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Biomedical subjects

S D Allen

Publications and source records attributed to S D Allen.

At least 73 records · Page 4Linked to original sources
PubMed1989

Multicenter in vitro evaluation of SM-7338, a new carbapenem.

A new carbapenem, SM-7338, was compared with imipenem, cefotaxime, and ceftazidime at five medical centers. Nearly 6,000 strains were tested by reference methods of the National Committee for Clinical Laboratory Standards, and SM-7338 inhibited the largest percentage of gram-negative bacilli. Its spectrum included all members of the family Enterobacteriaceae (99.7% were susceptible to less than or equal to 4 micrograms/ml), Pseudomonas spp. (but not Xanthomonas maltophilia), and Acinetobacter spp. The potency and spectrum of SM-7338 against the gram-positive organisms were less than those of imipenem and superior to those of ceftazidime. Only the enterococci and some oxacillin-resistant staphylococci were less susceptible to SM-7338 (MICs for 90% of isolates, greater than or equal to 8 micrograms/ml). Organisms resistant to ceftazidime were generally susceptible to SM-7338 and imipenem (76%). However, for one-third of the imipenem-resistant gram-negative bacilli (MICs, greater than 8 micrograms/ml), SM-7338 MICs were less than or equal to 4 micrograms/ml. Some endemic differences in patterns of SM-7338 activity against selected gram-negative species were found among some medical centers.

Anti-Bacterial Agents↗
PubMed1989

Selection of orally active antifungal agents from 3,5-substituted isoxazolidine derivatives based on acute efficacy-safety profiles.

Routine in vitro screening of a new synthetic series of 3,5-substituted 2-methylisoxazolidines revealed that three imidazole analogs (PR 967-248, PR 967-234, and PR 969-566) and, to a lesser extent, a triazole analog (PR 988-399) exerted rather potent antifungal activity against three systemic and four dermatophytic classes of fungi. When tested in vivo for ability to eradicate Candida vaginitis in the rat, the triazole derivative, PR 988-399, was effective after oral administration. In this in vivo test for efficacy, PR 967-234 and PR 969-566 reduced but did not eradicate the infection, while PR 967-248 was inactive. PR 988-399 was, moreover, 4- to 13-fold less potent than the three imidazoles in inhibiting testosterone synthesis in isolated rat Leydig cells. After oral or intravenous administration, PR 988-399 and PR 969-566 elicited the fewest cardiovascular and behavioural side effects in conscious dogs. The rat safety study consisted of oral dosing followed by evaluation of the exploratory motor activity of the naive animals in a novel environment. Motor activity was suppressed least by PR 988-399 and most by PR 969-566. In a battery of mouse behavioural-neuromuscular-drug interaction tests, PR 988-399 and PR 969-566 produced the fewest central-behavioural-neuromuscular signs. These efficacy-safety evaluations were performed with ketoconazole as a positive reference standard. The sequence of drug testing with respect to efficacy-safety considerations appears to be a suitable approach for early detection of orally active antifungal agents such as PR 988-399 for more advanced development.

Administration, Oral↗
PubMed1989

Quality control guidelines for testing cefotetan in the reference agar dilution procedure for susceptibility testing of anaerobic bacteria.

Reference values for quality control of in vitro susceptibility tests with cefotetan against anaerobic bacteria were determined in two independent multilaboratory studies with the approved National Committee for Clinical Laboratory Standards agar dilution method and three control strains (Bacteroides fragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29741, and Clostridium perfringens ATCC 13124). The results of the two studies were in agreement. The recommended MIC control limits for B. fragilis ATCC 25285 and B. thetaiotaomicron ATCC 29741 are 4.0 to 16 micrograms/ml and 32 to 128 micrograms/ml, respectively. MICs for C. perfringens ATCC 13124 were too variable to be useful for controlling tests with cefotetan.

Bacteria, Anaerobic↗
PubMed1989

Quality control limits for the standard anaerobic reference agar dilution susceptibility test procedure of the National Committee for Clinical Laboratory Standards.

Multilaboratory studies were performed to develop MIC quality control limits for the National Committee for Clinical Laboratory Standards reference agar dilution method for anaerobic susceptibility tests. Acceptable MICs were defined as those which include greater than 95% of all 100 MICs generated by the study. Most MIC control limits included either 2- or 3-dilution intervals rather than the more traditional 3-dilution intervals that are described as the mode +/- 1 doubling dilution.

Amoxicillin↗
PubMed1989

Characterization of anaerobic bacteria by using a commercially available rapid tube test for glutamic acid decarboxylase.

A rapid glutamic acid decarboxylase microdilution test for presumptive identification of certain anaerobic bacteria was marketed recently by Carr-Scarborough Microbiologicals, Inc., Stone Mountain, Ga. The test was evaluated with 474 clinical isolates, representing 11 genera and 54 species, and was found to be a useful aid in the presumptive identification of Bacteroides fragilis, B. distasonis, B. vulgatus, B. thetaiotaomicron, B. ovatus, B. uniformis, B. eggerthii, Clostridium perfringens, C. barati, C. sordellii, and Eubacterium limosum.

Bacteria, Anaerobic↗
PubMed1989

Studies on antifungal agents. 20. Effect of the nitrogen substitution on the in vitro activity of novel 3,5-substituted isoxazolidines.

The effect of the nitrogen substitution on the in vitro antifungal activity of a series of novel cis-3,5-substituted isoxazolidine derivatives is investigated. The 2-(N-methyl) analogues 4-6 were found to be the most active compounds when tested in vitro against Trichophyton rubrum, Aspergillus fumigatus and Candida albicans, with MIC values ranging between 0.7 and 70 micrograms/ml.

Antifungal Agents↗
PubMed1989

Influence of bovine intestinal fluid on the expression of K99 pili by Escherichia coli.

A study was conducted to determine whether intestinal fluid collected from various portions of bovine intestine differed in its effect on production of K99 pili by Escherichia coli. The small and large intestines of 7 calves, euthanatized 4 hours after a final feeding of milk, were divided into 6 to 9 segments from which intraluminal fluids were collected. Depending on the amount of fluid collected, up to 20 E coli strains that express K99 pili were grown on media prepared from the content of each specimen and then were tested for K99 pilus expression. In general, intestinal fluid from the most proximal small intestinal segments were more suppressive to K99 pilus expression than was fluid from more distal segments of small intestine. Only about 20% of the E coli test strains expressed K99 pili when grown on medium prepared from proximal small intestinal segmental fluid, whereas greater than 90% did when grown on medium prepared from distal small intestinal segmental fluid. Fluid from the large intestine varied considerably from calf to calf in its effect on K99 pilus expression. A correlation was found between K99 pilus expression and pH of the intestinal fluid, with the lower pH values (characteristic of proximal intestinal segmental fluid) being suppressive. The correlation between K99 pilus production and the pH of the medium was verified, using defined laboratory media adjusted to various pH values. Strains of E coli grown in medium at or below pH 5.5 failed to express K99 pili, whereas the same strains when grown in medium at or above pH 6.5 expressed K99 pili in abundance.

Amino Acids↗
PubMed1989

Studies on antifungal agents. 19. Effect of the C-5-aromatic substitution on the in vitro activity of novel 3,5-substituted isoxazolidines.

The influence of the C-5-aromatic substitution on the in vitro antifungal activity of novel cis-3,5-substituted isoxazolidine derivatives was investigated. Compounds having a C-5-(substituted phenoxy)methyl group were found to be the most active against Trichophyton rubrum, Aspergillus fumigatus and Candida albicans with MIC values ranging from 0.7 to 70.0 micrograms/ml. Replacing the phenoxymethyl group with either naphthyl or 2-oxo-1,3-benzoxathiol-6-yl groups resulted in a diminished in vitro activity.

Antifungal Agents↗
PubMed1988

5-( [aryl or aryloxy (or thio)]methyl)-3-(1H-imidazol-1-ylmethyl)-3- (2-thienyl)-2-methylisoxazolidine derivatives as novel antifungal agents.

The in vitro antifungal activity of a novel series of cis- and trans-5-([aryl or aryloxy (or thio)]methyl)-3-(1H-imidazol-1-ylmethyl)-3- (2-thienyl)-2-methylisoxazolidines (13-24) was evaluated and compared with ketoconazole. The title series of compounds was prepared via a 1,3-dipolar cycloaddition reaction of 1-(2-thienyl)-2-(1H-imidazol-1-yl)-N-methylethanimine N-oxides with appropriate styrenes, allyl phenyl ethers, or allyl phenyl thioether precursors. The resulting products were mixtures of the corresponding cis- and trans-diastereomers which were readily separated by flash chromatography on neutral silica gel. The majority of compounds 13-24, when tested in solid agar cultures, exhibited moderate to potent activity against Trichophyton rubrum, Aspergillus fumigatus, and Candida albicans at concentrations ranging between less than or equal to 2.0 and 70.0 micrograms/mL.

Antifungal Agents↗
PubMed1988

In vitro activity of FCE 22101, imipenem, and ceftazidime against over 6,000 bacterial isolates and MIC quality control limits of FCE 22101.

Six geographically separate laboratories within the USA tested 6,198 bacterial isolates against FCE 22101 (a penem), imipenem (a carbapenem) and ceftazidime (a third-generation cephalosporin). Ninety-three percent of 2,749 Enterobacteriaceae were inhibited by FCE 22101, while 95% were susceptible to ceftazidime and 99% were susceptible to imipenem. FCE 22101 had little activity against Pseudomonas spp. but was active against most gram-positive pathogens, including enterococci. FCE 22101 MICs for standard quality control strains were defined as 0.5-2.0 micrograms/ml for Escherichia coli ATCC 25922, 2-8 micrograms/ml for Enterococcus faecalis ATCC 29212 and 0.06-0.25 microgram/ml for Staphylococcus aureus ATCC 29213.

Anti-Bacterial Agents↗
PubMed1988

Effect of clavulanic acid on the susceptibility of clinical anaerobic bacteria to ticarcillin: a multicenter study.

Over 2,000 recent clinical isolates of anaerobic bacteria were tested at five medical centers for susceptibility to ticarcillin, ticarcillin plus clavulanic acid, clindamycin, and metronidazole. At 64 micrograms/ml, ticarcillin inhibited 92% of all isolates, but 98% were inhibited at this concentration when 2 micrograms/ml of clavulanic acid was added. With different Bacteroides species, clavulanic acid reduced ticarcillin MICs 2- to 32-fold; other anaerobic species were not significantly affected.

Bacteria, Anaerobic↗
PubMed1988

Antimicrobial activity of U-76,252 (CS-807), a new orally administered cephalosporin ester, including recommendations for MIC quality control.

U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807), was tested against 4,742 fresh clinical isolates from four large medical centers. U-76,253A was very active against nearly all species of Enterobacteriaceae (87.7% inhibited at less than or equal to 4.0 micrograms/ml). Staphylococcus spp., and the streptococci. The U-76,253A spectrum was superior to the comparison orally administered cephalosporins (cephalexin, cephradine, cefaclor). Pseudomonas spp., Acinetobacter spp., and the enterococci were resistant to U-76,253A and the other tested drugs. Broth microdilution MIC quality control (QC) limits were established for U-76,253A in a multilaboratory investigation using a minimum of 125 MIC determinations per organism. The following MIC QC ranges were recommended; Escherichia coli (ATCC 25922) = 0.25-1.0 micrograms/ml, Staphylococcus aureus (ATCC 29213) = 2.0-4.0 micrograms/ml and Pseudomonas aeruginosa (ATCC 27853) = greater than 32 micrograms/ml.

Administration, Oral↗
PubMed1988

Studies on antifungal agents. 23. Novel substituted 3,5-diphenyl-3-(1H-imidazol-1-ylmethyl)- 2-alkylisoxazolidine derivatives.

The synthesis and antifungal activity of a novel series of substituted 3,5-diphenyl-3-(1H-imidazol-1-ylmethyl)-2-alkylisoxazolidine derivatives (15-30) are described. The synthesis of the title compounds was accomplished via a 1,3-dipolar cycloaddition reaction of alpha-substituted ketonitrones with appropriate styrene precursors. The compounds when tested in vitro in solid agar cultures exerted a very potent antifungal activity against a wide variety of yeast and systemic mycoses and dermatophytes, especially Trichophyton and Microsporum sp., Epidermophyton floccosum and Candida stellatoidea. The in vitro activity against Aspergillus fumigatus and Candida albicans was moderate to potent. Overall, the two bis(4-chlorophenyl) analogues 18 and 19 were the most potent in vitro compounds, showing MIC values ranging between 0.2 and 7.0 microgram/mL, as compared to 0.2-20.0 micrograms/mL for ketoconazole, which was used as the positive standard in all assays. When tested in vivo in the rat vaginal candidiasis model, derivative 18, although showing significant antifungal activity when compared to controls, was less effective than ketoconazole. The title 3,5-substituted isoxazolidine compounds represent a novel class of potent antifungal agents.

Animals↗