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E Rubinstein

Publications and source records attributed to E Rubinstein.

At least 19 recordsLinked to original sources

Prevalence and genetic relatedness of community-acquired methicillin-resistant Staphylococcus aureus in Israel.

The aims of the study presented here were to determine the prevalence of Staphylococcus aureus carriage and, specifically, community-acquired methicillin-resistant S. aureus (CA-MRSA) carriage in children and their parents in Israel and to determine the genetic relatedness of these isolates. S. aureus was isolated from 580 of 3,373 (17.2%) individuals screened. The predominant type identified by pulsed-field gel electrophoresis was strain ST45-MSSA (25%). Five MRSA isolates were detected, and two of these were classified as CA-MRSA, based on the following criteria: no previous contact with a healthcare facility, absence of a multidrug-resistant (MDR) phenotype, and presence of SCCmec type IV. Isolates were negative for pvl and were classified as ST-45-MRSA. Although CA-MRSA is still rare in Israel, the genetic relatedness of the strains found in this study to a successful MSSA clone warrants close follow up.

Adolescent↗

A new approach for treatment of deep skin infections by an ethosomal antibiotic preparation: an in vivo study.

OBJECTIVES: Dermal and subdermal bacterial infections, caused mainly by Staphylococcus aureus, are currently treated by systemic antibiotics. The aim of the present study was to investigate a new approach to treat deep skin and soft tissue bacterial infections by dermal application of erythromycin in an ethosomal carrier. METHODS: A model for deep dermal S. aureus infection in mice was developed. The efficiency of ethosomal erythromycin applied to the skin-infected site was compared with intraperitoneal erythromycin administration and with local application of hydroethanolic erythromycin solution. The parameters evaluated were the development of dermal wound, histological sections and bacterial count of the infected tissue. RESULTS: The in vivo experiments demonstrated a very efficient healing of S. aureus-induced deep dermal infections when the mice were treated with ethosomal erythromycin. Bacterial counts and histological evaluation of the skin treated with ethosomal antibiotic revealed no bacterial growth and normal skin structure. On the contrary, no subdermal healing was observed in infected animals treated with topical hydroethanolic erythromycin solution. In this group, animals developed deep dermal abscesses and the dermal structures were destroyed where S. aureus colonies were present. Bacterial counts of the infected tissues were 1.06 x 10(7) and 0.27 x 10(7) cfu/g of tissue, respectively, on days 7 and 10. CONCLUSIONS: Therapy with ethosomal erythromycin applied to the skin of S. aureus-infected mice was as effective as systemically administered erythromycin, suggesting a new possibility to treat deep dermal infections by local application of antibiotic in ethosomal carrier.

Animals↗

Case clustering in infective endocarditis: the role of availability bias.

Limited data exist regarding the impact of variations in clinical practice and physicians' cognitive bias on the diagnosis of infective endocarditis (IE). As an illustration of these effects, unexpected clustering of IE diagnosis was encountered in a prospectively studied cohort. Transoesophageal echocardiography examinations for suspected IE were performed more frequently following a diagnosis of IE, and were associated with a subsequent cluster of IE cases. The cognitive bias of physicians resulting from a recent case of IE can lead to a transient increase in diagnosing additional cases of IE.

Bias↗

Selection of Bacillus anthracis isolates resistant to antibiotics.

OBJECTIVE: Long-term therapy for anthrax might induce antimicrobial resistance in Bacillus anthracis. The aim of the present study was to investigate the potential of 18 different antibiotics to select resistant isolates of B. anthracis, (ST-1 and Sterne strains). METHODS: Resistant isolates were selected by serial passages on brain heart infusion agar containing increasing concentrations of antibiotics (from the MIC upwards). RESULTS: The MICs of ciprofloxacin, ofloxacin and levofloxacin increased from 0.125-0.25 to 8 mg/L, that of moxifloxacin increased from 0.03-0.06 to 8 mg/L, in both strains, and the MIC of garenoxacin increased from 0.015 to 0.5 mg/L for the ST-1 strain and from 0.03 to 8 mg/L for the Sterne strain. The MICs of tetracycline and minocycline increased from 0.125 to 2-8 mg/L and 0.06 to 1 mg/L, respectively. The MIC of vancomycin increased from 2.5 to 20 mg/L for the ST-1 strain and from 5 to 20 mg/L for the Sterne strain. Linezolid exhibited an MIC increase from 2 to 4 mg/L for both strains. The MIC of quinupristin/dalfopristin increased from 0.125 to 64-128 mg/L. Erythromycin demonstrated an MIC increase from 1 to 128 mg/L, that of clarithromycin increased from 0.125 to 8-64 mg/L and that of telithromycin increased from 0.06-0.125 to 1-4 mg/L. The clindamycin MIC increased from 0.125-0.25 to 8 mg/L. Penicillin G and amoxicillin MICs increased from <1 mg/L to 128-512 mg/L. Isolates made resistant to one fluoroquinolone exhibited cross-resistance to the other quinolones except the ST-1 mutant strain which remained susceptible to garenoxacin. Cross-resistance to fluoroquinolones did not correlate with resistance to other antibiotics. CONCLUSION: The ease with which B. anthracis can be made resistant in vitro suggests that close monitoring of patients treated for anthrax is mandatory.

Anti-Bacterial Agents↗

In vitro post-antibiotic effect of fluoroquinolones, macrolides, beta-lactams, tetracyclines, vancomycin, clindamycin, linezolid, chloramphenicol, quinupristin/dalfopristin and rifampicin on Bacillus anthracis.

OBJECTIVES: The aim of this study was to investigate in vitro the post-antibiotic effect (PAE) of 19 antibacterial agents against two strains of Bacillus anthracis (ST-1 and Sterne strains). METHODS: PAE was determined by calculating the time required for the viable counts of antibiotic-exposed bacteria (at concentrations of 10x MIC and exposure for 2 h) at 37 degrees C to increase by 1 log10 above the counts observed immediately after antibiotic removal compared with the corresponding time for controls not exposed to antibiotics. RESULTS: The PAEs of the fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin and garenoxacin) were 2-5 h. The macrolide (erythromycin, clarithromycin and telithromycin) PAEs were 1-4 h, and that of clindamycin was 2 h. The PAEs induced by tetracycline and minocycline were 1-3 h. The PAEs induced by the beta-lactams (penicillin G, amoxicillin and ceftriaxone), vancomycin, linezolid and chloramphenicol were 1-2 h. The PAE induced by rifampicin was 4-5 h. Quinupristin/dalfopristin had the longest PAE, lasting for 7-8 h. CONCLUSIONS: Our results indicate that the PAE is unrelated to the MIC but may be related to the rapidity of bacterial kill. These observations may bear importance on treatment regimens of human anthrax.

Acetamides↗

Causative organisms of infective endocarditis according to host status.

A prospective study of infective endocarditis (IE) was conducted between 1994 and 2000 in Marseilles, France, and included 170 definite cases diagnosed with the use of modified Duke criteria. Classification of IE based on the aetiological agent was related to epidemiological characteristics, including age, gender and the nature of the injured valve. Enterococci and Streptococcus bovis were identified more frequently in older subjects (p 0.02), and S. bovis was also associated with mitral valve infection (p 0.03). Streptococcus spp. were found to be associated with native valves (p < 10(-3)), whereas coagulase-negative staphylococci and Coxiella burnetii were associated with intracardiac prosthetic material (p < 0.05). S. bovis and Staphylococcus aureus were the predominant species associated with presumably healthy valves (p < 0.05), whereas oral streptococci caused IE exclusively in patients with previous valve damage. The basic host status of IE patients has been linked to specific microorganisms, and this may be of value when empirical treatment is needed in patients who have received previous antibiotic therapy and whose blood cultures are negative.

Adolescent↗

Evaluation of Bacillus anthracis extractable antigen for testing anthrax immunity.

Three extractable Bacillus anthracis cell-wall-associated antigens were evaluated for potential use as skin testing agents, and as possible candidates for in-vitro diagnosis of anthrax immunity. Anthraxin and a partially purified extractable antigen (EAP) were produced from avirulent B. anthracis strain 34F2 (Sterne). The thermoextractable antigen used for the Ascoli reaction was obtained commercially. Guinea-pigs were immunised and boosted several times subcutaneously with the Sterne live veterinary anthrax vaccine. Four weeks after the last booster dose, animals were skin-tested with the three antigens. Serum antibody levels were also determined by ELISA, and the in-vitro T-cell response was evaluated by [3H]-thymidine incorporation. EAP was the most active antigen in both the serological and cellular reactions. EAP also elicited a distinct positive skin reaction in animals immunised with B. anthracis. The data obtained in this preliminary study indicated that extractable cell-wall antigens obtained from the vegetative form of B. anthracis may be used for skin tests and in-vitro testing of specific humoral and cell-mediated anthrax immunity.

Animals↗

Human corneal stromal tissue concentration after consecutive doses of topically applied 3.3% vancomycin.

AIMS: To evaluate vancomycin penetration into human corneal stromal tissue in patients treated with topical vancomycin eyedrops before penetrating keratoplasty (PKP). METHODS: Twenty four patients who underwent PKP, seven patients with keratoconus (group 1) and 17 patients with corneal scar or corneal decompensation (group 2). All patients received topical application of vancomycin eyedrops (concentration: 33 mg/ml) 10, 3, 2, 1 hour, and 15 minutes before the operation. Corneal cumulative vancomycin levels were assessed by bioassay. RESULTS: Mean vancomycin corneal stromal tissue concentration was 46.7 (SE 4.11) microg/g tissue. This value was four to 20-fold in excess of the MIC90 of vancomycin in Staphylococcus aureus (2-10 microg/ml). CONCLUSIONS: Vancomycin reached high corneal tissue concentrations that significantly exceeded the MIC90 (2-10 microg/ml) for most key Gram positive corneal pathogens. The ratio of vancomycin stromal concentration to protein concentration was statistically higher in group 2 (non-keratoconus).

Adult↗

Future trends in antimicrobial chemotherapy: expert opinion on the 43rd ICAAC.

The current document bestows an expert synopsis of key new information presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in 2003. Data is presented on the socio-political aspects of and policies on antimicrobial prescribing, novel mechanisms of resistance in Streptococcus pneumoniae, and current epidemiological trends in global resistance. Novel information on new (and existing) antimicrobial agents--new penicillins, cephalosporins, monobactams and oxipenem inhibitors, ketolides, glycopeptides, fluoroquinolones (and hybrids), peptides, daptomycin, aminomethylcyclines, glycylcyclines, and newer formulations of agents such as amoxycillin-clavulanate--provides renewed hope that resistant pathogens can be controlled through use of more potent agents. Improved strategies for the use of existing antimicrobial agents, such as the use of high-dose regimens, short-course therapy, also may delay or reduce the development of resistance and preserve the value of our antibiotic armamentarium.

Anti-Bacterial Agents↗

In vitro susceptibility of Bacillus anthracis to various antibacterial agents and their time-kill activity.

OBJECTIVES: To investigate the in vitro acquisition of resistance to antibiotics by Bacillus anthracis. METHODS: The in vitro activities of 18 antibacterial agents against two strains of B. anthracis, the Sterne strain and the Russian anthrax vaccine strain ST-1, were tested by determining the MICs and by measuring the rates of antibiotic kill at 5x and 10x MIC. RESULTS: The fluoroquinolones ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, the beta-lactams penicillin G and amoxicillin, the macrolide clarithromycin, the ketolide telithromycin, as well as clindamycin, rifampicin and quinupristin/dalfopristin had MICs in the range of 0.03-0.25 mg/L. Minocycline had an MIC of 0.03 mg/L, as did penicillin, against the ST-1 strain. Ciprofloxacin had an MIC of 0.03 mg/L against both strains. Erythromycin, vancomycin and the oxazolidinone linezolid were less active (MIC 0.5-2.5 mg/L). Ceftriaxone was the least active, having an MIC of 8.0 mg/L. Chloramphenicol was inactive (MIC > 256 mg/L). Quinupristin/dalfopristin, rifampicin and moxifloxacin showed the most rapid bacterial killing, achieving a complete eradication of detectable organisms (2 log(10) reduction within 0.5-3 h and 4 log(10) reduction within 0.5-4 h for both strains at concentrations of 5x and 10x the MIC). The beta-lactams and vancomycin demonstrated a 2-4 log(10) reduction within 5-15 h. Ceftriaxone had a similar effect to penicillin and amoxicillin against the ST-1 strain, but a slower effect than these two beta-lactams against the Sterne strain. The macrolides, tetracyclines and linezolid demonstrated a lower kill rate, while chloramphenicol did not kill at all. CONCLUSIONS: These data expand on the spectrum of agents recommended for the treatment of anthrax (ciprofloxacin, penicillin G and tetracyclines) and add new options, such as other fluoroquinolones, amoxicillin, rifampicin and quinupristin/dalfopristin, as potential therapeutic agents.

Anti-Bacterial Agents↗

Cefepime versus imipenem-cilastatin for treatment of nosocomial pneumonia in intensive care unit patients: a multicenter, evaluator-blind, prospective, randomized study.

In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (-16 to 8%) failed to exclude the predefined lower limit for noninferiority of -15%. In addition, therapy of pneumonia caused by an organism producing an extended-spectrum beta-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, -9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P = 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, -23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P = 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P = 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological efficacies. Cefepime appeared to be less active against organisms producing an ESBL, but primary and secondary resistance to imipenem was more common for P. aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia should be guided by local resistance patterns.

APACHE↗

Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence.

Widespread, increasing antibiotic resistance amongst the major respiratory pathogens has compromised traditional therapy of the major infective respiratory syndromes, including bacterial pneumonia and acute exacerbations of chronic bronchitis. Guidelines for antibiotic prescribing dating from the 1980s to 1990s, which attempted to address such problems, were commonly too prescriptive and difficult to apply, and took little account of end-user practice or locally prevalent resistance levels. Further confusion was caused by conflicting recommendations emanating from differing specialty groups. The evidence that such guidelines benefited either clinical outcomes or treatment costs has been disputed. They have probably had little effect on resistance emergence. We report the recommendations of an independent, multi-national, inter-disciplinary group, which met to identify principles underlying prescribing and guideline formulation in an age of increasing bacterial resistance. Unnecessary prescribing was recognized as the major factor in influencing resistance and costs. Antibiotic therapy must be limited to syndromes in which bacterial infection is the predominant cause and should attempt maximal reduction in bacterial load, with the ultimate aim of bacterial eradication. It should be appropriate in type and context of local resistance prevalence, and optimal in dosage for the pathogen(s) involved. Prescribing should be based on pharmacodynamic principles that predict efficacy, bacterial eradication and prevention of resistance emergence. Pharmacoeconomic analyses confirm that bacteriologically more effective antibiotics can reduce overall management costs, particularly with respect to consequential morbidity and hospital admission. Application of these principles should positively benefit therapeutic outcomes, resistance avoidance and management costs and will more accurately guide antibiotic choices by both individuals and formulary/guideline committees.

Community-Acquired Infections↗

Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes.

In addition to its known effects on keratinocyte proliferation and differentiation, the hormonal form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been shown to protect keratinocytes from UV- and chemotherapy-induced damage. Epidermal keratinocytes contain both the machinery needed to produce 1,25(OH)(2)D(3) and vitamin D receptors. The activation of the stress-activated protein kinases (SAPKs), such as c-Jun N-terminal kinase (JNK) and p38, is an early cellular response to stress signals and an important determinant of cell fate. This study examines whether modulation of these SAPKs is associated with the effects of 1,25(OH)(2)D(3) on keratinocytes under stress. HaCaT keratinocytes were exposed to heat shock, hyperosmotic concentrations of sorbitol, the epidermal growth factor receptor tyrosine kinase inhibitor AG1487, the pro-inflammatory cytokine tumor necrosis factor alpha, and H(2)O(2). These stresses activated both SAPKs. Pretreatment with 1,25(OH)(2)D(3) inhibited the activation of JNK by all stresses and the activation of p38 by heat shock, AG1478 and tumor necrosis factor alpha. Under the same conditions, treatment with 1,25(OH)(2)D(3) protected HaCaT keratinocytes from cytotoxicity induced by exposure to H(2)O(2) and hyperosmotic shock. The effect of 1,25(OH)(2)D(3) was dose-dependent, already apparent at nanomolar concentrations, and time-dependent, maximal after a 24-h pre-incubation. We suggest that inhibition of SAPK activation may account for some of the well-documented protective effects of 1,25(OH)(2)D(3) on epidermal cells during exposure to UV or chemotherapy and may also be related to the anti-inflammatory actions of the hormone in skin.

Calcitriol↗

CD9 and megakaryocyte differentiation.

It is shown that the tetraspanin CD9 has a complex pattern of distribution in hematopoietic cells and is heterogeneously expressed on human bone marrow CD34(+) cells. CD34(high)CD38(low)Thy1(+) primitive progenitors are contained in the population with intermediate CD9 expression, thus suggesting that CD9 expression may precede CD38 appearance. Cell sorting shows that colony-forming unit (CFU)-GEMM and CFU-GM are present in high proportions in this fraction and in the fraction with the lowest CD9 expression. Cells with the highest level of CD9 are committed to the B-lymphoid or megakaryocytic (MK) lineages, as shown by the co-expression of either CD19 or CD41/GPIIb and by their strong potential to give rise to CFU-MK. In liquid cultures, CD9(high)CD41(neg) cells give rise to cells with high CD41 expression as early as 2 days, and this was delayed by at least 3 to 4 days for the CD9(mid) cells; few CD41(high) cells could be detected in the CD9(low) cell culture, even after 6 days. Antibody ligation of cell surface CD9 increased the number of human CFU-MK progenitors and reduced the production of CD41(+) megakaryocytic cells in liquid culture. This was associated with a decreased expression of MK differentiation antigens and with an alteration of the membrane structure of MK cells. Altogether these data show a precise regulation of CD9 during hematopoiesis and suggest a role for this molecule in megakaryocytic differentiation, possibly by participation in membrane remodeling. (Blood. 2001;97:1982-1989)

ADP-ribosyl Cyclase↗

Do guidelines for community-acquired pneumonia improve the cost-effectiveness of hospital care?

There is growing pressure to demonstrate the value of practice guidelines. We have reviewed the evidence that guidelines for the treatment of community-acquired pneumonia (CAP) change current practices and that the standardization of practices reduces costs and/or improves outcome. The most obvious barrier to implementation of the guidelines is lack of knowledge about their content; equally important are the attitudes and behavior of professionals, patients, and their caregivers. Guidelines may improve the outcome of CAP, provided that there is an association between variations in outcome and some specific processes of care. Conversely, when there is no such relationship, guidelines may reduce the cost of care without having an adverse effect on outcome. The cost-effectiveness of CAP guidelines in an individual hospital depends on the systems that are available to identify patients with CAP and to measure the processes of care. There is good evidence that following the recommendations of the CAP guidelines does improve the cost-effectiveness of care and, therefore, that an audit of CAP may be worth the effort.

Community-Acquired Infections↗

Transepithelial intestinal excretion of ciprofloxacin in humans.

The excretion of ciprofloxacin in the small bowel was studied in 40 patients undergoing bowel surgery. Ciprofloxacin (200 mg) was administered iv, and intestinal samples were collected over a 120-min period. In ileal loops ciprofloxacin concentrations reached a peak of 4.0 mg/L, whereas in caecal fluid samples, concentrations were < 0.16 mg/L. Ciprofloxacin administered directly into the ileal and caecal loops did not result in measurable blood levels for 2 h. The results confirm that ciprofloxacin is selectively excreted into the small bowel.

Aged↗