Enterobacteriaceae bloodstream infections: presence of integrons, risk factors, and outcome

A prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae and to evaluate the clinical significance of integron carriage. Consecutive patients with Enterobacteriaceae BSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended-spectrum beta-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM-type metallo-beta-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of > or =4 (OR, 23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic policies and infection control measures.     

Proteus mirabilis bloodstream infections: risk factors and treatment outcome related to the expression of extended-spectrum beta-lactamases

Bloodstream infection (BSI) due to Proteus mirabilis strains is a relatively uncommon clinical entity, and its significance has received little attention. This study was initiated to evaluate risk factors and treatment outcome of BSI episodes due to P. mirabilis producing extended-spectrum beta-lactamases (ESBLs). Twenty-five BSI episodes caused by P. mirabilis occurred at our hospital (Ospedale di Circolo e Fondazione Macchi, Varese, Italy) over a 7.5-year period. Phenotypic and molecular methods were used to assess ESBL production. Clinical records of BSI patients were examined retrospectively. Demographic data, underlying diseases (according to McCabe and Jackson classification and Charlson weighted index), risk factors, and treatment outcome were investigated by comparing cases due to ESBL-positive strains to cases due to ESBL-negative strains. Eleven isolates were found to express ESBLs (TEM-52 or TEM-92). The remaining 14 isolates were ESBL negative and were uniformly susceptible to extended-spectrum cephalosporins and monobactams. Comparison of the two groups showed that previous hospitalization in a nursing home (P = 0.04) and use of bladder catheter (P = 0.01) were significant risk factors for infections due to ESBL-positive strains. In addition, cases due to ESBL-positive strains showed a significantly higher mortality attributable to BSI (P = 0.04). BSI cases due to ESBL-negative isolates uniformly responded to therapy, whereas 5/11 cases due to ESBL-positive isolates failed to respond (P < 0.01). Use of carbapenems was associated with complete response independently of ESBL production. Therapeutic failure and mortality may occur in BSI episodes caused by ESBL-positive P. mirabilis isolates. Thus, recognition of ESBL-positive strains appears to be critical for the clinical management of patients with systemic P. mirabilis infections.     

Epidemiology and outcome of bicycle injuries presenting to an emergency department in the United Kingdom.

OBJECTIVES: To describe the epidemiology, injuries sustained and outcomes of patients presenting to an emergency department after a bicycle accident in Cambridge, England. METHODS: A prospective study was conducted of all individuals treated as a result of a cycling accident between 1 April 2003 and 31 July 2003. Information was collected from injured cyclists or relatives by a standardized questionnaire. This included patient demographics, details relating to the accident, and injuries sustained. RESULTS: A total of 293 injured cyclists presented during the study period. The most commonly injured were men (65.5%) in isolated bicycle accidents on roads without cycle paths during daylight hours. Only 20.8% of patients wore helmets. The majority of those injured at night (62.5%) had consumed alcohol (P<0.05). Upper limb injuries were most frequently sustained (64%), with an even distribution of lower limb (24%), head (23%) and facial (22%) injuries. Truncal and neck injuries were uncommon. CONCLUSIONS: Although it is recognized that the use of bicycle helmets contributes to a decrease in mortality from head injuries, this should not be the only focus for decreasing the morbidity associated with cycling accidents. Campaigns for safer cycling practice, more dedicated cycle routes and to discourage cyclists from drinking and cycling are essential to decrease the numbers of these injuries.     

英国MRSA感染预防和治疗指南

近10年来，MRSA感染率明显升高。虽然社区MRSA感染率增加，但MRSA感染主要仍见于医院、护理院、疗养院，部分社区MRSA感染也存在于医疗机构。改变MRSA感染的预防和治疗用药，可能会诱发新的MRSA克隆，所以合理应用抗菌药物，尤其是喹诺酮类很重要。     

Candida infections in the intensive care unit: epidemiology,risk factors and therapeutic strategies

This article reviews the epidemiology, predisposing risk factors and outcome of systemic Candida spp. infections in the intensive care unit setting. Incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years; while diagnosis of serious Candida infection may be difficult, the clinical conditions which predispose patients to these infections are now better understood and effective antifungal therapies are becoming increasingly available. Severe fungal infections are generally associated with poor outcomes in these patients. Patients at highest risk for Candida infection may be potential candidates for early, presumptive therapy. In this article we review antifungal treatment, including the use of polyenes, azoles and echinocandines, and the role of prophylaxis.     

Candida infections in the intensive care unit: epidemiology, risk factors and therapeutic strategies

This article reviews the epidemiology, predisposing risk factors and outcome of systemic Candida spp. infections in the intensive care unit setting. Incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years; while diagnosis of serious Candida infection may be difficult, the clinical conditions which predispose patients to these infections are now better understood and effective antifungal therapies are becoming increasingly available. Severe fungal infections are generally associated with poor outcomes in these patients. Patients at highest risk for Candida infection may be potential candidates for early, presumptive therapy. In this article we review antifungal treatment, including the use of polyenes, azoles and echinocandines, and the role of prophylaxis.     

The use of fluconazole and itraconazole in the treatment of Candida albicans infections: a review

Candida albicans is responsible for most fungal infections in humans. Fluconazole is well established as a first-line management option for the treatment and prophylaxis of localized and systemic C. albicans infections. Fluconazole exhibits predictable pharmacokinetics and is effective, well tolerated and suitable for use in most patients with C. albicans infections, including children, the elderly and those with impaired immunity. Prophylactic administration of fluconazole can help to prevent fungal infections in patients receiving cytotoxic cancer therapy. The increasing use of fluconazole for the long-term prophylaxis and treatment of recurrent oral candidosis in AIDS patients has led to the emergence of C. albicans infections that are not responsive to conventional doses. Second-line therapy with a wider spectrum antifungal, such as itraconazole, should be sought if treatment with fluconazole fails. A solution formulation of itraconazole has recently been introduced to overcome the poor and variable absorption of its original capsule formulation. Efficacy and tolerability studies in HIV-positive or immunocompromised patients with C. albicans infections have shown that, although itraconazole solution is as effective as fluconazole, it is less well tolerated as first-line therapy. Itraconazole solution can be effective in AIDS patients with C. albicans infections that are non-responsive to fluconazole. No efficacy or tolerability data are available on the use of itraconazole solution in children or the elderly.     

Pleiotropic effects of thiazolidinediones on traditional and non‐traditional atherosclerotic risk factors

Background: The thiazolidinediones pioglitazone and rosiglitazone have established efficacy in improving insulin sensitivity, glycaemic control, dyslipidaemia, hypertension and microalbuminuria in patients with type 2 diabetes. As specific agonists of peroxisome proliferator‐activated receptor‐γ, thiazolidinediones have also demonstrated protective effects on a variety of atherosclerosis biomarkers and surrogate measures of cardiovascular disease. Aim: This paper reviews the evidence for pleiotropic effects on a variety of non‐traditional atherosclerotic risk factors. Discussion: Thiazolidinediones attenuate circulating levels of pro‐inflammatory mediators in patients with type 2 diabetes, including C‐reactive protein, interleukin‐6, CD40L, monocyte chemoattractant protein‐1 and metalloproteinase‐9. These agents also increase levels of the vascular protective adipokine, adiponectin. The clinical significance of these findings is supported by evidence of improved endothelial dysfunction, reduced carotid intima media thickness and improvements in stenosis following coronary artery stent implantation in patients treated with thiazolidinediones. Limited data suggest that thiazolidinediones might also improve the circulating levels and functional activity of angiogenic endothelial progenitor cells, which independently predict the incidence of cardiovascular events and death. It should be noted that the US Food and Drug Administration and the European Medicines Agency have requested changes to the prescribing information for rosiglitazone to highlight the possibility of an increased risk with this agent in patients with ischaemic heart disease; on review, no such amendment was required for the pioglitazone prescribing information. Both agencies continue to suggest that the benefits of both thiazolidinediones outweight any possible detrimental effects. Further research remains to be conducted to elucidate the potentially differential vascular protective effects of thiazolidinediones. In the US, there are black box heart failure warnings for both agents. Conclusion: In light of the established importance of reducing cardiovascular risk in patients with type 2 diabetes, current evidence continues to support the use of pioglitazone within multifactorial risk management strategies.     

Population-based assessment of intensive care unit-acquired bloodstream infections in adults: Incidence,risk factors,and associated mortality rate

OBJECTIVE: Nosocomial bloodstream infections have been extensively investigated, but relatively few studies have specifically evaluated the epidemiology of intensive care unit-acquired bloodstream infections. The study objective was to define the incidence, risk factors, microbiology, and clinical outcomes of intensive care unit-acquired bloodstream infections. DESIGN: Population-based prospective cohort. SETTING: Multidisciplinary intensive care units. PATIENTS: All Calgary Health Region (population 930,000) adult patients admitted to multidisciplinary intensive care units (>/=48 hrs) from May 1, 1999, to April 30, 2000. INTERVENTIONS: Blood sample analysis. MEASUREMENTS AND RESULTS: There were 1,158 admission episodes in 1,017 patients; 37% involved females, and mean +/- sd age and Acute Physiology and Chronic Health Evaluation II scores were 59.6 +/- 18.7 yrs and 23.4 +/- 7.7, respectively. Fifty-one patients developed intensive care unit-acquired bloodstream infections (first positive blood culture >/=48 hrs after intensive care unit admission) for an incidence of 4.4% and an incidence density of 5.2 per 1000 intensive care unit days. Younger age (adjusted odds ratio, 0.98; 95% confidence interval, 0.96-1.00, p =.01), longer intensive care unit length of stay (adjusted odds ratio, 4.74; 95% CI, 3.26-6.90, p <.001), and lower hematocrit (adjusted odds ratio, 0.95; 95% confidence interval, 0.90-1.00, p =.04) were significant independent predictors of intensive care unit-acquired bloodstream infections, and these infections were associated with an increased intensive care unit length of stay of 2.86 days (95% confidence interval, 2.29-3.57, p <.001). Staphylococcus aureus (27%), coagulase-negative staphylococci (14%), and Enterococcus faecium (12%) were most commonly isolated. Four (8%) bloodstream infections involved antibiotic-resistant organisms, and ten (20%) were polymicrobial. In multivariate analysis, intensive care unit-acquired bloodstream infection was associated with an increased intensive care unit mortality rate (adjusted odds ratio, 2.03; 95% confidence interval, 1.03-4.00, p = 0.04) but not overall hospital mortality rate. CONCLUSIONS: One patient in 20 admitted to Calgary Health Region intensive care units acquires bloodstream infection and suffers longer intensive care unit stay and increased mortality rates. In our region, multiple antibiotic-resistant organisms are uncommon causes of bloodstream infections, suggesting that it may be safe to use narrower spectrum empirical treatment regimens than current guidelines recommend.     

Incidence,risk factors,and predictors of outcome of candidemia. Survey in 2 Italian university hospitals

In recent decades, Candida spp. emerged as the fourth most common cause of nosocomial bloodstream infections. The incidence of candidemia was 0.13 per 100 persons. Eighty-three cases (61%) of candidemia were due to Candida albicans and 53 (39%) to nonalbicans Candida spp. Twelve strains of Candida (9%) had shown in vitro resistance to fluconazole, 5 (4%) to itraconazole, 2 (1.5%) to voriconazole, 12 (9%) to 5-flucytosine, and 1 (0.7%) to amphotericin B. Multivariate logistic regression analysis of risk factors showed that length of hospitalization, presence of a central venous catheter, previous episodes of candidemia or bacteremia, parenteral nutrition, and chronic renal failure were variables independently associated with the development of candidemia. Multivariate logistic regression analysis of prognostic indicators showed that the independent variables associated with poor prognosis were inadequate initial therapy (P < .001) and high APACHE III score (P = .004). The inadequate initial therapy associated with mortality indicates the need for additional investigations to define high-risk patients for beneficial antifungal prophylaxis.     

Blue dye and red light, a dynamic combination for prophylaxis and treatment of cutaneous Candida albicans infections in mice

The objective of this study was to investigate photodynamic therapy (PDT), using blue dye and red light, for prophylaxis and treatment of cutaneous Candida albicans infections in mice. A mouse model of skin abrasion infected with C. albicans was developed by inoculating wounds measuring 1.2 cm by 1.2 cm with 10(6) or 10(7) CFU. The use of a luciferase-expressing strain of C. albicans allowed real-time monitoring of the extent of infection in mice noninvasively through bioluminescence imaging. The phenothiazinium salts toluidine blue O (TBO), methylene blue (MB), and new methylene blue (NMB) were compared as photosensitizers (PS) for the photodynamic inactivation of C. albicans in vitro. PDT in vivo was initiated either at 30 min or at 24 h after fungal inoculation to investigate the efficacies of PDT for both prophylaxis and treatment of infections. Light at 635 ± 15 nm or 660 ± 15 nm was delivered with a light dose of 78 J/cm(2) (for PDT at 30 min postinfection) or 120 J/cm(2) (for PDT at 24 h postinfection) in multiple exposures with bioluminescence imaging taking place after each exposure of light. In vitro studies showed that NMB was superior to TBO and MB as the PS in the photodynamic inactivation of C. albicans. The efficacy of PDT was related to the ratio of PS concentration to fungal cell density. PDT in vivo initiated either at 30 min or at 24 h postinfection significantly reduced C. albicans burden in the infected mouse skin abrasion wounds. These data suggest that PDT is a viable approach for prophylaxis and treatment of cutaneous C. albicans infections.     

Systematic review of prognostic factors predicting outcome in non‐surgically treated patients with sciatica

Identification of prognostic factors for surgery in patients with sciatica is important to be able to predict surgery in an early stage. Identification of prognostic factors predicting persistent pain, disability and recovery are important for better understanding of the clinical course, to inform patient and physician and support decision making. Consequently, we aimed to systematically review prognostic factors predicting outcome in non‐surgically treated patients with sciatica. A search of Medline, Embase, Web of Science and Cinahl, up to March 2012 was performed for prospective cohort studies on prognostic factors for non‐surgically treated sciatica. Two reviewers independently selected studies for inclusion and assessed the risk of bias. Outcomes were pain, disability, recovery and surgery. A best evidence synthesis was carried out in order to assess and summarize the data. The initial search yielded 4392 articles of which 23 articles reporting on 14 original cohorts met the inclusion criteria. High clinical, methodological and statistical heterogeneity among studies was found. Reported evidence regarding prognostic factors predicting the outcome in sciatica is limited. The majority of factors that have been evaluated, e.g., age, body mass index, smoking and sensory disturbance, showed no association with outcome. The only positive association with strong evidence was found for leg pain intensity at baseline as prognostic factor for subsequent surgery.     

Epidemiology, risk factors, and treatment of chronic migraine: a focus on topiramate

The term chronic daily headache refers to a heterogeneous group of headache disorders characterized by a frequency of headaches on ≥15 days per month. Chronic migraine is a subtype of chronic daily headache. The prevalence of chronic migraine is ∼1%. Baseline attack frequency and acute medication overuse have been identified as potential risk factors for the progression of migraine from an episodic disorder to a chronic condition. There is an unmet patient need for effective and safe treatments for patients with chronic migraine, but data from rigorous controlled trials are limited. Previous studies have demonstrated that topiramate is an effective and safe preventive treatment for episodic migraine. In addition, pilot studies have suggested the utility of topiramate for the prevention of chronic migraine. Two randomized, double-blind, placebo-controlled, multicenter trials investigating the efficacy and safety of topiramate in the treatment of patients with chronic migraine have recently been completed. This review presents comparative data from these 2 clinical trials, which suggest that topiramate at a dose of 100 mg daily is effective and generally well tolerated in chronic migraine.     

Characteristics of hypertension‐related factors in female home caregivers in Japan—comparison with general community non‐caregivers

Aims and objectives. To examine the characteristics of hypertension‐related factors in female family caregivers in Japan who provide care in the home, in comparison with general community non‐caregivers. Background. Hypertension is more frequently encountered in female caregivers than in non‐caregivers. Lifestyle factors including sleep and eating habits differ in Japanese female caregivers and the general population. Therefore, hypertension‐related factors in caregivers may also differ from those in the general population. Design. A cross‐sectional study. Methods. The subjects were 150 female caregivers (aged 62·4, SD 12·2 years) who provided home care for persons with physical impairments and/or dementia and 154 female controls (aged 62·7, SD 2·2 years) who did not provide home care. Persons with a history of ischaemic heart disease or cerebral stroke were excluded. Subjects were examined using a self‐reporting questionnaire that included a food frequency questionnaire and the tri‐axial coping scale. Urine examinations and blood pressure measurements were also done. Logistic regression analysis was conducted for each group with the same variables as explanatory variables. Results. Hypertension was present in 46·7% of caregivers and 34·4% of controls (p < 0·05). Menopause was a factor related to hypertension in both the caregivers and controls. In the caregiver group, hypertension was associated with the estimated 24‐h Na excretion in urine and the carbohydrate‐energy ratio for nutriti. BMI was associated with hypertension in the control group, but not in the caregiver group. Conclusions. Hypertension was associated with nutritional factors, such as greater Na excretion in urine and higher carbohydrate energy ratio, in Japanese female caregivers and with obesity in non‐caregivers. Relevance to clinical practice. To prevent hypertension, it is necessary to carefully monitor salt intake and nutritional balance in female caregivers in Japan.