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Ethan Rubinstein

Publications and source records attributed to Ethan Rubinstein.

31 records · Page 2Linked to original sources
PubMed2003

Independent risk factors for carriage of penicillin-non-susceptible Streptococcus pneumoniae.

Antibiotic treatment, day-care center (DCC) attendance and young age are associated with penicillin-non-susceptible Streptococcus pneumoniae (PNSSp) carriage. Yet, it is unclear whether each is an independent risk factor for the individual. This cross-sectional surveillance study was designed to answer this question. Nasopharyngeal cultures were obtained from 429 children (< 6 y) during a visit to the pediatrician's office. Two risk rates were calculated: the individual's absolute risk to carry PNSSp [simple odds ratio (ORS)] and the risk of an individual who is already a carrier [conditional odds ratio (ORC)]. Streptococcus pneumoniae was isolated from 52.7% of 401 children. PNSSp was detected in 37.1% of carriers. Independent risk factors were: young age [ORS 2.24, 95% confidence interval (95% CI) 1.2-4.2], DCC attendance (ORS 3.8, 95% CI 1.9-7.5), having young siblings (ORS 2.3, 95% CI 0.95-5.57) and each antibiotic treatment during the previous 3 months (ORS 1.5, 95% CI 1.25-1.85). The only significant risk factor among carriers was prior antibiotic treatment (ORC 2.24, 95% CI 1.64-3.05). Young children, who attended DCC and received 1 antibiotic course (9% of the population) had a risk 12.9 times higher than children without these features.

Age Distribution↗
PubMed2003

Experimental pneumococcal pleural empyema model: the effect of moxifloxacin.

OBJECTIVES: Pleural empyema is a serious complication of pneumonia, the optimal therapy of which is still unknown. The objective of this study was to evaluate the use of moxifloxacin in this condition. METHODS: Pleural empyema was induced in rabbits by intrapleural administration of Pasteurella multocida (10(5-6) cfu) or turpentine (0.3 mL) followed 3 h later by instillation of Streptococcus pneumoniae (ATCC 49619) (10(6) cfu) into the pleural cavity. The MICs of moxifloxacin for S. pneumoniae and P. multocida were 0.4 and 0.05 mg/L, respectively. Starting 30 h following S. pneumoniae challenge intramuscular moxifloxacin 12.5 and 25 mg/kg was administered x 4 (every 12 h). Pleural empyema fluid samples were obtained for bacterial count at 12 h intervals following the first three moxifloxacin administrations. Moxifloxacin levels in pleural empyema and serum samples were obtained at 0, 30, 60, 120, 240, 360 and 480 min and 12 h after the 4th dose and determined by bioassay. RESULTS: In control animals, S. pneumoniae (and P. multocida) persisted in the pleural empyema. S. pneumoniae also persisted in the pleural empyema fluid when moxifloxacin was administered at 12.5 mg/kg (x4 administrations). Mean serum and pleural empyema peak moxifloxacin levels (following the 25 mg/kg dose) were 7.6 (+/-3.2) and 4.8 (+/-2.5) mg/L, respectively. Pleural empyema peak moxifloxacin concentration lagged 1 h after serum moxifloxacin. Serum and pleural empyema half-lives were approximately 1.5 and approximately 6 h, respectively. Serum AUC(1-12) was 29.4 (+/-6.8) mg.h/L and serum area under the inhibitory concentration curve (AUIC) was 73.5 mg.h/L. Pleural empyema AUC(1-12) was 34.3 (+/-11.7) mg/L and pleural empyema AUIC was 85.8 mg.h/L. S. pneumoniae was eradicated from pleural empyema following a single dose of moxifloxacin 25 mg/kg in 52% of the animals and in 96% following four doses. Moxifloxacin was also effective in eradication of P. multocida. The rate of pleural empyema sterilization was related to moxifloxacin serum AUIC (r = 0.82) as well as serum peak moxifloxacin level (r = 0.84), but not to pleural empyema AUIC (r = 0.19) or pleural empyema peak levels. The results were similar for both methods of induction of pleural empyema. CONCLUSIONS: Moxifloxacin appears to penetrate well into experimental pleural empyema and effectively sterilize it from S. pneumoniae. Sterilization of S. pneumoniae is related to serum AUIC rather than to moxifloxacin pharmacokinetics in pleural empyema.

Animals↗
PubMed2003

Worldwide assessment of linezolid's clinical safety and tolerability: comparator-controlled phase III studies.

Linezolid, an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens including multidrug-resistant staphylococci, enterococci, and pneumococci. Safety assessments were conducted for 2,046 linezolid-treated patients and 2,001 comparator drug-treated patients from seven controlled clinical trials comparing the activities of linezolid and comparator drugs against nosocomial and community-acquired pneumonia, skin and skin structure infections, and methicillin-resistant staphylococcal infections. Drug-related adverse events were primarily transient. The most frequent (> or = 2%) adverse events caused by linezolid and the comparator drugs were diarrhea (4.3 and 3.2%, respectively; P = 0.074), nausea (3.4 and 2.3%, respectively; P = 0.036), and headache (2.2 and 1.3%, respectively; P = 0.047). Treatment discontinuations due to drug-related events (2.4 and 1.9%, respectively), serious adverse events (11.4 and 10.6%, respectively), and deaths (4.8 and 4.9%, respectively) were similar. No clinically significant drug-related hematologic events were reported, and laboratory safety data were comparable. In the first 6 months of postmarketing surveillance, hematologic abnormalities were reported in 0.1% of linezolid-treated patients, but no irreversible blood dyscrasias were documented. The risk for transient, reversible hematologic effects from treatment with linezolid should be considered together with the clinical benefits associated with its use.

Acetamides↗
PubMed2002

Biological Warfare: Implications for Antimicrobial Use.

Biological warfare is intended to incapacitate a large number of individuals at a single exposure, creating epidemic-type disease, death, and social chaos. The organisms with potential for immediate use as bacteriologic weapons are Bacillus anthracis, Brucella melitensis, Yersinia pestis, and Vibrio cholera, all necessitating antibiotic therapy for a cure. It is reasonable, therefore, to assume that a biological attack, or even a hoax, would requiure thousands of individuals over a large area to begin antibiotic therapy. Issues such as antibiotic availability, logistical problems in antibiotic distribution, development of drug resistance, side effects influencing the individual, and adverse effects on the community due to the impact of mass therapy on the ecology, make biological warfare the most apocalyptic scenario for the creation of a "postantibiotic era."

Journal Article↗
PubMed2002

Novel agents for resistant Gram-positive infections--a review.

Gram-positive infections have increased in recent years, particularly those that are of nosocomial origin, leading to a broad use of agents with activity against these pathogens. Concomitantly, antimicrobial resistance of these pathogens also became widespread. Among the most common Gram-positive resistant pathogens are: Streptococcus pneumoniae, resistant to penicillin and macrolides, methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediately-resistant S. aureus (GISA), methicillin-resistant S. epidermidis, glycopeptide-resistant enterococci and vancomycin-resistant enterococci (VRE). The response of the pharmaceutical industry to this challenge was the development of new antibiotics active against these pathogens. Among these antibiotics, this review will focus on: linezolid, an oxazolidinone; GAR-936, a tetracycline derivative; daptomycin, a lipopeptide; and ortivancin (LY-333328), a glycopeptide related to vancomycin. Except for linezolid, which has been recently launched in many countries, all other agents referred to in this review are still at various developmental stages. It is hoped that in the near future most of these agents will be approved and thus the grim outlook of patients infected with resistant Gram-positive bacteria may improve.

Anti-Bacterial Agents↗
PubMed2002

Once-daily versus twice-daily intravenous administration of vancomycin for infections in hospitalized patients.

The efficacy and toxicity of once-daily (od) versus twice-daily (bd) dosing of vancomycin was compared in 121 hospitalized patients. Eighteen patients were then withdrawn from the study. Clinical and bacteriological responses were evaluated in all patients (n = 103). Nephrotoxicity was assessed in patients who did not receive nephrotoxic agents (n = 76). Ototoxicity was assessed in patients who completed two audiograms and were not receiving ototoxic agents (n = 63). No significant difference was found between the two groups for favourable clinical response: 47/51 (92.1%) and 49/52 (94.2%) in the od and bd groups, respectively. In 34 patients vancomycin was the only effective antibiotic. Fifteen of 18 (83.3%) evaluated episodes in the od and 12/16 (75.0%) evaluated episodes in the bd group showed a favourable bacteriological response. There were no significant differences between the od and bd groups for all adverse events. Nephrotoxicity developed in 4/37 (10.8%) and 3/39 (7.7%) patients, respectively. Hearing loss developed in 1/31 (3.2%) and 5/32 (15.6%). Phlebitis occurred in 7/51 (13.7%) and 12/52 (23.0%). Red man syndrome occurred in 7/51 (13.7%) and 5/52 (9.6%) in od and bd groups, respectively. The efficacy and safety profile of od administration of vancomycin is similar to that of the customary, but less convenient, bd administration.

Adolescent↗
PubMed2002

Appropriate use of antibiotics for respiratory infections: review of recent statements and position papers.

Respiratory infections are among the most common reasons for prescribing antibiotics. The excessive use of antibiotics in ambulatory practice has contributed to the emergence and spread of antibiotic resistance. The appropriate use of antimicrobial agents for respiratory infections could potentially reduce the emergence of antibiotic resistance. This article reviews recent guidelines and position papers on the appropriate antibiotic treatment for respiratory infections. There is a wide consensus that antibiotics are not appropriate for the treatment of most cases of acute bronchitis, pharyngitis, and rhinosinusitis. The recently published community-acquired pneumonia guidelines emphasized the importance of selecting antibiotic regimens active against both typical and atypical pathogens. However, there is disagreement regarding the routine use of the new quinolones.

Ambulatory Care↗
PubMed2002

Role of agr (RNAIII) in Staphylococcus aureus adherence to fibrinogen, fibronectin, platelets and endothelial cells under static and flow conditions.

In the present study, the adherence of Staphylococcus aureus (strain 83254) and its RNAIII mutant (WA400) to immobilised fibrinogen and fibronectin, and to human endothelial cells (EC), was studied. [3H]Thymidine-labelled bacteria in stationary phase were incubated on the test surfaces for 20 min under static or flow (200/s) conditions. The results showed: (a) increased adherence of the RNAIII mutant to fibrinogen under static conditions, and decreased adherence of the mutant to fibronectin and EC under both static and flow conditions compared with the parental strain; (b) stronger ability of the mutant compared with the parental strain to induce platelet aggregation in suspension; (c) greater adherence of the parental strain and the mutant to EC pre-treated with platelet-rich plasma compared with platelet-poor plasma, and to EC pre-treated with platelet-poor plasma compared with control; (d) increased adherence of S. aureus to EC pre-treated with PMA-activated platelets and decreased adherence to EC pre-treated with tirofiban, a platelet glycoprotein IIb-IlIa inhibitor, which paralleled with increased adherence of PMA-activated platelets and decreased adherence of glycoprotein IIb-IIIa-blocked platelets to EC in the absence of bacteria; and (e) adherence of the mutant was more sensitive to pre-treatment of EC with plasma and PMA-activated platelets. In conclusion, RNAIII down-regulates S. aureus adherence to fibrinogen under static condition and up-regulates S. aureus adherence to fibronectin and EC under both static and flow conditions. The potentiating role of activated platelets in the presence of plasma in S. aureus adherence to EC is down-regulated by RNAIII, probably due to down-regulation of adherence to fibrinogen, the important plasma protein bridging S. aureus, platelets and EC.

Bacterial Adhesion↗
PubMed1996

Macrolides as first line therapy in adult lower respiratory tract infections: pros and cons.

Certain guidelines exist to facilitate the decision as to which patients with lower respiratory tract infections require antibiotics. The decision as to which antibiotic to use must depend on a detailed knowledge of the disease and the patient's condition. Recent recommendations recognize four categories of patients with community-acquired pneumonia and adopt somewhat different treatment strategies for each. In industrialized countries, macrolides are regarded as either first- or second-choice therapy for community-acquired pneumonias of all grades of severity.

Journal Article↗
PubMedDate not supplied

Inhaled zanamivir versus placebo for the prevention of influenza outbreaks in an unvaccinated long-term care population.

BACKGROUND: Antiviral chemoprophylaxis effectiveness for influenza control has not been prospectively established for unvaccinated residents of long-term care facilities. This study evaluated the efficacy and tolerability of zanamivir against the standard of care (no intervention, ie, placebo) for influenza outbreak control in a largely unvaccinated institutionalized population. OBJECTIVE: To evaluate the efficacy and tolerability of zanamivir versus placebo for influenza outbreak control in long-term care facilities. METHODS: This double-blind, randomized, placebo-controlled study prospectively enrolled/followed residents of long-term care facilities (LTCF) at 12 centers for 1 to 3 influenza seasons (1997 to 2000). Following influenza outbreak declaration, asymptomatic subjects were randomized for prophylaxis to inhaled zanamivir 10 mg or inhaled placebo given once daily for 14 days. The proportion of randomized subjects who during prophylaxis developed symptomatic, laboratory-confirmed influenza (SLCI) was the primary end point. RESULTS: Influenza outbreaks were explosive. The attack rates varied from 9.5 to 14.8 per 100 residents. Of 1763 consents given and resulting in 494 randomizations, 49% received zanamivir and 51% placebo; 66% were elderly and 9% were vaccinated. SLCI occurred in 6% of zanamivir and 9% of placebo subjects (P = .355; protective efficacy for zanamivir = 29%, 95% confidence interval 31% to 62%), and symptomatic influenza confirmed by culture in 2% and 6%, respectively (P = .052; protective efficacy = 65%, 95% confidence interval 8.5% to 86%). Zanamivir use was also associated with a 70% (95% confidence interval 13% to 89%) reduction in laboratory-confirmed influenza with fever (2% vs 6%, P = .043). Influenza B was not detected. Zanamivir was well tolerated. No virus isolate demonstrated zanamivir resistance. CONCLUSIONS: The protective efficacy of zanamivir versus placebo for SLCI was marginal, for all laboratory confirmed illnesses, but significant against culture proven and febrile influenza, suggesting zanamivir can be effective for outbreak control and symptom reduction of unvaccinated institutionalized residents. Zanamivir had an acceptable safety profile in elderly, high-risk LTCF residents and was not associated with the emergence of resistant strains.

Administration, Inhalation↗