Risk scores' performance and their impact on operative decision-making in left-sided endocarditis: a cohort study.

The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91-98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.

Early in vitro development of daptomycin non-susceptibility in high-level aminoglycoside-resistant Enterococcus faecalis predicts the efficacy of the combination of high-dose daptomycin plus ampicillin in an in vivo model of experimental endocarditis.

Background: Previous studies showed development of daptomycin non-susceptibility (DNS: MIC >4 mg/L) in Enterococcus faecalis infections. However, no studies have assessed the efficacy of the combination of daptomycin/ampicillin against E. faecalis strains developing DNS in the experimental endocarditis (EE) model. Objectives: To assess the in vitro and in vivo efficacy of daptomycin at 10 mg/kg/day, daptomycin/ampicillin and ampicillin/ceftriaxone against two high-level aminoglycoside-resistant E. faecalis strains, one developing DNS after in vitro exposure to daptomycin and another that did not (DS). Methods: Subculture of 82 E. faecalis strains from patients with endocarditis with daptomycin MICs, time-kill and in vivo experiments using the EE model. Results: 33% of the strains (27 of 82) displayed DNS after subculture with daptomycin. Daptomycin MIC rose from 0.5-2 to 8-16 mg/L. In time-kill experiments, when using a high inoculum (10 8 cfu/mL), daptomycin/ampicillin was synergistic for one-third of DS strains and none of DNS strains, while ampicillin/ceftriaxone retained synergy in all cases. In the EE model, daptomycin did not significantly reduce cfu/g from vegetations compared with control against either strain, while daptomycin/ampicillin reduced significantly more cfu/g than daptomycin against the DS strain, but not against the DNS strain [2.9 (2.0-4.1) versus 6.1 (4.5-8.0); P = 0.002]. Ampicillin/ceftriaxone was synergistic and bactericidal against both strains, displaying the same activity as daptomycin/ampicillin against the DS strain. Conclusions: Performance of an Etest for daptomycin MIC after subculture with daptomycin inhibitory doses on strains of high-level aminoglycoside-resistant E. faecalis endocarditis may be an easy test to predict the in vivo efficacy of daptomycin/ampicillin.

Fosfomycin plus ß-Lactams as Synergistic Bactericidal Combinations for Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus.

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.

Epidemiology and outcome of bacteraemia in neutropenic patients in a single institution from 1991-2012.

This study was part of a bloodstream infection surveillance programme that prospectively collected data on consecutive patients with bacteraemia in our institution from 1991 to 2012. We included 2092 bacteraemias in neutropenic patients. Shock and mortality accounted for 299 and 349 cases, respectively (14% and 17%). The main microorganisms isolated were coagulase-negative staphylococci (CoNS, 634, 30%), Escherichia coli (468, 22%) and Pseudomonas aeruginosa (235, 11%). During 2006-2012, there were 155 (27%) E. coli isolates; of these, 73% were fluoroquinolone resistant and 26% cefotaxime resistant. The independent risk factors for mortality were shock on presentation, rapidly fatal prognosis of underlying disease, corticosteroid use, and polymicrobial bacteraemia. Factors associated with lower mortality were the isolation of CoNS [odds ratio (OR) 0·38, 95% confidence interval (CI) 0·20-0·73, P = 0·004] and empirical therapy with amikacin (OR 0·50, 95% CI 0·29-0·88, P = 0·016). The progressive increase of Gram-negative microorganisms resistant to antibiotics influences the choice of empirical treatment in febrile neutropenia and in our experience, the addition of amikacin could be beneficial for such patients.

Left ventricular diastolic function and cardiometabolic factors in obese normotensive children.

BACKGROUND AND AIM: Left ventricular (LV) hypertrophy and diastolic function have been found to be associated with obesity and hypertension in adults. However, there are scarce data about the association of obesity itself to cardiac alteration in children. The aim of this study was to detect early changes in LV structure and function in obese children and whether they are associated with the biomarkers of metabolic risk and endothelial activation. METHODS AND RESULTS: A total of 130 children aged 7-16 years (88 obese and 42 normal-weight children) were studied. All children had normal resting blood pressure. Two-dimensional ultrasound with M-mode imaging was performed to assess the LV mass index (LVMi), calculated as LV mass/height(2.7), and the peak diastolic of pulmonary venous flow velocity (PVFD). Tissue Doppler imaging was used to analyze ventricular performance through the ratio of the transmitral peak early filling velocity to the early average diastolic peak myocardial velocity (E/E'). The indicators of metabolic control, inflammation, and endothelial cell activation were evaluated. Compared to the controls, the obese subjects had significantly higher LVMi and E/E' and lower PVFD values, the two latest being found especially in severely obese subjects. In the multivariate analysis, the parameters of diastolic function (E/E' and PVFD) were independently associated with obesity, apolipoprotein A1, soluble vascular cell endothelial molecule-1 (sVCAM-1), and retinol-binding protein 4 (RBP4). CONCLUSION: An echocardiographic evaluation of diastolic function is a useful tool to detect early cardiac changes in obese children. Emergent cardiovascular risk markers such as apolipoprotein A1, RBP4, and sVCAM-1 are associated with the parameters of diastolic function.

Community-onset bacteraemia of unknown origin: clinical characteristics, epidemiology and outcome.

Bacteraemia of unknown origin is prevalent and has a high mortality rate. However, there are no recent reports focusing on this issue. From 2005 to 2011, all episodes of community onset bacteraemia of unknown origin (CO-BSI), diagnosed at a 700-bed university hospital were prospectively included. Risk factors for Enterobactericeae resistant to third-generation cephalosporins (3GCR-E), Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus spp, and predictors of mortality were assessed by logistic regression. Out of 4,598 consecutive episodes of CO-BSI, 745 (16.2 %) were of unknown origin. Risk factors for S. aureus were male gender (OR 2.26; 1.33-3.83), diabetes mellitus (OR 1.71; 1.01-2.91) and intravenous drug addiction (OR 17.24; 1.47-202); for P. aeruginosa were male gender (OR 2.19; 1.10-4.37) and health-care associated origin (OR 9.13; 3.23-25.83); for 3GCR-E was recent antibiotic exposure (OR 2.53; 1.47-4.35), while for enterococci, it was recent hospital admission (OR 3.02; 1.64-5.55). Seven and 30-day mortality were 8.1 % and 13.4 %, respectively. Age over 65 years (OR 2.13; 1.28-3.55), an ultimately or rapidly fatal underlying disease (OR 4.15; 2.23-7.60), bone marrow transplantation (OR 4.07; 1.24-13.31), absence of fever (OR 4.45; 2.25-8.81), shock on presentation (OR 10.48; 6.05-18.15) and isolation of S. aureus (OR 2.01; 1.00-4.04) were independently associated with mortality. In patients with bacteraemia of unknown origin, a limited number of clinical characteristics may be useful to predict its aetiology and to choose the appropriate empirical treatment. Although no modifiable prognostic factors have been found, management optimization of S. aureus should be considered a priority in this setting.

Epidemiology and prognostic determinants of bacteraemic biliary tract infection.

OBJECTIVES: To determine the epidemiology of bacteraemia due to biliary tract infection (BTI) and to identify independent predictors of mortality. METHODS: This study was part of a bloodstream infection surveillance study that prospectively collected data on consecutive patients with bacteraemia in our institution from 1991 to 2010. BTI was the confirmed source of 1373 patients with bacteraemia, and the independent prognostic factors of 30 day mortality were determined. RESULTS: The mean age of patients with biliary sepsis was 71 years (± 14 years). The most frequent comorbidities were biliary lithiasis and solid-organ cancer [484 cases (35%) and 362 cases (26%), respectively]. The BTI was healthcare-associated in 33% of patients. Shock and mortality accounted for 209 and 126 cases, respectively (15% and 9%). The most frequent microorganisms isolated were Escherichia coli (749, 55%), Klebsiella spp. (240, 17%), Enterococcus spp. (171, 12%), Pseudomonas aeruginosa (86, 6%) and Enterobacter spp. (63, 5%). There were 47 (3%) cefotaxime-resistant (CTX-R) E. coli or Klebsiella spp. Inappropriate empirical antibiotic treatment was an independent factor associated with mortality (OR 1.4, 95% CI 1.1-1.7). Inappropriate empirical treatment was more frequent in P. aeruginosa and CTX-R Enterobacteriaceae bacteraemia. These microorganisms were significantly more common in patients with previous antibiotic therapy, solid-organ cancer or transplantation and in healthcare-associated bacteraemia. CONCLUSIONS: In patients with bacteraemic BTI, inappropriate empirical therapy was more frequent in P. aeruginosa and CTX-R Enterobacteriaceae infection and was associated with a higher mortality rate. In patients with bacteraemia due to BTI and solid-organ cancer or transplantation, healthcare-associated infection or previous antibiotic treatment, initial therapy with piperacillin/tazobactam or a carbapenem would be advisable.

A comparative study of two different methods of sample preparation for positive blood cultures for the rapid identification of bacteria using MALDI-TOF MS.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has lately been implemented as a solid technology for rapid microorganism identification in microbiology laboratories. This study compares two methods for bacterial separation from 85 positive blood culture before MALDI-TOF MS: (1) a conventional method that we used in our laboratory to prepare bacteria for susceptibility testing and (2) a new commercialized technique (Sepsityper). There were no significant differences in the identification of Gram-negative bacilli regardless of the bacterial separation method used. However, identification was greater for Gram-positive cocci when the Sepsityper method was used (84.15% vs. 100% in the identification to a genus level in staphylococci and 57.14% vs. 85.71% in the identification to a genus level of enterococci with the in-house and Sepsityper methods, respectively). Therefore, the Sepsityper method to prepare bacteria from a positive blood culture is more adequate for the further identification of Gram-positive cocci by MALDI-TOF MS.

Cyclopropyl carboxamides, a chemically novel class of antimalarial agents identified in a phenotypic screen.

Malaria is one of the deadliest infectious diseases in the world, with the eukaryotic parasite Plasmodium falciparum causing the most severe form of the disease. Discovery of new classes of antimalarial drugs has become an urgent task to counteract the increasing problem of drug resistance. Screening directly for compounds able to inhibit parasite growth in vitro is one of the main approaches the malaria research community is now pursuing for the identification of novel antimalarial drug leads. Very recently, thousands of compounds with potent activity against the parasite P. falciparum have been identified and information about their molecular descriptors, antiplasmodial potency, and cytotoxicity is publicly available. Now the challenges are how to identify the most promising chemotypes for further development and how best to progress these compounds through a lead optimization program to generate antimalarial drug candidates. We report here the first chemical series to be characterized from one of those screenings, a completely novel chemical class with the generic name cyclopropyl carboxamides that has never before been described as having antimalarial or other pharmacological activities. Cyclopropyl carboxamides are potent inhibitors of drug-sensitive and -resistant strains of P. falciparum in vitro and show in vivo oral efficacy in malaria mouse models. In the present work, we describe the biological characterization of this chemical family, showing that inhibition of their still unknown target has very favorable pharmacological consequences but the compounds themselves seem to select for resistance at a high frequency.

Epidemiology and clinical outcomes of bloodstream infections among lupus patients.

Infection is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). This study was aimed at characterizing bloodstream infections in these patients and analysing factors associated with long term outcome. For this purpose, episodes of significant bacteraemia diagnosed from January 1991 to December 2006 among patients with SLE at a single centre were identified through a central database and clinical and analytical variables were recorded regarding short- and long-term follow-up. Univariate and multivariable analysis were performed to identify factors associated with long-term outcome. Thirty-eight SLE patients had 48 episodes of significant bacteraemia, with a 30-day mortality rate of 6.25%. Escherichia coli and Staphylococcus aureus were the leading Gram-negative and Gram-positive pathogens, respectively. After a median follow-up of 25 months, eight of these 38 patients (21.1%) had a further episode of bacteraemia and 13 of them (34.21%) died. Community-acquired bacteraemia and C reactive protein levels lower than 8 mg/dl during episodes were factors associated with lower long-term mortality. These results reinforce previous findings suggesting that lupus patients with bacteraemia episodes have poor long-term outcomes.

Cefotaxime resistance and outcome of Klebsiella spp bloodstream infection.

We attempt to describe the epidemiology and outcome associated with cefotaxime-resistant (CTX-R) Klebsiella spp bacteraemia. Klebsiella spp bloodstream infection episodes prospectively collected through a blood culture surveillance programme from January 1991 to December 2008 in a single institution were analysed. A total of 910 monomicrobial episodes of Klebsiella spp bacteraemia were identified during the study period. The most important sources were from urinary tract infection, unknown sources, billiary focus and catheter related infection. There were 112 (12%) CTX-R isolates. Out of 112 isolates, 98 were CTX-R by Extended-Spectrum ß-Lactamase production. Shock on presentation and mortality were significantly more frequent in CTX-R than in CTX susceptible isolates. Inappropriate empirical therapy was received in 50 (45%) cases in the CTX-R Klebsiella spp group (13 cases of death, 26%). Predictive factors associated with CTX-R Klebsiella spp isolate were: previous ß-lactam therapy (OR = 4.16), nosocomial acquired bacteraemia (OR = 1.93), solid organ trasplantation (OR = 2.09) and shock (OR = 1.90). Independent risk factors associated with mortality in Klebsiella spp bacteraemia were: age (OR = 1.03), liver cirrhosis (OR = 2.63), ultimately or rapidly fatal prognosis of underlying disease (OR = 2.44), shock (OR = 8.60), pneumonia (OR = 4.96) or intraabdominal (OR = 3.85) source of bacteraemia and CTX-R isolate (OR = 4.63). Klebsiella spp is an important cause of bloodstream infection. CTX-R isolates have been increasing since 2000. CTX-R is an independent factor associated with mortality in Klebsiella spp bacteraemia.

Influence of empiric therapy with a beta-lactam alone or combined with an aminoglycoside on prognosis of bacteremia due to gram-negative microorganisms.

Evidence supporting the combination of aminoglycosides with beta-lactams for gram-negative bacteremia is inconclusive. We have explored the influence on survival of empirical therapy with a beta-lactam alone versus that with a beta-lactam-aminoglycoside combination by retrospectively analyzing a series of bacteremic episodes due to aerobic or facultative gram-negative microorganisms treated with single or combination therapy. The outcome variable was a 30-day mortality. Prognostic factors were selected by regression logistic analysis. A total of 4,863 episodes were assessed, of which 678 (14%) received combination therapy and 467 (10%) were fatal. Factors independently associated with mortality included age greater than 65 (odds ratio [OR], 2; 95% confidence interval [CI], 1.6 to 2.6), hospital acquisition (OR, 1.5; 95% CI, 1.2 to 1.9), a rapidly or ultimately fatal underlying disease (OR, 2.5; 95% CI, 2 to 3.2), cirrhosis (OR, 1.9; 95% CI, 1.4 to 2.6), prior corticosteroids (OR, 1.5; 95% CI, 1.1 to 2), shock on presentation (OR, 8.8; 95% CI, 7 to 11), pneumonia (OR, 2.8; 95% CI, 1.9 to 4), and inappropriate empirical therapy (OR, 1.8; 95% CI, 1.3 to 2.5). Subgroup analysis revealed that combination therapy was an independent protective factor in episodes presenting shock (OR, 0.6; 95% CI, 0.4 to 0.9) or neutropenia (OR, 0.5; 95% CI, 0.3 to 0.9). Combination therapy improved the appropriateness of empirical therapy in episodes due to extended-spectrum beta-lactamase (ESBL)- or AmpC-producing Enterobacteriaceae and Pseudomonas aeruginosa. In patients with gram-negative bacteremia, we could not find an overall association between empirical beta-lactam-aminoglycoside combination therapy and prognosis. However, a survival advantage cannot be discarded for episodes presenting shock or neutropenia, hence in these situations the use of combination therapy may still be justified. Combination therapy also should be considered for patients at risk of being infected with resistant organisms, if only to increase the appropriateness of empirical therapy.

Daptomycin is effective for treatment of experimental endocarditis due to methicillin-resistant and glycopeptide-intermediate Staphylococcus epidermidis.

This study evaluated the daptomycin activity against two methicillin-resistant Staphylococcus epidermidis (MRSE) clinical isolates with different vancomycin susceptibilities: MRSE-375, with a vancomycin MIC of 2 microg/ml, and NRS6, a glycopeptide-intermediate S. epidermidis (GISE) strain with a vancomycin MIC of 8 microg/ml. The in vivo activity of daptomycin at two different doses (standard dose [SD-daptomycin], 6 mg/kg of body weight/day intravenously [i.v.]; high dose [HD-daptomycin], 10 mg/kg/day i.v.) was evaluated in a rabbit model of infective endocarditis and compared with that of a standard dose of vancomycin (SD-vancomycin; 1 g i.v. every 12 h) for 2 days. For the MRSE-375 strain, high-dose vancomycin (HD-vancomycin; 1 g i.v. every 6 h) was also studied. For MRSE-375, SD- and HD-daptomycin therapy sterilized significantly more vegetations than SD-vancomycin therapy (9/15 [60%] and 11/15 [73%] vegetations, respectively, versus 3/16 [19%] vegetations; P = 0.02 and P = 0.002, respectively). HD-daptomycin sterilized more vegetations than HD-vancomycin (11/15 [73%] versus 5/15 [33%] vegetations; P = 0.03) and was more effective than SD- and HD-vancomycin in reducing the density of bacteria in valve vegetations (0 log(10) CFU/g vegetation [interquartile range {IQR}, 0 to 1 log(10) CFU/g vegetation] versus 2 log(10) CFU/g vegetation [IQR, 2 to 2 log(10) CFU/g vegetation] and 2 log(10) CFU/g vegetation [IQR, 0 to 2.8 log(10) CFU/g vegetation]; P = 0.002 and P = 0.01, respectively). For the NRS6 strain, SD- and HD-daptomycin were significantly more effective than vancomycin in reducing the density of bacteria in valve vegetations (3.7 log(10) CFU/g vegetation [IQR, 2 to 6 log(10) CFU/g vegetation] versus 7.1 log(10) CFU/g vegetation [IQR, 5.2 to 8.5 log(10) CFU/g vegetation]; P = 0.02). In all treatment arms, isolates recovered from vegetations remained susceptible to daptomycin and vancomycin and had the same MICs. In conclusion, daptomycin at doses of 6 mg/kg/day or 10 mg/kg/day is more effective than vancomycin for the treatment of experimental endocarditis due to MRSE and GISE.

Candida spp. bloodstream infection: influence of antifungal treatment on outcome.

OBJECTIVES: To assess the influence of new antifungal treatments on candidaemia outcome. METHODS: Candidaemia episodes prospectively collected through a blood culture surveillance programme in a single institution. The study was divided into two periods of time, 1994-2003 (A) and 2004-2008 (B), according to the introduction of echinocandin treatment. Non-conditional logistic regression methods with mortality as the dependent variable were used. RESULTS: Four hundred and thirty-three (3%) candidaemias out of 15 628 bloodstream infection episodes were analysed. Candida albicans was the most frequent species (211; 49%). Mortality was noted in 132 cases (30%). A total of 262 and 171 candidaemias were reported in period A and B, respectively. There were 94 deaths in period A (36%) and 38 in period B (22%, P = 0.03). Treatment in period A was amphotericin B in 89 patients (41 dead, 46%) and fluconazole in 151 (41 dead, 27%, P = 0.003). In period B, 113 patients received a triazole (26 dead, 23%), 30 an echinocandin (3 dead, 10%, P = 0.08) and 9 (0 dead) were treated with combined therapy (echinocandin and triazole). Mortality was higher in period A (94 dead, 36%) than in period B (38 dead, 27%), P = 0.03. Independent risk factors associated with mortality in period B were: age, chronic renal failure, ultimately or rapidly fatal prognosis of underlying disease and shock. Echinocandin alone or in combination therapy was associated with better outcome (odds ratio = 0.22, 95% confidence interval = 0.06-0.81, P = 0.02). CONCLUSIONS: In patients with candidaemia, echinocandin therapy results in a better outcome.

Performance of differential time to positivity as a routine diagnostic test for catheter-related bloodstream infections: a single-centre experience.

OBJECTIVE: To assess the performance of differential time to positivity (DTP) for the diagnosis of catheter-related bloodstream infections (CRBSI). METHODS: From all episodes of bloodstream infections (BSI) diagnosed during a 15-year period (2003-17) those in which a paired set of blood cultures drawn from a catheter and a peripheral vein were positive for the same microorganism and had a clinically and/or microbiologically defined source were selected. To assess diagnostic discrimination ability and accuracy of DTP for CRBSI, area under the receiver operating characteristic curves (AUC) and performance characteristics of a DTP ≥2 h were computed. RESULTS: A total of 512 BSI were included, of which 302 (59%) were CRBSI. Discrimination ability of DTP was low for Staphylococcus aureus (AUC 0.656 ± 0.06), coagulase-negative staphylococci (AUC 0.618 ± 0.081), enterococci (AUC 0.554 ± 0.117) and non-AmpC-producing Enterobacteriaceae (AUC 0.653 ± 0.053); moderate for Pseudomonas aeruginosa (AUC 0.841 ± 0.073), and high for AmpC-producing Enterobacteriaceae (AUC 0.944 ± 0.039). For the entire sample, DTP had a low-to-moderate discrimination ability (AUC 0.698 ± 0.024). A DTP ≥2 h has a low sensitivity for coagulase-negative staphylococci (60%) and very low for S. aureus (34%), enterococci (40%) and non-AmpC-producing Enterobacteriaceae (42%). A DTP cut-off of 1 h improved sensitivity (90%) for AmpC-producing Enterobacteriaceae. CONCLUSIONS: Differential time to positivity performs well for diagnosing CRBSI only when AmpC-producing Enterobacteriaceae and P. aeruginosa are involved. Performance is low for common Gram-positive organisms and non-AmpC-producing enteric bacilli; a negative test should not be used to rule out CRBSI due to these microorganisms. A DTP ≥1 h may improve accuracy for AmpC-producing Enterobacteriaceae, particularly Enterobacter spp.

Addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

This study evaluated the activity of daptomycin combined with either gentamicin or rifampin against three methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates in vitro and one isolate in vivo against a representative strain (MRSA-572). Time-kill experiments showed that daptomycin was bactericidal against these strains at concentrations over the MIC. Daptomycin at sub-MIC concentrations plus gentamicin at 1x and 2x the MIC yielded synergy, while the addition of rifampin at 2 to 4 microg/ml resulted in indifference (two strains) or antagonism (one strain). The in vivo activity of daptomycin (6 mg/kg of body weight once a day) was evaluated +/- gentamicin (1 mg/kg intravenously [i.v.] every 8 h [q8h]) or rifampin (300 mg i.v. q8h) in a rabbit model of infective endocarditis by simulating human pharmacokinetics. Daptomycin plus gentamicin (median, 0 [interquartile range, 0 to 2] log10 CFU/g vegetation) was as effective as daptomycin alone (0 [0 to 2] log10 CFU/g vegetation) in reducing the density of bacteria in valve vegetations (P = 0.83), and both were more effective than daptomycin plus rifampin (3 [2 to 3.5] log10 CFU/g vegetation; P < 0.05) for the strain studied. In addition, daptomycin sterilized a ratio of vegetations that was similar to that of daptomycin plus gentamicin (10/15 [67%] versus 9/15 [60%]; P = 0.7), and both regimens did so more than daptomycin plus rifampin (3/15 [20%]; P = 0.01 and P = 0.02, respectively). No statistical difference was noted between daptomycin plus gentamicin and daptomycin alone for MRSA treatment. In the combination arm, all isolates from vegetations remained susceptible to daptomycin, gentamicin, and rifampin. Sixty-one percent of the isolates (8/13) acquired resistance to rifampin during monotherapy. In the daptomycin arm, resistance was detected in only one case, in which the daptomycin MIC rose to 2 microg/ml among the recovered bacteria. In conclusion, the addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in the treatment of experimental endocarditis due to MRSA.

Analysis of 4758 Escherichia coli bacteraemia episodes: predictive factors for isolation of an antibiotic-resistant strain and their impact on the outcome.

OBJECTIVES: To describe the predictive factors for the isolation of fluoroquinolone-resistant or extended- spectrum beta-lactamase (ESBL)-producing Escherichia coli and their impact on bacteraemia outcome. METHODS: Analysis of E. coli bacteraemia episodes prospectively collected through a blood culture surveillance programme from January 1991 to December 2007. RESULTS: Out of 18 080 episodes, 4758 (26%) E. coli bacteraemias were reported in the period of study. Mortality was noted in 440 cases (9%). Fluoroquinolone-resistant strains were reported in 1300 (27%) cases and ESBL-producing strains in 211 cases (4%). One hundred and seventy-eight strains out of 211 (84%) ESBL-producing E. coli were isolated since 2001. The two main independent risk factors for mortality were shock (OR: 10.28, P < 0.001) and inappropriate empirical therapy (OR: 4.83, P < 0.001). Inappropriate empirical therapy was significantly more frequent for infections caused by fluoroquinolone-resistant strains (n = 203, 16%, P < 0.001) and ESBL-producing strains (n = 110, 52%, P < 0.001). Independent factors associated with the isolation of a fluoroquinolone-resistant strain were: nosocomial origin (OR: 1.61, P < 0.001); urinary catheterization (OR: 2.44, P < 0.001); and previous therapy with a fluoroquinolone (OR: 7.41, P < 0.001). The independent risk factors associated with the isolation of an ESBL-producing strain were: nosocomial origin (OR: 1.68, P = 0.03); urinary catheterization (OR: 1.88, P = 0.001); and previous beta-lactam antibiotic therapy (OR: 2.81, P < 0.001). CONCLUSIONS: Inappropriate empirical therapy was the strongest independent factor that we could modify to improve mortality in E. coli bacteraemia and was more frequent in cases caused by fluoroquinolone-resistant or ESBL-producing strains. Nosocomial acquisition, urinary catheterization and previous therapy with a fluoroquinolone or beta-lactam were predictive factors for infection with an antibiotic-resistant strain.

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study.

BACKGROUND: We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. METHODS: From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. RESULTS: The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered "high risk" for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid-related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. CONCLUSIONS: The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid-related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

Bloodstream infections among human immunodeficiency virus-infected adult patients: epidemiology and risk factors for mortality.

This study was undertaken to describe the epidemiology and sensitivity pattern of pathogens causing community-acquired (CA) and nosocomial (N) bloodstream infection (BSI) in adult HIV-infected patients and to establish risk factors for mortality. The type of study was a retrospective analysis of BSI episodes prospectively collected through a blood culture surveillance program from January 1991 to December 2006. We used non-conditional logistic regression methods with death as a dependent variable. One thousand and seventy-seven episodes of BSI (6%) occurred in HIV-infected patients out of 16,946 episodes during the period of study. CA and N BSI were 634 (59%) and 443 (41%) respectively. S. pneumoniae and S. aureus were the most frequent pathogens (n = 279, 44%) in CA BSI. Coagulase-negative staphylococci and S. aureus were the most frequent micro-organisms isolated in N cases (n = 169, 38%). Cotrimoxazole resistance was common in CA and N BSI and was caused by gram-negative bacilli (50% and 61% respectively). However, resistance rates to ceftriaxone were low (3%). Crude mortality accounted for 140 cases (13%). The independent risk factors associated with mortality were: liver cirrhosis (OR: 2.90, p = 0.001), corticosteroids treatment (OR: 3.51, p < 0.001), neutropenia (OR: 2.21, p = 0.02), inappropriate empirical therapy (OR: 2.44, p = 0.006), and isolate of C. albicans (OR: 7.58, p = 0.010). BSI in adult HIV-infected patients was often caused by gram-positive pathogens in both CA and N settings. Inappropriate empirical therapy and the presence of other immunosuppressive factors were independent risk factors for mortality. Ceftriaxone could be used as the initial empiric therapy for HIV-infected patients with suspected CA BSI.

[Methicillin-resistant Staphylococcus aureus bacteremia. Predictor factors for an isolate with a vancomycin minimal inhibitory concentration > or =2 mg/l]. / Bacteriemia por Staphylococcus aureus resistente a meticilina. Factores asociados al aislamiento de cepas con concentración mínima inhibitoria de vancomicina > or = 2 mg/l.

A greater rate of treatment failures with vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has been reported recently when the minimum inhibitory concentration (MIC) is > or =2 mg/l. This study has aimed to evaluate if there are clinical and/or epidemiological factors that predict isolation of a MRSA strain with MIC of vancomycin of > or =2 mg/L in the bacteremia episodes collected during a 15 year period (January 1991 to December 2005) in a tertiary urban hospital. During the study period, a total of 478 episodes of MRSA bacteremia were studied prospectively. The following clinical variables were recorded for each one: age, gender, comorbidity, previous administration of vancomycin or another antibiotic, prognosis of baseline diseases, bacteremia focus, shock, empiric antibiotic received and mortality. The MIC of vancomycin of 419 strains (88%) was determined with the E-test. In 216 (52%) of the isolations the MIC of vancomycin was 1.50 mg/L, in 110 (26%) of the cases it was < or =1 mg/l and in 93 (22%) 2 mg/l. Uni-and multivariate analyses were made, comparing the clinical variables of the patients infected by strains with MIC of vancomycin > or =2 mg/l regarding the MIC strains < or =1 mg/l. In the last 3 years of the study (2003-2005) the proportion of the strains with MIC of vancomycin > or =2 mg/l was significantly greater than those isolated with MIC < or = 1 mg/L (44 % vs 3 %; p<0.001). In the multivariate analysis, the only clinical characteristic associated independently to the isolation of a strain with MIC > or =2 mg/l was the nosocomial-acquired infection OR (95 % CI): 1.94 (1.04-3.63); p=0.04. Although the isolation of a MRSA strain with MIC of vancomycin > or =2 mg/l is more frequent in the nosocomial-acquired bacteremia episodes, in the clinical practice, it is not a useful predictive parameter because the frequency of isolation of these strains in the community is also high.