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Biomedical subjects

S C Aronoff

Publications and source records attributed to S C Aronoff.

At least 19 recordsLinked to original sources
PubMed2001

Short-course versus conventional length antimicrobial therapy for uncomplicated lower urinary tract infections in children: a meta-analysis of 1279 patients.

OBJECTIVE: The objective was to compare the efficacies of single-dose, short-course (4 days or less), and standard course (5 days or greater) antimicrobial therapy for uncomplicated childhood cystitis. METHODS: Prospective, randomized, controlled trials comparing 4 days or less of therapy (short courses) with 5 days or more of therapy (conventional therapy) were included if all of the subjects were <18 years of age, the initial infection was documented by urine culture, at least 1 subsequent culture was obtained between 3 and 30 days of enrollment, and some attempt was made to separate upper tract from lower tract infection. Composite differences among treatment groups were compared with a fixed or random effects model, depending on the test for heterogeneity. RESULTS: Of the 517 citations identified by literature search, 37 were selected for detailed review, and 22 were included in the final meta-analysis. The overall difference in cure rates between short and conventional courses of therapy was significant (6.38%; 95% CI: 1.88% to 10.89%), favoring the conventional course. Similar results were obtained when only studies comparing the same agents in the short and conventional courses were included (7.92%; 95% CI: 2.09% to 13.8%). Short-course amoxicillin was inferior to conventional length course (difference in cure rate, 13%; 95% CI: 4% to 24%); no difference was found between short-course and conventional length courses of trimethoprim-sulfamethoxazole (difference in cure rate, 6.24%; 95% CI = -3.74% to 16.2%). CONCLUSIONS: We conclude that single-dose amoxicillin is inadequate therapy for uncomplicated cystitis of childhood. Three days of trimethoprim-sulfamethoxazole therapy appears to be as effective as conventional length courses of the drug.

Adolescent↗
PubMed1999

Prophylactic antibiotics with intracranial pressure monitors and external ventricular drains: a review of the evidence.

BACKGROUND: The role of prophylactic antibiotics (PABs) in preventing infections associated with intracranial pressure (ICP) monitors and external ventricular drains (EVD) is not well defined. METHODS: This study includes an analysis of published reports and a survey of current practices regarding the use of PABs with ICP monitors and EVDs. A computerized data search and a review of the abstracts from two major national neurosurgical meetings over the past decade yielded 85 related articles. Three independent investigators, blinded to the title, author(s), institution(s), results, and conclusions of the articles used predetermined inclusion criteria to select studies for meta-analysis. Thirty-six responses were returned from 98 questionnaires (37%) mailed to university neurosurgical programs. RESULTS: Among the articles reviewed, only two studies met the predetermined inclusion criteria for the meta-analysis, and they were of insufficient size to produce statistically significant results. Among the 36 programs that responded to the survey, 26 (72%) used PABs, mainly cephalosporins (46%) and semisynthetic penicillins (38%), with ICP monitors and EVDs. Twenty-two (85%) used one drug, and 4 (15%) used two drugs. Twenty-two (61%) of the total group reported intra-institutional variation in practices among individual staff neurosurgeons. Nineteen (53%) expressed interest in a retrospective study, and 27 (75%) expressed interest in a prospective study on the role of PABs in minor neurosurgical procedures. CONCLUSION: No consensus regarding the use of PABs with ICP monitors and EVDs is noted. Randomized controlled trials of sufficiently large size with appropriate blinding are needed to address this issue.

Anti-Bacterial Agents↗
PubMed1999

Use of the paraffin wax baiting system for identification of Pseudomonas aeruginosa clinical isolates.

Pseudomonas aeruginosa is the primary pathogen among the Pseudomonads and is known for its minimal nutritional requirements, capacity to use paraffin as a sole carbon source, and biofilm formation. Because the ability of Pseudomonads to grow on paraffin is not commonly found among human pathogens and the primary Pseudomonas human pathogen is P. aeruginosa, we studied the adaptation of the paraffin baiting system for the growth and identification of clinical isolates of P. aeruginosa. We also studied the effectiveness of combining a fluorescence assay measuring fluorescein (pyoverdin) production and oxidase test with the paraffin baiting assay for P. aeruginosa speciation. Strains were tested for the capacity to use paraffin as a sole carbon source using the paraffin baiting system with Czapek's minimal salt medium. Of 111 P. aeruginosa clinical isolates tested for using paraffin as a sole carbon source, 45% exhibited growth on paraffin at 24 h and 76.6% exhibited growth on paraffin at 48 h. The ability of the reference strains and clinical isolates were then tested for their ability to associate with the paraffin slide in the presence of an additional carbon source. Of 111 P. aeruginosa clinical isolates tested, 85 strains (76.6%), and 102 (93%) were associated with the paraffin surface at 24 and 48 h. We successfully combined fluorescence and oxidase assays with the paraffin baiting system for identification of P. aeruginosa. The simple and inexpensive paraffin baiting system is a useful method for the identification and study of P. aeruginosa suitable for both the clinical and research laboratory.

Biofilms↗
PubMed1999

Multidisciplinary evidence-based medicine journal clubs: curriculum design and participants' reactions.

BACKGROUND: Evidence-based medicine (EBM) is becoming an accepted educational paradigm in medical education at a variety of levels. It focuses on identifying the best evidence for medical decision making and applying that evidence to patient care. METHODS: Three EBM journal clubs were developed at the West Virginia University School of Medicine. One was for senior medical students, another for residents, and the third for primary care faculty members. In each, the sessions stressed answering clinical questions arising from actual patient-care issues. The curricular structure and development of the journal clubs are described. Participants anonymously evaluated aspects of the journal clubs regarding their educational value with Likert scale questions. RESULTS: Faculty members and residents generally gave high evaluations to all aspects of the EBM journal clubs. Student evaluations were more mixed. For each of the evaluation questions, the student means were lower than those of faculty and residents. However the differences reached statistical significance only in the responses to the usefulness of the sessions in understanding the medical literature (P < 0.01). Residents and faculty rated the EBM sessions more favorably than grand rounds or the resident lecture series. CONCLUSIONS: The establishment of evidence-based medicine journal clubs is feasible, and learners seem to value the sessions. More developed learners may gain more from the experience than those earlier in their medical education.

Curriculum↗
PubMed1999

Reduced interleukin-8 production by cystic fibrosis airway epithelial cells.

The acquisition of Pseudomonas aeruginosa in the airways of patients with cystic fibrosis (CF) is the initial event leading to bronchiectasis and lung disease. Although the host factors that permit initial airway colonization are largely unknown, recent studies suggest that secretion of interleukin (IL)-8 by airway epithelia and local recruitment of neutrophils is the final pathway in a pulmonary cytokine network. To determine whether differences in cytokine production exist between normal and CF airway epithelia, secretion of immunoreactive IL-8 and IL-10 as well as specific messenger RNA (mRNA) abundance were compared in airway epithelia expressing normal and mutant CF transmembrane regulator. After induction with IL-1beta, a CF airway cell line engineered to express the wild-type CF gene (CFT1-LCFSN) secreted significantly more immunoreactive IL-8 than did its isogenic parent that expressed the mutant CF gene (CFT1) or an isogenic vector control line (CFT1-LC3). Further studies with the three related cell lines demonstrated that expression of CFT1-LCFSN was associated with a significant increase in uninduced secretion of immunoreactive IL-8 as well as a 10- to 20-fold increase in IL-8 mRNA abundance when compared with the isogenic lines expressing the mutant gene. IL-1beta induction and intracellular accumulation of IL-8 appeared to be unaffected by CF genotype. These studies suggest that IL-8 secretion by CF airway epithelial cells is defective and may contribute to Pseudomonas persistence in the CF airway. Further studies are needed to confirm this difference in other cell lines and determine the linkage between IL-8 production and CF gene expression.

Bronchi↗
PubMed1994

Effective short-course treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis. Ten days of penicillin V vs 5 days or 10 days of cefpodoxime therapy in children.

OBJECTIVE: To compare bacteriologic and clinical efficacy and safety of 10 vs 5 days of cefpodoxime proxetil vs 10 days of penicillin V potassium for the treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis in children. DESIGN: Prospective, randomized, observer-blind, multicenter study. PATIENTS/INTERVENTIONS: Four hundred eighty-four children (age range, 2 to 17 years) with signs and symptoms of acute tonsillopharyngitis were enrolled; 377 had a positive throat culture for group A beta-hemolytic streptococci and were fully evaluable. One hundred twenty-one patients received cefpodoxime once a day for 10 days, 126 received cefpodoxime twice a day for 5 days, and 130 received penicillin V three times a day for 10 days. RESULTS: Cefpodoxime for 10 days vs cefpodoxime for 5 days vs penicillin V for 10 days produced bacteriologic eradication at the end of therapy in 95%, 90%, and 78% of the patients, respectively. The 10- and 5-day cefpodoxime treatment regimens were more efficacious than penicillin V (P = .003 and P = .02, respectively). The cumulative bacteriologic failure rate among assessable patients by the 32- to 38-day posttreatment visit was 20 (17%) of 121 patients who were treated with cefpodoxime for 10 days, 24 (19%) of 125 patients who were treated with cefpodoxime for 5 days, and 45 (35%) of 130 patients who were treated with penicillin V for 10 days (P = .001 and P = .005, respectively). Clinical cure or improvement was observed at the end of therapy in 96%, 94%, and 91% of the patients, respectively (P = not significant). Adverse events were infrequent and similar in all three treatment groups, with minor gastrointestinal side effects predominating. CONCLUSIONS: Five days of treatment with cefpodoxime is as efficacious in bacteriologic eradication and clinical response (cure plus improvement) as 10 days of cefpodoxime therapy, and both cefpodoxime regimens produced superior bacteriologic efficacy compared with a 10-day regimen of penicillin V in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis in children.

Acute Disease↗
PubMed1994

Effects of pentoxifylline on sputum neutrophil elastase and pulmonary function in patients with cystic fibrosis: preliminary observations.

High concentrations of free human neutrophil elastase in bronchial epithelial fluid are believed to be a major factor in the evolution of pulmonary injury in cystic fibrosis (CF). To test this hypothesis, we studied pentoxifylline, a compound that inhibits tumor necrosis factor alpha transcription and its stimulatory effect on polymorphonuclear neutrophils, in patients with CF who had chronic Pseudomonas bronchitis. Subjects older than 11 years of age randomly received placebo or pentoxifylline (1600 mg/day) orally, in a double-blind fashion, for 6 months. Pulmonary function and sputum elastase concentrations were determined before therapy and bimonthly during therapy; compliance was determined by measuring serum drug concentrations. Of the 16 patients who completed the study, 9 received pentoxifylline. The sputum elastase concentrations among placebo recipients were significantly increased from baseline at 4 and 6 months (F = 3.44; p < 0.05); the values remained unchanged in the treatment group. The mean forced vital capacity for the placebo group decreased from 59.2% +/- 15.4% predicted at baseline to 52.0% +/- 12.9% predicted at 6 months; the values in the treatment group remained largely unchanged. The forced vital capacity improved between baseline and 6 months for four of nine pentoxifylline recipients and none of the seven control patients (p = 0.09). During the study, four of seven placebo recipients experienced a significant pulmonary exacerbation compared with one of nine treated patients (p = 0.077). These findings support the hypothesis that polymorphonuclear neutrophil elastase is a factor in the evolution of CF lung disease; further studies are needed to define the role of pentoxifylline in the treatment of CF.

Administration, Oral↗
PubMed1991

Longitudinal serum IgG response to Pseudomonas cepacia surface antigens in cystic fibrosis.

In cystic fibrosis (CF), serum antibody against surface antigens of Pseudomonas aeruginosa is detected only after colonization. Since pulmonary acquisition of P. cepacia usually follows colonization with P. aeruginosa and since P. aeruginosa-colonized patients with CF have demonstrable antibody against outer membrane proteins of P. cepacia, it appears that acquisition of the latter organism occurs in the presence of specific serum antibody. To test this hypothesis, serum obtained from six P. aeruginosa-colonized patients 4 and 2 years prior to and 3 months and 2 years after P. cepacia colonization were assayed for total and specific IgG to P. cepacia outer membrane components. Four patients demonstrated 6-fold or greater increases in specific IgG titers to whole outer membranes following colonization. By immunoblot, all patients had demonstrable serum IgG against the 27- and 36-kDa outer membrane proteins of P. cepacia 4 and 2 years prior to colonization. Immunoblots after P. cepacia acquisition demonstrated an intensification of the 28- and 36-kDa bands and the appearance of antibody to a very low molecular weight compound which was not hydrolyzed by proteinase K and was present in purified LPS. These observations suggest that low serum titers of antibody against two P. cepacia outer membrane proteins are present in patients with CF prior to P. cepacia colonization, and that these antibodies fail to protect for intrinsic or extrinsic reasons.

Adolescent↗
PubMed1989

In vitro activity of YTR 830.

YTR 830, now known as tazobactam, is a new penicillanic acid sulfone beta-lactamase inhibitor. The in vitro activity of YTR 830 combined with various penicillins was determined and compared to that of clavulanate and sulbactam combined with the same agents. Combined with ampicillin or amoxicillin, all three inhibitors were active against beta-lactamase producing strains of Staphylococcus aureus, Haemophilus influenzae, Klebsiella, Citrobacter diversus, and all anaerobes except for Bacteroides fragilis homology group II. YTR 830 was also effective against Escherichia coli and indole-positive Proteus. The inhibitors had no effect against Enterobacter or Serratia. Overall, the activity of YTR 830 was comparable to that of clavulanate, and superior to that of sulbactam.

Ampicillin↗
PubMed1989

The emergence of beta-lactam resistance among strains of Enterobacter cloacae and Pseudomonas aeruginosa.

The development of multiresistant bacterial strains associated with the use of the new beta-lactam antibiotic agents has prompted investigation into the mechanisms involved. Factors influencing beta-lactamase production, alterations of target-protein structure or production and decreases in bacterial outer membrane permeability have been identified as the three general mechanisms of beta-lactam resistance in aerobic Gram-negative bacteria. Because there is no DNA interaction by beta-lactam agents, emergence of resistance results from either spontaneous mutation or the presence of resistant subpopulations; the presence of antibiotics allows for overgrowth of resistant strains. Studies have indicated that there is a significant relationship between the rate of emerging resistance and the ratio of the minimum inhibitory concentration of a beta-lactam to the drug concentration used to select for resistance in vitro or achieved at the infection site in vivo. It is concluded that the use of synergistic combinations of agents should reduce the emergence of beta-lactam-resistant bacterial strains. Thus the choice of an appropriate therapeutic agent requires thorough evaluation of the specific pathogen for susceptibility to a variety of beta-lactam agents and aminoglycosides.

Animals↗
PubMed1989

The effect of sodium on amiloride-tobramycin synergy in Pseudomonas cepacia.

Amiloride combined with subinhibitory concentrations of tobramycin is synergistic against Pseudomonas cepacia in vitro. It is known that amiloride blocks transmembrane sodium (Na+) flux in eukaryotic cells, but the mechanism of action in bacteria is unknown. Amiloride-mediated Na+ gradient changes might affect transcellular tobramycin transport, resulting in synergy between these two drugs. To examine this hypothesis, we studied the effect of extracellular [Na+] on amiloride-tobramycin synergy with a reference strain of P. cepacia. Control growth in Mueller-Hinton broth (MHB) alone, MHB supplemented with 200 mmol/L NaCl, and MHB dialyzed against a Na+-free solution was determined by absorbance at 650 nm over 3 hours. Inhibition in the presence of amiloride, tobramycin, or a combination was expressed as percentage of control growth. Growth in the presence of tobramycin alone was significantly higher in MHB + NaCl than in MHB or dialyzed MHB (81% +/- 5%; vs 57% +/- 5%; 35% +/- 4%; mean +/- SEM, respectively, p = 0.003). Growth in the presence of amiloride alone was not significantly different in the three media (84% +/- 4%; 80% +/- 3%; 80% +/- 1%; respectively, p = 0.746). Percent control growth was significantly lower when the two drugs were combined, but results were not statistically different among the three media (3.5% +/- 3%; 0.2% +/- 0.8%; 4% +/- 1%; respectively, p = 0.604). We conclude that growth inhibition of P. cepacia in the presence of tobramycin is antagonized by increasing extracellular [Na+]. This antagonistic effect of [Na+] is reversed by amiloride. Changes in [Na+] do not appear to directly affect amiloride-tobramycin synergy in P. cepacia.

Amiloride↗
PubMed1988

Derepressed beta-lactamase production as a mediator of high-level beta-lactam resistance in Pseudomonas cepacia.

A mechanism of high-level resistance to readily and poorly hydrolyzable beta-lactam substrates in Pseudomonas cepacia was identified using a hypersusceptible, beta-lactamase-inducible, non-CF clinical isolate, 75-26, and a drug-resistant mutant derived from this strain. Inoculation of 75-26 onto agar containing 16 micrograms/ml of ceftazidime produced a stable, beta-lactam-resistant mutant at a frequency of 1.7 x 10(-5). Baseline beta-lactamase production by a representative mutant isolate (75-26z) was almost 40-fold greater than the parent. Both strains produced major beta-lactamase bands with isoelectric points of 6.9, 7.8, 8.1, 8.5, and 9.2 by isoelectric focusing. Compared with the parental strain, multiple satellite bands associated with the major beta-lactamase bands were present in the mutant. Growth of an indicator strain, E. coli ATCC 25922, was inhibited by ceftazidime and piperacillin but was not inhibited after the compounds were preincubated with the beta-lactamase preparation from 75-26z. Preincubation of ceftazidime with beta-lactamase, followed by the addition of a beta-lactamase inhibitor, inhibited the growth of the indicator strain; piperacillin failed to inhibit growth of the indicator strain in a similar experiment. One mechanism of high-level resistance to both poorly and readily hydrolyzable beta-lactam substrates in P. cepacia is derepressed chromosomal beta-lactamase production.

Anti-Bacterial Agents↗
PubMed1988

Serum IgG antibody to outer membrane antigens of Pseudomonas cepacia and Pseudomonas aeruginosa in cystic fibrosis.

IgG antibody to the outer membrane of Pseudomonas cepacia was quantified in sera from controls without cystic fibrosis (CF) and from Pseudomonas aeruginosa- and P. cepacia-infected and noninfected patients with CF. The mean antibody titer in the P. cepacia-infected group was significantly higher than that in the other three groups; the mean titer in the P. aeruginosa-infected group was significantly higher than that in the noninfected and control groups. Preabsorption of CF sera with P. cepacia outer membrane produced a significantly lower mean antibody concentration than did matched samples preabsorbed with an equal amount of lipopolysaccharide. By western blot, significantly more P. cepacia-infected patients produced IgG to the 27- than the 36-kilodalton (kDa) porin protein of P. cepacia; 12 of 16 P. aeruginosa-infected patients produced IgG to the 27-kDa porin. Sera from all patients in both groups contained IgG to the porin protein of P. aeruginosa by western blot. We conclude that the 27-kDa porin of P. cepacia is antigenic in most P. cepacia-infected patients with CF and that some P. cepacia outer membrane components may be antigenically related to those of P. aeruginosa.

Adolescent↗
PubMed1988

Outer membrane permeability in Pseudomonas cepacia: diminished porin content in a beta-lactam-resistant mutant and in resistant cystic fibrosis isolates.

Since beta-lactam resistance is a feature of Pseudomonas cepacia isolates causing pulmonary infections in cystic fibrosis (CF), this study was undertaken to determine whether alterations in beta-lactam permeability mediate drug resistance in this species. A beta-lactam-susceptible non-CF isolate (strain 75-26), a resistant mutant derived from 75-26 by selection for cross-resistance to ciprofloxacin and ceftazidime, and two resistant CF isolates of P. cepacia were used. Permeability constants were calculated from the rate of nitrocefin hydrolysis in intact bacterial cells. Qualitative changes in outer membrane proteins were determined electrophoretically. The permeability constants of the mutant and the resistant CF isolates were lower than the value for the reference strain, 75-26. Whereas the lipopolysaccharide side chains were present in the test and reference strains, the resistant mutant and the CF isolates contained reduced amounts of the 36-kilodalton (kDa) outer membrane protein and failed to express the 27-kDa outer membrane protein. These observations suggest that the 27-kDa outer membrane protein may be a major porin or a major protein component of the porin complex in P. cepacia and that decreased expression of the 36-kDa outer membrane and loss of the 27-kDa porin are associated with high-level beta-lactam resistance in some CF isolates of P. cepacia.

Anti-Bacterial Agents↗
PubMed1988

In vitro activity of amiloride combined with tobramycin against Pseudomonas isolates from patients with cystic fibrosis.

The diuretic amiloride has been under recent investigation as adjunctive therapy for pulmonary disease in children with cystic fibrosis (CF). In preliminary studies, the antimicrobial activity of this agent alone or combined with beta-lactam agents against reference strains of Pseudomonas aeruginosa and P. cepacia was poor; however, amiloride was markedly synergistic with tobramycin against P. cepacia. The purpose of this study was to determine the extent of amiloride-tobramycin synergy against CF respiratory isolates of P. aeruginosa, P. cepacia, and P. maltophilia. The MICs of tobramycin and amiloride alone against the Pseudomonas test strains were determined by agar dilution. Synergy was determined by combining each of four subinhibitory concentrations of amiloride (at least fourfold below the MIC) with doubling dilutions of tobramycin and comparing the MIC of tobramycin alone and in combination for each strain. At the highest concentration tested, the drug combination synergistically inhibited 50% of the P. cepacia strains tested; the combination was synergistic against fewer isolates of P. aeruginosa and P. maltophilia. Only P. cepacia was inhibited by tobramycin combined with amiloride at achievable airway concentrations. We conclude that the combination of tobramycin and amiloride may be potentially useful in the treatment of P. cepacia infections in children with CF.

Amiloride↗