significant number of critical issues have been identified showing different procedures capable of avoiding, or at least of mitigating, the inherent potential pitfalls associated with each one. The recommendations made in the paper could increase the theoretical soundness of the multi-criteria distance function methods when this type of approach is applied in the sustainability field, thus increasing the accuracy and realism of the sustainability measurements obtained.

Genomic Evolution of Two Acinetobacter baumannii Clinical Strains from ST-2 Clones Isolated in 2000 and 2010 (ST-2_clon_2000 and ST-2_clon_2010).

Acinetobacter baumannii is a successful nosocomial pathogen due to its ability to persist in hospital environments by acquiring mobile elements such as transposons, plasmids, and phages. In this study, we compared two genomes of A. baumannii clinical strains isolated in 2000 (ST-2_clon_2000) and 2010 (ST-2_clon_2010) from GenBank project PRJNA308422.

Ranking of industrial forest plantations in terms of sustainability: A multicriteria approach.

As forest managers and owners must have precise assessments of sustainability, in this study we have proposed a methodology based on multi-criteria techniques for assessing sustainability in industrial forest plantations and establishing a ranking of these plantations in terms of sustainability. First, we identified and have briefly described a set of sustainability indicators (economic, environmental and social). Next, we developed a statistical procedure to determine if a linear relationship existed between the indicators. With this analysis, the final set of indicators was defined and normalized. Then, we formulated four goal programming models, by which to aggregate the different indicators. In these models, we introduced the preferences of the decision makers for each indicator, using a survey with questions formulated in a pairwise comparison format. The procedure was applied to 30 Eucalyptus globulus Labill. plantations in northwestern Spain and 11 indicators were selected in order to define the sustainability. The results showed several rankings under each goal programming model. Although the results may not be the same in the different models, some plantations are always the most sustainable, while others are always the worst in terms of sustainability. The combination of initial values of indicators, goal programming models and preferences of stakeholders (preferential weights and targets) influence the results, and it cannot be predicted a priori which plantation is the best/worst in terms of sustainability. In our case study, we show how changes in preferential weights and targets substantially modify the results obtained.

Efficacy of Lysophosphatidylcholine in Combination with Antimicrobial Agents against Acinetobacter baumannii in Experimental Murine Peritoneal Sepsis and Pneumonia Models.

Immune response stimulation to prevent infection progression may be an adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC) is an immunomodulator involved in immune cell recruitment and activation. In this study, we aimed to evaluate the efficacy of LPC in combination with colistin, tigecycline, or imipenem in experimental murine models of peritoneal sepsis and pneumonia. We used Acinetobacter baumannii strain Ab9, which is susceptible to colistin, tigecycline, and imipenem, and multidrug-resistant strain Ab186, which is susceptible to colistin and resistant to tigecycline and imipenem. Pharmacokinetic and pharmacodynamic parameters for colistin, tigecycline, and imipenem and the 100% minimal lethal dose (MLD100) were determined for both strains. The therapeutic efficacies of LPC, colistin (60 mg/kg of body weight/day), tigecycline (10 mg/kg/day), and imipenem (180 mg/kg/day), alone or in combination, were assessed against Ab9 and Ab186 at the MLD100 in murine peritoneal sepsis and pneumonia models. The levels of pro- and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA) for the same experimental models after inoculating mice with the MLD of both strains. LPC in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance of Ab9 and Ab186 from the spleen and lungs and reduced bacteremia and mouse mortality rates (P < 0.05) compared with those for colistin, tigecycline, and imipenem monotherapies. Moreover, at 4 h post-bacterial infection, Ab9 induced higher TNF-α and lower IL-10 levels than those with Ab186 (4 µg/ml versus 3 µg/ml [P < 0.05] and 2 µg/ml versus 3.4 µg/ml [P < 0.05], respectively). LPC treatment combined with colistin, tigecycline, or imipenem modestly reduced the severity of infection by A. baumannii strains with different resistance phenotypes compared to LPC monotherapy in both experimental models.

Efecto del ejercicio físico para el control de los factores de riesgo cardiovascular modificables del adulto mayor: revisión sistemática / Effects of physical exercise on cardiovascular risk factors of elderly people: systematic review

Objetivo. Determinar el efecto del ejercicio físico para el control de los factores de riesgo cardiovascular modificables en el adulto mayor. Materiales y métodos. Se desarrolló una búsqueda en las bases de datos PubMed, ScienceDirect, EBSCO, Annual Reviews, Medline, además de en las de organizaciones como el Colegio Americano de Medicina del Deporte (ACSM) durante el periodo 2008-2014. Resultados. Se analizaron 47 estudios. La mayoría de los estudios proponen intensidades moderadas y vigorosas de ejercicio físico, con una frecuencia de 2 a 5 días por semana y una duración por sesión de 150-300 min con el objetivo de modificar positivamente los factores de riesgo cardiovascular. Conclusión. Los programas de ejercicios aeróbicos y anaeróbicos informan sobre cambios significativos para el control de factores de riesgo cardiovascular que merecen ser incorporados en los nuevos modelos de programación con adultos mayores (AU)

Objective. To perform a systematic review analysing the relationship between physical activity and modifiable cardiovascular risk factors in elderly people. Materials and methods. We conducted a search of PubMed, ScienceDirect, EBSCO, Annual Reviews, and Medline, as well as organisations such as the American College of Sport and Medicine, to include all studies published on the topic from 2008 to 2014. Results. Forty-seven studies were analysed. Most studies proposed protocols for moderate to vigorous intensity exercise, with a frequency of between 2 and 5 times per week and a duration per session of 150 to 300 min, to achieve positive changes on modifiable cardiovascular risk factors. Conclusion. Both anaerobic and aerobic exercise have significant benefits on control of cardiovascular risk factors and should be included in physical activity programmes for elderly people (AU)

Monotherapy versus combination therapy for sepsis due to multidrug-resistant Acinetobacter baumannii: analysis of a multicentre prospective cohort.

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). METHODS: A prospective observational study was conducted in 28 Spanish hospitals. Patients with sepsis caused by MDRAB, defined according to strict criteria, and who received active antibiotic treatment (according to in vitro susceptibility testing) for at least 48 h, were included. The main outcome variable was all-cause 30 day mortality after initiation of targeted therapy. Multivariate analysis, including a propensity score (for receiving CT), was performed by Cox regression. RESULTS: One hundred and one patients were included in the analysis; 68 (67.3%) received MT and 33 (32.7%) received CT. Pneumonia was the most common infection (50.5%), 68.6% of cases being associated with mechanical ventilation. Colistin (67.6%) and carbapenems (14.7%) were the most common drugs used in MT; colistin plus tigecycline (27.3%) and carbapenem plus tigecycline (12.1%) were the most frequent combinations. Crude 30 day mortality was 23.5% and 24.2% for the MT and CT groups, respectively (RR = 1.03; 95% CI 0.49-2.16; P = 0.94). Multivariate analysis of 30 day survival showed no trend towards reduced 30 day mortality with CT (HR = 1.35; 95% CI 0.53-3.44; P = 0.53). Subgroup analysis showed similar results. CONCLUSIONS: Our data do not support an association of CT with reduced mortality in MDRAB infections. More data for specific types of infection and combinations are needed.

Contribution of efflux pumps, porins, and ß-lactamases to multidrug resistance in clinical isolates of Acinetobacter baumannii.

We investigated the mechanisms of resistance to carbapenems, aminoglycosides, glycylcyclines, tetracyclines, and quinolones in 90 multiresistant clinical strains of Acinetobacter baumannii isolated from two genetically unrelated A. baumannii clones: clone PFGE-ROC-1 (53 strains producing the OXA-58 ß-lactamase enzyme and 18 strains with the OXA-24 ß-lactamase) and clone PFGE-HUI-1 (19 strains susceptible to carbapenems). We used real-time reverse transcriptase PCR to correlate antimicrobial resistance (MICs) with expression of genes encoding chromosomal ß-lactamases (AmpC and OXA-51), porins (OmpA, CarO, Omp33, Dcap-like, OprB, Omp25, OprC, OprD, and OmpW), and proteins integral to six efflux systems (AdeABC, AdeIJK, AdeFGH, CraA, AbeM, and AmvA). Overexpression of the AdeABC system (level of expression relative to that by A. baumannii ATCC 17978, 30- to 45-fold) was significantly associated with resistance to tigecycline, minocycline, and gentamicin and other biological functions. However, hyperexpression of the AdeIJK efflux pump (level of expression relative to that by A. baumannii ATCC 17978, 8- to 10-fold) was significantly associated only with resistance to tigecycline and minocycline (to which the TetB efflux system also contributed). TetB and TetA(39) efflux pumps were detected in clinical strains and were associated with resistance to tetracyclines and doxycycline. The absence of the AdeABC system and the lack of expression of other mechanisms suggest that tigecycline-resistant strains of the PFGE-HUI-1 clone may be associated with a novel resistance-nodulation-cell efflux pump (decreased MICs in the presence of the inhibitor Phe-Arg ß-naphthylamide dihydrochloride) and the TetA(39) system.

Impact of qnrA1, qnrB1 and qnrS1 on the efficacy of ciprofloxacin and levofloxacin in an experimental pneumonia model caused by Escherichia coli with or without the GyrA mutation Ser83Leu.

OBJECTIVES: The aim of this study was to evaluate the impact of qnrA1, qnrB1 and qnrS1 on the in vivo efficacies of ciprofloxacin and levofloxacin in an experimental model of pneumonia caused by Escherichia coli. METHODS: Two isogenic groups of E. coli transformants, based on two ATCC 25922 strains, with or without the GyrA mutation Ser83Leu, and carrying qnrA1, qnrB1 or qnrS1, were used in an experimental pneumonia model. The efficacies of ciprofloxacin (40 mg/kg/day) and levofloxacin (50 and 150 mg/kg/day) were evaluated. RESULTS: For the pneumonia caused by the parental strains lacking qnr genes, both fluoroquinolones significantly (P<0.05) reduced the bacterial lung concentration by >7 log10 cfu/g against E. coli ATCC/pBK and between 5.09 and 6.34 log10 cfu/g against E. coli ATCC-S83L/pBK. The presence of any qnr genes in the strains of both isogenic groups diminished the reduction of bacterial lung concentration with any therapy (P<0.05). Furthermore, all therapeutic schemes reduced the percentage of positive blood cultures in both isogenic groups (P<0.05). Finally, the survival results suggest a higher mortality with the strains expressing qnr genes. CONCLUSIONS: The presence of qnrA1, qnrB1 and qnrS1 in E. coli reduced the efficacy of ciprofloxacin and levofloxacin in a murine pneumonia model.

Inoculum effect on the efficacies of amoxicillin-clavulanate, piperacillin-tazobactam, and imipenem against extended-spectrum ß-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli in an experimental murine sepsis model.

Escherichia coli is commonly involved in infections with a heavy bacterial burden. Piperacillin-tazobactam and carbapenems are among the recommended empirical treatments for health care-associated complicated intra-abdominal infections. In contrast to amoxicillin-clavulanate, both have reduced in vitro activity in the presence of high concentrations of extended-spectrum ß-lactamase (ESBL)-producing and non-ESBL-producing E. coli bacteria. Our goal was to compare the efficacy of these antimicrobials against different concentrations of two clinical E. coli strains, one an ESBL-producer and the other a non-ESBL-producer, in a murine sepsis model. An experimental sepsis model {~5.5 log10 CFU/g [low inoculum concentration (LI)] or ~7.5 log(10) CFU/g [high inoculum concentration (HI)]} using E. coli strains ATCC 25922 (non-ESBL producer) and Ec1062 (CTX-M-14 producer), which are susceptible to the three antimicrobials, was used. Amoxicillin-clavulanate (50/12.5 mg/kg given intramuscularly [i.m.]), piperacillin-tazobactam (25/3.125 mg/kg given intraperitoneally [i.p.]), and imipenem (30 mg/kg i.m.) were used. Piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (-2.53 and -2.14 log10 CFU/g [P < 0.05, respectively]) in the HI versus LI groups, while amoxicillin-clavulanate maintained its efficacy (-1.01 log10 CFU/g [no statistically significant difference]). Regarding the Ec1062 strain, the antimicrobials showed lower efficacy in the HI than in the LI groups: -0.73, -1.89, and -1.62 log10 CFU/g (P < 0.05, for piperacillin-tazobactam, imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). An adapted imipenem treatment (based on the time for which the serum drug concentration remained above the MIC obtained with a HI of the ATCC 25922 strain) improved its efficacy to -1.67 log10 CFU/g (P < 0.05). These results suggest that amoxicillin-clavulanate could be an alternative to imipenem treatment of infections caused by ESBL- and non-ESBL-producing E. coli strains in patients with therapeutic failure with piperacillin-tazobactam.

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.

Reduced incidence of pneumonia in influenza-vaccinated solid organ transplant recipients with influenza disease.

Whether influenza vaccination influences the severity of illness in cases of clinical failure in solid organ transplant (SOT) recipients receiving influenza vaccine has not been extensively studied. Our goal was to evaluate the frequency of influenza vaccination among SOT recipients with influenza disease and its impact on the illness severity during the 2010-2011 season. Adult SOT recipients with confirmed influenza infection were included from December 2010 to April 2011. Follow-up data were recorded and antibody titres were determined using a microneutralization assay. Sixty-four SOT recipients were included in the study, ten (15.6%) with severe disease, requiring admission to intensive care units, of whom four (6.3%) died. In all, 34 (53.1%) received the 2010-2011 seasonal influenza vaccine and 32 (50.0%) received the 2009-H1N1 pandemic vaccine, and none had detectable antibodies against influenza at the time of diagnosis of influenza infection. Twenty-three (67.6%) of the patients that received the vaccine required hospital admission and presented less dyspnoea (10, 29.4% versus 14 (50.0%), p 0.09) and pneumonia (8, 23.8% versus 15, 50.0%, p 0.03, relative risk 0.3, 95% CI 0.1-0.9) than unvaccinated patients, with relative risk reductions of 60% and 70%, respectively. Although influenza vaccination confers protection on SOT recipients against developing influenza pneumonia, the rate of clinical failure is still high. New strategies to improve influenza immunization are needed for this group of patients.

Unexpected severity of cases of influenza B infection in patients that required hospitalization during the first postpandemic wave.

OBJECTIVES: After the last pandemic the knowledge regarding influenza A infection has improved however, the outcomes of influenza B infection remain poorly studied. The aim of this study was to compare the features of influenza B versus influenza A(H1N1)pdm09 infections during the 2010-2011 epidemic-season. METHODS: A prospective, observational-cohort of adults with laboratory-confirmed influenza infection during the 2010-2011 epidemic-season was studied RESULTS: Fifty cases of influenza B and 80 of influenza A(H1N1)pdm09 infection were enrolled. Among patients with influenza B, the median age was 34 years-old (23-64), 30% pregnant, 24% obese, 34% transplant recipients and 14% with bacterial co-infection. Twenty-eight percent of patients had pneumonia with alveolar localized pattern and five (10%) died. Pneumonia was associated with delayed antiviral therapy, older age, higher Charlson score, invasive mechanical ventilation and bacterial co-infection. Obesity and pregnancy were not associated with complicated influenza B infection. The proportion of pneumonia, admission to the ICU and mortality did not differ between cases of influenza A(H1N1)pdm09 and influenza B infection. CONCLUSIONS: Influenza B infection causes severe infection and it is associated with pneumonia or death, similar to influenza A(H1N1)pdm09 infection. Rapid diagnosis and early antiviral therapy are necessary for managing influenza pneumonia during epidemic periods.

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.