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Y Schlesinger

Publications and source records attributed to Y Schlesinger.

At least 19 recordsLinked to original sources
PubMed2006

Prospective drug utilization evaluation of three broad-spectrum antimicrobials: cefepime, piperacillin-tazobactam and meropenem.

BACKGROUND: Cefepime, piperacillin-tazobactam and meropenem are among the broadest-spectrum and most expensive antimicrobials. AIM: To evaluate guidelines for appropriate use of these drugs. METHODS: We developed guidelines for use of these antibiotics, and conducted a two-phase drug utilization evaluation. We included all patients who received one of the study drugs during two 3-month periods, with an educational intervention in the intervening period. Appropriateness was determined for initiation of treatment, and for adaptation or continuation of established treatment. RESULTS: Overall, 205 patients received 271 courses with one of these antibiotics, for a total of 709 defined daily doses (DDD) of cefepime, 543 of piperacillin-tazobactam, and 680 of meropenem (8.3, 6.3 and 7.9 DDD/1000 admission days, respectively). Of these 271 courses, 234 were appropriate (86%). Treatment was continued for > or =5 days in 60%, of which 88% were appropriate (NS). Of the 271 courses, 210 (77%) were empirical (83% appropriate), while 61 (23%) were based on a relevant culture result (97% appropriate) (p < 0.001). Appropriateness differed significantly between departments (p < 0.001), and between the two phases (p < 0.001). The major difference between the two surveys was a decrease in meropenem usage (p < 0.05). DISCUSSION: The vast majority of courses with cefepime, piperacillin-tazobactam and meropenem are empirically selected and continued, underlying the importance of an optimal initial choice. Antibiotic guidelines, in conjunction with formal infectious disease consultation, can contribute to more appropriate use of these drugs.

Anti-Bacterial Agents↗
PubMed2006

Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram.

OBJECTIVE: To determine normal concentrations of procalcitonin in preterm infants shortly after birth and to assess its accuracy in detecting bacterial infection. METHODS: Blood samples of 100 preterm infants were prospectively drawn during the first 4 days of life for determination of procalcitonin concentration. Infants were classified into four groups according to their sepsis status. RESULTS: Mean (SD) gestational age and birth weight were 32 (2.9) weeks and 1682 (500) g respectively. A total of 283 procalcitonin concentrations from healthy infants were plotted to construct nomograms of physiologically raised procalcitonin concentration after birth, stratified by two groups to 24-30 and 31-36 weeks gestation. The peak 95th centile procalcitonin concentration was plotted at 28 hours of age; values return to normal after 4 days of life. Only 12 infants were infected, and 13 of their 16 procalcitonin concentrations after birth were higher than the 95th centile, whereas samples taken at birth were lower. In a multivariable analysis, gestational age, premature rupture of membrane, and sepsis status influenced procalcitonin concentration independently, but maternal infection status did not. CONCLUSIONS: The suggested neonatal nomograms of preterm infants are different from those of term infants. Procalcitonin concentrations exceeding the 95th centile may be helpful in detecting congenital infection, but not at birth.

Aging↗
PubMed2006

Assessment of the clinical significance of production of extended-spectrum beta-lactamases (ESBL) by Enterobacteriaceae.

BACKGROUND: We conducted a retrospective, cohort-controlled study to evaluate the effect of extended-spectrum beta-lactamase (ESBL) production by Enterobacteriaceae isolated from blood cultures, and of third or fourth generation cephalosporin treatment, on outcome. METHODS: Four hundred and fifty patient-unique Enterobacteriaceae, isolated from blood cultures during 2000 (before routine ESBL testing was introduced), were tested for ESBL by double-disk method and by E-test, assessing cefotaxime, ceftazidime and cefpodoxime, with and without clavulanate. Cases consisted of ESBL-positive (+) samples, originally reported as ceftazidime-susceptible; controls were ESBL-negative (-). Patient records were extensively reviewed. RESULTS: We identified 68 Enterobacteriaceae that were ESBL(+); they were compared with 186 ESBL(-) control organisms. Patients with sepsis due to an ESBL(+) organism more often had nosocomial infection, resided in nursing homes, were functionally dependent, had an indwelling catheter, had Klebsiella, and had a lower serum albumin level (all p < 0.001). Survival of patients with ESBL(+) and ESBL(-) sepsis was, respectively, 71% and 84% (p < 0.05). Multivariate analysis revealed that the only independent risk factor for death was a low serum albumin. Neither empiric nor definite treatment with cephalosporins was found to be an independent risk factor for death. Subset analysis was conducted on 15 patients with ESBL(+) sepsis and 21 controls with ESBL(-) sepsis, who had been treated with ceftazidime or cefepime only. In this subset, ESBL(+) patients more often resided in nursing homes (< 0.05), they had a significantly lower APACHE-II score (< 0.01) and the infection was more often nosocomial (< 0.005). Survival of ESBL(+) and ESBL(-) patients was 67% and 71%, respectively (NS). Time till defervescence did not differ between cases and controls. CONCLUSION: Mortality of patients with ESBL(+) sepsis was higher than that of patients with ESBL(-) sepsis. The reason appears to be related to other factors rather than to empiric treatment with cephalosporins or the nature or resistance pattern of the organism. This, at least, appears to be the case for patients with urosepsis, who constituted the majority of patients in this study.

Adult↗
PubMed2006

Group A streptococcus bacteraemia: comparison of adults and children in a single medical centre.

Group A streptococcus (GAS) bacteraemia is often associated with soft-tissue infection, with significant morbidity and mortality. Little is known concerning the differences between adults and children with GAS bacteraemia. Records for 98 of 116 cases of GAS bacteraemia (60 adults and 38 children, aged 7 days to 96 years) occurring during a 10-year period (1993-2002) were located and reviewed. GAS bacteraemia comprised 0.6% of all bacteraemias in adults, compared to 3.3% in children (p < 0.001). The rate of adult GAS bacteraemia was two cases/1000 hospitalisations, compared to 13/1000 in children (p < 0.001). Seventy-six (78%) patients had concomitant tissue involvement, with skin or soft-tissue infection being the most common (62%). Fifty-three (88%) of 60 adults and five (13%) of 38 children had underlying conditions (p < 0.001). Twelve patients died, only one of whom was a child. Parameters associated with mortality were older age, lower temperature, hypotension, a need for surgical intervention, toxic shock syndrome, disseminated intravascular coagulation, thrombocytopenia, lymphopenia, hypocalcaemia, renal failure and acidosis (p < 0.05).

Academic Medical Centers↗
PubMed2005

Prospective hospital-wide studies of 505 patients with nosocomial bacteraemia in 1997 and 2002.

We conducted surveys in 1997 and 2002 to determine the rate, underlying sources and outcome of nosocomial bacteraemia. Blood culture results were reviewed daily. All patients with positive cultures drawn >or=48 h after hospitalization were included in the study and their charts were reviewed. The underlying source of infection was determined by pre-defined clinical and/or microbiological criteria. Patients were followed until discharge or death. In 1997 and 2002, 851 and 857 patient-unique cases of bacteraemia were diagnosed, respectively, excluding contaminants; of these, 228 (27%) and 277 (32%) cases, respectively, were hospital acquired (P<0.05). The overall rate decreased from 7.5 to 7.0 per 1,000 admissions (P<0.001). The sources of bacteraemia in 1997 and 2002, respectively, were: intravascular catheters (36% and 27%, P<0.05), urinary tract (8% and 15%, P<0.05), respiratory tract (5% and 13%, P<0.01) and surgical sites (14% and 4%, P<0.001). In one-third of patients, the source of bacteraemia could not be determined. Only 52% and 54%, respectively, of these patients were discharged alive (difference was not significant). In 1997, Staphylococcus aureus was the most frequent isolate (26%), followed by coagulase-negative Staphylococcus (13%) and Klebsiella pneumoniae (11%). By 2002, the incidence of S. aureus had fallen to 11% (P<0.001), acinetobacter was the single most frequently isolated organism (increased from 6% to 17%) (P<0.001). In-hospital mortality associated with acinetobacter bacteraemia (57%) was significantly higher than that for other organisms (31-43%) (P<0.05). In conclusion, prospective surveys of nosocomial bacteraemias provide valuable information, facilitating the pursuit of successful interventions.

Acinetobacter↗
PubMed2005

Non-Typhi Salmonella gastroenteritis in children presenting to the emergency department: characteristics of patients with associated bacteraemia.

The records of children with Salmonella gastroenteritis only (n = 97), and those with associated bacteraemia (n = 64), seen in one medical centre during a 12-year period, were analysed retrospectively. Mean patient age was 2.24 +/- 2.8 years (range, 0.05-16 years), and 49% were male. Children with bacteraemia presented after a longer duration of symptoms (7.0 +/- 6.9 vs. 3.9 +/- 4.6 days, p 0.0002), and had higher erythrocyte sedimentation rates (45 +/- 22 vs. 33 +/- 22 mm/h, p < 0.02) and lactate dehydrogenase values (924 +/- 113 vs. 685 +/- 165 IU/L, p 0.001). There was a trend in bacteraemic children towards immunosuppression (6.3% vs. 1.0%, p 0.08) and a lower number of siblings (2.9 +/- 1.9 vs. 3.8 +/- 2.7, p 0.063). Non-bacteraemic children had a more severe clinical appearance, and a higher percentage had a moderate to bad general appearance (51.5 vs. 29.7%, p < 0.01), with dehydration (37.1 vs. 18.8%, p 0.02) and vomiting (58.8 vs. 39.0%, p 0.02). Laboratory dehydration indicators were also markedly worse in non-bacteraemic children, with urine specific gravity of 1020 +/- 9.4 vs. 1013 +/- 9.0 (p 0.0002), base excess of - 4.2 +/- 3.0 vs. - 2.5 +/- 3.4 mEq/L (p 0.01), and blood urea nitrogen of 10.1 +/- 7.0 vs. 7.4 +/- 4.5 mg% (p 0.002). Thus, the clinical presentation of bacteraemic children was more gradual, and associated gastroenteritis and dehydration was less pronounced. These findings may contribute in part to the inadvertent discharge of bacteraemic children from the emergency department.

Adolescent↗
PubMed2003

Susceptibility trends in bacteraemias: analyses of 7544 patient-unique bacteraemic episodes spanning 11 years (1990-2000).

The aim of the present study was to design more accurate tools for the selection of appropriate antimicrobial therapy for hospitalized patients with suspected sepsis. We created a large database comprising data on all patient-unique blood cultures obtained over an 11 year period (1 January, 1990 through 31 December, 2000). Improved statistical tools were applied to assess the trends in in vitro activity of individual antibiotic agents against various bacteria over time, and to calculate susceptibility rates of subsets of organisms. During the 11 year study period, 173571 blood cultures were obtained, of which 17703 (10.2%) were positive, with 7544 patient-unique blood cultures (4.3%). The mean annual number of positive, patient-unique cultures was 686 (standard deviation=79). The 10 most frequently isolated organisms were: Escherichia coli (1494), Staphylococcus aureus (1240), Klebsiella pneumoniae (779), Enterococcus spp. (631), Pseudomonas aeruginosa (488), Streptococcus pneumoniae (447), Enterobacter spp. (338), Acinetobacter spp. (298), Proteus mirabilis (260) and Candida spp. (254). No significant change was detected in the annual rates (means, standard deviations) per 1000 admissions of these organisms: the highest was E. coli (5.5, 1), the lowest was Candida (1, 0.3). Forty percent of organisms (N=2943) were obtained from patients in the emergency department (ED), 23% (1744) in medical departments, 15% (1134) in paediatric units, 13% (998) on surgical wards and 9% (709) in intensive care units (ICUs). Trend statistical analysis revealed a significant decrease in susceptibility in ED Enterobacteriaceae to eight of 15 (53%) tested antimicrobials, with a mean annual decrease of 1.6%+/-0.6%, in the ICU isolates, a significant decrease was detected in only five (33%) of the tested antimicrobials, with a mean annual decrease of 2.5%+/-1.3%. The difference in susceptibility between ED and ICU isolates was significant for all antimicrobials (P<0.001). A significant decrease in the susceptibility of E coli to nine of 15 drugs (60%) was detected, ranging from 0.7% to 2.7% annually. In K. pneumoniae a significant decrease in susceptibility of K. pneumoniae was detected with only two agents. Pseudomonas spp. isolates remained highly sensitive to all traditional anti-pseudomonal agents, without significant decay in sensitivity rates over time. Susceptibility of S. aureus to methicillin decreased significantly for several subsets of patients (P<0.001). Marked differences in susceptibility rates between the departments were detected. Trend statistical analyses, when appropriately applied to multi-year databases of microbial susceptibilities, may yield susceptibility tables that are significantly more accurate than traditional semi-annual or annual tables.

Anti-Bacterial Agents↗
PubMed2003

Urine polymerase chain reaction as a screening tool for the detection of congenital cytomegalovirus infection.

OBJECTIVES: To define the incidence of congenital cytomegalovirus (CMV) infection in a defined population in Israel as diagnosed by urine polymerase chain reaction (PCR), and to assess the utility of this method for screening for congenital CMV infection. DESIGN: A convenient sample of urine specimens from asymptomatic newborns were subjected to CMV PCR. Positive results were validated by urine tube culture and by determination of serum CMV IgM antibodies. Maternal CMV IgG was determined in a representative sample of mothers. Newborns with positive urine specimens underwent full clinical evaluation. Epidemiological characteristics of the mothers were extracted from the medical records. SETTINGS: Two medical centres in Israel with different population characteristics. PATIENTS: A total of 2000 newborns (1000 in each medical centre). MAIN OUTCOME MEASURE: Presence of CMV DNA in the urine. RESULTS: Despite significant epidemiological differences between the populations in the two hospitals, the CMV seroprevalence was similar, 80.5% and 85%. Fourteen of the 2000 newborns screened (0.7%) were PCR positive. Urine culture was positive in nine of 10 specimens; IgM was positive in only two of 13 newborns with positive PCR. Eleven newborns underwent full or partial evaluation, and only one (9%) was symptomatic. CONCLUSIONS: The incidence of congenital CMV infection in the study population was 0.7%; over 90% were asymptomatic. Urinary CMV PCR is a reliable, rapid, and convenient method, and thus may serve as a screening tool for the detection of congenital CMV infection.

Cytomegalovirus↗
PubMed2002

Changing epidemiology of infective endocarditis: a retrospective survey of 108 cases, 1990-1999.

The aim of this study was to report the experience with infective endocarditis over the past decade, describe the changing clinical and epidemiological features of the disease, and attempt to determine the optimal number of blood culture sets required for diagnosis. All cases diagnosed during a 10-year period were reviewed clinically and microbiologically. In addition, a retrospective assessment of blood culture data was performed. From the period 1990-1999, 108 cases that met the von Reyn or Duke's criteria were recorded. The major underlying cardiac condition was the presence of a prosthetic valve ( n=33 patients, 31%). Among patients with native valves, nonrheumatic valvular heart disease of the elderly was the most common underlying factor ( n=19 patients, 25%). Overall, 13 patients (11%) died. Predictors on admission for increased mortality were shortness of breath, age >60 years, time to defervescence, erythrocyturia, hemoglobin level <10 g/dl, and leukocytosis >15,000 (all P<0.05). Analysis of blood culture data showed that the diagnostic yield among groups from whom either only one or more than six blood culture sets were drawn was reduced compared with that among groups from whom between two and five culture sets had been taken. The outcome of endocarditis in this series from a community hospital was much more favorable compared with that reported in surveys from large tertiary centers. Moreover, obtaining more than two or three blood cultures is neither helpful nor cost-effective in the initial assessment of patients with suspected endocarditis.

Aged↗
PubMed2001

Adult patients with occult bacteremia discharged from the emergency department: epidemiological and clinical characteristics.

To determine the epidemiological and clinical characteristics of patients who were discharged from the emergency department (ED) and subsequently proved to have bacteremia, we prospectively assessed all patients examined in the ED during an 18-month period from whose blood cultures a significant organism was isolated. Discharged patients were contacted and reevaluated. Two case-control studies were conducted, in which each study patient was matched with a total of 4 control patients. During the study period, 46,336 patients were examined in the ED; 78% were adults and 22% were children. Blood cultures were performed for 25% of the adult patients and for 44% of the children. Although the occurrence of occult bacteremia in patients who were discharged from the ED is 3.7 times more common in children than in adults, the absolute numbers of discharged adults and children with occult bacteremia are similar. Careful clinical assessment will not prevent discharge of some of these patients; however, these patients in general do well and can be safely recalled for reevaluation and complementation of therapy.

Adolescent↗
PubMed2001

Influence of adenoviral fiber mutations on viral encapsidation, infectivity and in vivo tropism.

Targeting of adenovirus (Ad)-encoded therapeutic genes to specific cell types has become a major goal in gene therapy. Redirecting the specificity of infection requires the abrogation of the natural interaction between the viral fiber and its cellular receptors (CAR) and the simultaneous introduction of a new binding specificity into the viral capsid. To abrogate the natural affinity of the fiber, we have mutated residues presumed to be directly or indirectly involved in CAR-binding in the knob domain of the fiber protein. These residues are located in the AB loop (Ser408) and in the DG loop (Tyr491, Ala494, Ala503). The mutations Ser408Glu, Tyr491Asp, Ala494Asp and Ala503Asp did not prevent the incorporation of trimeric fibers in the viral capsid but led to loss of CAR binding in vitro. Infectivity of the mutant viruses could be restored in vitro by introducing a ligand at the C-terminal end of the knob, confirming that the reduced infectivity of the fiber-modified virus was due to an impaired interaction of the viral particle with the CAR receptor. However, after systemic delivery, the in vivo biodistribution of impaired CAR-binding viruses without addition of a specific ligand was not altered when compared with wild-type Ad.

Adenoviruses, Human↗
PubMed2001

Longitudinal surveillance of antibiotic use in the hospital.

We evaluated antimicrobial use in our hospital by department, including indications for use, source of infections, use of the microbiology laboratory, and appropriateness of prescribing, in a prospective, comparative, non-interventional study of all patients receiving antimicrobial agents. We excluded departments where antimicrobial use was negligible. The other 19 departments were followed for 3 (n=4) or 4 (n=15) months, including 2 consecutive months in the spring-summer and either 1 or 2 in the autumn-winter. Antimicrobial therapy was followed from initiation, through possible adaptations, and possible change from intravenous to oral therapy, until discontinuation of treatment. Overall, 6376 antibiotics were given to 2306 patients. Of the surveyed hospitalized patients, 62%+/-22% received antibiotics, with a range of 4-100% per department. Antibiotics were prescribed for infections acquired in the community (3037 instances, 47%), in the hospital (2182, 34%), in a nursing home (575, 9%), and for prophylaxis continued post-operatively (582, 9%). The most common indications for antimicrobial use were: respiratory tract infection (1729, 27%), urinary tract infection (955, 15%), sepsis (701, 11%), intra-abdominal infections (663, 10%), prophylaxis 582 (9%), soft-tissue infection (572, 9%), and surgical site infection (319, 5%). Univariate indicators for appropriateness of treatment were: age, department, site of infection, source of infection, antimicrobial drug and serum creatinine (all p<0.001). Forty-nine antimicrobials were prescribed in 279 combinations, 58% as single agent and 42% as drug combinations. Half of all antimicrobial use consisted of four agents: cefuroxime (19.1%), metronidazole (11.3%), gentamicin (10.6%) and ampicillin (10.2%), which together accounted for 20% of expenditure on antibiotics. Although use of as many as 53% of antimicrobials (26/49) surveyed was restricted, use in this category accounted for only 29% of all antimicrobial courses. Of 6376 antibiotic courses, 4101 (64%) were given intravenously and 2275 (36%) orally. Appropriateness of use of restricted drugs was lower (70%) than of unrestricted ones (84%, p<0.001). Of 24571 defined daily doses (DDD) given orally, 4587 (19%) were restricted, compared to 7264 (34%) of 21602 DDDs given intravenously (p<0.001). Antibiotic treatment in our hospital appears to be substantial and increasing, justifying efforts to improve appropriateness of therapy and improve clinical and financial results.

Administration, Oral↗
PubMed2000

Prospective surveillance of vancomycin-resistant enterococci in a neonatal intensive care unit.

A point-prevalence study of vancomycin-resistant enterococci colonization of the gastrointestinal tract in an Israeli hospital revealed that 14.7% of the 320 inpatients were colonized. Vancomycin-resistant enterococci colonization was detected in most departments except the neonatal intensive care unit. Hence, a prospective longitudinal study of the prevalence of vancomycin-resistant enterococci colonization in the neonatal intensive care unit was conducted. A rectal swab was obtained from every newborn on admission to the neonatal intensive care unit and once weekly thereafter until the patient was discharged. Enterococci were isolated and tested for susceptibility to vancomycin. A total of 84 neonates were enrolled and monitored on average for 3 weeks (SD +/- 3.9, range 1-20 weeks). Mean gestational age was 35.7 weeks (SD +/- 3.9, range 25-42 weeks), and mean birth weight was 2.4 kg (SD +/- 0.9, range 0.45-4.1 kg). Most patients had one or more of the known risk factors associated with colonization with vancomycin-resistant enterococci. Eighty percent of the patients received antibiotics during the study, and 14.3% received vancomycin. The median duration of vancomycin treatment was 12.5 days (SD +/- 16.8, range 5-55 days). Fifty-one of 84 (61%) patients acquired enterococci sensitive to vancomycin during the study period, but no newborn had vancomycin-resistant enterococci. Possible explanations for this finding may be physical isolation of the neonatal intensive care unit from the rest of the hospital, intrinsic differences in the bowel milieu of this age group and the lack of exposure to food and other environmental sources of vancomycin-resistant enterococci from the community.

Adolescent↗
PubMed2000

Assessment of knowledge of guidelines for the prevention of infective endocarditis amongst clinicians in a teaching hospital.

A significant minority of instances of endocarditis appear to be the result of invasive procedures performed in susceptible patients with underlying cardiac conditions. Absence, or inappropriate administration, of antimicrobial prophylaxis could expose the patient to the development of a potentially lethal infection. This study was formulated, therefore, to assess the knowledge of guidelines for the prevention of infective endocarditis among hospital-based physicians and surgeons. A multiple choice test was developed, including: (1) cardiac conditions at increased risk for development of infection; (2) procedures more likely to be associated with bacteraemia and endocarditis; and (3) type and route of antimicrobials prescribed when endocarditis prophylaxis is indicated. The quality of the test was determined in several ways. Success was defined as a pass rate of 11 of 18 questions (61%). The test was taken by 153 of 251 (60%) physicians employed by the hospital; 95 (62%) passed the test. No significant difference in success rates was found according to sex, professional status or medical school. Internists performed substantially better (with a pass rate of 41 of 53, 77%) than both paediatricians (13 of 26, 50%, P<0.05) and surgeons (41 of 74, 55%, P<0.01). The range of success varied from 100% to 36% according to specialty (P<0.001). The mean score was 69+/-21 in the study group and 94+/-10 in a control group of 20 infectious disease physicians (P<0.001). In conclusion, this study demonstrates the need for improved education of hospital-based clinicians regarding endocarditis prophylaxis recommendations.

Antibiotic Prophylaxis↗
PubMed2000

Practical guidelines for vancomycin usage, with prospective drug-utilization evaluation.

To strengthen guidelines for vancomycin use, practical guidelines were developed. A prospective survey was conducted of all patients receiving vancomycin during two 1-month periods, 1 year apart, during which significant improvements were noted. Practical guidelines may contribute to appropriateness of vancomycin use, serve as educational tools, and facilitate improved surveillance.

Drug Utilization Review↗