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Biomedical subjects

W H Traub

Publications and source records attributed to W H Traub.

At least 37 records · Page 2Linked to original sources

Metalloproteases of Serratia liquefaciens: degradation of purified human serum proteins.

Two representative strains of Serratia liquefaciens, SL 5 (serotype O5:H1) and SL 11 (serotype O1:H1), produced proteases characterized by molecular weights of 52.5 kilodaltons and isoelectric points of 6.2; both enzymes were inhibited by 50 mM EDTA. As demonstrated with SDS-PAGE electrophoresis, the two metalloproteases attacked the following purified human serum proteins: complement components C3, C4, C5, C6, C7, C8, and C9, transferrin, alpha 1-antitrypsin, alpha 2-macroglobulin, fibronectin, type III fibrinogen, immunoglobulin G (heavy chains), and IgM (heavy chains). However, C1q, IgA, haptoglobin, and C-reactive protein were refractory.

Blood Proteins↗

Collagenase of Clostridium perfringens type A: degradation of human complement component C1q.

The semipurified collagenases from Clostridium perfringens type A strains 2-Cli and ATCC 13124, both characterized by molecular weights of 79.4 kilodaltons, partially degraded purified human complement (C) component C1q. The following purified human serum proteins were refractory: C components C3, C4, C5, C6, C7, C8, and C9; immunoglobulin (Ig)A (from colostrum), IgG, and IgM; alpha 2-macroglobulin, haptoglobin, and C-reactive protein.

Blotting, Western↗

Teicoplanin combined with various antibiotics and human blood against a multiple-drug-resistant strain of Staphylococcus aureus.

Neither teicoplanin nor vancomycin at 2, 1 and 0.5 micrograms/ml consistently killed inocula of representative isolates of a multiple-drug-resistant (MDR) strain of Staphylococcus aureus in the presence of 65% (v/v) of fresh, defibrinated human blood, although both antibiotics sterilized tube contents in Mueller-Hinton broth (MHB). With added human blood, teicoplanin (1 microgram/ml) combined with rifampin (1 microgram/ml) was the most effective in vitro combination, followed by teicoplanin (1 microgram/ml) + amoxicillin (8 micrograms/ml) + clavulanate (3 micrograms/ml), ampicillin (8 micrograms/ml) + sulbactam (8 micrograms/ml), cefamandole (8 micrograms/ml), fosfomycin (4 micrograms/ml + 25 micrograms/ml glucose-6-phosphate), imipenem (8 micrograms/ml), netilmicin (4 micrograms/ml), trimethoprim + sulfamethoxazole (1/19 micrograms/ml) and vancomycin (1 microgram/ml), respectively. Conversely, teicoplanin (1 microgram/ml) combined with fusidic acid (0.5 micrograms/ml) and ofloxacin (4 micrograms/ml), respectively, proved ineffective with 65% (v/v) added human blood. In concurrent control tubes, however, all drug combinations were bactericidally active in MHB against the MDR strain of S. aureus.

Aminoglycosides↗

Immunobiology of Clostridium perfringens type A: passive protection of NMRI mice. Western blot analysis of immunoreactive polypeptides.

Polyvalent, equine antitoxin (250 IU/mouse) passively protected NMRI mice against 7 of 9 challenge strains of Clostridium perfringens type A. Two human immunoglobulin G (IgG) preparations (Polyglobin N and Sandoglobulin) and two rabbit immune sera prepared against formalinized cells of C. perfringens were ineffective. Cell homogenates of 4 C. perfringens strains revealed more than 15 polypeptides in SDS-PAGE electropherograms; the molecular weights ranged from 138 to 14.4 kD. Normal human serum from 2 donors revealed up to 3 immunoblot-reactive antibodies against 126-, 69.2-, 49- or 14.4-kD antigens, the two rabbit immune sera showed antibodies against 4-7 distinct antigens that ranged from 138 to 28.8 kD, whereas the two human IgG preparations revealed antibodies against up to 12 antigens (range 138.7-31.6 kD) and antibodies against lower-molecular-weight (less than 24.5-kD) components. Polyvalent, equine antitoxin reacted with at least 14 polypeptides (range 136.5-31 kD) and numerous smaller (less than 24-kD) components.

Animals↗

Virulence of clinical and fecal isolates of Clostridium perfringens type A for outbred NMRI mice.

Twelve clinical and 102 fecal isolates from healthy carriers of Clostridium perfringens type A were tested for virulence in juvenile, outbred NMRI mice (intramuscular route). There were marked differences (up to 1,000-fold) in virulence among strains of both groups of isolates. On average, clinical isolates were not more virulent than fecal isolates. Fresh epinephrine (10 micrograms/mouse and given concurrently with bacterial inocula) significantly augmented virulence. The murine model of Hill and Osterhout for experimental gas gangrene yielded reproducible results. Myelosuppressed (cyclophosphamide-pretreated) mice were somewhat more susceptible to C. perfringens as contrasted with mice that had been pretreated with either carrageenan type II or with zymosan. The murine virulence of C. perfringens was enhanced significantly by Escherichia coli.

Animals↗

Serotyping of clinical isolates of Acinetobacter: serovars of genospecies 3.

A total of 156 clinical isolates of genospecies 3, the second most commonly encountered member of the genus Acinetobacter at our institution, were identified with carbon source utilization tests among 400 Acinetobacter isolates. Checkerboard tube agglutination tests and reciprocal cross-absorption studies with polyclonal rabbit immune sera against heated (100 degrees C, 1 h) cells of serovar candidate strains of genospecies 3 permitted identification of 13 serovars. Minor one-way crossreactions were noted between serovars 10 and 8 and between serovars 2 and 12, respectively. Isolates of serovar 13 cross-reacted extensively one-way with serovar 2 and less so with serovars 4 and 12. Genospecies 3 serovars 3, 7, 8, and 9 cross-reacted with Acinetobacter baumannii serovars 19, 21, 6, and 15, respectively.

Acinetobacter↗

Humoral antibody response of rabbits against experimental Serratia marcescens septicemia.

Rabbits reconvalescent from experimental septicemia due to serologically defined strains of Serratia marcescens were examined for the diversity of their humoral antibody response with traditional serological procedures and the Western blot (immunoblotting) technique. Trichloracetic acid (TCA)-whole cell extracts of the homologous and heterologous O-antigen reference strains served as the antigen for the latter procedure. Reconvalescent rabbit sera contained antibodies against the homologous lipopolysaccharide (LPS) moiety (molecular weight (MW) range = 45-31 kilodaltons (= k] and antibodies against numerous heat-modifiable, cross-reactive proteins, in particular 7 proteins characterized by MWs of 117 k, 95 k, 91 k, 71 k, 68 k, 38 k, and 33 k in TCA-whole cell extracts from the homologous as well as from 11 heterologous S. marcescens O-antigen reference strains. Rabbits, which had been actively immunized with TCA-whole cell extracts from representative S. marcescens strains, mounted a humoral antibody response remarkably similar to that of rabbits which had recovered from septicemia, except that the sera from the actively immunized animals interacted somewhat more strongly with an additional cross-reactive protein (MW = 47 k). Conversely, conventional anti-O and anti-H rabbit immune sera revealed antibodies directed predominantly against the homologous LPS moiety (MW range = greater than or equal to 200 k - less than or equal to 15 k). It was concluded that numerous proteinaceous cellular constituents of S. marcescens accounted for immunoblot cross-reactivity.

Animals↗

Comparative in vitro bactericidal activity of 24 antimicrobial drugs against Clostridium perfringens.

Twenty-four antimicrobial drugs were examined for rapidity of onset and magnitude of bactericidal activity against selected strains of Clostridium perfringens. Ceftriaxone, imipenem, metronidazole, mezlocillin, penicillin G, piperacillin, and teicoplanin reduced colony counts by at least 3 log10 units within 2-4 h after exposure. Clindamycin, fluoroquinolones, josamycin, and tetracycline caused delayed kill (greater than or equal to 99.9% reduction of viable counts at 4-22 h after exposure). Chloramphenicol and rifampin lacked bactericidal activity against 2 of 4 strains, whereas erythromycin, fusidic acid, and fosfomycin (with added glucose-6-phosphate) were merely inhibitory for all 4 strains. Imipenem and penicillin G were combined with 9 and 12 antimicrobial drugs, respectively. Essentially all drug combinations yielded indifferent effects; only penicillin G plus doxycycline resulted in an antagonistic effect against C. perfringens.

Anti-Bacterial Agents↗

Antimicrobial drug susceptibility of clinical isolates of Acinetobacter species (A. baumannii, A. haemolyticus, genospecies 3, and genospecies 6).

A total of 144 clinical isolates of Acinetobacter species, i.e., A. baumannii (n = 60), genospecies 3 (n = 48), A. haemolyticus (n = 12), and genospecies 6 (n = 24), were examined comparatively with the agar dilution method of the National Committee for Clinical Laboratory Standards for susceptibility to 25 antimicrobial drugs. Only minor species differences were noted.

Acinetobacter↗

Acinetobacter baumannii serotyping for delineation of outbreaks of nosocomial cross-infection.

A total of 152 clinical isolates of Acinetobacter baumannii from 152 patients were identified by carbon source utilization tests and examined serologically. Polyclonal rabbit immune sera against A. baumannii strains were used in checkerboard tube agglutination tests, and 20 serovars were identified. One (serovar 19) cross-reacted with genospecies 3 (serovar 3), a closely related member of the genus Acinetobacter. Several outbreaks of nosocomial cross-infection caused by serovars 4 and 10 were delineated.

Acinetobacter↗

Pseudomonas aeruginosa: in vivo (murine) activity of five antimicrobial drugs, with and without human IgG immunoglobulin preparations.

Five antimicrobial drugs (ceftazidime, ciprofloxacin, imipenem, piperacillin and tobramycin) and two human, intravenously applicable, IgG immunoglobulin preparations (Psomaglobin, Polyglobin N) were examined alone and in various combinations for therapeutic efficacy in myelosuppressed as well as normal NMRI mice following systemic infection with 4 selected strains of Pseudomonas aeruginosa. Both IgG preparations alone invariably failed to passively protect neutropenic and normal mice, even though the preparations contained demonstrable antibodies against purified exotoxin A of P. aeruginosa and against numerous polypeptide and lipopolysaccharide constituents of the 4 test strains of P. aeruginosa. Among the antimicrobial drugs employed alone, ciprofloxacin and imipenem were the most effective. Tobramycin alone occupied an intermediate position, whereas monotherapy with ceftazidime and piperacillin invariably failed. All antimicrobial drug combinations were efficacious in myelo-suppressed as well as normal mice. Both IgG preparations failed to enhance the activities of ceftazidime and piperacillin in neutropenic mice; the activity of tobramycin was augmented against 1 of 2 P. aeruginosa strains, as well as that of ciprofloxacin. Both IgG preparations enhanced the activities of ceftazidime and tobramycin in normal NMRI mice, as well as that of piperacillin against 1 of 2 test strains. It was concluded that the two IgG preparations were more beneficial for normal rather than neutropenic mice, provided that the animals were treated with appropriate antimicrobial drugs as well.

Animals↗

Susceptibility of Acinetobacter calcoaceticus to antimicrobial drugs, alone and combined, with and without defibrinated human blood.

Twenty-five clinical isolates of Acinetobacter calcoaceticus were examined for susceptibility to 14 antimicrobial drugs. In terms of inhibitory and bactericidal activities, imipenem and polymyxin B were most active, followed by amikacin and ceftazidime. Four isolates were resistant against fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin). The isolates varied in susceptibility to aztreonam, cefotaxime, cotrimoxazole, gentamicin, mezlocillin, netilmicin and piperacillin. Fresh defibrinated human blood from 3 donors revealed similar killing kinetics against 8 selected isolates. In time-kill curve experiments, human blood enhanced the activity of amikacin more than that of ceftazidime, ciprofloxacin and imipenem against A. calcoaceticus. The combinations of amikacin + imipenem and amikacin + ceftazidime in the presence of human blood were effective against this microorganism. Human blood combined with ciprofloxacin + imipenem was more effective than blood with added ceftazidime + ciprofloxacin.

Acinetobacter↗

In vitro activity of three fluoroquinolones against enterococci and Pseudomonas aeruginosa: modified categorization system for discrepant broth dilution and agar disk diffusion test results.

The fluoroquinolones ciprofloxacin, norfloxacin, and ofloxacin were examined in vitro against 103 enterococcal isolates and 138 isolates of Pseudomonas aeruginosa, in an attempt to determine which respective proposed interpretive criteria (minimal inhibitory concentration (MIC) versus diameter of agar disk diffusion inhibition zones) correlated best, i.e., resulted in fewer discrepant results. A previously proposed system for grouping discrepant results (very major, major, and minor discrepancies) of Barry and co-workers was modified to comprise 6 categories (very major, major, minor, slight, minimal, and negligible); this expanded system rendered the encountered discrepant in vitro test results more transparent. Overall, the currently employed interpretive criteria for norfloxacin (MICs versus 10-micrograms disks) resulted in fewer discrepancies with the above two groups of bacterial isolates than those proposed for ciprofloxacin and ofloxacin (MICs versus 5-micrograms disks, respectively).

Ciprofloxacin↗

Failure of polymyxin B nonapeptide to augment bactericidal activities of novobiocin, rifampin, and of defibrinated human blood against Serratia marcescens.

Polymyxin B (PB) and polymyxin B nonapeptide (PBNP), when combined with rifampin or novobiocin, but not vancomycin, yielded additive inhibitory effects against test strains of Serratia marcescens of three varieties: those that produced cocarde growths around PB disks (coc+); those that grew adjacent to PB disks (coc-, 6); and those that yielded clear inhibition zones around PB disks (coc-, clear). However, time kill curve experiments disclosed that only the combination of rifampin + PB exerted a potent bactericidal effect against coc+ strains of S. marcescens; rifampin + PBNP and novobiocin + PB or PBNP merely effected transient decreases of colony counts. Assays involving 50% (v/v) of fresh defibrinated human blood + PB or PBNP revealed that only PB clearly augmented the antibacterial activity of blood against coc+, and less so against coc- test strains of S. marcescens.

Blood Bactericidal Activity↗

Pseudomonas aeruginosa: in vitro susceptibility to antimicrobial drugs, single and combined, with and without defibrinated human blood.

Twelve clinical isolates of Pseudomonas aeruginosa of distinct pyocin type varied in susceptibility to 14 of 17 antimicrobial drugs. The 2 x MIC concentrations of 16 antimicrobial drugs combined with 55% (v/v) of fresh, defibrinated human blood yielded additive effects. Additive effects were noted with blood plus the MIC concentrations of all drugs tested except cefoperazone, gentamicin, and netilmicin. Blood combined with subinhibitory (1/2 MIC) concentrations of aztreonam, ceftazidime, ciprofloxacin, fleroxacin, imipenem, and tobramycin, respectively, yielded additive effects; indifferent effects were observed with the remaining 10 blood plus 1/2 MIC drug combinations. The following drug combinations additively augmented the antibacterial activity of 65% (v/v) of human blood against two selected isolates of P. aeruginosa: tobramycin (1 microgram/ml) plus the MIC or 2 x MIC concentrations of azlocillin, aztreonam, ceftazidime, ciprofloxacin, imipenem, norfloxacin, ofloxacin, piperacillin, and ticarcillin, respectively. Imipenem (8 micrograms/ml) combined with ceftazidime, cefoperazone, and piperacillin, but not aztreonam, enhanced the bactericidal activity of human blood. Rifampin (2 micrograms/ml) plus tobramycin (0.5-1 microgram/ml) combined with 8 or 16 micrograms/ml of azlocillin, aztreonam, cefoperazone, ceftazidime, imipenem, and piperacillin, respectively, enhanced blood-mediated killing of three representative multiple-drug-resistant P. aeruginosa isolates. Additional effective triple-drug combinations with human blood were rifampin + tobramycin + polymyxin B, rifampin + ciprofloxacin + imipenem, and rifampin + amikacin + imipenem. Ciprofloxacin (2 micrograms/ml) was the most potent intraphagocytic bactericidal drug of 16 tested agents (greater than or equal to 2 x MBC concentrations) against P. aeruginosa control strain ATCC 27853.

Anti-Bacterial Agents↗

Staphylococcus haemolyticus: cocarde growth around imipenem disks.

Twelve multiple-drug-resistant isolates of coagulase-negative staphylococci from diverse clinical sources, which had yielded cocarde growths (double zones of inhibition) around 10 micrograms imipenem disks, were identified as Staphylococcus haemolyticus. This was the only staphylococcal species which exhibited this unusual phenotypic trait at our institution during a 7-month observation period.

Imipenem↗

Chemotherapy of experimental (murine) Clostridium perfringens type A gas gangrene.

Five antimicrobial drugs (ciprofloxacin, clindamycin, imipenem, penicillin G, and rifampin) were examined for therapeutic efficacy in a murine model gas gangrene due to Clostridium perfringens type A, following infection with large bacterial inocula. Imipenem was effective against all 6 strains of C. perfringens; conversely, penicillin G failed against these 6 strains. Ciprofloxacin, clindamycin, and rifampin occupied intermediate positions.

Animals↗