Search PubMed⌕ Search

Biomedical subjects

W E Sanders

Publications and source records attributed to W E Sanders.

At least 109 records · Page 6Linked to original sources
PubMed1978

In vitro studies with Sch 21420 and Sch 22591: activity in comparison with six other aminoglycosides and synergy with penicillin against enterococci.

In vitro tests were performed with Sch 21420 and Sch 22591 to determine (i) their activity in comparison to six other aminoglycosides against 343 clinical isolates, and (ii) whether synergy with penicillin G could be demonstrated with enterococci. In broth dilution tests, Sch 22591 was more active than the seven other aminoglycosides against Staphylococcus aureus, Enterobacteriaceae, and most nonfermenting gram-negative bacilli. Sch 22591 was as active as tobramycin against Pseudomonas aeruginosa. The activity of Sch 21420 was comparable to gentamicin, sisomicin, netilmicin, and tobramycin but greater than amikacin or kanamycin against S. aureus and most genera of Enterobacteriaceae. Sch 21420, amikacin, and kanamycin were (i) more active than the other five aminoglycosides against Proteus rettgeri and Providencia stuartii, but (ii) less active than the other five aminoglycosides against Neisseria gonorrhoeae, enterococci, most nonfermenting gram-negative bacilli, Proteus mirabilis, and Proteus morganii. Studies on the bactericidal activity of Sch 22591 with penicillin indicated a synergistic interaction against enterococci, including strains highly resistant to streptomycin and kanamycin. This could be demonstrated with combinations containing 3.0 to 6.0 mug of Sch 22591 per ml and was comparable to that observed with penicillin/gentamicin. Penicillin plus Sch 21420 (25 mug/ml) also demonstrated synergy against enterococci, including strains highly resistant to streptomycin. However, synergy did not occur against strains highly resistant to kanamycin. These latter results were similar to those obtained in tests with penicillin/kanamycin.

Aminoglycosides↗
PubMed1978

Comparison of 5-episisomicin (Sch 22591), gentamicin, sisomicin, and tobramycin in treatment of experimental Pseudomonas infections in mice.

Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12 Pseudomonas strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were </=6.2 mug/ml). Median 50% protective doses were 5.8, 6.4, 7.7, and 17.8 mg/kg for Sch 22591, tobramycin, sisomicin, and gentamicin, respectively. Those for Sch 22591 were significantly lower than gentamicin in five protection tests and significantly lower than both gentamicin and tobramycin in one test. Microbial analysis of the therapeutic effect indicated that protection from lethality by each of the four aminoglycosides was associated with either a complete eradication or a reduction in the number of challenge bacteria in both the heart blood and peritoneum. In rare instances, challenge isolates exhibiting decreased susceptibility to one or more of the aminoglycosides were recovered from animals. However, this in vivo selection of resistance did not appear related to either the aminoglycoside used in therapy or the outcome of therapy, and resistant isolates were recovered as frequently from untreated animals as from those receiving one of the four aminoglycosides.

Animals↗
PubMed1978

Suppression of lymphocyte responses by cephalosporins.

Human peripheral blood lymphocytes were cultured in several concentrations of each of several cephalosporins. Responses to phytohemagglutinin were compared with that of duplicate cultures containing penicillin-streptomycin, chloramphenicol, or no antibiotics. Possible effects of cephalosporins on responses of lymphocytes to concanavalin A and pokeweed mitogen were similarly determined. Significant suppression of responses to phytohemagglutinin and concanavalin A were seen in cultures containing 50 microgram each of cephalothin, cephalexin, or cephradine per ml. Lymphocyte responses to pokeweed mitogen were suppressed by 50 microgram of cephalexin, cephradine, or cefoxitin per ml. A higher concentration (100 microgram/ml) of all cephalosporins except cefoxitin and cefazolin suppressed the phytohemagglutinin response to less than 20% that of controls. Chloramphenicol (50 microgram/ml) did not inhibit the response to any mitogen used. These findings suggest that cephalosporins should not be used for prevention of bacterial overgrowth in certain cell cultures. Since many of the cephalosporins were suppressive in therapeutically attainable concentrations, these results may have potential clinical significance.

Cephalosporins↗
PubMed1978

Inhibition of Neisseria gonorrhoeae by aerobic and facultatively anaerobic components of the endocervical flora: evidence for a protective effect against infection.

The ability of aerobic and facultatively anaerobic endocervical flora to inhibit the growth of Neisseria gonorrhoeae in vitro was assayed. Factors influencing the occurrence of inhibitory components of the flora in vivo were evaluated. Endocervical swabs were obtained from 229 women at a local venereal disease clinic. Endocervical flora and N. gonorrhoeae were isolated and identified, and the ability of the flora to inhibit the growth of N. gonorrhoeae was determined by an agar overlay assay. Results revealed the most active inhibitors to be streptococci, staphylococci, and lactobacilli, in that order. Among only those women harboring inhibitory endocervical flora, inhibitory lactobacilli were recovered from fewer women infected with N. gonorrhoeae than uninfected women (P less than 0.05). Among women having contact with an infected partner, those who subsequently developed gonorrhea were less likely to have inhibitory lactobacilli than those who did not become infected (P less than 0.05). No other significant differences in the composition of the inhibitory flora were noted between infected and uninfected women. During the 2 weeks following menses, recovery of inhibitory lactobacilli on culture was highest, whereas recovery of N. gonorrhoeae was lowest. These observations suggest that the presence of certain lactobacilli may reduce risk of acquisition of N. gonorrhoeae following exposure to infected partners and that the potential protective effect may be greatest during the 2 weeks after menses.

Aerobiosis↗
PubMed1977

Bacterial interference. IV. Epidemiological determinants of the antagonistic activity of the normal throat flora against group A streptococci.

A study was performed to identify epidemiological factors such as age, race, sex, and time of culture that might influence the ability of the normal pharyngeal flora to interfere with growth of group A streptococci. From March 1974 through February 1975, throat swabs were obtained from 952 individuals. Cultures were assayed by an agar overlay procedure for the presence of bacteria capable of inhibiting growth of group A streptococci. The observed inhibition was then determined to be bacteriostatic or bactericidal by use of a broth filtrate technique. Regardless of age, race, or sex, subjects were more likely to harbor interfering flora if cultured during the months of March and April, which coincided with the highest prevalence of group A streptococci in the community. Race and sex of subjects appeared not to influence the inhibitory activity of throat flora either quantitatively or qualitatively. However, among individuals with interfering flora, the prevalence of bactericidal organisms increased and bacteriostatic organisms decreased with advancing age. Since the presence of bactericidal, and not bacteriostatic, organisms has been associated with resistance to colonization of the throat by group A streptococci, this higher prevalence of bactericidal organisms in older individuals suggests that bacterial interference may be one of the mechanisms that account for the greater resistance of adults than children to streptococcal throat infection.

Adolescent↗
PubMed1976

Bacterial interference: effects of oral antibiotics on the normal throat flora and its ability to interfere with group A streptococci.

The effects of orally administered penicillin and tetracycline on the composition of the normal throat flora and its interference with the growth of group A streptococci were evaluated by throat culture and an agar overlay technique. Tetracycline caused only a slight, transient quantitative decrease in the composition of the flora and interference activity. Penicillin caused significant quantitative and qualitative decreases in both the composition of the flora and interference activity. The diminution in interference activity persisted up to 3 weeks after therapy. The differences observed between the antibiotic regimens correlated with differences in initial susceptibility of the flora to the antibiotic used and emergence of the resistance during therapy. Results indicated that although effects of antibiotics on the composition of the flora are transient, effects on its ability to interfere with group A streptococci may persist long after therapy is discontinued. It is thus possible that penicillin therapy may enhance susceptibility of certain individuals to subsequent infection with group A streptococci.

Administration, Oral↗
PubMed1976

Rifampin.

In 1971, rifampin was approved for treatment of pulmonary tuberculosis and asymptomatic carriers of Neisseria meningitidis. At present, the approved indications remain the same. However, rifampin in conjunction with at least one other antituberculous drug may be of great value in therapy of extrapulmonary tuberculosis and infections due to other susceptible mycobacteria. In addition, results of clinical trials in leprosy have been highly encouraging. Rifampin appears to induce light chain proteinuria in a majority of patients and has been implicated in suppression of both humoral and cell-mediated immune responses. However, these effects appear to have been of little consequence to treated patients. A variety of possibly immunologically mediated reactions to rifampin has been closely associated with irregular administration of the drug. These reactions and hepatic toxcity may be preventable in many patients. Rifampin or one of its congeners, alone or in combination with other antibiotics, may prove useful in treatment of various infectious, and possibly malignant, diseases.

Animals↗
PubMed1975

Effects of procedural variations on the activity of aminoglycosides in vitro.

Am J Clin Pathol 63:438-445, 1975. The effects of procedural variations on the activities of gentamicin, tobramycin, sisomicin, kanamycin, and amikacin in vitro were evaluated using 134 clinical isolates. In broth dilution studies, a change in assay medium from brain-heart infusion broth to Mueller-Hinton broth resulted in significant changes in minimal inhibitory concentrations in 36% (242 of 670) of assays. A change in the bacterial population size utilized in broth dilution studies resulted in significant changes in minimal inhibitory concentrations in 34% (155 of 456) of assays. These variations in activities appeared to depend more on the organism tested than on the particular aminoglycoside used; with strains of Staphylococcus aureus, Proteus, and Providenica being most affected. For all five aminoglycosides, minimal inhibitory concentrations determined by broth dilution, regardless of medium, showed poor correlation with zone sizes obtained by the Bauer-Kirby technic. These results suggest that unless some standard assay procedure for activity of aminoglycosides is adopted, meaningful comparison of results within and among laboratories will not be possible.

Aminoglycosides↗
PubMed1975

Asymptomatic epidemic acquisition of group A Streptococcus: antibody response to extracellular and type-specific antigens.

The antibody response of 40 institutionalized children involved in an epidemic associated with asymptomatic pharyngeal acquisition of a group A, M-11, T-11 typeable Streptococcus was studied. Titers of antibody to streptolysin O and to deoxyribonuclease B determined in sera collected from patients within two weeks of positive throat cultures were significantly higher than those in sera of controls (P smaller than 0.001). However, there was no rise in antibody titers in sera obtained from these patients after an interval of three weeks. Type-specific antibody to the group A Streptococcus (type M-11) was assayed in the sera of 24 patients. No detectable antibody activity was found either in the initial sera or in sera collected eight months after the epidemic. Thus, the asymptomatic nature of this epidemic could not be attributed to the presence of detectable type-specific antibody in this population at the time of the epidemic. These observations suggest that asymptomatic pharyngeal acquisition of group A Streptococcus may occur in epidemic fashion in certain populations and may not be associated with evidence of an antibody response to the streptococcal organism.

Antibodies, Bacterial↗
PubMed1975

BL-P1654: a bacteriostatic penicillin?

In tube dilution studies, large discrepancies between inhibitory and bactericidal concentrations of BL-P1654 against Pseudomonas were observed. To explain these discrepancies which were not observed with carbenicillin, the kinetics of bacterial killing by these two penicillins were evaluated and compared. The kinetics of bacterial killing by both antimicrobial agents were characteristic of a penicillin, with killing initiating simultaneously with growth. Kill curves revealed the presence of a small number of cells resistant to BL-P1654 which were not detectable macroscopically. Studies on microbial resistance also showed the presence of a small but consistent number of cells resistant to BL-P1654 over a broad range of concentrations above its minimal inhibitory concentration. This pattern of resistance was not observed with carbenicillin. Thus, the discrepancies between inhibitory and bactericidal concentrations of BL-P1654 were not due to any unusual bacteriostatic activity but rather due to a small number of resistant cells whose presence could be detected only by sensitive subculturing techniques.

Carbenicillin↗
PubMed1974

Rosamicin: evaluation in vitro and comparison with erythromycin and lincomycin.

Rosamicin is a new macrolide antibiotic produced by Micromonospora rosaria. It shares certain chemical and biological characteristics with erythromycin. Activity against gram-positive strains was assayed by broth dilution and compared to that of erythromycin and lincomycin. Rosamicin was bacteriostatic and inhibited most strains of Staphylococcus aureus, Staphylococcus epidermidis, enterococci, viridans streptococci, and group A streptococci in concentrations of 0.02 to 4.0 mug/ml. Results were similar for erythromycin and for lincomycin (excluding enterococci). Cross-resistance of gram-positive organisms to these three antimicrobial agents was incomplete. Rosamicin was more active than erythromycin against Enterobacteriaceae and Pseudomonas at pH 7.2. Alkalinization of the medium enhanced the activity of both rosamicin and erythromycin; however, rosamicin was still more active than erythromycin against all gram-negative strains at pH 7.6 and 8.0. In view of the high degree of in vitro activity of rosamicin against gram-positive organisms, lack of complete cross-resistance with erythromycin and lincomycin, and the greater activity of rosamicin than erythromycin against gram-negative organisms, further investigation of this macrolide is warranted.

Anti-Bacterial Agents↗