Early infection after stroke is frequent but the clinical value of antibiotic prophylaxis in acute stroke has never been explored.
The Early Systemic Prophylaxis of Infection After Stroke (ESPIAS) is ...a randomized, double-blind, placebo-controlled study of antibiotic prophylaxis in patients older than 18 years with nonseptic ischemic or hemorrhagic stroke enrolled within 24 hours from clinical onset. Interventions included intravenous levofloxacin (500 mg/100 mL/d, for 3 days) or placebo (0.9% physiological serum) in addition to optimal care. A sample size of 240 patients was calculated to identify a 15% absolute risk reduction of the primary outcome measure, which was the incidence of infection at day 7 after stroke. Secondary outcome measures were neurological outcome and mortality at day 90.
Based on a preplanned futility analysis, the study was interrupted prematurely when 136 patients had been included. Levofloxacin and placebo patients had a cumulative rate of infection of 6% and 6% (P=0.96) at day 1; 10% and 12% (P=0.83) at day 2; 12% and 15% (P=0.66) at day 3; 16% and 19% (P=0.82) at day 7; and 30% and 33% (P=0.70), at day 90. Using logistic regression, favorable outcome at day 90 was inversely associated with baseline National Institutes of Health Stroke Scale (OR, 0.72; 95% CI, 0.59 to 0.89; P=0.002) and allocation to levofloxacin (OR, 0.19; 95% CI, 0.04 to 0.87; P=0.03).
Prophylactic administration of levofloxacin (500 mg/100 mL/day for 3 days) is not better than optimal care for the prevention of infections in patients with acute stroke.
The use of antibiotic-loaded cement is believed to prevent infection in primary total knee arthroplasty, but there is a lack of randomized studies to support this concept. The aim of this study was ...to evaluate the use of an antibiotic-loaded cement to reduce the infection rate in primary total knee arthroplasty.
This is a prospective randomized study with 2948 cemented total knee arthroplasties, in which bone cement without antibiotic was used in 1465 knees (the control group) and a bone cement loaded with erythromycin and colistin was used in 1483 knees (the study group). All patients received the same systemic prophylactic antibiotics. The patients were followed for a minimum of twelve months. The rate of infection was analyzed according to the criteria of the Centers for Disease Control and Prevention.
The rate of deep infection (1.4% in the control group and 1.35% in the study group; p = 0.96) and the rate of superficial infection (1.2% and 1.8%, respectively; p = 0.53) were similar in both groups. The factors related to a higher rate of deep infection in a multivariate analysis were male sex and an operating time of >125 minutes.
The use of erythromycin and colistin-loaded bone cement in total knee arthroplasty did not lead to a decrease in the rate of infection when systemic prophylactic antibiotics were used, a finding that suggests that the use of antibiotic-loaded bone cement would not be indicated in the general population. Further research is needed to assess whether its use is recommended for patients with a higher risk of infection.
Purpose Escherichia coli strains are the most frequent cause of urinary tract infections. Biofilm formation allows the strains to persist a long time in the genitourinary tract and interfere with ...bacterial eradication. We determined the possible relationships between the different urinary tract infections, and in vitro biofilm formation, the presence of urovirulence factors and nalidixic acid resistance. Materials and Methods A total of 151 E. coli strains collected from patients with cystitis (44 strains), pyelonephritis (75) and prostatitis (32) were analyzed for in vitro biofilm formation, the phylogenetic group, the presence of several urovirulence factors and resistance to nalidixic acid. Results E. coli strains causing prostatitis produced biofilm in vitro more frequently than those causing other urinary tract infections and had a higher frequency of hemolysin (p = 0.03 and 0.0002, respectively). However, only hemolysin was independently associated with prostatitis. On the other hand, strains forming biofilm presented a significantly higher frequency of hemolysin and type 1 fimbriae expression. Conclusions Although hemolysin is the main virulence factor by which E. coli causes acute prostatitis, the association between hemolysin and biofilm formation may result in increased ability of E. coli strains to persist in the prostate.
Purpose: To describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Pseudomonas aeruginosa (MDRP) treated with colistin (colistimethate sodium) and the ...adverse events observed with this treatment. Methods: Retrospective study of MDRP infections treated with colistin from 1997 to 2006. Results: 121 episodes were identified. The median daily intravenous dose was 240 mg/day; 28.9% of patients received intravenous and nebulized colistin. Clinical outcome was favorable in ten cases of bacteremia (62.5%, n = 16), 43 cases of bronchial infection (72.9%, n = 59), 13 cases of pneumonia (65%, n = 20), 11 cases of urinary infection (84.6%, n = 13), eight cases of skin and soft tissues (72.7%, n = 11), and in the one case of arthritis and one case of otitis. Eradication was achieved in 31 (34.8%) of the 89 patients with available bacteriologic data. Factors associated with bacteriological failure were smoking, chronic obstructive pulmonary disease (COPD), and previous infection with P. aeruginosa. Nephrotoxicity occurred in ten cases (8.3%), with the associated factors being previous chronic renal insufficiency, diabetes mellitus, and aminoglycoside use. Crude mortality was 16.5%, and related MDRP was 12.4%, and was higher in patients with pneumonia or bacteremia (36.1%) than in other types of infections (8.2%). Conclusions: Colistin is a safe option for the treatment of MDRP infections, with acceptable clinical outcomes. However, bacteriological eradication is difficult to achieve, especially in COPD patients.
Summary Objective To analyze the clinical and economic impact of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli requiring ...hospitalization. Methods Matched cohort study including adults with UTI caused by ESBL-producing E. coli admitted to a tertiary care hospital in Barcelona, Spain, between August 2010 and July 2013. Demographic, clinical and economic data were analyzed. Results One hundred and twenty episodes of UTI were studied: 60 due to ESBL-producing E. coli and 60 due to non-ESBL-producing E. coli . Bivariate analysis showed that prior antimicrobial treatment (p = 0.007) and ESBL production (p < 0.001) were related to clinical failure during the first 7 days. Multivariate analysis selected ESBL as the sole risk factor for clinical failure (p = 0.002). Regarding the economic impact of infections caused by ESBL-producing E. coli , an ESBL-producing infection cost more than a non-ESBL-producing E. coli infection (mean €4980 vs. €2612). Looking at hospital expenses separately, the total pharmacy costs and antibiotic costs of ESBL infections were considerably higher than for non-ESBL infections (p < 0.001), as was the need for outpatient parenteral antibiotic therapy (OPAT) and its related costs. Multivariate analysis performed for the higher costs of UTI episodes found statistically significant differences for males (p = 0.004), chronic renal failure (p = 0.025), ESBL production (p = 0.008) and OPAT (p = 0.009). Conclusion UTIs caused by EBSL-producing E. coli requiring hospital admission are associated with worse clinical and economic outcomes.
The high interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially ...toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualized dosing. A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients (65.4% male, 65.5 ±14.6 years) who underwent routine therapeutic drug monitoring for linezolid. Linezolid concentrations were analyzed by using high-performance liquid chromatography. Population pharmacokinetic modeling was performed using a nonparametric methodology with Pmetrics, and Monte Carlo simulations were employed to calculate the 100% time >MIC after the administration of a fixed regimen of 600 mg administered every 12 h (q12h) intravenously (i.v.). The dose of linezolid needed to achieve a PTA ≥ 90% for all susceptible isolates classified according to EUCAST was estimated to be as high as 2,400 mg q12h, which is 4 times higher than the maximum licensed linezolid dose. The final PK model was then used to construct software for dosage individualization, and the performance of the software was assessed using 10 new patients not used to construct the original population PK model. A three-compartment model with an absorptive compartment with zero-order i.v. input and first-order clearance from the central compartment best described the data. The dose optimization software tracked patients with a high degree of accuracy. The software may be a clinically useful tool to adjust linezolid dosages in real time to achieve prespecified drug exposure targets. A further prospective study is needed to examine the potential clinical utility of individualized therapy.
The clinical and microbiological characteristics of community-onset healthcare-associated (HCA) bacteraemia of urinary source are not well defined. We conducted a prospective cohort study at eight ...tertiary-care hospitals in Spain, from October 2010 to June 2011. All consecutive adult patients hospitalized with bacteraemic urinary tract infection (BUTI) were included. HCA-BUTI episodes were compared with community-acquired (CA) and hospital-acquired (HA) BUTI. A logistic regression analysis was performed to identify 30-day mortality risk factors. We included 667 episodes of BUTI (246 HCA, 279 CA and 142 HA). Differences between HCA-BUTI and CA-BUTI were female gender (40% vs 69%, p <0.001), McCabe score II–III (48% vs 14%, p <0.001), Pitt score ≥2 (40% vs 31%, p 0.03), isolation of extended spectrum β-lactamase-producing Enterobacteriaciae (13% vs 5%, p <0.001), median hospital stay (9 vs 7 days, p 0.03), inappropriate empirical antimicrobial therapy (21% vs 13%, p 0.02) and mortality (11.4% vs 3.9%, p 0.001). Pseudomonas aeruginosa was more frequently isolated in HA-BUTI (16%) than in HCA-BUTI (4%, p <0.001). Independent factors for mortality were age (OR 1.04; 95% CI 1.01–1.07), McCabe score II–III (OR 3.2; 95% CI 1.8–5.5), Pitt score ≥ 2 (OR 3.2 (1.8–5.5) and HA-BUTI OR 3.4 (1.2–9.0)). Patients with HCA-BUTI are a specific group with significant clinical and microbiological differences from patients with CA-BUTI, and some similarities with patients with HA-BUTI. Mortality was associated with patient condition, the severity of infection and hospital acquisition.
To assess the association between inclusion of a macrolide in a β-lactam—based empirical antibiotic regimen and mortality among patients with bacteremic pneumococcal pneumonia, 10 years of data from ...a database were analyzed. The total available set of putative prognostic factors was subjected to stepwise logistic regression, with in-hospital death as the dependent variable. Of the 409 patients analyzed, 238 (58%) received a β-lactam plus a macrolide and 171 (42%) received a β-lactam without a macrolide. Multivariate analysis revealed 4 variables to be independently associated with death: shock (P <.0001), age of ≥65 years (P =.02), infections with pathogens that have resistance to both penicillin and erythromycin (P =.04), and no inclusion of a macrolide in the initial antibiotic regimen (P =.03). For patients with bacteremic pneumococcal pneumonia, not adding a macrolide to a β-lactam—based initial antibiotic regimen is an independent predictor of in-hospital mortality. However, only a randomized study can definitively determine whether this association is due to a real effect of macrolides.
Highlights • In these patients, linezolid demonstrated good but variable penetration into the CNS. • A 3-compartment model was used; the mean value for linezolid clearance was 16.6 L/h and volume of ...distribution 101.3 L. • To ensure all patients achieve adequate CNS concentrations the use of higher than standard doses and TDM is necessary.
Rutin Inhibits Ovariectomy‐Induced Osteopenia in Rats Horcajada‐Molteni, Marie‐Noëlle; Crespy, Vanessa; Coxam, Véronique ...
Journal of bone and mineral research,
November 2000, Letnik:
15, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Several studies suggest that polyphenols might exert a protective effect against osteopenia. The present experiment was conducted to observe the effects of rutin (quercetin‐3‐O‐glucose rhamnose) on ...bone metabolism in ovariectomized (OVX) rats. Thirty 3‐month‐old Wistar rats were used. Twenty were OVX while the 10 controls were sham‐operated (SH). Among the 20 OVX, for 90 days after surgery 10 were fed the same synthetic diet as the SH or OVX ones, but 0. 25% rutin (OVX + R) was added. At necropsy, the decrease in uterine weight was not different in OVX and OVX + R rats. Ovariectomy also induced a significant decrease in both total and distal metaphyseal femoral mineral density, which was prevented by rutin consumption. Moreover, femoral failure load, which was not different in OVX and SH rats, was even higher in OVX + R rats than in OVX or SH rats. In the same way, on day 90, both urinary deoxypyridinoline (DPD) excretion (a marker for bone resorption) and calciuria were higher in OVX rats than in OVX + R or SH rats. Simultaneously, plasma osteocalcin (OC) concentration (a marker for osteoblastic activity) was higher in OVX + R rats than in SH rats. High‐performance liquid chromatography (HPLC) profiles of plasma samples from OVX + R rats revealed that mean plasma concentration of active metabolites (quercetin and isorhamnetin) from rutin was 9.46 + 1 μM, whereas it was undetectable in SH and OVX rats. These results indicate that rutin (and/or its metabolites), which appeared devoid of any uterotrophic activity, inhibits ovariectomy‐induced trabecular bone loss in rats, both by slowing down resorption and increasing osteoblastic activity.
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