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Biomedical subjects

M Drucker

Publications and source records attributed to M Drucker.

At least 37 records · Page 2Linked to original sources

The effect of topical ceftazidime on pseudomonas keratitis in rabbits.

Ceftazidime is a beta-lactam antibiotic highly effective against Pseudomonas aeruginosa infection. Using a rabbit model of Pseudomonas keratitis, 10(3) bacteria (in 20 microliters) were injected unilaterally into the corneal stroma of albino rabbits. Twenty-six hours after inoculation, topical Ceftazidime (50 mg/ml) drops were administered for 48 h, following which the corneal tissue was cultured. Eighteen of 20 corneal cultures (90%) from rabbits treated with Ceftazidime drops were negative. In comparison, all untreated control group cultures showed florid bacterial growth. These results suggest that topical Ceftazidime may be a useful agent in the treatment of P. aeruginosa keratitis.

Administration, Topical↗

High-molecular-weight forms of tyrosinase and the tyrosinase-related proteins: evidence for a melanogenic complex.

Tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2, (TRP-2, dopachrome tautomerase) were shown by immunoblotting and enzyme assays to copurify from extracts of Cloudman S91 melanoma cells. Antibodies to TRP-1 and TRP-2 immunoprecipitated tyrosinase activity, suggesting a stable interaction (complex) among these proteins. The tyrosine hydroxylase activity of tyrosinase was reduced in the complexed form; treatment with Triton X-100 dissociated the complex and activated the tyrosinase present within it. To further study this complex, we employed sucrose gradient density centrifugation of extracts from cultured murine melanocytes. Tyrosinase, TRP-1, and TRP-2 all existed in high molecular weight "multimers" of approximately 200 to > 700 kilodaltons. Extraction of cells with buffers containing the detergent CHAPS preserved the high molecular weight multimers; Triton X-100 caused their dissociation into monomers. Low pH, low ionic strength, and millimolar concentrations of calcium ions favored the maintenance of multimers. The results of this study demonstrate that the participation of tyrosinase, TRP-1, and TRP-2 in a multimeric complex could have important physiologic consequences, and raise the possibility that some of the well-known interactions between coat color genes may be explained by intermolecular interactions between the gene products.

Animals↗

Identification of a beta-type adaptin in plant clathrin-coated vesicles.

Plant clathrin-coated vesicles (CCV), suitably protected against proteolysis, were isolated from zucchini hypocotyls, and screened for the presence of adaptin-like polypeptides using monoclonal antibodies prepared against alpha, beta(beta') and gamma-adaptins of bovine brain. An immunoreactive polypeptide in plant CCV was only detected in the case of the beta(beta')-adaptin antibody. This polypeptide has a molecular mass of 108 kDa in SDS-PAGE, and gives rise to a major cleavage product of 70 kDa after proteolysis with trypsin. Gel filtration of 0.75 M MgCl2-dissociated coat proteins showed that the plant beta(beta')-type adaptin eluted with other polypeptides in a manner similar to the adaptor complexes of brain CCV. Upon subsequent hydroxyapatite chromatography the immunoreactive polypeptide eluted in fractions corresponding to Golgi (HA-I) rather than plasma membrane (HA-II) brain adaptor complexes. In addition, this polypeptide did not shift to a higher molecular mass when subjected to urea-SDS-PAGE. Confirmation of the presence of a beta-type adaptin in plants was provided by dot and Southern blotting experiments using genomic DNA from zucchini hypocotyls and a beta-adaptin cDNA clone from human fibroblasts.

Adaptor Protein Complex beta Subunits↗

Bacteremia in patients without known underlying disorders.

Of 2030 consecutive patients with bacteremia, only 102 were free from underlying disorders. 43 were males, and the median age was 66 years. The sources of infection were the urinary tract (in 48%), lower respiratory tract (13%), endocarditis (7%), biliary tract (6%) and the meninges (5%). The most common pathogens were Escherichia coli (in 45% of patients), Streptococcus pneumoniae (21%), Staphylococcus aureus (9%) and hemolytic streptococci (9%). Overall mortality rate was 13%, 4% in patients with urinary tract infection and 19% in patients with other sources. Half of the deaths occurred within 2 days of hospitalization, and 75% of them within 4 days. All patients with septic shock and all patients with meningitis died. Other factors related to mortality were residence in a nursing home, low functional capacity, advanced age, high blood urea nitrogen and creatinine and low albumin, and infections caused by Staphylococcus aureus, Neisseria meningitidis and polymicrobial infections. A protective effect of appropriate antimicrobial antibiotic therapy could not be demonstrated. In conclusion, bacteremic patients with no known underlying disorder and source of their infection other than the urinary tract should be given maximum supportive treatment and should be closely watched.

Adult↗

Childhood bacteremia in Israel: causes, age relation, predisposing factors and source.

To delineate the spectrum of childhood bacteremia in a tertiary medical center in Israel and to define the historical, clinical and environmental variables that affect it, 339 bacteremic episodes were studied. Ten of the episodes (3%) were polymicrobial and 148 (44%) were hospital acquired. Staphylococcus epidermidis (17%), Staph. aureus (10%), gram-negative bacilli and Haemophilus influenzae (7%) were the most frequent etiologic pathogens. Some organisms (e.g., H. influenzae, Streptococcus pneumoniae) caused mainly community-acquired bacteremia, while Klebsiella sp., Enterococcus faecalis, and Acinetobacter sp. caused mainly nosocomial bacteremia. Underlying conditions were noted in 72% of the bacteremic children. A source of the bacteremia was identified in 60% of the episodes; the most common was i.v.-line infection. Age, underlying condition, source and location in the hospital markedly affected the profile of microorganisms causing childhood bacteremia. Each of these variables defined 3-5 organisms that were most prominent. In each episode of suspected bacteremia, these variables should be considered, thus defining the most likely causative pathogen(s), which should be covered by appropriate empiric antimicrobial treatment.

Adolescent↗

Ambulatory treatment with ceftriaxone in febrile neutropenic children.

We conducted a prospective nonrandomized study of outpatient therapy with ceftriaxone as a single agent in 50 episodes of fever and neutropenia in children treated with various myelosuppressive regimens for different malignancies. All patients underwent clinical and radiological evaluation and blood/urine cultures taken before starting therapy. Patients with dehydration, hypotension, rigor and clinical exit-site infection of indwelling right-sided catheters were excluded. Forty-one patients completed an antibiotic course of 7 days: in 12 patients fever returned to normal on day 2, in 10 patients on day 3, and in 8 patients on day 4. The duration of neutropenia following the initial febrile episode was 3-10 days. In some patients fever returned to normal after 2 days, but neutropenia persisted up to 10 days. Two patients were bacteremic--Escherichia coli in one, and Acinetobacter/Staphylococcus coagulase negative in another; all isolates were sensitive to ceftriaxone. In nine episodes, antimicrobial therapy was modified because of persistent fever > 39 degrees C in five patients, bacteremia in two, enterocolitis in one, breakthrough fever in two, and bronchopneumonia in one. The low incidence of bacterial isolation is probably attributed to the selection of patients with low risk features. Patients and parents complied with and favored outpatient therapy to hospitalization.

Ambulatory Care↗

Bloodstream infections in patients older than eighty years.

During a period of 3 years in a University Hospital in Israel, 339 episodes of bacteraemia were observed in patients 80 years of age or older, and 658 episodes in patients 60-79 years of age. Patients older than 80 were more often residents of nursing homes, frequently had a history of a cerebrovascular accident, but were less often neutropenic. Twenty-four per cent of bacteraemia episodes in the very old were hospital acquired compared with 40% in the old patients. The most common source of bacteraemia was the urinary tract, 50% of episodes in the very old, and 34% of episodes in the old. The percentage of episodes in which anaerobic bacteria were isolated was 5% in the very old and 1% in the old, and the difference was significant when corrected for the sources of bacteraemia. All cases of community-acquired bacterial endocarditis in patients of 80 or over were caused by pathogens originating from the gut. Thirty-five per cent of patients of 80 and over and 30% of patients aged 60-79 years died during hospitalization. Fatality was not associated with advanced age in the very old. Factors significantly and independently associated with fatality in both groups were a hospital-acquired infection, shock, low serum albumin, renal dysfunction and inappropriate antibiotic treatment.

Aged↗

Clinical index to predict bacteraemia caused by staphylococci.

OBJECTIVES: To define risk factors associated with bacteraemia caused by Staphylococcus aureus or coagulase-negative staphylococci; and to use them to define patients in need of empiric anti-staphylococcal antibiotic treatment. DESIGN: Derivation set: observational, prospective study; validation set: retrospective analysis of a prospectively collected database. SETTING: Derivation set: Beilinson Medical Centre, Petah Tiqva, Israel--a 900-bed university hospital. Validation set: St Thomas's Hospital, London, UK--an 800-bed teaching hospital. SUBJECTS: All episodes of bacteraemia detected at Beilinson Medical Centre between March 1988 and September 1990 (derivation set, n = 1410), and at St Thomas's Hospital during 1987-1990 (validation set, n = 1040). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Percentage of staphylococcal bacteraemia in groups of patients defined by the models. RESULTS: The following factors were associated with Staphylococcus aureus bacteraemia: focus of infection (whether high or low risk), haemodialysis, intravenous drug abuse and infection acquired in the orthopaedic ward. A logistic model was used to divide the derivation set into three groups with percentages of Staphylococcus aureus bacteraemia of 1.8%, 13.2% and 33.7% (P < 0.0001); and the validation group 2.5%, 18.2% and 53.2% (P < 0.0001). Factors associated with coagulase-negative staphylococcal bacteraemia were: central or peripheral intravenous catheter as the focus of infection, a preterm neonate, the presence of a central intravenous catheter, low temperature, and a low white blood cell count. A second model including those factors was used to divide the derivation set into three groups with percentages of coagulase-negative staphylococcal bacteraemia of 1.9%, 22.8%, and 43% (P < 0.0001). In the validation set, the percentages were 2.9%, 22.4% and 31.0% (P < 0.001). CONCLUSIONS: The present study defines groups at high risk for staphylococcal bloodstream infection, in which empiric treatment should include an anti-staphylococcal drug.

Adolescent↗

Patterns of multiple resistance to antibiotics in gram-negative bacteria demonstrated by factor analysis.

Principal component analysis was used to demonstrate the main associations between patterns of resistance to antibiotic drugs in 670 gram-negative bacteria consecutively isolated from blood cultures over a period of two years. Six factors were derived, which accounted for 84% of the total variance of the original matrix. Each factor represented an association between resistance to certain antibiotics as follows: factor 1: aztreonam, third generation cephalosporins and aminoglycosides; factor 2: first and second generation cephalosporins; factor 3: tetracycline and chloramphenicol; factor 4: ampicillin and ureidopenicillins; factor 5: trimethoprim/sulfamethoxazole; factor 6: fluoroquinolones. On two-way analysis of variance the difference in the factor scores was significant between bacteria for all factors except factor 5. The difference in factor scores between community and hospital acquired strains was significant only for factors 1, 2 and 6. Only the score of factor 6 showed a clear trend to increase with time during the two-year study period. Patients who were treated with antibiotics prior to bacteremia had higher scores for all factors, the difference being most marked in patients treated with fluoroquinolones. Factor analysis can be used to describe phenotypic associations between resistance to antibiotics, and the factor score used to compare groups of isolates and to demonstrate temporal and other trends.

Ampicillin↗

Bacteremia and fungemia of unknown origin in adults.

Two hundred fifteen (23%) of 955 episodes of bacteremia (defined as including fungemia) detected in adult patients during 2 years were of unknown origin. Sixty-six percent of episodes of unknown origin were hospital acquired. The median age of patients with bacteremia of unknown origin was 65 years, and their most common underlying disorders were solid malignancy (28% of patients) and diabetes mellitus (18%). Only three factors were associated with bacteremia of unknown origin (as opposed to episodes with a known source): peripheral venous catheterization, hemodialysis, and plasmapheresis. Gram-negative bacteria were isolated from the blood in 62% of episodes of unknown origin; 10% of episodes were polymicrobial. Staphylococci were isolated from 67% of patients undergoing hemodialysis and from 37% of those with diabetes; Pseudomonas species from 15% of patients with hospital-acquired episodes; and Candida species from 21% of patients with a central venous catheter. Fifteen percent of episodes in cancer patients were polymicrobial. Empirical antibiotic treatment was inappropriate in 49% of episodes of unknown origin and in 35% of episodes with a known source (P less than .001). Death rates were 44% and 25% in episodes of unknown and known origin, respectively. An unknown source of bacteremia was independently associated with a fatal outcome.

Adolescent↗

Risk factors for mortality due to bacteremia and fungemia in childhood.

To define risk factors for mortality due to bacteremia and fungemia of childhood, 242 episodes (for which the mortality rate was 19%) were studied prospectively by univariate and multivariate analyses. The mortality rate was higher in neonates (23%) and in individuals 10-18 years old (26%) than in infants and young children (10%-16%). The mortality rate was 29% for children who had neutropenia, 29% for those who had received therapy with steroids, 26% for those who had received antibiotics, and 75% for those who were in septic shock. The fatality rates for polymicrobial bacteremia (40%), recurrent bacteremia (67%), and hospital-acquired bacteremia (28%) were higher than those for other types of bacteremia; the fatality rate was related to inappropriate empiric antibiotic treatment or to the specific organism isolated (mortality rates associated with the latter ranged from 0 to 60%). Seven variables that independently and significantly affected mortality were defined with use of multivariate logistic regression analysis: septic shock (odds ratio [OR], 26.4); polymicrobial (OR, 5.4), recurrent (OR, 4.5), or hospital-acquired (OR, 4.3) bacteremia; candidemia (OR, 3.6); inappropriate antibiotic treatment (OR, 2.4); and neutropenia (OR, 2.3). These variables should be considered for adequate management of bacteremic patients who are at high risk for death.

Adolescent↗

Patients at risk for inappropriate antibiotic treatment of bacteraemia.

In order to define patients at high risk for inappropriate antibiotic treatment of bacteraemia, we compared 682 bacteraemic patients, treated with an antibiotic drug to which the infecting micro-organism was susceptible, with 419 patients who were inappropriately treated. On a multivariate logistic regression analysis including only clinical variables, four factors were found to be both significantly and independently associated with inappropriate antibiotic treatment: hospital-acquired bacteraemia (odds-ratio (OR) of 1.9), antibiotic treatment in the month prior to the bacteraemia (OR 1.9), residence in a nursing home (OR 1.8), and the presence of a central line (OR 1.7). A second model, including bacteriological data, showed four micro-organisms to be independently associated with inappropriate antibiotic treatment: Candida sp. (OR 14.2), Acinetobacter sp. (OR 5.0), Enterococcus sp. (OR 3.6) and Pseudomonas sp. (OR 2.2). In this model, only two clinical features were included: hospital-acquired infection and previous antibiotic treatment. Special efforts should be made to improve empirical antibiotic treatment in the groups defined above, and to facilitate early laboratory diagnosis of the micro-organisms associated with inappropriate treatment.

Anti-Bacterial Agents↗

Predictive index for optimizing empiric treatment of gram-negative bacteremia.

In a survey of 296 episodes of gram-negative bacteremia in 286 patients (aged 13-99 years), four clinical variables were found to predict both significantly and independently the subsequent isolation of a multiresistant strain; hospital acquisition of the infection, antibiotic treatment before the bacteremic episode, endotracheal intubation, and thermal trauma as the cause of hospitalization. These variables were combined in an index that served to classify the patients into four groups with an increasing prevalence of multiresistant strains, Pseudomonas isolates, and isolates resistant to each of the antibiotic drugs in common use. For example, the percentage of isolates susceptible to cefuroxime in the four groups were 79%, 56%, 34% and 25%, and to gentamicin, 89%, 79%, 46%, and 33% (P less than .001 for both comparisons). The performance of the index was validated in a second group of 144 episodes of gram-negative bacteremia. The index kept its discriminative power. Compared with the prescriptions of the attending physicians, the index could probably have improved empiric antibiotic treatment in 24% of patients.

Adolescent↗

Bacteremia in adult diabetic patients.

OBJECTIVE: To compare the microbiology, sources, complications, and outcome of bacteremia in diabetic and nondiabetic patients. RESEARCH DESIGN AND METHODS: A prospective study was conducted of all episodes of bacteremia in hospitalized diabetic and nondiabetic patients. The study consisted of patients greater than or equal to 18 yr of age with bacteremia detected within a 19-mo interval. RESULTS: We compared 124 episodes of bacteremia in 119 diabetic patients to 508 episodes in 480 nondiabetic patients. Diabetic patients were older than nondiabetic patients (median age 74 vs. 68 yr, P = 0.0001). In patients with an indwelling urinary catheter and bacteremic urinary tract infection, the percentage of Klebsiella in diabetic patients was 60% (6 of 10) and in nondiabetic patients was 17% (4 of 23, P = 0.04). In patients without an obvious source of bacteremia, the percentage of staphylococcal isolates in diabetic patients was 29% (10 of 35) and in nondiabetic patients was 14% (24 of 176, P = 0.04). Staphylococci were a common cause of bacteremic infections of the extremities in diabetic patients (12 of 19, 63%) and nondiabetic patients (20 of 50, 40%). Septic shock was the only complication that was more common in diabetic patients. The mortality in diabetic and nondiabetic patients was 28 and 29%, respectively. CONCLUSIONS: Our results represent elderly patients with non-insulin-dependent diabetes mellitus. In this group, empirical treatment for suspected bacteremic urinary tract infection in patients with a urinary catheter should include coverage for Klebsiella. Empiric treatment for suspected bacteremia of unknown origin or caused by infection of the extremities should include an antistaphylococcal drug. The prognosis of bacteremia in diabetic and nondiabetic patients was similar.

Adult↗

Thrombocytosis after pneumonia with empyema and other bacterial infections in children.

Thrombocytosis is seen in association with many conditions, including infectious diseases. We studied thrombocytosis after severe bacterial infections, particularly pneumonia with empyema in children. A systematic survey of the phenomenon was conducted. Twenty-seven children admitted for pneumonia with empyema were studied. Thrombocytosis (platelet counts greater than 500 x 10(3)/microliters) was present in 92.5%. Platelet counts reached their maximum at 15.1 +/- 3.7 days (range, 7 to 25) and declined to normal after 3 weeks of illness. Compared with a healthy control group, significant thrombocytosis, but of lower incidence, was also noted in children with lobar pneumonia without pleural effusion, bacterial meningitis and osteomyelitis. Platelet functions were examined in seven of the children but no abnormalities were observed. Bone marrow aspiration of three children with pneumonia and empyema showed megakaryocytic hyperplasia. We found no correlation between thrombocytosis, neutrophilia, fever, the clinical course, complications, prognosis or treatment. Neither thromboembolic nor hemorrhagic phenomena were observed.

Bacterial Infections↗