In-vitro activity of trospectromycin against gram-positive cocci.
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Biomedical subjects
Publications and source records attributed to E A Gorzynski.
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The in vitro activity of sparfloxacin was compared with the activities of ciprofloxacin, ofloxacin, and six other antimicrobial agents against 323 bloodstream isolates of staphylococci (both oxacillin susceptible and resistant) enterococci, and pneumococci. Sparfloxacin was more active than both ciprofloxacin and ofloxacin against all the isolates tested. Its activity (MIC for 90% of strains tested < or = 0.10 microgram/ml) against oxacillin-susceptible staphylococci was superior to that of ciprofloxacin and ofloxacin by at least fourfold. Sparfloxacin was also more potent against pneumococci. However, fluoroquinolone resistance was noted among oxacillin-resistant strains of Staphylococcus aureus and coagulase-negative staphylococci.
The susceptibilities of 316 gram-positive bacteremic isolates to ramoplanin, vancomycin, and teicoplanin and seven other antibiotics were tested. Ramoplanin demonstrated MICs of < or = 0.25 microgram/ml for at least 99% of Staphylococcus aureus isolates and 100% of coagulase-negative staphylococci tested. For both oxacillin-susceptible and oxacillin-resistant S. aureus and coagulase-negative staphylococci, the activity of ramoplanin surpassed those of both vancomycin and teicoplanin. Ramoplanin and teicoplanin had comparable activities against enterococci and Streptococcus pneumoniae and were superior to vancomycin.
Temafloxacin, a new fluoroquinolone with enhanced activity against Gram-positive bacteria, was compared with other antibiotics. A review of the literature on the in-vitro activity of temafloxacin was also done. The susceptibility of Gram-positive cocci isolated from blood cultures was determined using a broth microdilution method. Temafloxacin MIC90s for Staphylococcus aureus (oxacillin-sensitive and -resistant) and Streptococcus pneumoniae were less than 0.12, less than 0.12 and 0.76 mg/L respectively. Temafloxacin was more active than either ciprofloxacin or ofloxacin against these organisms. A review of the literature supported these findings. Temafloxacin was the most active of the quinolones tested against a small number of S. pneumoniae with decreased sensitivity to penicillin. Temafloxacin activity was not appreciably affected by changes in pH or the presence of serum, but activity was slightly reduced in urine at pH 6.5-7.2, and at high magnesium ion concentrations. With the exception of S. pneumoniae at high concentration, no significant inoculum effect was observed.
The in vitro activities of teicoplanin and vancomycin were compared with those of six other antimicrobial agents against 460 bacteremic isolates of gram-positive cocci. Teicoplanin was as active as vancomycin but less active than ciprofloxacin against staphylococci. Teicoplanin was the most potent of all agents tested against enterococci and had excellent activity against pneumococci.
The activities of fluoroquinolones and a new macrolide against 30 clinical isolates of Mycobacterium tuberculosis were determined in vitro by agar diffusion. In order of relative potencies against M. tuberculosis, temafloxacin (MIC for 90% of isolates [MIC90], 2.3 micrograms/ml) was at least as active as the reference quinolones ofloxacin (MIC90, 2.4 micrograms/ml) and ciprofloxacin (MIC90, 4.3 micrograms/ml). Less active were difloxacin (MIC90, 4.7 micrograms/ml), pefloxacin (MIC90, 6.7 micrograms/ml), and enoxacin (MIC90, 8.3 micrograms/ml). The macrolide clarithromycin was more potent than erythromycin but less potent than the fluoroquinolones. Our results suggest that the newer fluoroquinolones and clarithromycin should be included with ciprofloxacin and ofloxacin in pharmacokinetic studies that may lead to trials in human subjects with mycobacterial infections.
Enterobacterial common antigen (ECA) has attracted considerable interest since the original publication by Kunin in 1962. In the present study we demonstrated this antigen directly in the urine from patients with urinary tract infections (UTI) elicited by enterobacteria. Sheep erythrocytes were incubated with UTI urine; this resulted in their coating with ECA, which was studied by means of hemagglutination by anti-ECA serum. Test tube hemagglutination and the more simple slide hemagglutination were employed and with both procedures similar results were obtained. Positive results were observed in 94-99% of urine specimens from enterobacterial UTI collected in The Buffalo Children's Hospital in the 1960s. ECA in urine could also be demonstrated by hemagglutination inhibition. In this test, antibodies in anti-ECA serum were neutralized as a result of incubation of this serum with urine, and agglutination by the antiserum of sheep erythrocytes coated with a standard ECA preparation was prevented or reduced. By means of this latter test, ECA could be demonstrated in 67-88% of urine specimens from enterobacterial UTI. The possible diagnostic application of these tests has been discussed.
An enzyme immunoassay for detection of bacterial antigens in urine specimens from urinary tract infections (UTI) was developed. The antigens detected in infections by Enterobacteriaceae: Escherichia coli, Enterobacter aerogenes, and Proteus sp. were different from the enterobacterial common antigen (ECA). They were digested by trypsin and were characterized by remarkable thermostability; their molecular weights were approximately 34,000 and 31,000. They were detected by means of antisera to ECA or to suspension of E. coli. The frequency of positive results with urine specimens from enterobacterial UTI was 87-99%. In contrast, the urine specimens of UTI by Pseudomonas aeruginosa were positive in fewer than 20% with anti-E. coli sera, but were positive in more than 85% in tests with antiserum to P. aeruginosa. The possible diagnostic application of the described tests was discussed.
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Thirteen serogroups of Escherichia coli most frequently are responsible for urinary tract infections in humans. Knowledge of serogroup is required for epidemiological reasons and to help differentiate between new and reemergent strains in infected patients. Coagglutination and bacterial agglutination were compared as serodiagnostic tools for identifying groups of E. coli associated with these infections. In contradistinction to bacterial agglutination, coagglutination showed no cross-reactions for 12 of the 13 known strains obtained from the Center for Disease Control. A single antiserum, E. coli O4, caused bacterial agglutination and not coagglutination. In addition, staphylococcal cells that were coated with antiserum reacted with sheep erythrocytes that had been treated with soluble extract of E. coli. The latter reaction, cohemagglutination, was as specific and rapid as coagglutination; easily visible patterns of clumping developed within 1 min after sensitized staphylococci and E. coli reagent were mixed. These results revealed a method that is sensitive and reproducible for identifying serogroups of E. coli responsible for urinary tract infections.
Immunoglobulin G was present only in those Escherichia coli antisera causing coagglutination, as determined by immunoelectrophoretic patterns in eluates of antigen-antibody complexes.
Livers, sera, and erythrocytes of MAXX, BN, and Wistar rats were examined for an antigen (CRA) that cross-reacts with enterobacterial common antigen (ECA). Extracts of these tissues were tested for their capacity to reduce anti-ECA titers. By this parameter, CRA was present in certain, although not all, extracts of rat tissue. None of the extracts modified red blood cells (RBC) for agglutination by anti-ECA antisera, nor did MAXX liver extracts engender anti-ECA activity in rabbits. It was speculated that a repressor is present in rat tissue that affects both antigenicity and immunogenicity of CRA. To test this concept, extracts of mixtures of enterobacterial suspensions and liver homogenates were prepared. ECA in the presence of tissue did not modify RBC for anti-ECA activity as did ECA alone, nor did enterobacteria-liver extracts significantly reduce anti-ECA titers. Administration of ethanol-soluble fractions of enterobacteria-liver mixtures to rabbits did not elicit an anti-ECA antibody response as did ECA alone. The finding of CRA in certain rat tissues, sera, and erythrocytes may account, in part, for rats being refractory to immunization with ECA. It is proposed that repressors may mask or abrogate the expression of CRA in animal tissue.
Sterile tissues of human subjects free from infection and malignancy were assessed for an antigen that cross-reacts with the enterobacterial common antigen (ECA). Extracts of heated homogenates (HE) and ethanol-soluble (ES) fractions of liver, kidney, muscle, and heart tissues were examined for their capacities to react with ECA antibodies, as measured by hemagglutination procedures, and to elicit ECA humoral antibodies in rabbits. Both HE and ES extracts of human liver and kidney tissues specifically inhibited ECA hemagglutination. However, ES fractions of HE preparations demonstrated significantly greater inhibiton than their HE sources. In addition, both liver and kidney ES fractions primed rabbits for a rapid and specific secondary ECA humoral response to a single administration of ECA. The cross-reactivity noted between human tissue and ECA cannot be attributed to indigenous microorganisms present in the tissues, as subcultures of tissue homogenates were always sterile. Moreover, preliminary experiments with human fetal subjects, devoid of microbial flora, yielded similar results.
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The immunogenicity of enterobacterial common antigen (CA)-treated horse or mouse erythrocytes was determined in Swiss white albino mice by comparing survival rates with control mice, immunized with P. aeruginosa fraction-treated RBC and challenged in parallel with 10 LD50 S. typhimurium. The administration of small amounts of CA on horse, but not mouse, RBC significantly delayed mortality; protection was only marginally less than that evoked with 12-fold larger amounts of CA in the absence of RBC. Survival in infected animals was transient; independent of immunogen or control preparation employed, all mice were dead by day 15 after challenge.
Organs of Swiss white albino and C57BL/6Ha mice were assessed for an antigen (CRA) which cross-reacts with common enterobacterial antigen (CA). To this end, supernatant fluids (HKS) and ethanol-soluble fractions (ES) of heated homogenates of spleens, kidneys, and livers were examined for their capacities to react with CA hemagglutinins and to engender humoral and cellular events in the rabbit. The immunogenicity of CRA in the rabbit can not be predicted on the basis of CA hemagglutinin neutralization studies alone; although CRA was identified in the liver extracts of both mouse strains, according to this parameter, only the liver fraction of Swiss white albino mice elicited significant numbers of rosette-forming cells (RFC) in the spleens of rabbits. Also, kidney fractions, which primed the rabbits for booster with CA, were less effective in stimulating RFC in the spleens failed to inhibit CA hemagglutination and did not prime rabbits for a CA hemagglutinin response, these same preparations clearly evoked RFC in rabbit spleens. Thus, the antigenicity and immunogenicity of CRA in target organs of mice reflect the mouse strain, extraction procedure, and testing method employed.