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Biomedical subjects

R Ramphal

Publications and source records attributed to R Ramphal.

At least 73 records · Page 4Linked to original sources
PubMed1987

Effects of subminimal inhibitory concentrations of antibiotics on the adherence of Pseudomonas aeruginosa to tracheobronchial mucin.

Bacterial adherence to mucins may be important in tracheobronchial infections in cystic fibrosis. Sublethal concentrations of antibiotics reduce bacterial adherence to epithelial cells and mucins. This reduction in adherence may be a component of antimicrobial effects in infections at anatomical sites where bactericidal concentrations of antibiotics are difficult to achieve. We therefore tested the effects of sublethal concentrations of an aminoglycoside, tobramycin, and a beta-lactam antibiotic, ceftazidime, on the adherence of Pseudomonas aeruginosa to tracheobronchial mucin, since mucus secretions are often colonized by P. aeruginosa in cystic fibrosis. Adherence of the mucoid strains tested was inhibited by ceftazidime, but not by tobramycin. This effect of ceftazidime may partially explain its efficacy in patients with cystic fibrosis despite variables achieved in sputum.

Bacterial Adhesion↗
PubMed1987

Pseudomonas aeruginosa adhesins for tracheobronchial mucin.

Mucins of the tracheobronchial tree are preferential sites for adherence and colonization by Pseudomonas aeruginosa. They possess specific receptors for this organism that have amino sugars as their principal constituents. Since mucins probably reflect the receptors on the cellular surfaces, we hypothesized that the bacterial adhesins previously shown to mediate the binding of P. aeruginosa to cells would also mediate bacterial binding to mucins. We therefore tested the roles of the exopolysaccharide from mucoid strains of P. aeruginosa and pili from nonmucoid strains to see whether they are indeed the adhesins for mucins. Using a microtiter plate assay of adherence to mucins, we demonstrated that the mucoid exopolysaccharide bound to mucins and enhanced the adherence of mucoid strains to this substance. Antibodies raised against the exopolysaccharide from a single mucoid strain inhibited the adherence of all mucoid strains tested. Purified pili from nonmucoid strains inhibited the binding of nonmucoid strains but not of mucoid strains. Inhibition of adherence by antibody to pili was quite specific, antibody being able to inhibit only the binding of the homologous nonmucoid strain. These data support our previous observations with tracheal cells, confirming the similarity of the adhesins for respiratory tract cells and the mucins which cover them.

Adhesins, Bacterial↗
PubMed1986

Nosocomial infections and bacterial antibiotic resistance in a university equine hospital.

A base-line study of bacteria isolated from horses admitted to the Veterinary Medical Teaching Hospital during a 6-month period was performed to determine the extent of multiresistant nosocomial infections caused by gram-negative aerobic bacteria other than Salmonella spp. Results of this study indicated that 21.9% of the 105 horses from which cultures and sensitivities were available had developed nosocomial gram-negative aerobic infections, with high rates of resistance to gentamicin, kanamycin, and trimethoprim sulfadiazine, three of the most often prescribed antibiotics in this hospital. In addition, a prospective study of antibiotic-resistant bacteria of fecal origin was performed to determine whether there was a change in the degree of antibiotic resistance of a horse's intestinal flora while the horse was hospitalized. Bacterial culturing for gram-negative lactose fermenting bacteria was done on fecal specimens collected directly from the rectum on day 1 and day 7 of a horse's hospitalization. Susceptibility testing was done on each isolant. Of the 24 paired fecal specimens obtained, Escherichia coli and Klebsiella sp isolated on day 7 were resistant to a significantly higher number of antibiotics than day 1 isolants (P = 0.003, P = 0.043, respectively).

Animals↗
PubMed1986

Randomized comparison between two ceftazidime-containing regimens and cephalothin-gentamicin-carbenicillin in febrile granulocytopenic cancer patients.

Because the results of our published trial [R. Ramphal, B. S. Kramer, K. H. Rand, R. S. Weiner, and J. W. Shands, Jr., J. Antimicrob. Chemother. 12(Suppl. A):81-88, 1983] of ceftazidime versus cephalothin, gentamicin, and carbenicillin (KGC) revealed a preponderance of gram-positive superinfections, including those caused by clostridia, in patients treated with ceftazidime, we added vancomycin to the ceftazidime regimen at study entry 49 and continued with a 2:1 randomized comparison of ceftazidime-vancomycin (CV) versus KGC. Criteria for study entry were fever (temperature, greater than or equal to 38.5 degrees C on one occasion or greater than or equal to 38 degrees C on two occasions 6 h apart) and granulocytopenia (less than 500/mm3 or a falling count anticipated to be less than 500/mm3). Ninety-five entries (79 patients) were evaluable. The numbers of initial clinical responses for ceftazidime-, KGC-, and CV-treated patients were 9 of 21 (43%), 21 of 37 (57%), and 21 of 37 (57%), respectively; differences were not significant. The death rate was lower with CV (2 of 37 patients) than with KGC (10 of 37 patients) (P less than 0.05 by two-tailed analysis) or with ceftazidime alone (7 of 21 patients) (P less than 0.025). Death from presumed infections occurred in 9 of 37 KGC-treated patients versus 1 of 37 CV-treated patients (P less than 0.025). Superinfections occurred in five ceftazidime-treated patients (24%) versus 7 KGC-treated patients (19%) but not in CV-treated patients (CV versus KGC, P less than 0.05; CV versus ceftazidime, P less than 0.01). CV appears to be superior to KGC or ceftazidime alone in the management of febrile granulocytopenic cancer patients.

Adult↗
PubMed1985

Further characterization of the tracheal receptor for Pseudomonas aeruginosa.

The purpose of this study was to obtain more information on the nature of the macromolecule to which Pseudomonas aeruginosa adheres. Acid-injured tracheal epithelium was treated with trypsin or lipase to determine whether the receptor molecule was a protein or a lipid. Lipase treatment significantly reduced adherence to these cells, whereas trypsin had no effect. Since the receptor appeared to be a lipid containing sialic acid, gangliosides were used to test whether they would inhibit adherence. Crude ganglioside preparations inhibited adherence in a dose-dependent manner when added to the bacteria before exposure to tracheal cells. Lastly, fibronectin, which presumably binds to gangliosides, significantly reduced the adherence of these organisms. According to these findings Pseudomonas aeruginosa appears to adhere to a sialic acid-containing glycolipid on cell surfaces, probably a ganglioside.

Adhesiveness↗
PubMed1985

Alterations of myoelectric activity associated with Campylobacter jejuni and its cell-free filtrate in the small intestine of rabbits.

We evaluated the effects of a culture of Campylobacter jejuni and its cell-free filtrate on myoelectric activity of isolated ileal segments in New Zealand White rabbits. Hematoxylin and eosin staining and scanning electron microscopy were used to assess the association between histologic changes and alterations in intestinal myoelectric activity. A culture of C. jejuni was shown to cause a significant increase in repetitive bursts of action potentials (RBAPs) (6.9 +/- 1.2 RBAP/h; p less than 0.001) compared with controls (0.3 +/- 0.1). Cell-free filtrates of C. jejuni cultures were also observed to induce RBAPs (5.0 +/- 0.9 RBAP/h; p less than 0.001). The fraction within the filtrate that induces alterations in motility was not destroyed by heating to 100 degrees C for 15 min (6.3 +/- 1.2 RBAP/h). Although no gross histologic changes were noted by hematoxylin and eosin staining of intestine exposed to a culture of C. jejuni for 8 h, blunting of villi with a cellular infiltrate was noted in rabbits exposed for 24 h. Scanning electron microscopy disclosed patchy villous tip damage in 3 of 5 animals exposed to cell-free filtrates for 8 h. These studies suggest C. jejuni is pathogenic and produces a heat-stable substance that alters intestinal myoelectric activity in rabbits.

Action Potentials↗
PubMed1985

Role of Pseudomonas aeruginosa mucoid exopolysaccharide in adherence to tracheal cells.

The mucoid exopolysaccharide of Pseudomonas aeruginosa is thought to confer antiphagocytic properties on mucoid strains of P. aeruginosa, thus allowing them to persist in the respiratory tract. It has also been speculated that the mucoid exopolysaccharide may be the adhesin for mucoid strains, but proof is lacking. We studied the role of the mucoid exopolysaccharide in adherence of mucoid strains in competitive experiments with purified mucoid exopolysaccharide, by measuring the binding of 14C-labeled mucoid exopolysaccharide to injured tracheas and testing whether an antibody against the major epitope of the mucoid exopolysaccharide inhibits adherence of these organisms. Our data show that the purified mucoid exopolysaccharide increased the adherence of four of the mucoid strains tested (by 50 to 300%; P less than 0.001) instead of inhibiting adherence. Radiolabeled mucoid exopolysaccharide bound much better to injured tracheal cells than to normal tracheal cells (P less than 0.001), and antibody against the antigen of strain 2192, the strain from which mucoid exopolysaccharide was prepared, inhibited the adherence of four of five mucoid strains but not the strain lacking this antigen. This antibody also failed to inhibit a nonmucoid revertant from strain 2192, which was previously shown to be inhibited by pili. These data strongly support the thesis that the mucoid exopolysaccharide is the adhesion for mucoid strains of P. aeruginosa.

Animals↗
PubMed1985

Tracheobronchial mucin receptor for Pseudomonas aeruginosa: predominance of amino sugars in binding sites.

Pseudomonas aeruginosa, a common respiratory tract colonizer and pathogen, adheres to injured tracheal cells and to tracheobronchial mucin. These phenomena suggest that there are specific receptors for this organism in the respiratory tract. The receptor on injured tracheal cells contains n-acetylneuraminic acid as the principal sugar, but the structure of the receptor in mucin has not been described. Using a microtiter plate assay to study bacterial adherence to mucin, we have partially characterized the mucin receptor for P. aeruginosa. The receptor for both nonmucoid and mucoid strains is sensitive to periodate oxidation, suggesting that it is carbohydrate in nature, and the amino sugars n-acetylglucosamine and n-acetylneuraminic acid inhibited the adherence of both types of strains. Nonmucoid strains were more sensitive to inhibition by n-acetylneuraminic acid than to inhibition by n-acetylglucosamine, but the mucoid strains varied in their sensitivities to inhibition by each amino sugar. Preincubation of mucin with heat-inactivated influenza A virus (which binds to neuraminic acid) significantly reduced the adherence of P. aeruginosa. Treatment of mucin with Clostridium perfringens neuraminidase also reduced bacterial adherence significantly. Treatment of mucin with pronase did not affect adherence. Our results suggest that n-acetylglucosamine and n-acetylneuraminic acid are important constituents of the binding sites for P. aeruginosa on human tracheobronchial mucin.

Acetylglucosamine↗
PubMed1985

Necrotizing soft-tissue infections caused by marine vibrios.

Halophilic, noncholera marine Vibrio bacteria can cause septicemia, gastroenteritis, cellulitis, and necrotizing fasciitis. We describe six patients with necrotizing fasciitis and review 12 cases described previously. The 18 patients included 14 men and four women. Their ages ranged from 32 to 79 years (average 58.1 years). Eleven patients were older than 55 years. Nine infections were caused by V. vulnificus, three by V. parahaemolyticus, and one by V. alginolyticus. In five cases the Vibrio species was not identified. Twelve patients had associated conditions that might have made them more susceptible to these infections, such as cirrhosis, steroid therapy, hemochromatosis, and multiple myeloma. These infections usually occur in apparently insignificant wounds (puncture wounds, insect bites) exposed to sea water or fish. Treatment is by debridement and antibiotic therapy. Three patients required amputation to control the infection. Six (33.3%) of the 18 patients died.

Adult↗
PubMed1984

Role of pili in the adherence of Pseudomonas aeruginosa to injured tracheal epithelium.

Pili have been demonstrated to be the adhesins of nonmucoid Pseudomonas aeruginosa for buccal cells. In this study, we examined their role in the adherence of both mucoid and nonmucoid strains to injured tracheal cells. Pili incubated with tracheal cells inhibited the adherence of a nonmucoid strain in a dose-dependent manner. Both homologous and heterologous pili inhibited this nonmucoid strain. Antibody against pili from the nonmucoid strain inhibited adherence of the homologous but not a heterologous strain. Pili failed to inhibit two mucoid strains, but inhibited nonmucoid variants derived from mucoid strains. These studies suggest that pili mediate the adherence of nonmucoid strains to injured tracheal cells but that they are not the final mediators of adherence of mucoid strains. It is also inferred that there are differences in the receptor for mucoid and nonmucoid strains.

Animals↗
PubMed1984

Adherence of Pseudomonas aeruginosa to human tracheobronchial mucin.

A microtiter plate assay was developed to study the adherence of Pseudomonas aeruginosa to purified human tracheobronchial mucin. The wells of the plates were treated with silicon to minimize nonspecific binding of bacteria and then coated with a solution of purified human tracheobronchial mucin. Bacteria were added to the wells, and the plates were incubated at 37 degrees C. The wells were washed 15 times in an automated microtiter plate washer, and the bacteria bound to wells were desorbed with Triton X-100 and plated for enumeration. Scanning electron microscopy verified bacterial adherence to the mucin-coated wells and desorption of bacteria by Triton X-100. Adherence of P. aeruginosa increased as the concentration of mucin used to coat the wells was increased, with saturation occurring at 0.5 microgram of mucin protein per ml. Other parameters that affected adherence included the time of incubation and concentration of bacteria. Similar studies with strains of Escherichia coli and Klebsiella pneumoniae indicated a relative lack of binding of these bacteria to mucin. In comparing different strains of P. aeruginosa, there were small differences in binding between strains. It is inferred that there may be specific sites on human tracheobronchial mucin which facilitate this preferential binding.

Bronchi↗
PubMed1983

Early results of a comparative trial of ceftazidime versus cephalothin, carbenicillin and gentamicin in the treatment of febrile granulocytopenic patients.

Ceftazidime was compared with a combination of cephalothin, carbenicillin and gentamicin as empirical therapy for fever in granulocytopenic patients. Forty-eight patients were studied in this randomized trial. In the 44 evaluable cases, favourable clinical responses were seen in 9/21 ceftazidime-treated cases and 13/23 patients treated with the combination. Four of 5 bacteraemias were cured with ceftazidime and 3 of 4 with triple therapy. Comparable numbers of patients developed new fevers while on therapy. Five ceftazidime-treated patients developed documented superinfection compared to 6 patients in the other group. Five patients treated with ceftazidime died from the initial infection or a superinfection compared with 3 on the combination. The overall results appear to be similar at this time. However, remarkable differences were observed between the types of superinfecting organisms with the two regimens. If all 48 patients are considered the isolates were as follows: ceftazidime treatment--5 clostridia, 3 enterococci, 1 Staphylococcus epidermidis and 1 Citrobacter; cephalothin-carbenicillin-gentamicin treatment--4 Pseudomonas, 1 Escherichia coli, 1 Bacteroides fragilis and 2 Candida spp. These results suggest that Gram-positive coverage should be added to ceftazidime in the empirical treatment of febrile granulocytopenic patients.

Adult↗
PubMed1983

Bacteriostatic and fungostatic action of catecholamide iron chelators.

Iron starvation as a means of controlling the proliferation of microorganisms was evaluated in vitro with spermidine catecholamide iron chelators. The growth of Escherichia coli and Pseudomonas aeruginosa was sensitive only to (D,L)-parabactin, whereas the growth of Candida albicans and Staphylococcus aureus was sensitive to a variety of catecholamide chelators. The disappearance of catecholamide activity upon methylation of the catechol hydroxyls, as well as iron reversal experiments, strongly suggests that the mechanism by which these compounds suppress growth is dependent upon their ability to sequester iron.

Amides↗
PubMed1983

Chronic colonization of rat airways with Pseudomonas aeruginosa.

Colonization of the airways of rats by Pseudomonas aeruginosa was established by treating the animals with hexamethylphosphoramide (HMPA) and inoculating with P. aeruginosa. Male Sprague-Dawley rats were given tap water (controls) or HMPA in the drinking water at 2 or 4 mg/ml. The ciliated cells of the airway epithelium were denuded, and microulcerative lesions in the epithelium were induced in the HMPA-treated rats. After 2 weeks of treatment, the rats were inoculated by transoral intratracheal instillation with 5 X 10(7) CFU of P. aeruginosa obtained from a cystic fibrosis patient. Two weeks after inoculation, P. aeruginosa was cultured from the airways, and scanning and transmission electron microscopy showed bacilli adhering to or invading the injured airway epithelium. P. aeruginosa was present in tracheal and intrapulmonary tissue homogenates of 9% of the P. aeruginosa-inoculated control rats (n = 22) as compared with 61% of the 2-mg/ml (n = 18) and 65% of the 4-mg/ml (n = 20) HMPA-treated rats (P less than 0.05). No dose-response relationship was found between 2 and 4 mg of HMPA per ml and colonization. Contamination of 47% of all of the rats with Mycoplasma pulmonis, as indicated by a positive enzyme-linked immunosorbent assay for immunoglobulin G, had no discernible significant effect on colonization by P. aeruginosa. These results indicate that colonization of the rat airway by P. aeruginosa can be achieved experimentally by treating the animals with HMPA. This research supports the hypothesis that colonization by P. aeruginosa may occur in airways where the ciliated epithelium has been injured and epithelial lesions exist.

Animals↗
PubMed1983

Evidence for mucins and sialic acid as receptors for Pseudomonas aeruginosa in the lower respiratory tract.

The nature of the receptors for mucoid and nonmucoid Pseudomonas aeruginosa was investigated by using adherence to injured tracheal epithelium as a model. Bovine submaxillary mucin and crude rat tracheal mucin inhibited the adherence of both types of P. aeruginosa. Among the sugars present in these mucins only N-aceylneuraminic acid inhibited adherence. Inhibition of adherence probably involved the binding of N-acetylneuraminic acid to the bacterial cells and not to the tracheal cells. The mucoid strain appeared to be much more sensitive to inhibition by N-acetylneuraminic acid. Periodate oxidation and cholera filtrate also reduced the adherence of both strains, but Clostridium perfringens neuraminidase treatment did not alter adherence. A nonmucoid isogenic mutant of an unstable mucoid strain was also inhibited by N-acetylneuraminic acid. These data suggest that the receptor for P. aeruginosa is a sialic acid moiety on cell surfaces or in mucins.

Adhesiveness↗
PubMed1983

Adherence of mucoid and nonmucoid Pseudomonas aeruginosa to acid-injured tracheal epithelium.

A model of the adherence of Pseudomonas aeruginosa to injured lower respiratory tract cells is described. Mouse tracheas were injured by exposure to 0.1 N HCl for 15 min, cut into pieces of 2 to 4 rings, and placed in petri dishes for adherence studies. Adherence was quantitated by direct count of the number of bacteria attached to a fixed surface area as viewed by scanning electron microscopy. Optimal conditions for study were 1 h of incubation with an inoculum of 10(7) to 10(8) CFU/ml. Both mucoid and nonmucoid P. aeruginosa adhered to the injured cells in this system, and no major differences in adherence between these strains was apparent. Adherence to injured tracheal cells was a phenomenon limited to P. aeruginosa and did not occur with Escherichia coli and Klebsiella pneumoniae. Besides adherence to injured cells, this model allowed the demonstration of adherence of mucoid P. aeruginosa and K. pneumoniae to mucin strands of uninjured control tracheas. This model is an alternative to the buccal cell model and has the advantage of allowing the study of the adherence of both mucoid and nonmucoid strains of P. aeruginosa.

Adhesiveness↗
PubMed1983

Antibiotic restriction in hospitals associated with medical schools.

Restriction of antibiotic use in 112 hospitals that are primary teaching facilities for medical schools was studied by mail questionnaire to pharmacy directors and infectious disease physicians. Questions involved whether use of certain antipseudomonal penicillins, aminoglycosides, and second- and third-generation cephalosporins was restricted, reasons for restrictions, existence of a formal education program on new antibiotics, whether the physician respondents agreed with the practice of antibiotic restriction, what percent of requests for use of restricted agents was denied, formulary status of the drugs, the procedure for authorizing dispensing of restricted agents, and the percent of drug expenditures represented by restricted agents. Direct control (specialist authorization or restricted indications for use) was used in 62 (57%) of 108 institutions responding. Nonformulary status indirectly controlled use in 35 institutions. No significant differences in the prevalence of restrictions were found for hospital size, ownership, physician's view of the restrictions, or presence of an education program. Most (85%) of the physicians agreed with restriction practices. Cost was the reason given most frequently for restriction of the penicillins and cephalosporins, while aminoglycosides were most frequently restricted because of bacterial resistance. The specialist's oral authorization was the most common method of approval for use of restricted agents. Expenditures for restricted drugs varied widely, suggesting that different levels of control were considered "restriction" by the responding institutions. Control of antibiotic use is common in these teaching hospitals associated with medical schools. No best method for antibiotic restriction was evident.

Anti-Bacterial Agents↗